Abstract

Background and Aims

The risk of heart failure progression or mortality in patients with peri-partum cardiomyopathy (PPCM) during subsequent pregnancies (SSPs) is a significant concern for patients, their families, and healthcare providers. However, there is limited contemporary, prospective data on SSP outcomes in PPCM patients from diverse ethnic and sociodemographic groups. This study aimed to assess maternal and neonatal outcomes in PPCM patients undergoing SSPs.

Methods

This is a sub-study on PPCM and SSPs of the global European Society of Cardiology PPCM Registry that recruited patients from 2012 to 2023. Maternal and neonatal outcomes were reported.

Results

From 332 patients with PPCM, there were 98 SSPs among 73 women. Of these, 25 (26%) SSPs ended prematurely due to therapeutic termination (20/25), miscarriage (4/25), and stillbirth (1/25). The median follow-up from the end of the SSP was 198 days (inter-quartile range 160–240). Left ventricular ejection fraction (LVEF) was persistently reduced to <50% prior to the SSP in 26% of patients, with only 6% having an LVEF <40%. Patient characteristics were similar, irrespective of SSP baseline LVEF. Clinical worsening [composite of all-cause death, cardiovascular rehospitalization, or decline in LVEF ≥10% (percentage points) and to <50%] occurred in 20% SSPs, with 2% all-cause maternal mortality. Signs/symptoms of heart failure and worsening of New York Heart Association class occurred in 26% and 22% of SSPs, respectively. At follow-up, the mean LVEF was 50% (±12%), and in 69% of SSPs, the LVEF was ≥50%. African women had similar outcome as the other ethnic groups. Pre-term delivery occurred in 24% of SSPs, 20% of babies were of low birth weight, and there was 3% all-cause neonatal mortality. Compared with women with SSP baseline LVEF <50%, fewer women with LVEF ≥50% were on heart failure pharmacotherapies prior to the SSP, and in this group of women, there was a significant decline in LVEF.

Conclusions

Maternal morbidity and mortality rates were lower than anticipated. Baseline LVEF <50% was not associated with an increased frequency of adverse maternal outcomes, and no further decline in LVEF was observed in this group. In contrast, women with SSPs and a baseline LVEF ≥50% experienced a decline in LVEF, potentially attributable to reduced use of heart failure pharmacotherapy during pregnancy and the post-partum period. Therapeutic termination was performed in approximately a fifth of cases. The findings suggest that reclassification of a SSP with persisting mild left ventricular impairment from modified World Health Organization (mWHO) Class IV (contraindicated) to mWHO III may be considered, while remaining under the care of an experienced medical team and with appropriate pharmacological management.

Outcome of pregnancies in women with a previously diagnosed Peripartum Cardiomyopathy. EORP, EuroObservational Research Programme; LV, left ventricular; LVEF, LV ejection fraction; PPCM, peri-partum cardiomyopathy; SSP, subsequent pregnancy.
Structured Graphical Abstract

Outcome of pregnancies in women with a previously diagnosed Peripartum Cardiomyopathy. EORP, EuroObservational Research Programme; LV, left ventricular; LVEF, LV ejection fraction; PPCM, peri-partum cardiomyopathy; SSP, subsequent pregnancy.

See the editorial comment for this article ‘How can we counsel patients desiring subsequent pregnancy after peripartum cardiomyopathy?’, by O. Agboola and G. Sharma, https://doi.org/10.1093/eurheartj/ehae888.

Introduction

Peri-partum cardiomyopathy (PPCM) is a potentially serious condition that manifests as heart failure with reduced ejection fraction (EF), occurring either late in pregnancy or within the months after childbirth.1,2 Over the past two decades, significant progress has been made in understanding the pathophysiology and treatment of this condition3,4; however, numerous uncertainties persist.5

Women with a diagnosis of PPCM may consider having another pregnancy, but the data supporting existing guideline recommendations for subsequent pregnancies (SSPs) are scarce. In their 2018 Guidelines for the Management of Cardiovascular Diseases during Pregnancy, the European Society of Cardiology (ESC) classify women with PPCM with any residual left ventricular (LV) impairment as being at ‘extremely high risk of maternal mortality or severe morbidity’ [modified World Health Organization (mWHO) Class IV], quoting a maternal risk of cardiac event (40%–100%) and suggesting that termination of pregnancy should be discussed. In women with previous PPCM, without any residual LV impairment, the ESC describe a ‘significantly increased risk of maternal mortality or severe morbidity’ (mWHO Class III), quoting a maternal risk of cardiac event (19%–27%).6 These estimates are not specific to women with PPCM, and both mWHO classes contain a number of other conditions. There is therefore a need for contemporary, prospective data to inform discussions with women with PPCM regarding maternal and neonatal risks in this context.

Methods

The ESC EuroObservational Research Programme (EORP) PPCM Registry is a worldwide, prospective registry, which included 752 women with PPCM from 51 countries, enrolling patients from 2012, with a follow-up period of up to 36 months post-diagnosis. Only newly diagnosed cases (those who consented within 6 months of the diagnosis of PPCM) were eligible. Study design, patient selection, and data collection have been published previously.7,8 Eligibility criteria for participating centres were as follows: (i) availability of echocardiography, (ii) clinical expertise to make the diagnosis, and (iii) the ability to follow-up patients for 6 months. A dedicated central study management team co-ordinating the EORP Heart House assisted physicians with regulatory and ethical approval and with data entry. Mandatory inclusion criteria for patients were as follows: (i) peri-partum state, (ii) signs and/or symptoms of heart failure, (iii) LVEF ≤45%, and (iv) exclusion of other causes of heart failure.

In 2021, centres were invited to participate in a dedicated sub-study on SSPs, the aim of which was to capture comprehensive data on maternal and neonatal morbidity and mortality associated with an SSP until December 2023. The secondary objectives of the sub-study were evaluation of differences in above outcomes in Africans and non-Africans. Additional subgroups of interest were one vs. multiple SSPs and terminated vs. continued SSPs. Recruiting countries are shown in Figure 1.

Countries participating in the EORP PPCM registry, which contributed to the sub-study on subsequent pregnancies
Figure 1

Countries participating in the EORP PPCM registry, which contributed to the sub-study on subsequent pregnancies

An SSP was defined as a pregnancy that occurred following the pregnancy initially linked to the first diagnosis of PPCM, which led to inclusion in the main EORP PPCM Registry. Data collected in the main registry (i.e. that of the initial PPCM diagnosis) were merged with prospective data collected in the SSP study. The SSP baseline visit was defined as the first review during the SSP. Echocardiography in the main study was performed at the time of the index PPCM presentation and at 6 and 12 month follow-up. In the SSP sub-study, echocardiographic data were captured where available. In a number of sites, echocardiography had to be paid out-of-pocket and was not performed for economic reasons. These additional echocardiographic data were categorized at SSP baseline, during the SSP, and after delivery at the SSP follow-up. Left ventricular ejection fraction at SSP baseline was defined as the LVEF during the first trimester (<12 weeks) or the last available LVEF prior to the SSP. Information on pharmacological therapy was collected and included guideline-recommended heart failure therapies, anticoagulation, and bromocriptine.

Maternal outcomes reported were as follows: LVEF at follow-up (when available and could be afforded), all-cause mortality, cardiovascular (CV) hospitalization, and clinical worsening [defined as a composite of all-cause death or CV hospitalization or decline in LVEF by ≥10% (percentage points) and to a value <50%] as previously defined.9 We also documented a composite of all-cause death or LVEF ≤35% at follow-up, development of heart failure during the SSP [defined as symptoms (breathlessness, chest pain, palpitations, dizziness) or signs (pulmonary rales, peri-pheral oedema, jugular venous distension, or third heart sound) of heart failure], and worsening of New York Heart Association (NYHA) class.10 Differences in patient characteristics and outcomes were examined according to SSP baseline categories of LVEF (i.e. LVEF <50% vs. LVEF ≥50%), ethnicity (African vs. other), number of SSPs (i.e. single SSP vs. more than one SSP), and terminated (i.e. therapeutic or spontaneous) or vs. continued pregnancy.

Neonatal outcomes reported were as follows: all-cause mortality, premature delivery (defined as estimated gestation <37 weeks), and low birthweight.

Continuous variables are reported as means and standard deviations or medians and inter-quartile ranges (IQRs). Between-group comparisons for continuous variables were made by using t-tests or Kruskal–Wallis testing. Categorical variables are reported as percentages. Between-group comparisons for categorical variables were made using the χ2 test. A two-sided P-value <.05 was considered statistically significant. Analyses were performed using Stata v18 (StataCorp LLC, College Station, TX, USA). Missing data were excluded.

Results

Enrolment

Eleven sites across Europe, the Middle East, Asia-Pacific, and Africa (Figure 1) that had enrolled 332 patients with PPCM in the EORP PPCM Registry7,8 included 73 patients with 98 SSPs in this study. The main findings are displayed in the Structured Graphical Abstract. The numbers with available data for different characteristics and outcomes are shown in Supplementary data online, Table S1, as well as in each respective table.

Clinical and obstetric characteristics

The mean age at the onset of the SSP was 30 (±5) years (Table 1). Overall, 14% of the women were Asian, 36% were of African ethnicity, 27% were Caucasian, and 13% were Middle Eastern. In total, 12% of SSPs were complicated by hypertension (defined as pre-existing hypertension, gestational hypertension, or pre-eclampsia). The majority of women (83%) were asymptomatic (NYHA Class I) at baseline. Baseline LVEF data for SSPs were available for 84 of 98 (86%) pregnancies. The baseline LVEF for SSPs (defined as LVEF measured in the first trimester or the last available LVEF prior to the SSP) was 54% (±10). At baseline, 26% of SSPs had an LVEF <50%, while 74% had an LVEF ≥50%. At the SSP baseline, LVEF was <40% in five women (6%), and only one woman had an LVEF <30%. Differences in characteristics according to whether or not a follow-up echocardiogram was performed are shown in Supplementary data online, Table S2.

Table 1

Clinical and obstetric characteristics of subsequent pregnancies in women with previous peri-partum cardiomyopathy

 All SSPs (N = 98)SSPs with known baseline LVEF (N = 84)SSP with
baseline LVEF <50% (N = 22)
SSP with
baseline LVEF ≥50% (N = 62)
P-valueMissing
Age at index presentation (years)27 ± 527 ± 527 ± 528 ± 5.377
Age at SSP delivery (years)30 ± 531 ± 530 ± 631 ± 5.447
Parity at index presentation2 (1–2)2 (1–2)2 (1–2)2 (1–2).9655
Hypertension (any) during SSP10 (11.9)9 (12.2)1 (5.3)8 (14.5).2914
Diabetes2 (2.1)2 (2.5)0 (0.0)2 (3.3).404
NYHA class.2833
 I54 (83.1)51 (83.6)12 (75.0)39 (86.7)
 II11 (16.9)10 (16.4)4 (25.0)6 (13.3)
Ethnicity.618
 Asian13 (14.4)12 (15.6)3 (14.3)9 (16.1)
 Black36 (40.0)30 (39.0)6 (28.6)24 (42.9)
 Caucasian24 (26.7)21 (27.3)6 (28.6)15 (26.8)
 Middle Eastern12 (13.3)10 (13.0)4 (19.0)6 (10.7)
 Other5 (5.6)4 (5.2)2 (9.5)2 (3.6)
African35 (35.7)28 (33.3)8 (36.4)20 (32.3).730
LVEF at index presentation (%)32 ± 1032 ± 1030 ± 933 ± 10.225
LVEF at SSP baseline (%)54 ± 1054 ± 1042 ± 759 ± 6<.00114
Categories of LVEF at SSP baseline<.00114
 LVEF <30%1 (1.2)1 (1.2)1 (4.5)0 (0.0)
 LVEF 30%–39%4 (4.8)4 (4.8)4 (18.2)0 (0.0)
 LVEF 40%–49%17 (20.2)17 (20.2)17 (77.3)0 (0.0)
 LVEF ≥50%62 (73.8)62 (73.8)0 (0.0)62 (100.0)
Mode of SSP delivery.600
 Vaginal34 (34.7)28 (33.3)7 (31.8)21 (33.9)
 Elective C-section32 (32.7)30 (35.7)7 (31.8)23 (37.1)
 Emergency C-section7 (7.1)5 (6.0)1 (4.5)4 (6.5)
 Therapeutic termination20 (20.4)17 (20.2)7 (31.8)10 (16.1)
 Miscarriage4 (4.1)3 (3.6)0 (0.0)3 (4.8)
 Stillbirth1 (1.0)1 (1.2)0 (0.0)1 (1.6)
Estimated gestation (weeks)38 (37–39)38 (36–39)37 (36–38)38 (37–39).2944
 All SSPs (N = 98)SSPs with known baseline LVEF (N = 84)SSP with
baseline LVEF <50% (N = 22)
SSP with
baseline LVEF ≥50% (N = 62)
P-valueMissing
Age at index presentation (years)27 ± 527 ± 527 ± 528 ± 5.377
Age at SSP delivery (years)30 ± 531 ± 530 ± 631 ± 5.447
Parity at index presentation2 (1–2)2 (1–2)2 (1–2)2 (1–2).9655
Hypertension (any) during SSP10 (11.9)9 (12.2)1 (5.3)8 (14.5).2914
Diabetes2 (2.1)2 (2.5)0 (0.0)2 (3.3).404
NYHA class.2833
 I54 (83.1)51 (83.6)12 (75.0)39 (86.7)
 II11 (16.9)10 (16.4)4 (25.0)6 (13.3)
Ethnicity.618
 Asian13 (14.4)12 (15.6)3 (14.3)9 (16.1)
 Black36 (40.0)30 (39.0)6 (28.6)24 (42.9)
 Caucasian24 (26.7)21 (27.3)6 (28.6)15 (26.8)
 Middle Eastern12 (13.3)10 (13.0)4 (19.0)6 (10.7)
 Other5 (5.6)4 (5.2)2 (9.5)2 (3.6)
African35 (35.7)28 (33.3)8 (36.4)20 (32.3).730
LVEF at index presentation (%)32 ± 1032 ± 1030 ± 933 ± 10.225
LVEF at SSP baseline (%)54 ± 1054 ± 1042 ± 759 ± 6<.00114
Categories of LVEF at SSP baseline<.00114
 LVEF <30%1 (1.2)1 (1.2)1 (4.5)0 (0.0)
 LVEF 30%–39%4 (4.8)4 (4.8)4 (18.2)0 (0.0)
 LVEF 40%–49%17 (20.2)17 (20.2)17 (77.3)0 (0.0)
 LVEF ≥50%62 (73.8)62 (73.8)0 (0.0)62 (100.0)
Mode of SSP delivery.600
 Vaginal34 (34.7)28 (33.3)7 (31.8)21 (33.9)
 Elective C-section32 (32.7)30 (35.7)7 (31.8)23 (37.1)
 Emergency C-section7 (7.1)5 (6.0)1 (4.5)4 (6.5)
 Therapeutic termination20 (20.4)17 (20.2)7 (31.8)10 (16.1)
 Miscarriage4 (4.1)3 (3.6)0 (0.0)3 (4.8)
 Stillbirth1 (1.0)1 (1.2)0 (0.0)1 (1.6)
Estimated gestation (weeks)38 (37–39)38 (36–39)37 (36–38)38 (37–39).2944

Data are presented as mean ± SD or median (IQR) for continuous measures and n (%) for categorical measures.

Table 1

Clinical and obstetric characteristics of subsequent pregnancies in women with previous peri-partum cardiomyopathy

 All SSPs (N = 98)SSPs with known baseline LVEF (N = 84)SSP with
baseline LVEF <50% (N = 22)
SSP with
baseline LVEF ≥50% (N = 62)
P-valueMissing
Age at index presentation (years)27 ± 527 ± 527 ± 528 ± 5.377
Age at SSP delivery (years)30 ± 531 ± 530 ± 631 ± 5.447
Parity at index presentation2 (1–2)2 (1–2)2 (1–2)2 (1–2).9655
Hypertension (any) during SSP10 (11.9)9 (12.2)1 (5.3)8 (14.5).2914
Diabetes2 (2.1)2 (2.5)0 (0.0)2 (3.3).404
NYHA class.2833
 I54 (83.1)51 (83.6)12 (75.0)39 (86.7)
 II11 (16.9)10 (16.4)4 (25.0)6 (13.3)
Ethnicity.618
 Asian13 (14.4)12 (15.6)3 (14.3)9 (16.1)
 Black36 (40.0)30 (39.0)6 (28.6)24 (42.9)
 Caucasian24 (26.7)21 (27.3)6 (28.6)15 (26.8)
 Middle Eastern12 (13.3)10 (13.0)4 (19.0)6 (10.7)
 Other5 (5.6)4 (5.2)2 (9.5)2 (3.6)
African35 (35.7)28 (33.3)8 (36.4)20 (32.3).730
LVEF at index presentation (%)32 ± 1032 ± 1030 ± 933 ± 10.225
LVEF at SSP baseline (%)54 ± 1054 ± 1042 ± 759 ± 6<.00114
Categories of LVEF at SSP baseline<.00114
 LVEF <30%1 (1.2)1 (1.2)1 (4.5)0 (0.0)
 LVEF 30%–39%4 (4.8)4 (4.8)4 (18.2)0 (0.0)
 LVEF 40%–49%17 (20.2)17 (20.2)17 (77.3)0 (0.0)
 LVEF ≥50%62 (73.8)62 (73.8)0 (0.0)62 (100.0)
Mode of SSP delivery.600
 Vaginal34 (34.7)28 (33.3)7 (31.8)21 (33.9)
 Elective C-section32 (32.7)30 (35.7)7 (31.8)23 (37.1)
 Emergency C-section7 (7.1)5 (6.0)1 (4.5)4 (6.5)
 Therapeutic termination20 (20.4)17 (20.2)7 (31.8)10 (16.1)
 Miscarriage4 (4.1)3 (3.6)0 (0.0)3 (4.8)
 Stillbirth1 (1.0)1 (1.2)0 (0.0)1 (1.6)
Estimated gestation (weeks)38 (37–39)38 (36–39)37 (36–38)38 (37–39).2944
 All SSPs (N = 98)SSPs with known baseline LVEF (N = 84)SSP with
baseline LVEF <50% (N = 22)
SSP with
baseline LVEF ≥50% (N = 62)
P-valueMissing
Age at index presentation (years)27 ± 527 ± 527 ± 528 ± 5.377
Age at SSP delivery (years)30 ± 531 ± 530 ± 631 ± 5.447
Parity at index presentation2 (1–2)2 (1–2)2 (1–2)2 (1–2).9655
Hypertension (any) during SSP10 (11.9)9 (12.2)1 (5.3)8 (14.5).2914
Diabetes2 (2.1)2 (2.5)0 (0.0)2 (3.3).404
NYHA class.2833
 I54 (83.1)51 (83.6)12 (75.0)39 (86.7)
 II11 (16.9)10 (16.4)4 (25.0)6 (13.3)
Ethnicity.618
 Asian13 (14.4)12 (15.6)3 (14.3)9 (16.1)
 Black36 (40.0)30 (39.0)6 (28.6)24 (42.9)
 Caucasian24 (26.7)21 (27.3)6 (28.6)15 (26.8)
 Middle Eastern12 (13.3)10 (13.0)4 (19.0)6 (10.7)
 Other5 (5.6)4 (5.2)2 (9.5)2 (3.6)
African35 (35.7)28 (33.3)8 (36.4)20 (32.3).730
LVEF at index presentation (%)32 ± 1032 ± 1030 ± 933 ± 10.225
LVEF at SSP baseline (%)54 ± 1054 ± 1042 ± 759 ± 6<.00114
Categories of LVEF at SSP baseline<.00114
 LVEF <30%1 (1.2)1 (1.2)1 (4.5)0 (0.0)
 LVEF 30%–39%4 (4.8)4 (4.8)4 (18.2)0 (0.0)
 LVEF 40%–49%17 (20.2)17 (20.2)17 (77.3)0 (0.0)
 LVEF ≥50%62 (73.8)62 (73.8)0 (0.0)62 (100.0)
Mode of SSP delivery.600
 Vaginal34 (34.7)28 (33.3)7 (31.8)21 (33.9)
 Elective C-section32 (32.7)30 (35.7)7 (31.8)23 (37.1)
 Emergency C-section7 (7.1)5 (6.0)1 (4.5)4 (6.5)
 Therapeutic termination20 (20.4)17 (20.2)7 (31.8)10 (16.1)
 Miscarriage4 (4.1)3 (3.6)0 (0.0)3 (4.8)
 Stillbirth1 (1.0)1 (1.2)0 (0.0)1 (1.6)
Estimated gestation (weeks)38 (37–39)38 (36–39)37 (36–38)38 (37–39).2944

Data are presented as mean ± SD or median (IQR) for continuous measures and n (%) for categorical measures.

The median parity at the time of the index presentation of PPCM was 2 (IQR 1–2). A total of 25 (26%) SSPs ended prematurely due to therapeutic termination (20/25), miscarriage (4/25), and stillbirth (1/25). Overall, 73 (74%) resulted in live deliveries (n = 74 neonates). The mode of SSP delivery was vaginal in 35% of cases, elective caesarean section in 33%, and emergency caesarean section in 7%. Among those who had a live delivery, the median gestation was 38 weeks (IQR 37–39).

Patient characteristics were similar irrespective of whether SSP baseline LVEF was <50% or ≥50%, including the LVEF at the index PPCM presentation. Patient characteristics, excluding those pregnancies ending in a therapeutic or spontaneous termination, are shown in Supplementary data online, Table S3.

Maternal outcomes in all women

The median follow-up period was 198 days (IQR 160–242) after the end of the SSP. Median echocardiographic follow-up was comparable at 206 days (IQR 134–283). Mortality data were available for 94 of 98 (96%) SSPs. Follow-up LVEF data were available for 55 of 98 (56%) SSPs. Death from any cause occurred in two (2%) women (one with LVEF <50% and one with LVEF ≥50%) and hospitalization for a CV cause in two (2%) women (Table 2). Both deaths occurred post-partum; the cause of death was only reported in one (ischaemic stroke). Both CV hospitalizations occurred in the post-partum period. Clinical worsening (composite of all-cause death, CV hospitalization, or decline in LVEF by ≥10% and to <50%) occurred in 20% and the composite of death or LVEF ≤35% occurred in 16%. Symptoms or signs of heart failure (defined as breathlessness, chest pain, palpitations, dizziness, pulmonary rales, peri-pheral oedema, jugular venous distension, or third heart sound) developed during 26% of SSPs, and in 22%, there was a worsening of NYHA class, either during the SSP or after delivery. Left ventricular ejection fraction at follow-up was 50% (±12) and in 69% of SSPs the LVEF was ≥50% at follow-up. Maternal outcomes, excluding those pregnancies ending in a therapeutic or spontaneous termination, are shown in Supplementary data online, Table S4.

Table 2

Maternal and neonatal outcomes of subsequent pregnancies in women with previous peri-partum cardiomyopathy

 Total SSPs (N = 98)Total with SSP baseline LVEF (N = 84)SSP baseline LVEF <50% (N = 22)SSP baseline LVEF ≥50% (N = 62)P-valueMissing
Follow-up LVEF (%)50 ± 1251 ± 1145 ± 1153 ± 11.04043
Follow-up LVEF ≥50%38 (69.1)35 (70.0)6 (46.2)29 (78.4).02943
CV hospitalizationa2 (2.2)0 (0.0)0 (0.0)0 (0.0)21
All-cause deatha2 (2.1)2 (2.5)1 (4.5)1 (1.6).4440
All-cause death, CV hospitalization or decline in LVEF of ≥10% and to <50%a12 (19.7)10 (16.9)2 (13.3)8 (18.2).678
Decline in LVEF of ≥10% and to <50%a8 (13.1)8 (13.1)1 (6.2)7 (15.6).344
All-cause death or LVEF ≤35%a9 (16.1)7 (13.7)2 (15.4)5 (13.2).8437
Heart failure during SSP20 (26.0)18 (26.5)6 (33.3)12 (24.0).4437
Worsening of NYHA classa13 (22.4)13 (23.6)4 (26.7)9 (22.5).7542
Pre-term delivery (estimated gestation <37 weeks)13 (24.1)13 (26.0)4 (33.3)9 (23.7).5144
Neonatal birthweight (g)2877 (2500–3300)2820 (2500–3200)2680 (2470–3065)2820 (2500–3200).6047
Low birth weight (<2500 g)10 (19.6)10 (21.3)3 (33.3)7 (18.4).3347
Neonatal all-cause death2 (2.9)2 (3.4)1 (7.1)1 (2.2).3732
 Total SSPs (N = 98)Total with SSP baseline LVEF (N = 84)SSP baseline LVEF <50% (N = 22)SSP baseline LVEF ≥50% (N = 62)P-valueMissing
Follow-up LVEF (%)50 ± 1251 ± 1145 ± 1153 ± 11.04043
Follow-up LVEF ≥50%38 (69.1)35 (70.0)6 (46.2)29 (78.4).02943
CV hospitalizationa2 (2.2)0 (0.0)0 (0.0)0 (0.0)21
All-cause deatha2 (2.1)2 (2.5)1 (4.5)1 (1.6).4440
All-cause death, CV hospitalization or decline in LVEF of ≥10% and to <50%a12 (19.7)10 (16.9)2 (13.3)8 (18.2).678
Decline in LVEF of ≥10% and to <50%a8 (13.1)8 (13.1)1 (6.2)7 (15.6).344
All-cause death or LVEF ≤35%a9 (16.1)7 (13.7)2 (15.4)5 (13.2).8437
Heart failure during SSP20 (26.0)18 (26.5)6 (33.3)12 (24.0).4437
Worsening of NYHA classa13 (22.4)13 (23.6)4 (26.7)9 (22.5).7542
Pre-term delivery (estimated gestation <37 weeks)13 (24.1)13 (26.0)4 (33.3)9 (23.7).5144
Neonatal birthweight (g)2877 (2500–3300)2820 (2500–3200)2680 (2470–3065)2820 (2500–3200).6047
Low birth weight (<2500 g)10 (19.6)10 (21.3)3 (33.3)7 (18.4).3347
Neonatal all-cause death2 (2.9)2 (3.4)1 (7.1)1 (2.2).3732

Data are presented as mean ± SD or median (IQR) for continuous measures and n (%) for categorical measures.

aDuring SSP to end of follow-up.

Table 2

Maternal and neonatal outcomes of subsequent pregnancies in women with previous peri-partum cardiomyopathy

 Total SSPs (N = 98)Total with SSP baseline LVEF (N = 84)SSP baseline LVEF <50% (N = 22)SSP baseline LVEF ≥50% (N = 62)P-valueMissing
Follow-up LVEF (%)50 ± 1251 ± 1145 ± 1153 ± 11.04043
Follow-up LVEF ≥50%38 (69.1)35 (70.0)6 (46.2)29 (78.4).02943
CV hospitalizationa2 (2.2)0 (0.0)0 (0.0)0 (0.0)21
All-cause deatha2 (2.1)2 (2.5)1 (4.5)1 (1.6).4440
All-cause death, CV hospitalization or decline in LVEF of ≥10% and to <50%a12 (19.7)10 (16.9)2 (13.3)8 (18.2).678
Decline in LVEF of ≥10% and to <50%a8 (13.1)8 (13.1)1 (6.2)7 (15.6).344
All-cause death or LVEF ≤35%a9 (16.1)7 (13.7)2 (15.4)5 (13.2).8437
Heart failure during SSP20 (26.0)18 (26.5)6 (33.3)12 (24.0).4437
Worsening of NYHA classa13 (22.4)13 (23.6)4 (26.7)9 (22.5).7542
Pre-term delivery (estimated gestation <37 weeks)13 (24.1)13 (26.0)4 (33.3)9 (23.7).5144
Neonatal birthweight (g)2877 (2500–3300)2820 (2500–3200)2680 (2470–3065)2820 (2500–3200).6047
Low birth weight (<2500 g)10 (19.6)10 (21.3)3 (33.3)7 (18.4).3347
Neonatal all-cause death2 (2.9)2 (3.4)1 (7.1)1 (2.2).3732
 Total SSPs (N = 98)Total with SSP baseline LVEF (N = 84)SSP baseline LVEF <50% (N = 22)SSP baseline LVEF ≥50% (N = 62)P-valueMissing
Follow-up LVEF (%)50 ± 1251 ± 1145 ± 1153 ± 11.04043
Follow-up LVEF ≥50%38 (69.1)35 (70.0)6 (46.2)29 (78.4).02943
CV hospitalizationa2 (2.2)0 (0.0)0 (0.0)0 (0.0)21
All-cause deatha2 (2.1)2 (2.5)1 (4.5)1 (1.6).4440
All-cause death, CV hospitalization or decline in LVEF of ≥10% and to <50%a12 (19.7)10 (16.9)2 (13.3)8 (18.2).678
Decline in LVEF of ≥10% and to <50%a8 (13.1)8 (13.1)1 (6.2)7 (15.6).344
All-cause death or LVEF ≤35%a9 (16.1)7 (13.7)2 (15.4)5 (13.2).8437
Heart failure during SSP20 (26.0)18 (26.5)6 (33.3)12 (24.0).4437
Worsening of NYHA classa13 (22.4)13 (23.6)4 (26.7)9 (22.5).7542
Pre-term delivery (estimated gestation <37 weeks)13 (24.1)13 (26.0)4 (33.3)9 (23.7).5144
Neonatal birthweight (g)2877 (2500–3300)2820 (2500–3200)2680 (2470–3065)2820 (2500–3200).6047
Low birth weight (<2500 g)10 (19.6)10 (21.3)3 (33.3)7 (18.4).3347
Neonatal all-cause death2 (2.9)2 (3.4)1 (7.1)1 (2.2).3732

Data are presented as mean ± SD or median (IQR) for continuous measures and n (%) for categorical measures.

aDuring SSP to end of follow-up.

Maternal outcomes according to subsequent pregnancy baseline left ventricular ejection fraction

Women starting a SSP with impaired LVEF <50% remained with a lower LVEF at post-delivery follow-up compared with those commencing SSP with baseline LVEF ≥50% (45% vs. 53%, P = .040, Table 2). There was no significant difference in the proportion of women with clinical worsening (all-cause death, CV hospitalization, or decline in LVEF by ≥10% and to <50%) according to SSP baseline LVEF category, although numerically the proportion was greater in women with SSP baseline LVEF ≥50% than in those with LVEF <50%. Similarly, although numerically heart failure and worsening of NYHA class occurred more often in women with SSP baseline LVEF <50%, these differences were not statistically different. One death occurred in a woman with SSP baseline LVEF <50% and the other in a woman with SSP baseline LVEF ≥50%. The frequency of the composite of death or LVEF ≤35% was similar, irrespective of SSP baseline LVEF group.

Figure 2 illustrates the change in LVEF over time, according to SSP baseline LVEF. The mean change in LVEF in women with SSP baseline LVEF ≥50% was −5% (±10) (P = .002) and in women with SSP baseline LVEF <50% was +3% (±9) (P = .26).

Change in left ventricular ejection fraction according to subsequent pregnancy baseline left ventricular ejection fraction in women with previous peri-partum cardiomyopathy
Figure 2

Change in left ventricular ejection fraction according to subsequent pregnancy baseline left ventricular ejection fraction in women with previous peri-partum cardiomyopathy

Women with and without clinical worsening

Women with clinical worsening (composite of all-cause death, CV hospitalization, or decline in LVEF by ≥10% and to <50%) were more frequently Asian and had hypertension, than those without (Table 3). There was a trend towards greater parity, higher (i.e. worse) NYHA class, lower LVEF, and shorter gestation in women with clinical worsening than in those without.

Table 3

Characteristics of subsequent pregnancies with and without clinical worsening (composite of all-cause death, cardiovascular hospitalization, or decline in left ventricular ejection fraction by ≥10% and to <50%) in women with previous peri-partum cardiomyopathy

 No clinical worsening (N = 52)Clinical worsening (N = 12)P-valueMissing
Age at index presentation (years)28 ± 526 ± 6.516
Age at SSP delivery (years)31 ± 530 ± 5.636
Ethnicity.0177
 Asian7 (15.9)6 (60.0)
 Black12 (27.3)2 (20.0)
 Caucasian16 (36.4)0 (0.0)
 Middle Eastern8 (18.2)1 (10.0)
 Other1 (2.3)1 (10.0)
African10 (20.4)3 (25.0).730
Parity at index presentation1 (1–2)3 (1–6).08332
Hypertension (any) during SSP2 (4.4)3 (37.5).0038
Diabetes2 (4.1)0 (0.0).501
NYHA class.07713
 I35 (85.4)4 (57.1)
 II6 (14.6)3 (42.9)
LVEF at index presentation (%)32 ± 928 ± 7.224
LVEF at SSP baseline (%)55 ± 950 ± 7.0522
Categories of LVEF at SSP baseline.0212
 LVEF <30%0 (0.0)0 (0.0)
 LVEF 30%–39%1 (2.0)2 (20.0)
 LVEF 40%–49%12 (24.5)0 (0.0)
 LVEF ≥50%36 (73.5)8 (80.0)
Mode of SSP delivery.550
 Vaginal14 (28.6)2 (16.7)
 Elective C-section20 (40.8)8 (66.7)
 Emergency C-section4 (8.2)1 (8.3)
 Therapeutic termination8 (16.3)1 (8.3)
 Miscarriage3 (6.1)0 (0.0)
Estimated gestation (weeks)38 (37–39)36 (32–38).07724
 No clinical worsening (N = 52)Clinical worsening (N = 12)P-valueMissing
Age at index presentation (years)28 ± 526 ± 6.516
Age at SSP delivery (years)31 ± 530 ± 5.636
Ethnicity.0177
 Asian7 (15.9)6 (60.0)
 Black12 (27.3)2 (20.0)
 Caucasian16 (36.4)0 (0.0)
 Middle Eastern8 (18.2)1 (10.0)
 Other1 (2.3)1 (10.0)
African10 (20.4)3 (25.0).730
Parity at index presentation1 (1–2)3 (1–6).08332
Hypertension (any) during SSP2 (4.4)3 (37.5).0038
Diabetes2 (4.1)0 (0.0).501
NYHA class.07713
 I35 (85.4)4 (57.1)
 II6 (14.6)3 (42.9)
LVEF at index presentation (%)32 ± 928 ± 7.224
LVEF at SSP baseline (%)55 ± 950 ± 7.0522
Categories of LVEF at SSP baseline.0212
 LVEF <30%0 (0.0)0 (0.0)
 LVEF 30%–39%1 (2.0)2 (20.0)
 LVEF 40%–49%12 (24.5)0 (0.0)
 LVEF ≥50%36 (73.5)8 (80.0)
Mode of SSP delivery.550
 Vaginal14 (28.6)2 (16.7)
 Elective C-section20 (40.8)8 (66.7)
 Emergency C-section4 (8.2)1 (8.3)
 Therapeutic termination8 (16.3)1 (8.3)
 Miscarriage3 (6.1)0 (0.0)
Estimated gestation (weeks)38 (37–39)36 (32–38).07724

Data are presented as mean ± SD or median (IQR) for continuous measures and n (%) for categorical measures.

Table 3

Characteristics of subsequent pregnancies with and without clinical worsening (composite of all-cause death, cardiovascular hospitalization, or decline in left ventricular ejection fraction by ≥10% and to <50%) in women with previous peri-partum cardiomyopathy

 No clinical worsening (N = 52)Clinical worsening (N = 12)P-valueMissing
Age at index presentation (years)28 ± 526 ± 6.516
Age at SSP delivery (years)31 ± 530 ± 5.636
Ethnicity.0177
 Asian7 (15.9)6 (60.0)
 Black12 (27.3)2 (20.0)
 Caucasian16 (36.4)0 (0.0)
 Middle Eastern8 (18.2)1 (10.0)
 Other1 (2.3)1 (10.0)
African10 (20.4)3 (25.0).730
Parity at index presentation1 (1–2)3 (1–6).08332
Hypertension (any) during SSP2 (4.4)3 (37.5).0038
Diabetes2 (4.1)0 (0.0).501
NYHA class.07713
 I35 (85.4)4 (57.1)
 II6 (14.6)3 (42.9)
LVEF at index presentation (%)32 ± 928 ± 7.224
LVEF at SSP baseline (%)55 ± 950 ± 7.0522
Categories of LVEF at SSP baseline.0212
 LVEF <30%0 (0.0)0 (0.0)
 LVEF 30%–39%1 (2.0)2 (20.0)
 LVEF 40%–49%12 (24.5)0 (0.0)
 LVEF ≥50%36 (73.5)8 (80.0)
Mode of SSP delivery.550
 Vaginal14 (28.6)2 (16.7)
 Elective C-section20 (40.8)8 (66.7)
 Emergency C-section4 (8.2)1 (8.3)
 Therapeutic termination8 (16.3)1 (8.3)
 Miscarriage3 (6.1)0 (0.0)
Estimated gestation (weeks)38 (37–39)36 (32–38).07724
 No clinical worsening (N = 52)Clinical worsening (N = 12)P-valueMissing
Age at index presentation (years)28 ± 526 ± 6.516
Age at SSP delivery (years)31 ± 530 ± 5.636
Ethnicity.0177
 Asian7 (15.9)6 (60.0)
 Black12 (27.3)2 (20.0)
 Caucasian16 (36.4)0 (0.0)
 Middle Eastern8 (18.2)1 (10.0)
 Other1 (2.3)1 (10.0)
African10 (20.4)3 (25.0).730
Parity at index presentation1 (1–2)3 (1–6).08332
Hypertension (any) during SSP2 (4.4)3 (37.5).0038
Diabetes2 (4.1)0 (0.0).501
NYHA class.07713
 I35 (85.4)4 (57.1)
 II6 (14.6)3 (42.9)
LVEF at index presentation (%)32 ± 928 ± 7.224
LVEF at SSP baseline (%)55 ± 950 ± 7.0522
Categories of LVEF at SSP baseline.0212
 LVEF <30%0 (0.0)0 (0.0)
 LVEF 30%–39%1 (2.0)2 (20.0)
 LVEF 40%–49%12 (24.5)0 (0.0)
 LVEF ≥50%36 (73.5)8 (80.0)
Mode of SSP delivery.550
 Vaginal14 (28.6)2 (16.7)
 Elective C-section20 (40.8)8 (66.7)
 Emergency C-section4 (8.2)1 (8.3)
 Therapeutic termination8 (16.3)1 (8.3)
 Miscarriage3 (6.1)0 (0.0)
Estimated gestation (weeks)38 (37–39)36 (32–38).07724

Data are presented as mean ± SD or median (IQR) for continuous measures and n (%) for categorical measures.

Neonatal outcomes

Data on neonatal mortality were available for 68 of 74 (92%) live deliveries. There were two neonatal deaths (3% all-cause neonatal mortality); one in a baby born to a woman with a SSP baseline LVEF 35%, delivered by emergency caesarean section at 26 weeks’ gestation, and the other in a twin (the only set of twins) born to a woman with a SSP baseline LVEF ≥50%. Pre-term delivery (estimated gestation <37 weeks) occurred in 24% of SSPs and low birth weight in 19% of neonates (Table 2).

Pharmacological therapy

Data on pharmacological therapy prior to the SSP were recorded for 92 (94%) pregnancies, during the SSP (at first physician visit of the SSP) for 86 (88%) pregnancies and after the SSP (from end of pregnancy to end follow-up) for 73 (74%) pregnancies (Figure 3).

Cardiovascular medication use before, during, and after the subsequent pregnancy in women with previous peri-partum cardiomyopathy
Figure 3

Cardiovascular medication use before, during, and after the subsequent pregnancy in women with previous peri-partum cardiomyopathy

Before onset of the SSP, diuretics were used in 21%, beta-blockers in 51%, mineralocorticoid receptor antagonists (MRAs) in 17%, angiotensin-converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARBs) or angiotensin receptor-neprilysin inhibitors (ARNIs) in 48%, and ACEi, ARB, or ARNI plus a beta-blocker in 40%. No women were treated with an anticoagulant before the SSP.

At first physician visit of the SSP, diuretics were used in 22%, beta-blockers in 55%, MRAs in 6%, and ACEi, ARB, or ARNI in 19% (plus a beta-blocker in 14%). No women were treated with an anticoagulant or bromocriptine during pregnancy.

After the SSP, diuretics were used in 26%, beta-blockers in 45%, MRAs in 15%, and ACEi, ARB, or ARNI in 34% (plus a beta-blocker in 27%). Bromocriptine and anticoagulants were used in 16% and 1%, respectively, after the SSP.

Compared with women with SSP baseline LVEF ≥50%, those with SSP baseline LVEF <50% were more often treated with diuretics, beta-blockers, and MRAs before the SSP (see Supplementary data online, Figure S1). During the SSP, more women with LVEF <50% were treated with diuretics and beta-blockers than those with LVEF ≥50%. After the SSP, more women with SSP baseline LVEF <50% were treated with a beta-blocker. There was no between-group difference in use of bromocriptine according to SSP baseline LVEF, either before, during, or after the SSP.

Analysis of specific subgroups of interest

African vs. non-African

There were 35 SSPs from patients residing in Africa and 63 from patients in other (non-African) countries. The African subgroup was younger than the non-African subgroup at the time of the index PPCM presentation (25 vs. 28 years), as well as at the time of the SSP delivery (29 vs. 31 years; see Supplementary data online, Table S2). Compared with women from other regions, there was a trend towards more frequent hypertension in the African subgroup (20% vs. 7%), and they were more often asymptomatic (NYHA Class I). The SSP baseline LVEF was similar in both subgroups, despite a lower LVEF at the index presentation of PPCM in women from African countries compared with non-African countries (29% vs. 34%). Follow-up LVEF was similar in both groups, with no significant difference in all-cause mortality (though event rates were small), clinical worsening, or the composite of death or LVEF ≤35%. The trend in LVEF for African vs. non-African SSPs is shown in Supplementary data online, Figure S2.

One subsequent pregnancy vs. more than one subsequent pregnancy

Of the 98 SSPs, 43 (44%) were in women with more than one SSP. Supplementary data online, Table S3 shows maternal clinical and obstetric characteristics and outcomes, comparing one SSP with multiple SSPs. The SSPs in women with more than one SSPs were less often from Africa and had a longer gestation period (39 vs. 38 weeks). There were no significant differences in maternal outcomes. Notably, over the course of time, there were no differences in LVEF among those with one vs. more than one SSP (see Supplementary data online, Figure S3). The two deaths in the cohort occurred in women with one SSP.

Terminated vs. continued pregnancy

Any kind of termination (therapeutic or spontaneous) occurred in 24 of 98 (24%) SSPs (see Supplementary data online, Table S4). Maternal clinical and obstetric characteristics and outcomes were similar irrespective of whether or not the pregnancy was terminated or continued, although overall numbers were small. Nevertheless, as shown in Supplementary data online, Figure S4, there were no significant changes in LVEF between women in whom the pregnancy was therapeutically or spontaneously terminated and those in whom it was not. The two deaths in the cohort occurred in women without a terminated pregnancy.

Therapeutic pregnancy termination was performed in 20 SSPs. At the time of index presentation for PPCM, these individuals had a mean age of 28 years (±5) and a LVEF of 35% (±6). At SSP baseline, 83% were asymptomatic (NYHA Class I), with a mean LVEF of 52% (±8), and the majority had an LVEF >50%, indicating normalized cardiac function. These findings suggest that most women experienced recovery of cardiac function prior to their pregnancies.

Discussion

The ESC PPCM Registry is a worldwide, prospective registry including detailed clinical, echocardiographic, socioeconomic, and outcome data on more than 750 women from 51 countries with PPCM with an up to 3-year follow-up period.7,8,11 It is the largest ever prospective cohort of patients with PPCM and offered a unique opportunity, on a global scale, to gather rich data on a number of aspects relating to PPCM, including SSPs. Our main findings of the current SSP study were as follows: (i) approximately one-fifth of the pregnancies ended due to therapeutic terminations; (ii) there was a lower-than-expected mortality, and LVEF <50% at baseline was not associated with higher rates of poor outcome, although only few patients displayed LVEF <40%; (iii) there were no significant differences in the outcomes of SSP in patients from Africa, compared with the other regions, in contrast to studies conducted previously; and (iv) women with LVEF ≥50% at SSP baseline were less likely to be on heart failure therapies (before the SSP) than women with LVEF <50% at SSP.

The findings from this prospective study contrasts with previously published retrospective studies in a number of aspects. Pachariyanon et al.12 recently reported a retrospective review of the outcomes of 137 PPCM patients, including a total of 45 patients with a SSP. This study was single-centre, conducted in the USA, over a period of almost 40 years, and 80% of the patients were of African American descent. Thirty-four of the 45 patients (76%) came from a low socioeconomic background. In this cohort, an SSP was associated with a slight decrease in LVEF, from 45% to 41% at follow-up. Although the study provides long-term follow-up, it is limited by its retrospective design, the relatively small patient volume accumulated over nearly four decades, and potential variations in data over time related to the measurement of LV function via echocardiography and clinical management practices.

The number of cases from another study conducted in the USA from 1997 to 1998 was similar in number, with 44 women and a total of 60 SSPs.13 The data were obtained by sending a questionnaire to all members of the American College of Cardiology in the USA. Medical records and the physicians were interviewed. A total of 3 of the 44 women died, and all deaths were in women starting the pregnancy with impaired cardiac function. There was a significant overall decrease in LVEF from 49% to 42% for the whole cohort.

The data from this study are consistent with a recent study by Goland et al., conducted at two medical centres in Israel. Their study found that an SSP in patients with recovered LVEF was associated with an average LVEF decrease of 2.1% and a relapse rate of 25%, but no reported mortality.14

We conducted a separate analysis comparing patients of African ethnicity with those from non-African regions. Previous studies, including those on African American patients in the USA,12,13 but also a smaller study in 29 patients from Burkina Faso15 have reported particularly high mortality rates among these women. The study conducted in Burkina Faso reported a maternal mortality rate of 48% associated with an impaired LV systolic function at the onset of a SSP. The authors speculate that the very high mortality rate may have resulted from women being lost to follow-up during the peri-partum period, which could have led to a lack of access to appropriate care. In our current study, no differences were observed in maternal and foetal outcomes between patients of African ethnicity and those from other regions. This suggests that ethnicity may be less significant compared with the importance of adequate follow-up and access to medical therapy. This is supported by a recent dedicated publication analysing the impact of country-level and patient-level socioeconomic data on maternal and neonatal outcomes in women with PPCM.16 Six-month mortality and LV non-recovery was higher in countries with low health expenditure and a lower level of maternal education, irrespective of region, suggesting that attempts should be made to allocate adequate resources to health and education, in order to improve maternal and foetal outcomes in PPCM.17

Finally, our data indicate that women with an LVEF ≥50% at the SSP baseline were less likely to be on heart failure therapies, such as beta-blockers, ACEi, and MRAs, prior to the SSP compared with those with an LVEF <50%. However, there is currently no evidence suggesting that women with PPCM and an LVEF ≥50% who are planning an SSP should be prescribed any pharmacological therapy. Women who commenced an SSP with an LVEF ≥50% were also less likely to receive heart failure medication post-partum. However, in the cohort with LVEF ≥50% at SSP baseline, a statistically significant, albeit modest, decline in LVEF was observed at follow-up. This finding suggests that discontinuation of beta-blockers may not be advisable and that reinstating beta-blocker therapy could be beneficial, irrespective of baseline LV systolic function. Nonetheless, we recognize the inherent limitations of this observational, registry-based study. We therefore call for a prospective study of prophylactic beta-blocker use in women with recovered PPCM who undergo SSP. However, achieving a sufficient sample size will be a significant challenge.

Limitations

As with most registries conducted at a global level, there are some limitations. Only core information was validated by monitors. Follow-up was not as complete as would be seen in an industry-funded clinical trial (participation into the registry and sub-study was voluntarily and unpaid). Many centres lacked extensive resources or did not have universal healthcare. In some regions, costs may have prevented patients from returning for follow-up. Additionally, in several countries, investigations such as echocardiography are funded by patients themselves and may not be performed routinely, such as at the onset of a SSP or during follow-up. A degree of selection bias for centres interested in this condition is likely and could explain better outcomes than were previously reported. Furthermore, only few patients entered a SSP with an LVEF <40%. Thus, our data regarding SSP in PPCM patients with an LVEF <50% mainly relate to patients with only mildly reduced EF. The study design does not permit a comparison of outcomes between patients with PPCM who experienced an SSP and those who did not. Although this is the largest prospective study of SSPs in women with PPCM, the cohort is still small, which limits the statistical power.

Conclusions

In this prospective multi-country study, SSPs had similar outcomes across all ethnic groups, with morbidity and mortality rates lower than expected. However, one out of five women underwent a therapeutic termination of pregnancy. Our data suggest that, in many women with PPCM and improved LVEF, a SSP could be considered under careful pre- and post-partum observation and with appropriate medical therapy. Reclassification of an SSP in PPCM patients with persisting mild LV impairment (e.g. heart failure with mid-range ejection fraction, EF 40%–50%) from mWHO IV to mWHO III could be considered, when continuous surveillance is ensured by an experienced medical team and with appropriate pharmacological management.

Acknowledgements

The EORP Oversight Committee and PPCM Registry Executive Committee members are listed in  Appendix 1. Data collection was conducted by the EORP department of the ESC and includes Afiah Zabre and Emmanuelle Mouraux as Clinical Project Managers, Gabrielle Bonneville as Project Officer, and Sandrine Anglars as Data Manager. Statistical analyses were performed by Alice Jackson and Charle Viljoen. We acknowledge the support of Dr Fareda Jakoet-Bassier for the logistical aspects related to the study and Sylvia Dennis from the Cape Heart Institute, who helped prepare the manuscripts. We also acknowledge the participation of all investigators who entered patients into the sub-study (also listed in  Appendix 1).

Supplementary data

Supplementary data are available at European Heart Journal online.

Declarations

Disclosure of Interest

All have been submitted via the ESC EORP program officer Gabrielle Bonville.

Data Availability

Upon reasonable request, the data that support the findings of this study are available from the Registries team: [email protected].

Funding

All authors declare no funding for this contribution.

Ethical Approval

Ethical approval was not required.

Pre-registered Clinical Trial Number

None supplied.

Appendix 1

Australia: Elizabeth Vale: M. Arstall, G. Mahadavan, E. Aldridge, G. Dekker, Y.Y. Chow, M. Wittwer, Germany: Hannover: T.J. Pfeffer, D. Berliner, T. Koenig, V.A. Moulig, D. Hilfiker-Kleiner, J. Bauersachs, Indonesia: Bandung: H. Sasmaya Prameswari, T.I. Dewi, Iraq: Bagdad: H. Ali Farhan, I.F. Yaseen, Israel: Rehovot: S. Goland, M. Biener, Mozambique: Maputo: A. Damasceno, M. Machava, A. Magaia, A. Mateus, C. Novela, J. Chemane, V. Govo, Nigeria: Lagos: A. Mbakwem, C. Amadi, B. Afolabi, M. Kehinde, M. Kilasho, Poland: Warsaw: M. Demkow, Z. Dzielinska, J. Henzel, K. Kryczka, South Africa: Cape Town: K. Sliwa, C. Viljoen, J. Hovelmann, F. Jakoet-Bassier, Sweden: Goteborg: M. Schaufelberger, C. Basic, V. Goloskokova, Uzbekistan: Tashkent: T. Abdullaev, I. Tsoy, S. Mirzarakhimova.

References

1

Sliwa
 
K
,
Hilfiker-Kleiner
 
D
,
Petrie
 
MC
,
Mebazaa
 
A
,
Pieske
 
B
,
Buchmann
 
E
, et al.  
Current state of knowledge on aetiology, diagnosis, management, and therapy of peripartum cardiomyopathy: a position statement from the Heart Failure Association of the European Society of Cardiology Working Group on peripartum cardiomyopathy
.
Eur J Heart Fail
 
2010
;
12
:
767
78
.

2

Bauersachs
 
J
,
Konig
 
T
,
van der Meer
 
P
,
Petrie
 
MC
,
Hilfiker-Kleiner
 
D
,
Mbakwem
 
A
, et al.  
Pathophysiology, diagnosis and management of peripartum cardiomyopathy: a position statement from the Heart Failure Association of the European Society of Cardiology Study Group on peripartum cardiomyopathy
.
Eur J Heart Fail
 
2019
;
21
:
827
43
.

3

McNamara
 
DM
,
Elkayam
 
U
,
Alharethi
 
R
,
Damp
 
J
,
Hsich
 
E
,
Ewald
 
G
, et al.  
Clinical outcomes for peripartum cardiomyopathy in North America: results of the IPAC study (Investigations of Pregnancy-Associated Cardiomyopathy)
.
J Am Coll Cardiol
 
2015
;
66
:
905
14
.

4

Hoevelmann
 
J
,
Engel
 
ME
,
Muller
 
E
,
Hohlfeld
 
A
,
Bohm
 
M
,
Sliwa
 
K
, et al.  
A global perspective on the management and outcomes of peripartum cardiomyopathy: a systematic review and meta-analysis
.
Eur J Heart Fail
 
2022
;
24
:
1719
36
.

5

Sliwa
 
K
,
Bauersachs
 
J
,
Arany
 
Z
,
Spracklen
 
T
,
Hilfiker-Kleiner
 
D
.
Peripartum cardiomyopathy: from genetics to management
.
Eur Heart J
 
2021
;
42
:
3094
102
.

6

Regitz-Zagrosek
 
V
,
Roos-Hesselink
 
JW
,
Bauersachs
 
J
,
Blomstrom-Lundqvist
 
C
,
Cifkova
 
R
,
De Bonis
 
M
, et al.  
2018 ESC guidelines for the management of cardiovascular diseases during pregnancy
.
Eur Heart J
 
2018
;
39
:
3165
241
.

7

Sliwa
 
K
,
Hilfiker-Kleiner
 
D
,
Mebazaa
 
A
,
Petrie
 
MC
,
Maggioni
 
AP
,
Regitz-Zagrosek
 
V
, et al.  
EURObservational research programme: a worldwide registry on peripartum cardiomyopathy (PPCM) in conjunction with the Heart Failure Association of the European Society of Cardiology Working Group on PPCM
.
Eur J Heart Fail
 
2014
;
16
:
583
91
.

8

Sliwa
 
K
,
Mebazaa
 
A
,
Hilfiker-Kleiner
 
D
,
Petrie
 
MC
,
Maggioni
 
AP
,
Laroche
 
C
, et al.  
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
.
Eur J Heart Fail
 
2017
;
19
:
1131
41
.

9

Sliwa
 
K
,
Petrie
 
MC
,
Hilfiker-Kleiner
 
D
,
Mebazaa
 
A
,
Jackson
 
A
,
Johnson
 
MR
, et al.  
Long-term prognosis, subsequent pregnancy, contraception and overall management of peripartum cardiomyopathy: practical guidance paper from the Heart Failure Association of the European Society of Cardiology Study Group on Peripartum Cardiomyopathy
.
Eur J Heart Fail
 
2018
;
20
:
951
62
.

10

Hilfiker-Kleiner
 
D
,
Haghikia
 
A
,
Masuko
 
D
,
Nonhoff
 
J
,
Held
 
D
,
Libhaber
 
E
, et al.  
Outcome of subsequent pregnancies in patients with a history of peripartum cardiomyopathy
.
Eur J Heart Fail
 
2017
;
19
:
1723
8
.

11

Sliwa
 
K
,
Petrie
 
MC
,
van der Meer
 
P
,
Mebazaa
 
A
,
Hilfiker-Kleiner
 
D
,
Jackson
 
AM
, et al.  
Clinical presentation, management, and 6-month outcomes in women with peripartum cardiomyopathy: an ESC EORP registry
.
Eur Heart J
 
2020
;
41
:
3787
97
.

12

Pachariyanon
 
P
,
Bogabathina
 
H
,
Jaisingh
 
K
,
Modi
 
M
,
Modi
 
K
.
Long-term outcomes of women with peripartum cardiomyopathy having subsequent pregnancies
.
J Am Coll Cardiol
 
2023
;
82
:
16
26
.

13

Elkayam
 
U
,
Tummala
 
PP
,
Rao
 
K
,
Akhter
 
MW
,
Karaalp
 
IS
,
Wani
 
OR
, et al.  
Maternal and fetal outcomes of subsequent pregnancies in women with peripartum cardiomyopathy
.
N Engl J Med
 
2001
;
344
:
1567
71
.

14

Goland
 
S
,
George
 
J
,
Elkayam
 
U
,
Shimoni
 
S
,
Fugenfirov
 
I
,
Vaisbuch
 
E
, et al.  
Contemporary outcome of subsequent pregnancies in patients with previous peripartum cardiomyopathy
.
ESC Heart Fail
 
2022
;
9
:
4262
70
.

15

Yameogo
 
NV
,
Samadoulougou
 
AK
,
Kagambega
 
LJ
,
Kologo
 
KJ
,
Millogo
 
GRC
,
Thiam
 
A
, et al.  
Maternal and fetal prognosis of subsequent pregnancy in black African women with peripartum cardiomyopathy
.
BMC Cardiovasc Disord
 
2018
;
18
:
119
.

16

Sliwa
 
K
,
van der Meer
 
P
,
Jackson
 
A
,
Petrie
 
MC
,
Mebazaa
 
A
,
Hilfiker-Kleiner
 
D
, et al.  
Socio-economic factors determine maternal and neonatal outcomes in women with peripartum cardiomyopathy: a study of the ESC EORP PPCM registry
.
Int J Cardiol
 
2024
;
398
:
131596
.

17

Sliwa
 
K
,
van der Meer
 
P
,
Petrie
 
MC
,
Frogoudaki
 
A
,
Johnson
 
MR
,
Hilfiker-Kleiner
 
D
, et al.  
Risk stratification and management of women with cardiomyopathy/heart failure planning pregnancy or presenting during/after pregnancy: a position statement from the Heart Failure Association of the European Society of Cardiology Study Group on Peripartum Cardiomyopathy
.
Eur J Heart Fail
 
2021
;
23
:
527
40
. .

Author notes

Karen Sliwa and Alice Jackson Shared first authors.

This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://dbpia.nl.go.kr/pages/standard-publication-reuse-rights)

Supplementary data