Abstract
Background: Predictors of the clinical characteristics of pregnant women at risk of peripartum cardiomyopathy (PPCM) remain unclear.
Methods and Results: We enrolled 450 cases of high-risk pregnancy with any risk factor from among ≥35 years of age, hypertensive disorders of pregnancy (HDP), multiple gestation, or other systemic or obstetric complications except for a history of cardiac disease. All the women underwent echocardiography and plasma B-type natriuretic peptide (BNP) measurement during the second/third trimester and the early/late postpartum period. Logistic regression analyses identified clinical factors associated with left ventricular (LV) dysfunction. The incidence of PPCM was 0.89%, which was higher than in previous reports. Early diastolic mitral annular velocity (e′) was significantly negatively associated with the occurrence of PPCM, and the BNP level showed a significant positive association with the occurrence of PPCM. The percentages of cases of e′ <7 cm/s, and BNP level ≥100 pg/mL were 25.3%, and 20.4%, respectively. Multivariate regression analysis revealed that HDP was independently associated with e′. A negative correlation between e′ and BNP level was observed in HDP.
Conclusions: High-risk pregnancy was associated with an increased incidence of PPCM. Measurement of BNP levels and echocardiographic assessment of LV diastolic function during pregnancy may be useful in predicting PPCM.
Peripartum cardiomyopathy (PPCM) is a rare myocardial disease that leads to heart failure (HF) in pregnant women without any history or cause of cardiac disease. PPCM is characterized by the development of HF with reduced left ventricular ejection fraction (LVEF) towards the end of pregnancy or in the months after delivery.1,2 Although the etiology of PPCM remains unknown, several factors have been suggested to increase the risk of its development: African descent, advanced maternal age, hypertensive disorders of pregnancy (HDP), multiple gestation, multiparity, and general risk factors for cardiovascular disease such as diabetes mellitus.1–3 High-risk pregnancy has been identified as a risk factor for PPCM, and one of the possible reasons for the increased incidence of PPCM in the USA is the increasing rates of advanced maternal age, preeclampsia, multiple gestation, and cardiovascular risk factors.2–4 However, there has not been a prospective study on the development of PPCM, and the clinical characteristics of pregnant women who may develop LV dysfunction remain unclear.
It has been reported that the early diastolic mitral annular velocity (e′) and the ratio of early diastolic mitral flow velocity to early diastolic mitral annular velocity (E/e′), the most representative indicators of diastolic cardiac function, do not change during normal pregnancy.5,6 It has also been reported that the level of B-type natriuretic peptide (BNP), the representative biomarker of HF, does not change significantly during normal pregnancy and the postpartum period.7,8
In this study we sought to determine which clinical characteristics could identify pregnant women who will develop LV systolic dysfunction by analyzing the data from women with a high-risk pregnancy and carefully monitored sequential changes in maternal LV function.
Methods
Study Design and Participants
The study protocol was approved by the Ethics Committee of Toyota Memorial Hospital, Aichi Prefecture (reference number R437). Written informed consent for minimally invasive data collection was obtained from all participants after explanation of the benefits of close monitoring of high-risk pregnancies, which may require more intensive care than standard practice.
This study enrolled participants from June 2007 to July 2012, and followed them through 2023 at Toyota Memorial Hospital. There is not a clear definition of a high-risk pregnancy in the clinical guidelines issued by Japanese academic societies. Therefore, we developed a definition based on those of the National Institute of Child Health and Human Development in the USA and the University Hospitals Sussex National Health Service Foundation Trust in the UK.9,10
Pregnant women were enrolled if they were aged ≥35 years, had undergone a previous cesarean delivery, had eclampsia/preeclampsia, gestational hypertension, superimposed preeclampsia, chronic hypertension, multiple gestation, fetal anomalies including fetal growth restriction, obesity, bronchial asthma, mental disorders or complications of systemic diseases such as diabetes, thyroid disorders, and autoimmune diseases.
All the women with a high-risk pregnancy underwent echocardiography in 4 terms when possible: second and third trimesters of pregnancy, early postpartum period within 1 month of delivery, and late postpartum period from 1 to 3 months after delivery. BNP levels were measured at the same time as echocardiography, and at a minimum, during the third trimester and early postpartum period.
The diagnosis of PPCM was based on criteria that were proposed by Demakis and Rahimtoola in 1971,1 Hibbard et al.11 and at a workshop organized by the National Heart, Lung, and Blood Institute and the Office of Rare Diseases Research:12 (1) development of HF in the last month of pregnancy or within 5 months of delivery, (2) absence of another identifiable cause of HF, (3) absence of identifiable heart disease prior to the last month of pregnancy, (4) LV systolic dysfunction with LVEF <45% by echocardiography and/or fractional shortening <30% at presentation. HDP was categorized according to the Report of the National High Blood Pressure Education Program Working Group on High Blood Pressure in Pregnancy as follows.13 Gestational hypertension: systolic blood pressure (BP) ≥140 mmHg and/or diastolic BP ≥90 mmHg for the first time after 20 weeks of gestation, and no proteinuria. Preeclampsia: gestational hypertension with proteinuria ≥300 mg/day or 0.3 g/g Cre. Superimposed preeclampsia: new-onset proteinuria ≥300 mg/day or 0.3 g/g Cre in women with preexisting hypertension before 20 weeks of gestation, such as chronic hypertension or kidney disease. Chronic hypertension: systolic/diastolic BP ≥140/90 mmHg before pregnancy or diagnosed before 20 weeks of gestation.
Echocardiography and BNP Measurement
Echocardiography was performed using iE33 (Philips, Bothell, WA, USA) and Aplio400 (Toshiba Medical Systems Corporation, Otawara, Japan). LV diastolic dimension (LVDd), LV systolic dimension (LVDs), left atrial dimension (LAD), interventricular septal thickness (IVST), posterior wall thickness (PWT), inferior vena cava (IVC) diameter, peak mitral E-wave velocity (E), peak mitral A-wave velocity (A), mitral E/A ratio, early diastolic septal mitral annular velocity (e′), and E/e′ ratio were measured according to the standardized protocol recommended by the American Society of Echocardiography.14
LVEF was measured by M-mode imaging from the parasternal long-axis view or by the modified Simpson’s method from the apical 4-chamber view.
In this study, LV systolic dysfunction was defined as LVEF <45% and LV diastolic dysfunction was defined as e′ <7 cm/s or E/e′ >14.15 The BNP level with a cutoff of 100 pg/mL was the diagnostic criterion for HF.7 We classified cardiac function using the minimum or maximum values of each parameter observed during the study period for each participant.
Statistical Analysis
All statistical analyses were performed with R (The R Foundation for Statistical Computing, Vienna, Austria, version 4.3.0). Continuous variables are expressed as mean±standard deviation. Variables were compared between groups using Student’s t-test or the Mann-Whitney U test, as appropriate. To assess the serial changes in echocardiographic parameters and BNP levels, we used the Friedman test to compare data across 4 time points (second and third trimester of pregnancy, early postpartum, and late postpartum), given the repeated measures design and non-normal distribution of the data. When a significant difference was found, post-hoc pairwise comparisons were conducted using the Wilcoxon signed-rank test with Bonferroni correction to account for multiple comparisons. Binary variables are presented as counts and percentages, and differences between groups with and without LV dysfunction were assessed using the chi-squared test or Fisher’s exact test, as appropriate. Because the distribution of BNP was skewed, natural logarithm-transformed values were used for statistical comparison. For presentation purposes, BNP levels are presented as median (interquartile range). A P value <0.05 was considered statistically significant. Independent predictors of LV systolic and diastolic dysfunction were determined using a logistic regression model with forced entry method. Variables that were evaluated in the multivariate logistic regression analysis included those with a significant association in the univariate analysis as well as those without statistical significance in the univariate analysis but with prognostic impact demonstrated in previous studies.3,12 The following variables were entered into the multivariable model for LV systolic dysfunction: HDP, maternal age, and multiple gestation and parity.
Results
Study Cohort
As shown in Figure 1, of 550 pregnant women with risk factors, 100 were excluded and the remaining 450 without prior cardiac disease or a family history of cardiac disease were enrolled. None had African descent.
The mean maternal age was 33.6±5.7 years and 195 women were older than 35 years (43.3%). The mean parity was 0.6 times and 256 women were primiparous (56.9%). HDP and multiple gestation were observed in 222 (49.4%) and 156 women (34.7%), respectively. Fetal growth restriction occurred in 73 women (16.2%). The mean gestational age was 37.3±2.8 weeks. The mean gestational weight gain during pregnancy was 10.7±5.2 kg. A total of 143 women (31.8%) underwent emergency cesarean delivery (Table 1).
Table 1.
Baseline Clinical Characteristics and Findings in the Study Group of Women With High-Risk Pregnancy
| Maternal age, years |
33.6±5.7 |
| ≥35 years, n (%) |
195 (43.3) |
| ≥40 years, n (%) |
83 (18.4) |
| Gravidity, times |
1.1±1.3 |
| Parity, times |
0.6±0.8 |
| Primiparity, n (%) |
256 (56.9) |
| Hypertension in previous pregnancies, n (%) |
47 (10.4) |
| Previous cesarean delivery, n (%) |
55 (12.2) |
| Hypertensive disorders of pregnancy, n (%) |
222 (49.4) |
| Eclampsia/preeclampsia, n (%) |
129 (28.7) |
| Gestational hypertension, n (%) |
69 (15.3) |
| Superimposed preeclampsia, n (%) |
8 (1.8) |
| Chronic hypertension, n (%) |
16 (3.6) |
| Multiple gestation, n (%) |
156 (34.7) |
| Tocolytic therapy, n (%) |
134 (29.8) |
| Diabetes mellitus, n (%) |
10 (2.2) |
| Gestational diabetes mellitus, n (%) |
23 (5.1) |
| Thyroid disease, n (%) |
14 (3.1) |
| Other, n (%) |
48 (10.7) |
| Fetal growth restriction, n (%) |
73 (16.2) |
| Systolic blood pressure, mmHg |
130±23 |
| Diastolic blood pressure, mmHg |
80±15 |
| Gestational weeks at delivery |
37.3±2.8 |
| Preterm delivery <37 gestational weeks, n (%) |
165 (36.7) |
| Preterm delivery <32 gestational weeks, n (%) |
24 (5.3) |
| Body weight before pregnancy, kg |
55.2±11.9 |
| Body mass index |
22.1±4.7 |
| ≥25, n (%) |
84 (18.7) |
| ≥30, n (%) |
26 (5.8) |
| Body weight gain during pregnancy, kg |
10.7±5.2 |
| Birth weight, g |
2,472±670 |
| Emergency cesarean delivery, n (%) |
143 (31.8) |
| All cesarean delivery, n (%) |
204 (45.3) |
Data are expressed as mean±SD or number (percentage).
Incidence and Clinical Characteristics of PPCM
PPCM occurred in 4 of 450 women, an incidence rate of 0.89%. Table 2 summarizes the clinical characteristics of the 4 cases of PPCM. All had HDP and in cases 1, 3, and 4 the women were of advanced maternal age. All the women had a low parity number of zero or one. In cases 1, 2, and 4 the women underwent emergency cesarean delivery. The onset of PPCM in cases 1, 2, and 3 occurred in the first month after delivery. We obtained clinical data for cases 1, 2, and 3 before the onset of PPCM. In cases 1 and 2, the E/e’ ratio was >14 and BNP levels were ≥100 pg/mL before the development of reduced LVEF (Supplementary Table 1). In case 3, there was also a high E/e′ ratio before the development of reduced LVEF. All PPCM cases had an e′ value <7 cm/s. The woman in Case 4 experienced a sudden worsening of symptoms a few days before admission. She was diagnosed with PPCM before delivery and underwent emergency cesarean section with non-invasive positive pressure ventilation. In almost all cases the women were treated with medical therapy including a diuretic and a β-blocker. In all cases of PPCM, LVEF recovered to >60% within 6 months of delivery. No recurrence of PPCM was observed in any of the cases.
Table 2.
Summary of Clinical Characteristics of Pregnant Women Who Developed PPCM
| Case no. |
Age,
years |
G/P |
Risk factors |
Delivery
mode |
Onset |
Condition |
Treatment |
| 1 |
38 |
0/0 |
Age, GH |
eCS |
3 weeks after
delivery |
Congestion
Leg edema |
Furosemide
Spironolactone
Digitalis |
| 2 |
22 |
2/1 |
Preeclampsia,
twin pregnancy,
Basedow disease |
eCS |
1 month after
delivery |
Congestion |
Furosemide
Carvedilol |
| 3 |
36 |
0/0 |
Age, GH |
Vaginal |
3 days after
delivery |
Pleural effusion
Leg edema |
Observation |
| 4 |
36 |
1/1 |
Age, preeclampsia |
eCS |
Before delivery |
Pulmonary
edema |
NPPV
Carperitide
Nitroglycerin
Furosemide
Spironolactone
Digitalis |
Age, advanced maternal age; eCS, emergency cesarean section; G/P, gravidity/parity; GH, gestational hypertension; NPPV, noninvasive positive pressure ventilation.
The trends of each parameter for the PPCM cases and non-PPCM cases are shown in Figure 2. In the PPCM cases, LVDd and LVDs tended to be larger than in the non-PPCM cases. Moreover, enlargement of LVDd and LVDs and increased BNP levels were observed before the decline in LVEF. We also observed a decrease in e′ and an increase in E/e′ before the decline in LVEF.
Because there were only 4 cases of PPCM, a highly reliable analysis of LV systolic dysfunction using conventional logistic regression was not feasible. To address this limitation, we used Bayesian logistic regression analysis using the ‘brms’ package in R to evaluate the association between PPCM occurrence and the independent variables of diastolic function (e′) and BNP levels.16
A total of 450 observations were analyzed using this approach. The results indicated that e′ had a significant negative association with the occurrence of PPCM (adjusted odds ratio=0.35, 95% Credible Interval=0.07 to 0.93), while BNP level showed a significant positive association (adjusted odds ratio=1.20, 95% Credible Interval=1.03 to 1.46) in the current sample.
Diastolic dysfunction, defined as either an e′ value <7 cm/s or an E/e′ ratio >14 during follow-up, was found in 136 of 450 women (30.2%), of whom 114 (25.3%) had an e′ value <7 cm/s, and 56 women (12.4%) had an E/e′ ratio >14. In addition, 92 of 450 women (20.4%) had elevated BNP level (≥100 pg/mL). The third trimester was the most typical time of diagnosis of diastolic dysfunction as indicated by an e′ value <7 cm/s, occurring in 70 of 114 women. The mean time of diagnosis of diastolic dysfunction was −7.0 days after delivery. In contrast, the mean time of diagnosis for PPCM was 14.5 days after delivery. First-time elevated BNP levels were found in 2 women (2.2%) in the second trimester, in 36 women (39.1%) in the third trimester, and in 54 of 92 women (58.7%) in the early postpartum period. The mean time to detect BNP level ≥100 pg/mL was 0.6 days after delivery.
LV Diastolic Dysfunction in High-Risk Pregnancies
Echocardiographic parameters and BNP levels in the high-risk pregnancies underwent sequential changes during follow-up (Supplementary Table 2). The number of women undergoing echocardiography in the second trimester, the third trimester, early postpartum, and late postpartum was 132, 324, 415, and 235, respectively. In the third trimester (mean examination date: 35.5±3.1 gestational weeks) and in the early postpartum (mean examination date: 4.0±1.6 days after delivery), mean LVDd and LVDs were significantly greater, and mean LV wall thickness was significantly thicker compared with those in the second trimester. In contrast, mean LVEF did not change during follow-up. Mean e′ was significantly decreased in the third trimester and early postpartum. The number of women in which BNP measurement was performed in the second trimester, the third trimester, early postpartum, and late postpartum was 42, 232, 415, and 90, respectively.
Women with LV diastolic dysfunction had a significantly higher incidence of hypertension in previous pregnancies, HDP, and higher body mass index than women without LV diastolic dysfunction (Table 3). Table 4 shows that an increased risk of LV diastolic dysfunction was significantly associated with HDP (odds ratio, 4.76; P<0.001).
Table 3.
Clinical Characteristics of Women With a High-Risk Pregnancy With and Without Left Ventricular Diastolic Dysfunction as Indicated by e′ <7 cm/s
| |
e′ <7
(n=114) |
e′ ≥7
(n=336) |
P value |
| Maternal age, years |
34.2±4.9 |
33.4±5.9 |
0.202 |
| ≥35 years, n (%) |
54 (47.4) |
141 (42.0) |
0.370 |
| Gravidity, times |
1.1±1.3 |
1.0±1.3 |
0.390 |
| Parity, times |
0.7±0.9 |
0.6±0.8 |
0.155 |
| Primiparity, n (%) |
59 (51.8) |
197 (58.6) |
0.241 |
| Hypertension in previous pregnancies, n (%) |
23 (20.2) |
24 (7.1) |
<0.001 |
| Previous cesarean delivery, n (%) |
14 (12.3) |
41 (12.2) |
0.720 |
| Hypertensive disorders of pregnancy, n (%) |
84 (73.7) |
138 (41.1) |
<0.001 |
| Eclampsia/preeclampsia, n (%) |
50 (43.9) |
79 (23.5) |
<0.001 |
| Gestational hypertension, n (%) |
25 (21.9) |
44 (13.1) |
0.035 |
| Superimposed preeclampsia, n (%) |
3 (2.6) |
5 (1.5) |
0.424 |
| Chronic hypertension, n (%) |
6 (5.3) |
10 (3.0) |
0.252 |
| Multiple gestation, n (%) |
24 (21.1) |
132 (39.3) |
<0.001 |
| Tocolytic therapy, n (%) |
27 (23.7) |
107 (31.8) |
0.127 |
| Fetal growth restriction, n (%) |
20 (17.5) |
53 (15.8) |
0.767 |
| Systolic blood pressure, mmHg |
140±25 |
127±21 |
<0.001 |
| Diastolic blood pressure, mmHg |
87±15 |
78±14 |
<0.001 |
| Gestational weeks at delivery |
37.0±2.9 |
37.4±2.8 |
0.247 |
| Preterm labor, n (%) |
49 (43.0) |
116 (34.5) |
0.132 |
| Body mass index |
23.1±5.3 |
21.8±4.4 |
0.003 |
| ≥25, n (%) |
28 (24.6) |
56 (16.7) |
0.089 |
| Body weight gain during pregnancy, kg |
10.2±5.1 |
10.8±5.2 |
0.387 |
| Birth weight, g |
2,409±674 |
2,493±668 |
0.250 |
| Emergency cesarean delivery, n (%) |
38 (33.3) |
105 (31.3) |
0.767 |
| All cesarean delivery, n (%) |
47 (41.2) |
157 (46.7) |
0.363 |
Data are expressed as mean±SD or number (percentage). e′, early diastolic septal mitral annular velocity.
Table 4.
Multivariable Predictors of e′ <7 cm/s
| Factors |
OR |
95% CI |
P value |
| Maternal age |
1.04 |
0.99–1.09 |
0.076 |
| Parity |
1.24 |
0.95–1.62 |
0.110 |
| Hypertensive disorders of pregnancy |
4.76 |
2.67–8.74 |
<0.001 |
| Multiple gestation |
1.14 |
0.59–2.17 |
0.694 |
CI, confidence interval; OR, odds ratio.
In the HDP cases, LVDd, LVDs, and IVC diameter values in the third trimester were significantly greater than those in pregnant women without HDP (Figure 3). IVS and PWT in HDP cases in the third trimester and early postpartum were significantly greater than those in the pregnant women without HDP. In addition, the women with HDP had significantly lower e′ velocity and higher E/e′ ratio in the third trimester and early postpartum than non-HDP cases. In our classification of LV diastolic function, HDP cases tended to have lower e′ velocity and higher E/e′ ratio than non-HDP cases (Figure 4A).
Relationship Between BNP Level and LV Diastolic Dysfunction
It appears that hypertension leads to diastolic dysfunction by stressing the cardiac structure. Figure 3 shows the BNP levels in pregnant women with and without HDP during each trimester and postpartum. In the third trimester, BNP levels were significantly higher in HDP than in non-HDP cases. A negative correlation between e′ and BNP levels was found in HDP cases as well as in all cases (all: rho=−0.24, P<0.001, HDP: rho=−0.24, P<0.001, non-HDP: rho=−0.12, P=0.069) (Figure 4B).
Discussion
The present study was an observational study of women with a high-risk pregnancy, some of whom developed LV dysfunction that progressed to PPCM. We highlight our 3 major findings. First, the incidence of PPCM in this group of pregnant women (4 of 450, 0.89%) was higher than in previous reports in all pregnant women. Second, LV diastolic dysfunction preceded systolic dysfunction in these women, and diastolic dysfunction was most strongly associated with HDP. Third, the results demonstrated that mitral annular velocity e′ and BNP level were significantly associated with the occurrence of PPCM and that there was a significant positive correlation between e′ and BNP levels in HDP cases.
Our present study focused on a cohort of women with a high-risk pregnancy, who are distinct from normally pregnant women and those with pregnancy-induced hypertension. A high-risk pregnancy was defined as age ≥35 years of age or with eclampsia/preeclampsia, gestational hypertension, chronic hypertension, multiple gestation, diabetes, or thyroid disease without a preexisting cardiovascular burden. Longitudinal measurement of echocardiographic parameters and BNP levels from early pregnancy in high-risk pregnant women, who does not have cardiovascular disease other than hypertension, represents a novel and unprecedented approach. Our new findings suggest that in high-risk pregnancies, early measurement of BNP levels during pregnancy and assessment of LV diastolic function by echocardiography may be useful in predicting the onset of PPCM.
Incidence of PPCM
PPCM is rare and its etiology and pathogenesis are still not fully understood, but likely to be multifactorial. There are several reports that typical preeclampsia and some types of hypertension are strongly associated with PPCM, and that hypertension-related PPCM has a good prognosis for cardiac function.3,17 In recent years, a model of the pathogenesis of PPCM has been proposed, suggesting that some specific hormones produced by the pituitary and the placenta during the peripartum period, or their breakdown products, may lead to cardiac dysfunction by causing excessive anti-angiogenic signaling or damage to the cardiac vasculature.18,19
The reported incidence of PPCM has varied depending on the study population or region.3 According to previous studies, it is 1/3,000–1/4,000 live births in the USA and 1/20,000 births in Japan.2,17 In the present study, the incidence of PPCM in the study women was remarkably higher than in previous reports. To our knowledge, a prospective study of PPCM in women with high-risk pregnancies has not yet been reported. The present study identified cardiac risk factors and clinical warning signs that may lead to cardiac dysfunction.
Changes in Echocardiographic Parameters
Umazume et al. clearly reported the longitudinal changes in echocardiographic indices in normal pregnant women, and the differences in imaging between HDP and normotensive pregnant women during pregnancy and the postpartum period.20,21 In normal pregnancy, LV mass, left atrial volume, and LVDd gradually increase and peak shortly after delivery. Additionally, the IVC diameter decreases as pregnancy progresses but increases immediately after delivery. In women with HDP, left atrial volume and IVC diameter are larger, and e′ values lower compared with normotensive women, and these changes persist until immediately after delivery. The echocardiographic parameters of the PPCM and HDP cases in the present study were consistent with those findings.
Significantly, the longitudinal observations in the present study revealed changes in cardiac structure before the onset of PPCM. Specifically, we observed an increase in LVDd and LVDs before the decline in LVEF, compared with non-PPCM cases, consistent with the findings reported by Aoyama et al.22 Furthermore, the present study is valuable because a decline in LV diastolic function was observed prior to the systolic dysfunction. Previous reports have focused on LV systolic function before the onset of PPCM, but did not observe LV diastolic function.22,23
PPCM and HDP
Although 60–70% of PPCM cases have occurred in women with normotensive pregnancies, HDP is associated with a significant increase in the risk of PPCM, depending on the severity of HDP.24,25 In fact, the Japanese Society for the Study of Hypertension in Pregnancy Committee Report warned that women with HDP are at high risk for PPCM.26 Based on a report that gestational hypertension, a component of HDP, impairs both LV systolic and diastolic function,27 it has been speculated that repeated measurements of LV function may make it possible to predict the onset of PPCM.28 Additionally, Umazume et al. suggested that predicting the decline in LV relaxation function in HDP may be critical to preventing future risk of PPCM and HF.21 HDP may represent an additional cardiac stressor during pregnancy. The present study also provides evidence that high-risk pregnancies are associated with an increased incidence of PPCM. In fact, in the cases of PPCM with HDP there was a decrease in e′ that preceded the decline in LVEF. However, because of the very low incidence of PPCM in the present study, it was difficult to identify predictive factors. A larger cohort from a multicenter study may be needed to address this issue. Assessment of LV diastolic function may provide further insight to identifying women who require closer monitoring during the peripartum period.
LV Diastolic Dysfunction in High-Risk Pregnancies
In the present study, LV diastolic dysfunction as indicated by e′ <7 cm/s was detected in approximately 25% of the high-risk pregnancies by close follow-up with echocardiography. The mechanisms of diastolic dysfunction generally appear to be due to increased LV stiffness. As assessed by tissue Doppler imaging, there is a slowing of myocardial relaxation, which may account for the decrease in e′ velocity. Therefore, the E/e′ ratio increases, which is very rarely >14 in normal subjects, although it is important to recognize that the E/e′ ratio is an indicator of elevated LV filling pressure.15
Cases of peripartum HF have been reported in which only diastolic dysfunction was observed in the absence of systolic dysfunction,29,30 which suggests that diastolic dysfunction may precede systolic dysfunction in the pathophysiology of PPCM. In the present study, peripartum HF characterized by such diastolic dysfunction alone was not observed.
BNP Level and LV Diastolic Dysfunction
BNP is a biomarker of increased myocardial stress and a sensitive diagnostic marker of HF. The BNP levels are slightly elevated in women with preeclampsia and have been significantly associated with adverse maternal outcomes.31,32 Previous reports have demonstrated a correlation between the degree of cardiac diastolic dysfunction and BNP levels in HDP cases, and the peak level of BNP occurs immediately after delivery.21,33 The present study also demonstrated a significant positive correlation between LV diastolic dysfunction and the BNP level in HDP cases, but not in non-HDP cases.
Umazume et al. reported that a lower estimated glomerular filtration rate correlated with a decrease in e′.20,21 However, renal function was not evaluated in this study and further investigation is warranted.
According to previous reports, early-onset preeclampsia is associated with poor maternal and fetal prognosis, and the women have higher BNP levels than other HDP cases in early pregnancy.34 Screening for HF using BNP measurement in high-risk pregnancies, especially from the early stages of pregnancy, may be beneficial.
In Japan, it has been reported that >60% of PPCM patients were initially seen by an obstetrician, and when they complained of HF symptoms, <10% were primarily treated by a cardiologist.17 In Japanese clinical practice, it is relatively easy to measure BNP levels, either by diagnostic test kit or under health insurance coverage. Because BNP can be easily measured by non-cardiologists, we recommend measuring this biomarker during pregnancy.
Study Limitations
First, the sample size was limited because the study was conducted at a single institution. Second, cardiac dysfunction due to genetic predisposition, which is common in dilated cardiomyopathy, could not be completely excluded because genetic testing was not performed. Third, we were unable to obtain all sequential echocardiographic measurements in each trimester and in the postpartum period, because either the referred pregnant women presented to hospital shortly before the delivery after deterioration in their condition and/or women dropped out of the study after delivery. High dropout rates are common in this type of longitudinal study. Finally, the BNP testing was performed less frequently than echocardiography, because the attending obstetricians selectively performed BNP testing in pregnant women with severe hypertension or symptoms such as shortness of breath and leg edema, except in the peripartum period.
Conclusions
The incidence of PPCM in a high-risk subgroup of Japanese pregnant women was higher than in previous reports. In the present study, LV diastolic dysfunction was most strongly associated with HDP. We suggest that measurement of BNP levels from early pregnancy and e′ by peripartum echocardiography may be useful for screening LV dysfunction, and predicting the development of PPCM.
Disclosures
T.M. is a Senior Advisory Editor of Circulation Reports.
IRB Information
The present study was approved by the Ethics Committee of Toyota Memorial Hospital (reference no. R437).
Data Availability
Deidentified participant data will not be shared.
Supplementary Files
Please find supplementary file(s);
https://doi.org/10.1253/circrep.CR-24-0154
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