Peripartum cardiomyopathy is a rare form of pregnancy-specific idiopathic dilated heart failure with onset during the last month of pregnancy through 5 months postpartum.1 Multiple theories regarding the causes of peripartum cardiomyopathy have been proposed, yet its underlying mechanism remains uncertain.2
The reported incidence of peripartum cardiomyopathy has increased with time; a recent study noted an incidence of 1 in 968 births, possibly as a result of improved awareness of the disease and changes in maternal demographics.3 Its clinical course varies tremendously, with some patients achieving full recovery within 2–6 months and others requiring emergent mechanical circulatory support or cardiac transplantation and experience major extracardiac morbidity. Historically, a 10–30% mortality rate has been described, typically associated with refractory heart failure, thromboembolic events, or sudden death.4–6
With improvements in cardiac care, disease recognition, and rehabilitation programs, more patients now survive, posing the question of advisability of future pregnancy.1 The few studies that have described outcomes in this population report a heart failure relapse risk of at least 30%.7,8 Preconception cardiac stress testing, although theoretically prognostic, appears to have a limited predictive role in clinical practice.9 Data about obstetric and fetal outcomes in subsequent pregnancies remain sparse, making evidence-based both preconception and postconception counseling for these patients challenging.
The purpose of this study was to describe cardiac and obstetric outcomes in subsequent pregnancies of patients with a history of peripartum cardiomyopathy as well as maternal, obstetric, and fetal characteristics of index pregnancies.
MATERIALS AND METHODS
This study was approved by the Mayo Clinic institutional review board. All study patients provided written informed consent to allow use of their medical records for research purposes.
We performed a retrospective cohort study of all pregnancies in patients with a prior diagnosis of peripartum cardiomyopathy seen at the Mayo Clinic (Rochester, Minnesota) from January 2000 through March 2017. Patients with a diagnosis of peripartum cardiomyopathy met the following criteria: 1) development of cardiac failure in the last month of pregnancy or within 5 months of delivery, 2) absence of an identifiable cause of cardiac failure, 3) absence of recognizable structural heart disease before the last month of pregnancy, and 4) left ventricular (LV) systolic dysfunction with an LV ejection fraction (LVEF) less than 45%.10 Patients were excluded if the diagnosis of peripartum cardiomyopathy could not be confirmed or if subsequent pregnancy outcome data were not available.
Medical history was abstracted from the institutional electronic health record. Data collected included maternal, obstetric, and neonatal outcomes of index and subsequent pregnancies. Echocardiograms were reviewed by a subspecialty echocardiography-trained cardiologist (L.A.B.) with independent verification of LVEF, right ventricular (RV) dysfunction, and LV dilatation (end-diastolic diameter 56 mm or greater). If echocardiographic images were not available, data were abstracted from the formal report. Recovery of LV function was defined as an increase of LVEF to 50% or greater. Relapse of peripartum cardiomyopathy during a subsequent pregnancy was diagnosed according to the definition from Fett et al11: 1) decrease of LVEF to 45% or less with or without symptoms or 2) absolute decrease in LVEF of 10% or greater in patients with LVEF 50% or less at the start of the subsequent pregnancy (eg, decline in LVEF from 45% to 35%).
Continuous variables were reported as median (range), and binary variables were reported as count (percentage). Statistical analyses were performed using JMP 10.0.
Twenty-five patients with a history of peripartum cardiomyopathy and one or more subsequent pregnancies were identified. Baseline characteristics of the index pregnancy are shown in Table 1. Median maternal age at delivery was 26 years (range 15–37 years). The majority of patients were non-Hispanic white (n=20 [80%]) and nulliparous (n=19 [76%]). Ten (40%) patients had a prior diagnosis of a mood disorder, five (20%) of whom were receiving psychiatric medication(s) at the time of the index pregnancy. Migraine headaches were noted in 20% (n=5). Only a small proportion of patients had pre-existing cardiovascular disease: one (4%) patient had chronic hypertension, and two (8%) had Wolff-Parkinson-White syndrome. Body mass index data (calculated as weight (kg)/[height (m)]2) were available for only nine patients (median 25.7, range 19.7–45.0).
All index pregnancies resulted in live births, with six (24%) preterm deliveries. Four (16%) pregnancies were twin gestations. Causes of prematurity were preterm prelabor rupture of membranes in one patient who delivered at 29 weeks of gestation and hypertensive disorders of pregnancy in five patients, all of whom had late preterm deliveries at 34 0/7–36 6/7 weeks of gestation. Median gestational age at delivery of all 25 index pregnancies was 38 weeks. Of note, the majority of pregnancies (n=15 [60%]) were complicated by a hypertensive disorder of pregnancy with three (12%) patients diagnosed with gestational hypertension, nine (36%) with preeclampsia, and three (12%) with confirmed eclampsia. Other complications of pregnancy were infrequent; four patients (16%) had preterm labor, but none required tocolytic therapy and only the aforementioned one patient had preterm prelabor rupture of membranes. Nine (36%) patients had induction of labor, all for the diagnosis of a hypertensive disorder of pregnancy. Most patients (n=14 [56%]) underwent cesarean delivery for obstetric indications. Median neonatal birth weight was 3.09 kg (range 1.28–4.17 kg) and 58.6% (n=17/29) of newborns were female. Data regarding lactation were limited to 14 (56%) patients, of whom 10 (71.4%) reported breastfeeding. Obstetric and neonatal details of index pregnancies are outlined in Table 1.
Peripartum cardiomyopathy was diagnosed antenatally in only four (16%) patients. Of the 21 (84%) patients who developed peripartum cardiomyopathy in the postpartum period, the majority (n=14 [56%]) had onset of symptoms within the first week after delivery; the latest diagnosis occurred 12 weeks postpartum. Dyspnea was the presenting symptom in 80% (n=20) of patients (n=20). Echocardiographic findings are listed in Table 2. Median LVEF at diagnosis was 33.5%; six (26.1%) patients had concurrent RV dysfunction and 12 (56.2%) had LV dilatation.
Although individual clinical management was not standardized over the study interval, all patients were treated with guideline-directed medical therapy for heart failure as tolerated, consisting of inotropic and afterload-reducing agents with anticoagulation usually reserved for patients with LVEF less than 35% or arrhythmia. Patients were not routinely advised to take aspirin. Intensive care unit admission was required for eight (32%) patients, of whom one experienced cardiac arrest. None required cardiac transplantation and all patients but one (n=24 [96%]) recovered LV function (defined as LVEF 50% or greater). Median time to recovery was 4 months. Before the subsequent pregnancy, all patients with RV dysfunction recovered normal RV function, and 10 of the 12 patients (83.3%) with LV dilatation at diagnosis had normalization of LV dimensions.
A total of 43 subsequent pregnancies among the 25 patients were recorded: 15 (60%) patients had only one subsequent pregnancy, six (24%) had two subsequent pregnancies, and four (16%) had three or more subsequent pregnancies (Fig. 1). Median interval between the index and first subsequent pregnancy was 29 months (range 5–77 months). Only a minority of pregnancies were terminated (n=4 [9.3%]), and six (14.0%) pregnancies resulted in miscarriage. Thirty-three (76.7%) pregnancies resulted in a live birth, of which four were delivered late preterm (36 weeks of gestation).
Details of the 33 subsequent pregnancies that resulted in a live birth are outlined in Table 3. Obstetric and fetal complications were uncommon. The rate of intrauterine growth restriction was low (n=1 [3%]) and two (6%) newborns were small for gestational age at birth. Three (9%) patients had gestational diabetes mellitus and four (12.1%) patients had a hypertensive disorder of pregnancy. Five (15.2%) patients had induction of labor at term; of these, only one was for peripartum cardiomyopathy relapse. Approximately half of the patients (n=17 [51.5%]) had cesarean delivery for obstetric indications. The main obstetric complication after delivery was postpartum hemorrhage, which affected four (12.1%) pregnancies. No cases of chorioamnionitis or endomyometritis were recorded. Data regarding lactation were available for 24 pregnancies: 19 (79.2%) breastfed their newborns, and the overall rates of lactation among pregnancies with and without relapse were similar (71.4% vs 75%, respectively).
Peripartum cardiomyopathy relapse occurred in nine individual patients (9/43 subsequent pregnancies [20.9%]). Relapses were diagnosed during the last month of pregnancy (n=4 [44.4%]) and in the postpartum period (n=5 [55.6%]). Similar to the index presentation, three (33.3%) occurred within a week of delivery and one (11.1%) at 1 month postpartum. Seven relapses occurred during the first subsequent pregnancy and two in the second subsequent pregnancy (Fig. 1). The single patient in this study with an unrecovered LVEF did not relapse. The relapse rate was similar in patients with and without a hypertensive disorder of pregnancy during the index pregnancy (4/20 [20%] vs 5/23 [22%]). No patients were treated with bromocriptine at any time before, during, or after the index or subsequent pregnancies. β-blockers were administered during 19 of 43 (44%) subsequent pregnancies; of these, six (31.6%) pregnancies had relapse. No patients treated with β-blockers were diagnosed with intrauterine growth restriction during pregnancy.
The median decline in LVEF in patients with relapse was 15% with a median nadir LVEF of 43% (Table 4). No patients had a nadir LVEF as low as during the index pregnancy. Left ventricular dilatation occurred in three (33.3%) of the nine patients with relapse, but RV function remained normal in all relapse cases. Three patients with relapse were admitted to the intensive care unit, but no cardiac arrests or deaths occurred. All patients with relapse later normalized their LVEF; the median time to LV recovery was 1 month (range 0–24 months).
As medical care improves and peripartum cardiomyopathy mortality rates decrease, more patients are seeking consultation about future childbearing.12 The 2011 European Society of Cardiology guidelines state that subsequent pregnancies should be discouraged in patients with nonrecovered ventricular function, providing the nondirective recommendation of the “need for counselling because of the risk of recurrence with a new pregnancy” in patients who recover LV function.1 A recent scientific statement from the American Heart Association makes very similar recommendations.13 The lack of evidence-based guidelines regarding reproductive counseling and obstetric management of patients with prior peripartum cardiomyopathy leaves health care providers in a dilemma, which the current study begins to address.
The peripartum cardiomyopathy relapse rate in our cohort (20.9%) was marginally less than previously reported; most studies have described a rate of 30% or higher.7,8,14–17 However, direct comparison with previous studies is difficult because the definition of relapse varies in the literature. Numerous studies have associated development of heart failure symptoms during subsequent pregnancy with relapse despite no objective decrease in LVEF.7,15,18 The report by Fett et al11 is the only study with clearly defined parameters; relapse occurred in 17% of pregnancies in patients with an LVEF of 55% or greater before the subsequent pregnancy and in 36% of the pregnancies in patients with an LVEF 55% or less.
Of the nine relapses observed in the current study, the LVEF nadir was not as low as at the index diagnosis, possibly indicating a milder form of cardiomyopathy during subsequent pregnancies. Of even greater clinical importance, every patient with relapse recovered LV function within a median of 1 month. It thus seems reasonable to propose that patients with prior peripartum cardiomyopathy who have recovered LV function be counseled that they have approximately a 20% risk of relapse in a future pregnancy and that the odds of LV recovery after relapse are excellent.
Of note, we have insufficient data about obstetric and cardiac outcomes among patients with nonrecovered LVEF before the subsequent pregnancy; thus, we do not offer guidance regarding pregnancy counseling for this subgroup of patients. The risk of relapse with LVEF less than 50% before the subsequent pregnancy ranges from 37% to 53% in studies of 10 or more patients, suggesting an increased risk of further deterioration of LV function in this subgroup.7,11,19,20
The obstetric outcomes in both index and subsequent pregnancies in our cohort were reassuring; there were no cases of stillbirth, the miscarriage rate was comparable with that of the general population (8–31%), and all live births occurred at 36 weeks of gestation or greater.21,22 Postpartum hemorrhage and hypertensive disorders were prevalent in index pregnancies with corresponding elevated recurrence rates in subsequent pregnancies.23,24
An interesting finding in this cohort was the high rate of lactation in subsequent pregnancies. Breastfeeding provides nutritional and immunologic benefit to the neonate, improves maternal–infant bonding, and lowers maternal risk of breast cancer and cardiovascular disease.27 Although our study was observational and not intended to evaluate the role of lactation in influencing cardiac function after peripartum cardiomyopathy, it is empirically reassuring to find similar rates in patients with and without relapse.
A recent multicenter study of subsequent pregnancy outcomes among patients with a history of peripartum cardiomyopathy suggested that the addition of bromocriptine to heart failure therapy was associated with better outcomes.14 Although none of the patients in our cohort received bromocriptine, outcomes remained favorable. Because the vast majority of the patients in our study had recovered LVEF before their subsequent pregnancy, it may be that bromocriptine does not provide meaningful clinical benefit in this subset of patients.
All patients in this study were managed by a dedicated group of specialists at a tertiary care center. It must be emphasized that the results of this study may not necessarily be replicated in centers with more limited resources.
A major strength of our study is the relatively large number of subsequent pregnancies from a single institution. Representing a rare complication of pregnancy, large studies of peripartum cardiomyopathy are not feasible. Inherent limitations include the relatively small patient volume accrued over almost two decades with potential variation in clinical management, lack of ethnic and racial diversity in our patient population, and variations in clinical management. Accrual of patients with multiple successive pregnancies renders data collection fundamentally challenging.
In conclusion, the present study provides crucial and encouraging information about obstetric and cardiac outcomes of subsequent pregnancies in patients with a history of peripartum cardiomyopathy. Further investigation is warranted to verify our results in different populations and determine optimal management strategies.
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