UNASSIGNED: Peripartum cardiomyopathy (PPCM) is a common cause of heart failure (HF) in the peripartum. Some medications are considered safe while breastfeeding. However, sacubitril/valsartan (Entresto), while efficacious, is not recommended in breastfeeding women due to concerns about adverse infant development, and no published data suggest otherwise.
UNASSIGNED: This study aimed to assess the transfer of sacubitril/valsartan into human milk and evaluate the infant\'s risk of drug exposure.
UNASSIGNED: The InfantRisk Human Milk Biorepository released samples and corresponding health information from five breastfeeding maternal-infant dyads exposed to sacubitril/valsartan. Sacubitril, valsartan, and LBQ657 (sacubitril active metabolite) concentrations were determined using liquid chromatography-mass spectrometry (LC/MS/MS) from timed samples 0, 1, 2, 4, 6, 8, 10, and 12 h following medication administration at steady state conditions.
UNASSIGNED: Valsartan levels were below the detection limit of 0.19 ng/mL in all milk samples. Sacubitril was measurable in all milk samples of the five participants, peaking 1 h after drug administration at a mean concentration of 1.52 ng/mL for a total infant dose of 0.00049 mg/kg/12 h and a relative infant dose (RID) calculated at 0.01%. The maximum concentration of its active metabolite LBQ657 in the milk samples was observed 4 h after medication administration and declined over the remaining 12-h dosing interval, for an average concentration of 9.5 ng/mL. The total infant dose was 0.00071 mg/kg/12 h, and the RID was 0.22%. Two mothers reported continuing to breastfeed while taking sacubitril/valsartan; both mothers stated observing no negative effects in their breastfed infants.
UNASSIGNED: The transfer of sacubitril/valsartan into human milk is minimal. These concentrations are unlikely to pose a significant risk to breastfeeding infants, with a combined calculated RID of <0.25%, which is far lower than the industry safety standards (RID <10%).

UNASSIGNED: Women with peripartum cardiomyopathy (PPCM) are at an increased risk of arterial and venous thromboembolic events. The review summarizes the evidence on the incidence of thromboembolic complications in women with PPCM, diagnostic approaches, related outcomes, and effects of therapies that have been used.
UNASSIGNED: English articles were retrieved from Web of Science and PubMed using search terms to capture studies related to PPCM (or postpartum cardiomyopathy) and all combinations of thrombosis- and embolism-related keywords. A total of 347 articles from PubMed and 85 from Web of Science were obtained, and after removing duplicates, 327 articles were screened for original data and classified into four domains: epidemiology, risk factors, diagnosis, and therapy of thromboembolism in PPCM. Ultimately, 30 articles were included. Data were synthesized in summary tables for each domain.
UNASSIGNED: Studies in the United States and Europe reported varying incidence for thromboembolism in PPCM, up to 14% in 6 months. Risk factors include elevated levels of coagulation factors, decreased protein C and S activity, decreased fibrinolysis, and a low left ventricular ejection fraction (LVEF). Cesarean delivery and post-operative status were correlated with a higher incidence of thromboembolic complications. Diagnosis relied mostly on ultrasonography and magnetic resonance and depended on the suspected location of thrombus. Anticoagulation has been used mostly for PPCM patients with a reduced LVEF, with the duration varying across guidelines and healthcare systems. Unfractionated heparin and low molecular weight heparin (LMWH) were considered safe choices during pregnancy, while warfarin and novel oral anticoagulants (NOACs) were used postpartum. The association of bromocriptine with risk of thromboembolic complications remains debated.
UNASSIGNED: There are important gaps in our understanding of the epidemiology, risk stratification, and optimal secondary prevention of thromboembolism in PPCM. Larger prospective studies with detailed phenotyping are required.

UNASSIGNED: Cardiac arrest (CA) caused by peripartum cardiomyopathy (PPCM) is a catastrophic disease that can lead to a high mortality rate in young women. Cardiopulmonary resuscitation (CPR) is the initial first aid measure to be taken and unfortunately, does not always lead to the restoration of spontaneous circulation (ROSC). We shared a rare successful case of extracorporeal cardiopulmonary oxygenation-assisted resuscitation (ECPR) in a patient with CA for up to 5.5 hours due to PPCM.
UNASSIGNED: A previously healthy 31-year-old woman at 34 weeks of gestation was admitted to the emergency department with fever and arrhythmia. Two days later, the patient had postpartum CA. She underwent CPR for up to 5 hours before receiving V-A extracorporeal membrane oxygenation (ECMO) support and eventually regained spontaneous circulation after half an hour. Based on the clinical manifestations, the patient was diagnosed with PPCM and received treatment. The patient was successfully removed from ECMO after 9 days. The patient experienced ECMO-related complications, including thrombocytopenia and intracranial hemorrhage (ICH). Although treatment was difficult, the patient was discharged after 2 months without any neurological complications. We followed up for 1 year and the patient was able to work normally as a teacher. In our mini-review, we found that the success rate of ECPR in perinatal CA was high, and ECPR is worthy of promotion and application.
UNASSIGNED: As an advanced life support method, ECPR can save patients undergoing postpartum CA. However, effective CPR and avoidance of ICH are necessary for the recovery of brain function.

OBJECTIVE: Peripartum cardiomyopathy (PPCM) is a rare heart disease, occurring in previously heart-healthy women during the last month of pregnancy or the first months after delivery due to left ventricular (LV) systolic dysfunction. A common pathomechanistic pathway of PPCM includes increased oxidative stress and the subsequent generation of a cleaved prolactin fragment (16 kDa PRL), which promotes the onset of heart failure (HF) in a microRNA (miR)-146a-dependent manner. Inhibition of prolactin secretion with the dopamine D2 receptor (D2R) agonist bromocriptine combined with standard HF therapy supports cardiac recovery. This study examined whether treatment with the more selective D2R agonist cabergoline prevents HF development in an experimental PPCM mouse model and might be used as an alternative treatment regime for PPCM.
RESULTS: Postpartum (PP) female PPCM-prone mice with a cardiomyocyte restricted STAT3-deficiency (αMHC-Cretg/+ ; Stat3fl/fl ; CKO) were treated over two consecutive nursing periods with cabergoline (CKO Cab, 0.5 mg/kg/day) and were compared with bromocriptine treated CKO (CKO Br) and postpartum-matched WT and CKO mice. Cabergoline treatment in CKO PP mice preserved cardiac function [fractional shortening (FS): CKO Cab: 34.5 ± 9.4% vs. CKO: 22.1 ± 9%, P < 0.05] and prevented the development of cardiac hypertrophy, fibrosis, and inflammation as effective as bromocriptine therapy (FS: CKO Br: 33.4 ± 5.6%). The myocardial up-regulation of the PPCM biomarkers plasminogen inhibitor activator 1 (PAI-1) and miR-146a were prevented by both cabergoline and bromocriptine therapy. A small cohort of three PPCM patients from the German PPCM Registry was treated with cabergoline (1 mg per week for 2 weeks, followed by 0.5 mg per week for another 6 weeks) due to a temporary unavailability of bromocriptine. All PPCM patients initially presented with a severely reduced LV ejection fraction (LVEF: 26 ± 2%). However, at 6 months of follow-up, LV function (LVEF: 56 ± 2%) fully recovered in all three PPCM patients, and no adverse events were detected.
CONCLUSIONS: In the experimental PPCM mouse model, the selective D2R agonist cabergoline prevents the onset of postpartum HF similar to bromocriptine. In PPCM patients, cabergoline treatment was safe and effective as all patients fully recovered. Cabergoline might serve as a promising alternative to bromocriptine. However, these findings are based on experimental data and a small case series and thus have to be interpreted with caution and should be validated in a larger clinical trial.

There is limited data on the impact of atrial fibrillation (Afib) on hospital outcomes in females with peripartum cardiomyopathy (PPCM). The National Inpatient Sample (NIS) 2011-2019 was used to find patients with PPCM. PPCM patients were divided into two groups: with and without Afib. Baseline characteristics were compared between both groups. Logistic regression was used to find independent predictors of Afib. Out of 13,840 PPCM patients, 249 (1.8%) also had a diagnosis of Afib. The Afib group was older and had a high burden of comorbidities. PPCM patients with Afib had higher in-hospital mortality (4-vs-0.7%, p=0.02), mean length of stay (11.3-vs-4.3 days, p<0.001) and healthcare resource utilization. Old age, low-income quartile, liver disease, obstructive sleep apnea and acute posthemorrhagic anemia were significant predictors of Afib. In conclusion, Afib is associated with higher in-hospital mortality and worse outcomes in females with PPCM. Further research is needed to improve these outcomes.

BACKGROUND: Over the past decades the use of assisted reproduction technology (ART) increased worldwide. ARTs are associated with an elevated risk for cardiovascular complications. However, a potential relation between subfertility/ARTs and the heart disease peripartum cardiomyopathy (PPCM) has not been systematically analyzed yet.
METHODS: A retrospective cohort study was carried out, including n = 111 PPCM patients from the German PPCM registry. Data from PPCM patients were compared to those from postpartum women in the German general population.
RESULTS: The prevalence of reported subfertility was high among PPCM patients (30%; 33/111). Most of the subfertile PPCM patients (55%; 18/33) obtained vitro fertilizations (IVF) or intracytoplasmic sperm injections (ICSI). PPCM patients were older (p < 0.0001), the percentage of born infants conceived by IVF/ICSI was higher (p < 0.0001) with a higher multiple birth (p < 0.0001), C-section (p < 0.0001) and preeclampsia rate (p < 0.0001), compared to postpartum women. The cardiac outcome was comparable between subfertile and fertile PPCM patients. Whole exome sequencing in a subset of n = 15 subfertile PPCM patients revealed that 33% (5/15) carried pathogenic or likely pathogenic gene variants associated with cardiomyopathies and/or cancer predisposition syndrome.
CONCLUSIONS: Subfertility occurred frequently among PPCM patients and was associated with increased age, hormonal disorders, higher twin pregnancy rate and high prevalence of pathogenic gene variants suggesting a causal relationship between subfertility and PPCM. Although this study found no evidence that the ART treatment per se increases the risk for PPCM or the risk for an adverse outcome, women with subfertility should be closely monitored for signs of peripartum heart failure.

Peripartum cardiomyopathy (PPCM) is a pregnancy-associated cardiomyopathy that occurs in previously heart-healthy women towards the end of pregnancy or in the first months after delivery and is characterized by heart failure due to systolic dysfunction. The clinical course of PPCM differs between mild symptoms and severe forms with acute heart failure complicated by cardiogenic shock (CS). Treatment of CS complicating PPCM is challenging, as β-adrenergic receptor (β-AR) stimulation seems to be associated with progression of heart failure and adverse outcome. This experimental study aims to examine whether postpartum treatment with the glucose uptake-promoting drug perhexiline alone or as co-treatment with β-AR stimulation prevents heart failure in the experimental PPCM mouse model.
Postpartum (PP) female PPCM-prone mice with a cardiomyocyte-restricted STAT3-deficiency (αMHC-Cretg/+ ;Stat3fl/fl ; CKO) were treated with perhexiline over two to three pregnancies and nursing periods (2/3PP) or were co-treated with perhexiline after one pregnancy (1PP) under chronic β-AR stimulation using isoproterenol (Iso) infusion. Perhexiline was not able to prevent onset of PPCM in CKO mice (FS: CKO Pexsig-2/3PP: 25 ± 12% vs. CKO Ctrl-2/3PP: 24 ± 9%, n.s.) but attenuated worsening of left ventricular function in response to treatment with the β-AR agonist Iso (FS: CKO Pexsig-Iso-1PP: 19 ± 4% vs. CKO Ctrl-Iso-1PP: 11 ± 5%, P < 0.05).
Treatment of PPCM patients with β-AR agonists should be avoided whenever possible. In cases with CS complicating PPCM, when treatment with β-AR agonists cannot be prevented, co-medication with perhexiline might help to reduce the cardiotoxic side effects of β-AR stimulation. Clinical data are necessary to further validate this therapeutic approach.

Peripartum cardiomyopathy (PPCM) is an idiopathic dilated cardiomyopathy, in which previously healthy women present with heart failure secondary to left ventricular (LV) systolic dysfunction during the last months of pregnancy or up to 5 months postpartum. PPCM occurs worldwide. The incidence seems to be increasing, possibly due to increasing awareness of the condition and diagnosis thereof. Women diagnosed with PPCM present with symptoms and signs of heart failure, thromboembolism or arrhythmia. Although the incidence of arrhythmias in this condition is not well documented, patients with PPCM often have rhythm disturbances. Indeed, life-threating arrhythmias contribute significantly to sudden cardiac death (SCD) in this population, especially when patients have poor systolic function. In this review, we summarize the evidence on atrial and ventricular arrhythmias in PPCM, as detected by various diagnostic modalities. Furthermore, we summarize the management of arrhythmias in PPCM, as recommended by contemporary guidelines.

This case report highlights the rare occurrence of postpartum psychosis in the setting of peripartum cardiomyopathy, which can have rare presentations like arrhythmias and pulmonary edema; and the challenges one should anticipate while managing these conditions together. Caution is advised whenever antipsychotic drugs are to be administered to a patient with a cardiac condition as these drugs potentially increase the risk of arrhythmias and sudden death.
A 35 year old grand multiparous woman who was 1 week into puerperium was admitted with severe difficulty in breathing at rest, chest congestion and pain. She also had easy fatigability, orthopnea, paroxysmal nocturnal dyspnea, edema, tachycardia, tachypnea, irregularly irregular heart rate with a pulse deficit, elevated jugular venous pressure, cardiomegaly, hepatomegaly and pulmonary crepitations. On the sixth day while improving on standard drugs for heart failure, she developed bizarre behavior and confusion. She also had auditory, visual and olfactory hallucinations; violence to the baby and the husband; and refusal to feed and take medication. There was no altered sensorium and the vital signs were normal. She was diagnosed with puerperal psychosis during the management of peripartum cardiomyopathy.
In the rare occurrence of puerperal psychosis in the course of management of peripartum cardiomyopathy one must be acutely aware of the risk of sudden cardiac death occasioned by use of antipsychotics, either directly or due to arrhythmias. Continuous electrocardiogram (ECG) monitoring or use of alternative management modalities is thus highly advised.

BACKGROUND: Concentrations of the anti-angiogenic factor soluble fms-like tyrosine kinase-1 (sFlt-1) are altered in peripartum cardiomyopathy (PPCM). In this study we investigated changes in the angiogenesis balance in PPCM.Methods and Results:Plasma concentrations of sFlt-1 and the pro-angiogenic placenta growth factor (PlGF) were determined in patients with PPCM during the post-partum phase (n=83), in healthy women at delivery (n=30), and in patients with acute heart failure (AHF; n=65). Women with cardiac failure prepartum or associated with any form of hypertension, including pre-eclampsia, were excluded. Compared with non-pregnant women, in women with AHF and PPCM, median PlGF concentrations were greater (19 [IQR 16-22] and 98 [IQR 78-126] ng/mL, respectively; P<0.001) and the sFlt-1/PlGF ratio was lower (9.8 [6.6-11.3] and 1.2 [0.9-2.8], respectively; P<0.001). The sFlt-1/PlGF ratio was lower in PPCM than in normal deliveries (1.2 [0.9-2.8] vs. 94.8 [68.8-194.1], respectively; P<0.0001). The area under the curve for PlGF (cut-off value: 50ng/mL) and/or the sFlt-1/PlGF ratio (cut-off value: 4) to distinguish PPCM from either normal delivery or AHF was >0.94. Median plasma concentrations of the anti-angiogenic factor relaxin-2 were lower in PPCM and AHF (0.3 [IQR 0.3-1.7] and 0.3 [IQR 0.3-1] ng/mL, respectively) compared with normal deliveries (1,807 [IQR 1,101-4,050] ng/mL; P<0.001).
CONCLUSIONS: Plasma of PPCM patients shows imbalanced angiogenesis. High PlGF and/or low sFlt-1/PlGF may be used to diagnose PPCM.