RARE DISEASE
Peripartum cardiomyopathy
Peripartum cardiomyopathy
Peripartum cardiomyopathy
Synonyms: Postpartum cardiomyopathy
Synonyms: Postpartum cardiomyopathy
Synonyms: Postpartum cardiomyopathy
Drug discovery
623
papers
On emerging therapies
Overview
Peripartum cardiomyopathy (PPCM) is an idiopathic cardiomyopathy characterized by left ventricular systolic dysfunction (LVEF <45%) presenting in the last month of pregnancy or within five months postpartum, without other identifiable causes. It leads to heart failure with variable outcomes, ranging from complete recovery to persistent cardiomyopathy, severe complications (e.g., thromboembolism, cardiogenic shock), or death. Diagnosis requires exclusion of alternative etiologies, and management aligns with heart failure therapies adapted for pregnancy/lactation [1][2][4][5].
Burden
Global incidence varies widely (1:100 to 1:20,000 deliveries), with mortality rates exceeding 40% in low-resource settings versus 4–15% in high-income countries. Social vulnerability, delayed diagnosis, and limited healthcare access exacerbate poor outcomes, contributing to long-term morbidity in 30–50% of survivors [4][5][7][14][15].
Therapies
Guideline-directed heart failure therapy (diuretics, β-blockers, ACE inhibitors/ARBs postpartum), bromocriptine (Class IIb recommendation) to inhibit prolactin cleavage, anticoagulation for LV thrombus prevention, and advanced interventions (mechanical circulatory support, transplant) in refractory cases [1][3][6][8].
Categories: rare cardiac diseases, rare gynecological and obstetric diseases, rare transplant-related disorders
Research Papers
623 drug discovery papers about Peripartum cardiomyopathy, with 2 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
623 drug discovery papers about Peripartum cardiomyopathy, with 2 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
small molecules
2026-09-13 | Left Ventricular Recovery Following Bromocriptine Initiation at Different Stages of Peripartum Cardiomyopathy: A Report of Two Cases.
Peripartum cardiomyopathy (PPCM) is a rare yet potentially life-threatening form of heart failure that occurs during late pregnancy or within the months following delivery. Bromocriptine, which suppresses prolactin secretion, has emerged as a promising adjunctive therapy for PPCM; however, the optimal timing of its initiation remains uncertain. We describe two patients with PPCM who received bromocriptine at different stages of the disease course. The first patient was a 30-year-old woman who presented 33 days after delivery with cardiogenic shock, a left ventricular ejection fraction (LVEF) of 12%, and a left ventricular thrombus. Despite treatment with intra-aortic balloon pumping, venoarterial extracorporeal membrane oxygenation, anticoagulation, and guideline-directed medical therapy, recovery of left ventricular function plateaued. Bromocriptine was initiated on hospital day 44, after which LVEF increased from 38% to 53% within seven days and subsequently recovered to 60%. The second patient was a 35-year-old woman who developed acute heart failure nine days after delivery with an LVEF of 28%. Because left ventricular function remained markedly impaired despite standard heart failure therapy, bromocriptine was initiated on hospital day seven. Her LVEF improved to 39% by hospital day 15 and ultimately recovered to 61%. These cases demonstrate a temporal association between bromocriptine initiation and subsequent improvement in left ventricular systolic function at different stages of the clinical course of PPCM.
2026-08-14 | Pharmacokinetics of oral bromocriptine in postpartum patients.
Cardiomyopathy is a leading cause of maternal morbidity and mortality. A prolactin fragment has been implicated in the pathogenesis, and preliminary data suggest that bromocriptine-a dopamine receptor agonist that inhibits prolactin secretion-is a promising adjunctive therapy. However, bromocriptine pharmacokinetic (PK) data are largely derived from healthy males. Our objective was to conduct a postpartum oral bromocriptine PK study to inform a future trial to test the potential benefit of bromocriptine for add-on peripartum cardiomyopathy (PPCM) therapy. We conducted an oral bromocriptine PK study including healthy postpartum participants during the delivery-associated hospitalization who delivered ≥1 fetus at ≥28 weeks' gestation. Patients on CYP34A inhibitors or inducers, those with clinical contraindications according to the FDA package insert, and those who planned to express breastmilk (given the potential negative effects of bromocriptine on lactation) were excluded. Whole blood was collected pre-dose and 1, 2, 3, 4, 6, 8, and 12 h after an observed dose of 5 mg bromocriptine. Plasma was analyzed using mass spectrometry. Parameters of interest included 12-h area-under-the-curve (AUC12), elimination half-life (t1/2), maximum concentration (Cmax), and time to Cmax (T max). Non-compartmental PK analysis was conducted on nine participants, demonstrating mean ± SD AUC12, t 1/2, Cmax, and Tmax were 180 ± 207 pg h/mL, 5.4 ± 4.8 h, 56 ± 64 pg/mL, and 1.6 ± 1.1 h, respectively. In this modest sample, several PK parameters of oral bromocriptine in healthy postpartum participants differed from those reported in the literature, which may be due to physiological changes in pregnancy. The association between PK parameters and clinical outcomes in patients with PPCM warrants further evaluation.
2026-08-01 | Impairment of the DNA damage response pathway as a potential contributor towards peripartum cardiomyopathy
Abstract Background and purpose Peripartum cardiomyopathy (PPCM) affects prior heart-healthy women in the peripartum phase and is characterized by systolic heart failure (HF). Data from a German/ Swedish PPCM cohort revealed a 16-fold increased cancer prevalence. Several patients who were diagnosed with both, PPCM and cancer, carried gene variants located on DNA-damage-response (DDR) genes and/or received anthracycline based chemotherapies prior to their PPCM diagnosis. Here, we investigated juvenile anthracycline treatment prior to pregnancy as well as the effect of DDR impairment during the peripartum phase using mice heterozygous for Ataxia-Telangiectasia-Mutated (ATM), and determined the frequency of ATM gene variants and plasma levels of ATM-targeting miRNAs in PPCM patients. Methods and results Female C57BL/6N mice who received juvenile doxorubicin (DOX, 4x4mg/kgBW) treatment prior to pregnancy showed high mortality in the late peripartum phase. DOX-treated mice who survived two pregnancies and nursing periods exhibited reduced cardiac function compared to untreated (wildtype) WT mice (ctrl). RNAseq analysis of LV tissue from ctrl postpartum (PP) mice had shown peripartum induced upregulation of several DDR related transcripts compared with nulli-pari (NP) mice. This upregulation did not occur among PP mice who received juvenile DOX treatment. Whole exome sequencing in 80 PPCM patients from the German PPCM registry identified 7 carriers of heterozygous ATM gene variants classified as variants of uncertain significance (VUS, n=6) or pathogenic (P, n=1). MiRNA-screening by using human TaqMan Array Cards identified elevated plasma levels of 5 miRNAs potentially targeting ATM in PPCM patients compared to heart-healthy PP-matched women. Overexpression of miRNA precursors of two of these miRNAs, miR-18a-5p and miR-18b-5p, resulted in the reduction of ATM protein levels in HL1 cardiomyocytes. As proof-of-concept, we used a heterozygous ATM (ATM+/-) mouse model carrying a targeted mutation (Atmins5790neo) leading to a reduced protein expression. After 4 pregnancies and nursing periods (4xPP) ATM+/- mice showed systolic dysfunction and cardiac hypertrophy in contrast to WT 4xPP, ATM+/- NP and WT NP mice (FAC%: WT: 49±5 vs ATM+/-: 37±9; P<0.001). Moreover, mice with PPCM due to cardiac STAT3 deficiency (aMHCxCretg/+;STAT3flox/flox, CKO) and additional ATM heterozygosity showed an aggravated heart failure phenotype compared with CKO PP mice (FS%: CKO: 23.8±3 vs CKO/ATM+/-: 17.3±3.3; P<0.0005) associated with an induction of cell-cycle regulators p21 and Caspase 3. In conclusion, our data suggests that the DDR pathway may be an important link between cancer and PPCM. Latent side effects of DOX therapy by DDR suppression as well as detrimental effects of DDR related gene variants are potential shared mechanisms. In line, reduced ATM expression induces cardiac dysfunction and hypertrophy in the ATM+/-PP mice and aggravates HF in CKO;ATM+/- PP mice.
2026-07-23 | Management of Peripartum Cardiomyopathy With and Without Bromocriptine: A Comparative Study
Introduction: Peripartum cardiomyopathy is an uncommon but potentially severe cause of pregnancy-associated systolic heart failure. Bromocriptine has been proposed as an adjunctive therapy because it suppresses prolactin release, but its interpretation depends on the background heart failure regimen, dose, anticoagulation practice, and patient selection. This study compared short-term left ventricular ejection fraction (LVEF) recovery in patients managed with standard therapy with or without low-dose bromocriptine. Methods: This prospective comparative observational study was conducted at a tertiary care center in South India from October 2020 to October 2021. A total of 50 patients with peripartum cardiomyopathy and LVEF below 45% were analyzed according to treatment received. Group A (n=25) received bromocriptine 2.5 mg once daily for one week in addition to standard pregnancy/postpartum-compatible heart failure therapy, and Group B (n=25) received standard therapy alone. Treatment allocation was not randomized, and no allocation concealment was used. Echocardiography was used to assess LVEF at baseline, discharge, and one month. Continuous variables were compared with the independent samples Student's t-test, and categorical variables were compared with the chi-square test or Fisher's exact test. Results: Baseline LVEF did not differ significantly between Group A and Group B (38.36 ± 2.40% vs 39.00 ± 1.19%; p = 0.238). Important baseline differences were present, including gestational age at presentation (33.76 ± 7.84 vs 37.72 ± 1.57 weeks; p = 0.017), body mass index (22.49 ± 3.10 vs 24.01 ± 1.75 kg/m2; p = 0.037), comorbidity distribution (p = 0.033), electrocardiographic findings (p = 0.033), and chest radiographic findings (p = 0.004). At discharge, mean LVEF was 47.52 ± 2.52% in Group A and 46.56 ± 2.82% in Group B (p = 0.210). At one month, mean LVEF was higher in Group A than in Group B (57.00 ± 1.71% vs 49.84 ± 1.38%; p < 0.001). Gestational age at delivery (p = 0.031) and birth weight (p = 0.010) differed between the groups; neonatal intensive care unit admission did not (p = 0.560). Recorded Apgar score distributions were retained as abstracted, but the uniform control-group values require cautious interpretation. Conclusion: Both groups showed improvement in left ventricular function. Low-dose one-week bromocriptine was associated with greater one-month LVEF in this cohort, but the non-randomized design, baseline imbalances, limited documentation of background therapy and anticoagulation, and short follow-up preclude causal claims. The findings should be interpreted as hypothesis-generating and require confirmation in larger protocolized studies with adjustment for confounding and longer follow-up.
2026-07-19 | Diagnosis and treatment of peripartum cardiomyopathy: a case report
Peripartum cardiomyopathy (PPCM) is a rare heart muscle disease that affects women during the last month of pregnancy or within five months after childbirth. The disease manifests as acute and/or chronic heart failure (CHF). In addition to standard CHF therapy, PPCM treatment includes bromocriptine, which blocks the production of anti-angiogenic 16kDa low-molecular-weight prolactin. This prolactin plays an important role in PPCM pathogenesis. Although effective treatments are available, some aspects of managing this condition remain unresolved, ranging from epidemiology to treatment duration. This article presents a clinical case report of a patient with PCMP and details the monitoring of her clinical, instrumental, and laboratory data over a 15-month period.
antibodies
2025-01-01 | Immune dysregulation as a key driver of peripartum cardiomyopathy - an exploratory advanced imaging and biomarker study
Aims Peripartum cardiomyopathy (PPCM) is an idiopathic cardiomyopathy occurring in women in the late stages of pregnancy or in the postpartum period and is associated with significant morbidity, mortality, and persistent left ventricular dysfunction. PPCM pathogenesis involves multiple putative mechanisms including inflammation. We aimed to explore the acute inflammatory processes in PPCM using 18F-fluorodeoxyglucose positron emission tomography-computed tomography (18FDG-PET-CT), cardiovascular magnetic resonance (CMR), and inflammasome profiling. Methods and results Women with a new diagnosis of PPCM (n = 10, all within 3 months postpartum), five healthy postpartum controls (HPC), and five healthy non-postpartum controls (HNPC), underwent 18FDG-PET-CT, CMR, and serum inflammatory proteomic profiling. PPCM patients had a median age of 34 years (interquartile range [IQR] 30.3–38.5, similar in control groups), and a median parity of 3 (IQR 1–4). PPCM patients presented with severe, symptomatic heart failure (all New York Heart Association functional class III/IV), reduced median left ventricular ejection fraction of 35.5% (IQR 18.1–37.9). PPCM and HPC groups showed higher myocardial and splenic 18FDG uptake compared to HNPC. On CMR, myocardial interstitial fibrosis (elevated T1 time, extracellular volume, and late gadolinium enhancement mass) was solely present in PPCM. Inflammatory profiling showed pro-inflammatory cytokine dysregulation in PPCM (elevated neutrophil-to-lymphocyte ratio, C-reactive protein, interleukin-6, tumour necrosis factor-α, chemokine (C-C motif) ligand 3, hepatocyte growth factor, chemokine (C-X-C motif) ligand 10 and colony-stimulating factor-1) compared to controls. Conclusions Patients with PPCM exhibited a dysregulated immune response, associated with early myocardial interstitial fibrosis and adverse cardiac remodelling. This highlights the importance of rapid initiation of guideline-directed medical therapy especially with drugs documented to have anti-fibrotic effects.
2024-07-13 | Cardio-obstetrics de novo: a state-level, evidence-based approach for addressing maternal mortality and severe maternal morbidity in Georgia.
Georgia has a higher rate of severe maternal morbidity and mortality when compared with the rest of the United States. Evidence gained from the Georgia Maternal Mortality Review Committee identified areas of focus for high-yield clinical initiatives for improvement in maternal health outcomes. Cardiovascular disease, including cardiomyopathy, coronary conditions, and preeclampsia with or without eclampsia, is the most common cause of pregnancy-related death in non-Hispanic Black women in Georgia. The development of a cardio-obstetrics program is an initiative to advance health equity by decreasing cardiovascular morbidity and mortality. This report describes the following: (1) state-level advocacy for improving maternal health outcomes with funding gained through the legislative process and partnership with a governmental agency; (2) cardio-obstetrics program development based on evidence gained from the maternal mortality review process; and (3) implementation of a cardio-obstetrics service, beginning with a focused approach for capacity building and understanding barriers to care.
2024-04-19 | Placental senescence pathophysiology is shared between peripartum cardiomyopathy and preeclampsia in mouse and human.
Peripartum cardiomyopathy (PPCM) is an idiopathic form of pregnancy-induced heart failure associated with preeclampsia. Circulating factors in late pregnancy are thought to contribute to both diseases, suggesting a common underlying pathophysiological process. However, what drives this process remains unclear. Using serum proteomics, we identified the senescence-associated secretory phenotype (SASP), a marker of cellular senescence associated with biological aging, as the most highly up-regulated pathway in young women with PPCM or preeclampsia. Placentas from women with preeclampsia displayed multiple markers of amplified senescence and tissue aging, as well as overall increased gene expression of 28 circulating proteins that contributed to SASP pathway enrichment in serum samples from patients with preeclampsia or PPCM. The most highly expressed placental SASP factor, activin A, was associated with cardiac dysfunction or heart failure severity in women with preeclampsia or PPCM. In a murine model of PPCM induced by cardiomyocyte-specific deletion of the gene encoding peroxisome proliferator-activated receptor γ coactivator-1α, inhibiting activin A signaling in the early postpartum period with a monoclonal antibody to the activin type II receptor improved heart function. In addition, attenuating placental senescence with the senolytic compound fisetin in late pregnancy improved cardiac function in these animals. These findings link senescence biology to cardiac dysfunction in pregnancy and help to elucidate the pathogenesis underlying cardiovascular diseases of pregnancy.
2023-01-16 | [Case of peripartum cardiomyopathy misdiagnosed as pulmonary changes due to COVID-19].
A 37-year-old female patient was admitted 16 days after delivery in a hospital for infectious diseases with cough, shortness of breath, and infiltrative changes in the lungs that were interpreted as viral pneumonia. Considering the failure of therapy and the history, peripartum cardiomyopathy was suspected. Examination revealed a decrease in left ventricular ejection fraction to 30 %, ultrasonic signs of lung congestion and bilateral hydrothorax. The patient was diagnosed with peripartum cardiomyopathy accompanied by functional class 4 heart failure. A specific feature of this case was fast positive dynamics with complete regression of the clinical picture of congestion and improvement of the left ventricular myocardial function associated with the treatment.
2021-07-09 | Complement-Mediated Disorders in Pregnancy.
Complement-mediated disorders in pregnancy span a large spectrum and have been implicated in all three complement pathways: classical, lectin, and alternative. Our understanding of these disorders in recent years has advanced due to a better understanding of complement regulatory proteins, such as complement factor H, complement factor I, membrane cofactor protein, and thrombomodulin that particularly affect the alternative complement pathway. Enthusiasm in genotyping for mutations that encode these proteins has allowed us to study the presence of genetic variants which may predispose women to develop conditions such as pregnancy-associated hemolytic uremic syndrome (P-aHUS), thrombotic thrombocytopenic purpura, preeclampsia/hemolysis, elevated liver enzymes, low platelets (HELLP), systemic lupus erythematosus/antiphospholipid syndrome, and peripartum cardiomyopathy. The advent of the anti-C5-antibody eculizumab to quench the complement cascade has already proven in small case series to improve maternal kidney outcomes in complement-mediated obstetric catastrophes such as P-aHUS and HELLP. In this review, we will detail the pathogenesis behind these complement-mediated pregnancy disorders, the role of complement variants in disease phenotype, and the most up-to-date experience with eculizumab in this population.
proteins
2026-07-15 | Recurrent bilateral lower limb arterial embolism secondary to left ventricular thrombus in peripartum cardiomyopathy successfully treated with systemic streptokinase thrombolysis: a rare case report.
Peripartum cardiomyopathy (PPCM) is an uncommon but potentially life-threatening form of heart failure occurring toward the end of pregnancy or during the months following delivery in women without pre-existing heart disease. Left ventricular systolic dysfunction predisposes patients to intracardiac thrombus formation and systemic thromboembolic complications, which are associated with significant morbidity and mortality. A 35-year-old multiparous woman presented shortly after spontaneous vaginal delivery of an intrauterine fetal demise with acute right lower-limb ischemia and heart failure. Transthoracic echocardiography demonstrated severe left ventricular systolic dysfunction (LVEF approximately 35%), severe functional mitral regurgitation, pulmonary hypertension, and a large left ventricular thrombus. She underwent urgent Fogarty embolectomy followed by therapeutic anticoagulation with unfractionated heparin and warfarin. Despite therapeutic anticoagulation (INR 2.0 and activated partial thromboplastin time approximately 90 seconds), she developed recurrent bilateral acute lower-limb ischemia five days later. Because of profound hemodynamic instability and prohibitive surgical risk, systemic streptokinase thrombolysis was administered. Repeat echocardiography performed immediately after thrombolysis demonstrated complete resolution of the left ventricular thrombus. Follow-up echocardiography one week later showed significant recovery of left ventricular systolic function (LVEF 45-50%), improvement of mitral regurgitation to mild-to-moderate, and reduction in pulmonary artery systolic pressure. This case highlights the importance of early recognition of thromboembolic complications in PPCM and demonstrates that systemic streptokinase thrombolysis may represent an effective life- and limb-saving therapeutic option in carefully selected patients when surgical or catheter-based interventions are not feasible.
2025-07-31 | Ufmylation Suppresses Unfolded Protein Response to Prevent Peripartum Cardiomyopathy.
Ufmylation is a novel ubiquitin-like protein modification that plays a critical role in maintaining the homeostasis of different tissues, but its role in the heart remains poorly understood. Here, we showed that mice lacking UFM1 ligase 1 (UFL1), an enzyme essential for ufmylation, in the heart developed peripartum cardiomyopathy. Loss of UFL1 reversed pregnancy-induced adaptive cardiac transcriptome alterations. Moreover, loss of UFL1 triggered excessive endoplasmic reticulum stress, inhibited mitochondrial oxidative metabolism, and caused augmented mTOR signaling, leading to pronounced pathological remodeling and heart failure. These results demonstrate that ufmylation is essential for physiological cardiac remodeling and that disruption of ufmylation predisposes the heart to peripartum cardiomyopathy.
2023-06-19 | RNA sequencing identifies human placentalIL3RAas a potential predictor of adverse cardiovascular outcomes in patients with severe preeclampsia
Abstract Background Mortality from preeclampsia (PE) and PE-associated morbidities are 3-to 5-fold higher in persons of African ancestry than in those of Asian and European ancestries. The placenta is central to the etiology of PE. However, how and to what extent the placenta contributes to worse PE outcomes in persons of African ancestry is yet to be fully elucidated. Objective We aimed to identify molecular pathways that are unique or enriched in placentas of parturient persons of African ancestry with PE with severe features (sPE) compared to those of Asian and European ancestry with sPE. Study design Bulk RNA sequencing was performed on 50 placentas from parturient persons with sPE of African (n=9), Asian (n=18) and European (n=23) ancestries and 73 normotensive controls of African (n=9), Asian (n=15) and European (n=49) ancestries. Results Metabolism, hormone regulation and hypoxia/angiogenesis genes, previously described to be upregulated in PE, including: LEP , PAPPA2 , INHA , FSTL3 , FLT1, PHYHIP and ENG , were upregulated in sPE across ancestries, with high expression of FSTL3 being additionally associated with intrauterine growth restriction (p = .0047). Notably, the upregulation of, FLT1 , LEP and PHYHIP was significantly higher in sPE placentas from parturient persons of African versus Asian ancestry (p = .0.35, .020 and .012 respectively). Genes associated with allograft rejection and adaptive immune response were upregulated in placentas from parturients of African ancestry but not in those of Asian and European ancestries. Among the allograft rejection/adaptive immune response genes, IL3RA was of particular interest because the patient with the highest placental IL3RA level, a woman of African ancestry with IL3RA levels 4.5-fold above the average for African ancestry parturients with sPE, developed postpartum cardiomyopathy, and was the only patient out of 123, that developed this condition. Interestingly, the sPE patients with the highest IL3RA levels among parturients of Asian and European ancestries developed unexplained tachycardia peripartum, necessitating echocardiography in the European ancestry patient. The association between elevated placental IL3RA levels and unexplained tachycardia or peripartum cardiomyopathy was found to be significant in the 50 sPE patients (p = .0005). Conclusions Placentas from parturients of African ancestry express higher levels of metabolism ( LEP ) and hypoxia/angiogenesis ( FLT1 ) genes, as well as allograft rejection/adaptive immune response genes, including IL3RA . High placental expression of IL3RA may predict worse maternal cardiovascular outcomes, including peripartum cardiomyopathy. Studies evaluating placental IL3RA levels in peripartum cardiomyopathy cohorts are therefore warranted, as are broader studies evaluating placental factors in maternal cardiovascular outcomes postpartum.
2022-09-22 | Pregnancy-induced Physiological Hypertrophic Preconditioning Attenuates Pathological Myocardial Hypertrophy by Mnemonic Activation of FoxO3a/GSK3β Pathway
Abstract Previous studies show a woman’s age at final pregnancy is correlated with post-reproductive longevity and nulliparity is associated with higher risk of incident heart failure, and we previously reported a cardioprotective phenomenon termed myocardial hypertrophic preconditioning, but it is unknown whether pregnancy-induced physiological hypertrophic preconditioning can also protect the heart against subsequent pathological hypertrophic stress. Here, we found that compared with nulliparous mice, pathological cardiac hypertrophy induced by Ang Ⅱ infusion or TAC was significantly attenuated and heart failure induced by TAC was markedly improved in mice with pregnant preconditioning. Activation of FoxO3a was significantly enhanced in the hearts of postpartum mice. FoxO3a inhibited myocardial hypertrophy by suppressing signaling pathway of phosphorylated glycogen synthase kinase-3β (p-GSK3β)/β-catenin/Cyclin D1. Silencing or overexpression of FoxO3a attenuated or enhanced the anti-hypertrophic effect of pregnant preconditioning in mice with pathological stimulation. Our findings demonstrate that pregnancy-induced myocardial hypertrophic preconditioning confers resistance to subsequent hypertrophic stress and slows progression to heart failure through activation of FoxO3a/GSK3β pathway.
2021-06-07 | The HGR motif is the antiangiogenic determinant of vasoinhibin: implications for a therapeutic orally active oligopeptide
The hormone prolactin acquires antiangiogenic and antivasopermeability properties after undergoing proteolytic cleavage to vasoinhibin, an endogenous prolactin fragment of 123 or more amino acids that inhibits the action of multiple proangiogenic factors. Preclinical and clinical evidence supports the therapeutic potential of vasoinhibin against angiogenesis-related diseases including diabetic retinopathy, peripartum cardiomyopathy, rheumatoid arthritis, and cancer. However, the use of vasoinhibin in the clinic has been limited by difficulties in its production. Here, we removed this barrier to using vasoinhibin as a therapeutic agent by showing that a short linear motif of just three residues (His46-Gly47-Arg48) (HGR) is the functional determinant of vasoinhibin. The HGR motif is conserved throughout evolution, its mutation led to vasoinhibin loss of function, and oligopeptides containing this sequence inhibited angiogenesis and vasopermeability with the same potency as whole vasoinhibin. Furthermore, the oral administration of an optimized cyclic retro-inverse vasoinhibin heptapeptide containing HGR inhibited melanoma tumor growth and vascularization in mice and exhibited equal or higher antiangiogenic potency than other antiangiogenic molecules currently used as anti-cancer drugs in the clinic. Finally, by unveiling the mechanism that obscures the HGR motif in prolactin, we anticipate the development of vasoinhibin-specific antibodies to solve the on-going challenge of measuring endogenous vasoinhibin levels for diagnostic and interventional purposes, the design of vasoinhibin antagonists for managing insufficient angiogenesis, and the identification of putative therapeutic proteins containing HGR.
cell therapies
2026-09-19 | Venoarterial extracorporeal membrane oxygenation for peripartum cardiomyopathy complicated by severe preeclampsia: a case report with 5-year follow-up.
Peripartum cardiomyopathy (PPCM) coexisting with severe preeclampsia is uncommon and diagnostically challenging because dyspnea, pulmonary edema, and cardiac dysfunction may be attributed to either condition. Long-term outcomes after rescue mechanical support remain poorly documented. A 28-year-old primigravida at 37 + 6 weeks presented with 2 days of worsening orthopnea, dyspnea, and cough. At 15 + 3 weeks, electrocardiography had shown complete left bundle branch block, although left ventricular ejection fraction (LVEF) was 61%. On admission, blood pressure was 159/120 mmHg, heart rate 157 beats/min, urine protein was positive, N-terminal pro-B-type natriuretic peptide (NT-proBNP) was 5,660 pg/ml, and echocardiography showed an LVEF of 26%. Severe preeclampsia and acute heart failure due to PPCM were diagnosed. Labetalol, magnesium sulfate, and furosemide were administered, followed by emergency cesarean delivery of a 2,880-g male infant (Apgar scores, 8 and 10). Persistent postoperative hemodynamic instability despite mechanical ventilation and pharmacotherapy prompted multidisciplinary initiation of venoarterial extracorporeal membrane oxygenation (VA-ECMO). She was successfully decannulated on day 4 and discharged on day 21 with an LVEF of 44%. NT-proBNP normalized by 6 months, LVEF exceeded 50% by 9 months, and at 5 years LVEF was 59% and NT-proBNP was 20.9 pg/ml. This case provides rare 5-year documentation of sustained myocardial recovery after VA-ECMO in PPCM with severe preeclampsia. In peripartum patients with severe hypertension and respiratory symptoms, an LVEF below 45% should prompt evaluation for PPCM; timely echocardiography, multidisciplinary care, and early VA-ECMO may bridge refractory hemodynamic instability to recovery, followed by prolonged cardiac surveillance.
2026-08-14 | The spectrum of pregnancy-induced cardiac remodeling: transitioning from healthy adaptive hypertrophy to peripartum cardiomyopathy.
Pregnancy imposes profound hemodynamic, metabolic, and biomechanical stresses on the heart, requiring coordinated structural and molecular adaptations to preserve cardiac function. To compensate, the cardiovascular system undergoes significant reversible adaptations, such as increased blood volume and elevated cardiac output. Such alterations induce physiological left ventricular hypertrophy that is regulated, in part, by mechanotransduction, a process by which cells convert mechanical stimuli such as stretch and pressure into biochemical pathways. Integrin-mediated complexes link cardiomyocytes with the extracellular matrix (ECM), allowing the myocardium to sense increased wall stress/stretch and activate cardioprotective signaling cascades. Together, these pathways preserve cytoskeletal integrity, sustain cardiomyocyte viability, and promote adaptive hypertrophic growth that regresses post-partum as hemodynamic load returns to pre-pregnancy levels. However, within a subset of pregnant women, this healthy adaptive response becomes dysregulated and adaptive hypertrophy transitions into maladaptive, leading to peripartum cardiomyopathy (PPCM) with heart failure (HF). PPCM has a mortality rate between 7% and 15%, establishing it as a significant cause of maternal death globally. Here, we discuss integration of mechanotransduction and cell survival pathways to support cardiac adaptation during pregnancy. Elucidating the role of gene variants and mechanotransduction in the pregnant heart may lead to improved patient outcomes in PPCM and HF.
2026-01-10 | Successful use of immunoadsorption therapy in advanced dilated cardiomyopathy: A case report.
Dilated cardiomyopathy (DCM) is a major cause of chronic heart failure, and some patients continue to deteriorate despite guideline-directed medical therapy. Immunoadsorption (IA), which removes pathogenic autoantibodies, has been proposed as a potential adjunctive therapy, but its clinical use remains limited. This case illustrates the potential benefits of IA in advanced, treatment-refractory DCM. A 53-year-old woman with a 9-year history of DCM presented with recurrent chest tightness and dyspnea. Despite long-term guideline-directed medical therapy, her symptoms progressively worsened. The patient had chronic DCM initially diagnosed in the peripartum period, with a left ventricular ejection fraction (LVEF) of 11% at onset. Before IA, echocardiography demonstrated severe systolic dysfunction (LVEF 22%-24%) with significant mitral regurgitation, and laboratory evaluation showed markedly elevated pro-BNP (4454 pg/mL). The patient underwent two sessions of immunoadsorption in September 2024, followed by high-dose intravenous immunoglobulin (IVIG) as per standard protocols. Following treatment, her symptoms improved, pro-BNP decreased to 2109 pg/mL, and repeat echocardiography showed an increase in LVEF to 29.2%. This case suggests that immunoadsorption may offer clinical benefit in patients with advanced, refractory DCM. While promising, IA remains experimental and requires further investigation in larger, controlled studies.
2025-09-27 | A CASE OF ORTHOTOPIC BICAVAL HEART TRANSPLANTATION IN A PATIENT WITH PERIPARTUM CARDIOMYOPATHY
This paper presents a clinical case of orthotopic bicaval heart transplantation in a patient with end-stage chronic heart failure that developed against the background of peripartum cardiomyopathy. The disease manifested itself in the second trimester of pregnancy, complicated by severe preeclampsia and progressive heart failure. In the absence of an available donor organ, the patient was implanted with a left ventricular assist device HeartMate 3 as a «bridge to transplantation». Four years after left ventricular assist device implantation, when a donor appeared, orthotopic heart transplantation was successfully performed. The case demonstrates the effectiveness of a multidisciplinary approach in conditions of a limited donor resource and emphasizes the need for early diagnosis, systemic prevention and development of transplantation services to improve outcomes in patients with peripartum cardiomyopathy.
2025-08-16 | Cardiac Transplantation for Peripartum Cardiomyopathy in a Patient With Sickle Cell Disease.
Cardiac surgery, particularly cardiac transplantation, is considered high risk in patients with sickle cell hemoglobinopathies and rarely reported in the literature. We present a case of a 33-year-old woman with sickle cell β+ thalassemia and peripartum cardiomyopathy, who presented with sickling crisis and cardiogenic shock requiring temporary mechanical support. The patient ultimately successfully underwent heart transplantation. This case illustrates how careful use of mechanical circulatory support, appropriate perisurgical planning including preoperative exchange transfusion and avoidance of hypothermia, allowed for successful orthotopic heart transplantation in a woman with sickle cell hemoglobinopathy and cardiogenic shock in the postpartum setting. Cardiac transplantation in patients with hemoglobinopathies is rare but achievable. A tailored perioperative approach, developed by a collaborative multidisciplinary team, can optimize outcomes and lead to successful transplantation in these complex cases.
other
2025-02-23 | Polygenic susceptibility to dilated cardiomyopathy underlies peripartum, alcohol-induced, and cancer therapy-related cardiomyopathies
ABSTRACT Background Rare (monogenic) variants linked to non-ischemic dilated cardiomyopathy (DCM) are enriched among individuals with peripartum (PPCM), alcohol-induced (ALCM), and cancer therapy-related (CCM) cardiomyopathies, but are present in less than 15% of cases. Whether a common variant (polygenic) predisposition to DCM also pervades these secondary cardiomyopathies remains unclear. Methods We evaluated the association of a DCM polygenic score with PPCM, ALCM, and CCM in the Mass General Brigham (MGB) Biobank (n = 42,137), with replication in the UK Biobank (n = 295,160) and FinnGen (n = 417,950). We then assessed the proportion of cases with a monogenic variant and/or a high polygenic score (defined as > 80 th percentile of the score distribution). Finally, we queried medical charts to ascertain whether cardiomyopathy onset in those at high polygenic risk might have been heralded by relevant clinical risk factors. Results We identified 415 individuals with a secondary cardiomyopathy (30 with PPCM, 275 with ALCM, and 110 for CCM) across the three cohorts. The DCM polygenic score associated with PPCM (OR = 1.88 per 1 standard deviation (SD) increase in polygenic score, p= 0.001), ALCM (OR per SD = 1.38, p = 1.46E-07), and CCM (OR per SD = 1.58, p = 2.97E-06). Monogenic DCM variants were strongly associated with PPCM, ALCM, and CCM, but were present in less than 10% of cases. Roughly 40% of all secondary cardiomyopathy cases had a high polygenic score, which conferred ∼3-fold odds of cardiomyopathy (p <0.001). Most secondary cardiomyopathy cases lacked known antecedent clinical risk factors. Conclusion Cases of PPCM, ALCM, and CCM are enriched for monogenic DCM variants and a high DCM polygenic score, further supporting a shared genetic susceptibility influenced by distinct environmental precipitants. Considering both monogenic and polygenic risk for DCM may improve identification of individuals predisposed to secondary cardiomyopathies, particularly among those lacking established clinical risk factors.
2003-07-15 | Uncoupling Protein-2 Overexpression Inhibits Mitochondrial Death Pathway in Cardiomyocytes
Uncoupling proteins (UCPs) are located in the mitochondrial inner membrane and partially dissipate the transmembrane proton electrochemical gradient. UCP2 is expressed in various human and rodent tissues, including the heart, where its functional role is unknown. In the present study, we tested the hypothesis that UCP2 overexpression could protect cardiomyocytes from oxidative stress–induced cell death by reducing reactive oxygen species (ROS) production in mitochondria. Using an adenoviral vector containing human UCP2, we investigated the effects of UCP2 overexpression on the mitochondrial death pathway induced by oxidative stress (100 μmol/L H 2 O 2 ) in cultured neonatal cardiomyocytes. UCP2 overexpression significantly suppressed markers of cell death, including TUNEL positivity, phosphatidylserine exposure, propidium iodide uptake, and caspase-3 cleavage. Furthermore, UCP2 remarkably prevented the catastrophic loss of mitochondrial inner membrane potential induced by H 2 O 2 , which is a critical early event in cell death. Ca 2+ overload and the production of ROS in mitochondria, both of which contribute to mitochondrial inner membrane potential loss, were dramatically attenuated by UCP2 overexpression. Thus, overexpression of UCP2 attenuates ROS generation and prevents mitochondrial Ca 2+ overload, revealing a novel mechanism of cardioprotection.
small molecules
2026-09-13 | Left Ventricular Recovery Following Bromocriptine Initiation at Different Stages of Peripartum Cardiomyopathy: A Report of Two Cases.
Peripartum cardiomyopathy (PPCM) is a rare yet potentially life-threatening form of heart failure that occurs during late pregnancy or within the months following delivery. Bromocriptine, which suppresses prolactin secretion, has emerged as a promising adjunctive therapy for PPCM; however, the optimal timing of its initiation remains uncertain. We describe two patients with PPCM who received bromocriptine at different stages of the disease course. The first patient was a 30-year-old woman who presented 33 days after delivery with cardiogenic shock, a left ventricular ejection fraction (LVEF) of 12%, and a left ventricular thrombus. Despite treatment with intra-aortic balloon pumping, venoarterial extracorporeal membrane oxygenation, anticoagulation, and guideline-directed medical therapy, recovery of left ventricular function plateaued. Bromocriptine was initiated on hospital day 44, after which LVEF increased from 38% to 53% within seven days and subsequently recovered to 60%. The second patient was a 35-year-old woman who developed acute heart failure nine days after delivery with an LVEF of 28%. Because left ventricular function remained markedly impaired despite standard heart failure therapy, bromocriptine was initiated on hospital day seven. Her LVEF improved to 39% by hospital day 15 and ultimately recovered to 61%. These cases demonstrate a temporal association between bromocriptine initiation and subsequent improvement in left ventricular systolic function at different stages of the clinical course of PPCM.
2026-08-14 | Pharmacokinetics of oral bromocriptine in postpartum patients.
Cardiomyopathy is a leading cause of maternal morbidity and mortality. A prolactin fragment has been implicated in the pathogenesis, and preliminary data suggest that bromocriptine-a dopamine receptor agonist that inhibits prolactin secretion-is a promising adjunctive therapy. However, bromocriptine pharmacokinetic (PK) data are largely derived from healthy males. Our objective was to conduct a postpartum oral bromocriptine PK study to inform a future trial to test the potential benefit of bromocriptine for add-on peripartum cardiomyopathy (PPCM) therapy. We conducted an oral bromocriptine PK study including healthy postpartum participants during the delivery-associated hospitalization who delivered ≥1 fetus at ≥28 weeks' gestation. Patients on CYP34A inhibitors or inducers, those with clinical contraindications according to the FDA package insert, and those who planned to express breastmilk (given the potential negative effects of bromocriptine on lactation) were excluded. Whole blood was collected pre-dose and 1, 2, 3, 4, 6, 8, and 12 h after an observed dose of 5 mg bromocriptine. Plasma was analyzed using mass spectrometry. Parameters of interest included 12-h area-under-the-curve (AUC12), elimination half-life (t1/2), maximum concentration (Cmax), and time to Cmax (T max). Non-compartmental PK analysis was conducted on nine participants, demonstrating mean ± SD AUC12, t 1/2, Cmax, and Tmax were 180 ± 207 pg h/mL, 5.4 ± 4.8 h, 56 ± 64 pg/mL, and 1.6 ± 1.1 h, respectively. In this modest sample, several PK parameters of oral bromocriptine in healthy postpartum participants differed from those reported in the literature, which may be due to physiological changes in pregnancy. The association between PK parameters and clinical outcomes in patients with PPCM warrants further evaluation.
2026-08-01 | Impairment of the DNA damage response pathway as a potential contributor towards peripartum cardiomyopathy
Abstract Background and purpose Peripartum cardiomyopathy (PPCM) affects prior heart-healthy women in the peripartum phase and is characterized by systolic heart failure (HF). Data from a German/ Swedish PPCM cohort revealed a 16-fold increased cancer prevalence. Several patients who were diagnosed with both, PPCM and cancer, carried gene variants located on DNA-damage-response (DDR) genes and/or received anthracycline based chemotherapies prior to their PPCM diagnosis. Here, we investigated juvenile anthracycline treatment prior to pregnancy as well as the effect of DDR impairment during the peripartum phase using mice heterozygous for Ataxia-Telangiectasia-Mutated (ATM), and determined the frequency of ATM gene variants and plasma levels of ATM-targeting miRNAs in PPCM patients. Methods and results Female C57BL/6N mice who received juvenile doxorubicin (DOX, 4x4mg/kgBW) treatment prior to pregnancy showed high mortality in the late peripartum phase. DOX-treated mice who survived two pregnancies and nursing periods exhibited reduced cardiac function compared to untreated (wildtype) WT mice (ctrl). RNAseq analysis of LV tissue from ctrl postpartum (PP) mice had shown peripartum induced upregulation of several DDR related transcripts compared with nulli-pari (NP) mice. This upregulation did not occur among PP mice who received juvenile DOX treatment. Whole exome sequencing in 80 PPCM patients from the German PPCM registry identified 7 carriers of heterozygous ATM gene variants classified as variants of uncertain significance (VUS, n=6) or pathogenic (P, n=1). MiRNA-screening by using human TaqMan Array Cards identified elevated plasma levels of 5 miRNAs potentially targeting ATM in PPCM patients compared to heart-healthy PP-matched women. Overexpression of miRNA precursors of two of these miRNAs, miR-18a-5p and miR-18b-5p, resulted in the reduction of ATM protein levels in HL1 cardiomyocytes. As proof-of-concept, we used a heterozygous ATM (ATM+/-) mouse model carrying a targeted mutation (Atmins5790neo) leading to a reduced protein expression. After 4 pregnancies and nursing periods (4xPP) ATM+/- mice showed systolic dysfunction and cardiac hypertrophy in contrast to WT 4xPP, ATM+/- NP and WT NP mice (FAC%: WT: 49±5 vs ATM+/-: 37±9; P<0.001). Moreover, mice with PPCM due to cardiac STAT3 deficiency (aMHCxCretg/+;STAT3flox/flox, CKO) and additional ATM heterozygosity showed an aggravated heart failure phenotype compared with CKO PP mice (FS%: CKO: 23.8±3 vs CKO/ATM+/-: 17.3±3.3; P<0.0005) associated with an induction of cell-cycle regulators p21 and Caspase 3. In conclusion, our data suggests that the DDR pathway may be an important link between cancer and PPCM. Latent side effects of DOX therapy by DDR suppression as well as detrimental effects of DDR related gene variants are potential shared mechanisms. In line, reduced ATM expression induces cardiac dysfunction and hypertrophy in the ATM+/-PP mice and aggravates HF in CKO;ATM+/- PP mice.
2026-07-23 | Management of Peripartum Cardiomyopathy With and Without Bromocriptine: A Comparative Study
Introduction: Peripartum cardiomyopathy is an uncommon but potentially severe cause of pregnancy-associated systolic heart failure. Bromocriptine has been proposed as an adjunctive therapy because it suppresses prolactin release, but its interpretation depends on the background heart failure regimen, dose, anticoagulation practice, and patient selection. This study compared short-term left ventricular ejection fraction (LVEF) recovery in patients managed with standard therapy with or without low-dose bromocriptine. Methods: This prospective comparative observational study was conducted at a tertiary care center in South India from October 2020 to October 2021. A total of 50 patients with peripartum cardiomyopathy and LVEF below 45% were analyzed according to treatment received. Group A (n=25) received bromocriptine 2.5 mg once daily for one week in addition to standard pregnancy/postpartum-compatible heart failure therapy, and Group B (n=25) received standard therapy alone. Treatment allocation was not randomized, and no allocation concealment was used. Echocardiography was used to assess LVEF at baseline, discharge, and one month. Continuous variables were compared with the independent samples Student's t-test, and categorical variables were compared with the chi-square test or Fisher's exact test. Results: Baseline LVEF did not differ significantly between Group A and Group B (38.36 ± 2.40% vs 39.00 ± 1.19%; p = 0.238). Important baseline differences were present, including gestational age at presentation (33.76 ± 7.84 vs 37.72 ± 1.57 weeks; p = 0.017), body mass index (22.49 ± 3.10 vs 24.01 ± 1.75 kg/m2; p = 0.037), comorbidity distribution (p = 0.033), electrocardiographic findings (p = 0.033), and chest radiographic findings (p = 0.004). At discharge, mean LVEF was 47.52 ± 2.52% in Group A and 46.56 ± 2.82% in Group B (p = 0.210). At one month, mean LVEF was higher in Group A than in Group B (57.00 ± 1.71% vs 49.84 ± 1.38%; p < 0.001). Gestational age at delivery (p = 0.031) and birth weight (p = 0.010) differed between the groups; neonatal intensive care unit admission did not (p = 0.560). Recorded Apgar score distributions were retained as abstracted, but the uniform control-group values require cautious interpretation. Conclusion: Both groups showed improvement in left ventricular function. Low-dose one-week bromocriptine was associated with greater one-month LVEF in this cohort, but the non-randomized design, baseline imbalances, limited documentation of background therapy and anticoagulation, and short follow-up preclude causal claims. The findings should be interpreted as hypothesis-generating and require confirmation in larger protocolized studies with adjustment for confounding and longer follow-up.
2026-07-19 | Diagnosis and treatment of peripartum cardiomyopathy: a case report
Peripartum cardiomyopathy (PPCM) is a rare heart muscle disease that affects women during the last month of pregnancy or within five months after childbirth. The disease manifests as acute and/or chronic heart failure (CHF). In addition to standard CHF therapy, PPCM treatment includes bromocriptine, which blocks the production of anti-angiogenic 16kDa low-molecular-weight prolactin. This prolactin plays an important role in PPCM pathogenesis. Although effective treatments are available, some aspects of managing this condition remain unresolved, ranging from epidemiology to treatment duration. This article presents a clinical case report of a patient with PCMP and details the monitoring of her clinical, instrumental, and laboratory data over a 15-month period.
antibodies
2025-01-01 | Immune dysregulation as a key driver of peripartum cardiomyopathy - an exploratory advanced imaging and biomarker study
Aims Peripartum cardiomyopathy (PPCM) is an idiopathic cardiomyopathy occurring in women in the late stages of pregnancy or in the postpartum period and is associated with significant morbidity, mortality, and persistent left ventricular dysfunction. PPCM pathogenesis involves multiple putative mechanisms including inflammation. We aimed to explore the acute inflammatory processes in PPCM using 18F-fluorodeoxyglucose positron emission tomography-computed tomography (18FDG-PET-CT), cardiovascular magnetic resonance (CMR), and inflammasome profiling. Methods and results Women with a new diagnosis of PPCM (n = 10, all within 3 months postpartum), five healthy postpartum controls (HPC), and five healthy non-postpartum controls (HNPC), underwent 18FDG-PET-CT, CMR, and serum inflammatory proteomic profiling. PPCM patients had a median age of 34 years (interquartile range [IQR] 30.3–38.5, similar in control groups), and a median parity of 3 (IQR 1–4). PPCM patients presented with severe, symptomatic heart failure (all New York Heart Association functional class III/IV), reduced median left ventricular ejection fraction of 35.5% (IQR 18.1–37.9). PPCM and HPC groups showed higher myocardial and splenic 18FDG uptake compared to HNPC. On CMR, myocardial interstitial fibrosis (elevated T1 time, extracellular volume, and late gadolinium enhancement mass) was solely present in PPCM. Inflammatory profiling showed pro-inflammatory cytokine dysregulation in PPCM (elevated neutrophil-to-lymphocyte ratio, C-reactive protein, interleukin-6, tumour necrosis factor-α, chemokine (C-C motif) ligand 3, hepatocyte growth factor, chemokine (C-X-C motif) ligand 10 and colony-stimulating factor-1) compared to controls. Conclusions Patients with PPCM exhibited a dysregulated immune response, associated with early myocardial interstitial fibrosis and adverse cardiac remodelling. This highlights the importance of rapid initiation of guideline-directed medical therapy especially with drugs documented to have anti-fibrotic effects.
2024-07-13 | Cardio-obstetrics de novo: a state-level, evidence-based approach for addressing maternal mortality and severe maternal morbidity in Georgia.
Georgia has a higher rate of severe maternal morbidity and mortality when compared with the rest of the United States. Evidence gained from the Georgia Maternal Mortality Review Committee identified areas of focus for high-yield clinical initiatives for improvement in maternal health outcomes. Cardiovascular disease, including cardiomyopathy, coronary conditions, and preeclampsia with or without eclampsia, is the most common cause of pregnancy-related death in non-Hispanic Black women in Georgia. The development of a cardio-obstetrics program is an initiative to advance health equity by decreasing cardiovascular morbidity and mortality. This report describes the following: (1) state-level advocacy for improving maternal health outcomes with funding gained through the legislative process and partnership with a governmental agency; (2) cardio-obstetrics program development based on evidence gained from the maternal mortality review process; and (3) implementation of a cardio-obstetrics service, beginning with a focused approach for capacity building and understanding barriers to care.
2024-04-19 | Placental senescence pathophysiology is shared between peripartum cardiomyopathy and preeclampsia in mouse and human.
Peripartum cardiomyopathy (PPCM) is an idiopathic form of pregnancy-induced heart failure associated with preeclampsia. Circulating factors in late pregnancy are thought to contribute to both diseases, suggesting a common underlying pathophysiological process. However, what drives this process remains unclear. Using serum proteomics, we identified the senescence-associated secretory phenotype (SASP), a marker of cellular senescence associated with biological aging, as the most highly up-regulated pathway in young women with PPCM or preeclampsia. Placentas from women with preeclampsia displayed multiple markers of amplified senescence and tissue aging, as well as overall increased gene expression of 28 circulating proteins that contributed to SASP pathway enrichment in serum samples from patients with preeclampsia or PPCM. The most highly expressed placental SASP factor, activin A, was associated with cardiac dysfunction or heart failure severity in women with preeclampsia or PPCM. In a murine model of PPCM induced by cardiomyocyte-specific deletion of the gene encoding peroxisome proliferator-activated receptor γ coactivator-1α, inhibiting activin A signaling in the early postpartum period with a monoclonal antibody to the activin type II receptor improved heart function. In addition, attenuating placental senescence with the senolytic compound fisetin in late pregnancy improved cardiac function in these animals. These findings link senescence biology to cardiac dysfunction in pregnancy and help to elucidate the pathogenesis underlying cardiovascular diseases of pregnancy.
2023-01-16 | [Case of peripartum cardiomyopathy misdiagnosed as pulmonary changes due to COVID-19].
A 37-year-old female patient was admitted 16 days after delivery in a hospital for infectious diseases with cough, shortness of breath, and infiltrative changes in the lungs that were interpreted as viral pneumonia. Considering the failure of therapy and the history, peripartum cardiomyopathy was suspected. Examination revealed a decrease in left ventricular ejection fraction to 30 %, ultrasonic signs of lung congestion and bilateral hydrothorax. The patient was diagnosed with peripartum cardiomyopathy accompanied by functional class 4 heart failure. A specific feature of this case was fast positive dynamics with complete regression of the clinical picture of congestion and improvement of the left ventricular myocardial function associated with the treatment.
2021-07-09 | Complement-Mediated Disorders in Pregnancy.
Complement-mediated disorders in pregnancy span a large spectrum and have been implicated in all three complement pathways: classical, lectin, and alternative. Our understanding of these disorders in recent years has advanced due to a better understanding of complement regulatory proteins, such as complement factor H, complement factor I, membrane cofactor protein, and thrombomodulin that particularly affect the alternative complement pathway. Enthusiasm in genotyping for mutations that encode these proteins has allowed us to study the presence of genetic variants which may predispose women to develop conditions such as pregnancy-associated hemolytic uremic syndrome (P-aHUS), thrombotic thrombocytopenic purpura, preeclampsia/hemolysis, elevated liver enzymes, low platelets (HELLP), systemic lupus erythematosus/antiphospholipid syndrome, and peripartum cardiomyopathy. The advent of the anti-C5-antibody eculizumab to quench the complement cascade has already proven in small case series to improve maternal kidney outcomes in complement-mediated obstetric catastrophes such as P-aHUS and HELLP. In this review, we will detail the pathogenesis behind these complement-mediated pregnancy disorders, the role of complement variants in disease phenotype, and the most up-to-date experience with eculizumab in this population.
proteins
2026-07-15 | Recurrent bilateral lower limb arterial embolism secondary to left ventricular thrombus in peripartum cardiomyopathy successfully treated with systemic streptokinase thrombolysis: a rare case report.
Peripartum cardiomyopathy (PPCM) is an uncommon but potentially life-threatening form of heart failure occurring toward the end of pregnancy or during the months following delivery in women without pre-existing heart disease. Left ventricular systolic dysfunction predisposes patients to intracardiac thrombus formation and systemic thromboembolic complications, which are associated with significant morbidity and mortality. A 35-year-old multiparous woman presented shortly after spontaneous vaginal delivery of an intrauterine fetal demise with acute right lower-limb ischemia and heart failure. Transthoracic echocardiography demonstrated severe left ventricular systolic dysfunction (LVEF approximately 35%), severe functional mitral regurgitation, pulmonary hypertension, and a large left ventricular thrombus. She underwent urgent Fogarty embolectomy followed by therapeutic anticoagulation with unfractionated heparin and warfarin. Despite therapeutic anticoagulation (INR 2.0 and activated partial thromboplastin time approximately 90 seconds), she developed recurrent bilateral acute lower-limb ischemia five days later. Because of profound hemodynamic instability and prohibitive surgical risk, systemic streptokinase thrombolysis was administered. Repeat echocardiography performed immediately after thrombolysis demonstrated complete resolution of the left ventricular thrombus. Follow-up echocardiography one week later showed significant recovery of left ventricular systolic function (LVEF 45-50%), improvement of mitral regurgitation to mild-to-moderate, and reduction in pulmonary artery systolic pressure. This case highlights the importance of early recognition of thromboembolic complications in PPCM and demonstrates that systemic streptokinase thrombolysis may represent an effective life- and limb-saving therapeutic option in carefully selected patients when surgical or catheter-based interventions are not feasible.
2025-07-31 | Ufmylation Suppresses Unfolded Protein Response to Prevent Peripartum Cardiomyopathy.
Ufmylation is a novel ubiquitin-like protein modification that plays a critical role in maintaining the homeostasis of different tissues, but its role in the heart remains poorly understood. Here, we showed that mice lacking UFM1 ligase 1 (UFL1), an enzyme essential for ufmylation, in the heart developed peripartum cardiomyopathy. Loss of UFL1 reversed pregnancy-induced adaptive cardiac transcriptome alterations. Moreover, loss of UFL1 triggered excessive endoplasmic reticulum stress, inhibited mitochondrial oxidative metabolism, and caused augmented mTOR signaling, leading to pronounced pathological remodeling and heart failure. These results demonstrate that ufmylation is essential for physiological cardiac remodeling and that disruption of ufmylation predisposes the heart to peripartum cardiomyopathy.
2023-06-19 | RNA sequencing identifies human placentalIL3RAas a potential predictor of adverse cardiovascular outcomes in patients with severe preeclampsia
Abstract Background Mortality from preeclampsia (PE) and PE-associated morbidities are 3-to 5-fold higher in persons of African ancestry than in those of Asian and European ancestries. The placenta is central to the etiology of PE. However, how and to what extent the placenta contributes to worse PE outcomes in persons of African ancestry is yet to be fully elucidated. Objective We aimed to identify molecular pathways that are unique or enriched in placentas of parturient persons of African ancestry with PE with severe features (sPE) compared to those of Asian and European ancestry with sPE. Study design Bulk RNA sequencing was performed on 50 placentas from parturient persons with sPE of African (n=9), Asian (n=18) and European (n=23) ancestries and 73 normotensive controls of African (n=9), Asian (n=15) and European (n=49) ancestries. Results Metabolism, hormone regulation and hypoxia/angiogenesis genes, previously described to be upregulated in PE, including: LEP , PAPPA2 , INHA , FSTL3 , FLT1, PHYHIP and ENG , were upregulated in sPE across ancestries, with high expression of FSTL3 being additionally associated with intrauterine growth restriction (p = .0047). Notably, the upregulation of, FLT1 , LEP and PHYHIP was significantly higher in sPE placentas from parturient persons of African versus Asian ancestry (p = .0.35, .020 and .012 respectively). Genes associated with allograft rejection and adaptive immune response were upregulated in placentas from parturients of African ancestry but not in those of Asian and European ancestries. Among the allograft rejection/adaptive immune response genes, IL3RA was of particular interest because the patient with the highest placental IL3RA level, a woman of African ancestry with IL3RA levels 4.5-fold above the average for African ancestry parturients with sPE, developed postpartum cardiomyopathy, and was the only patient out of 123, that developed this condition. Interestingly, the sPE patients with the highest IL3RA levels among parturients of Asian and European ancestries developed unexplained tachycardia peripartum, necessitating echocardiography in the European ancestry patient. The association between elevated placental IL3RA levels and unexplained tachycardia or peripartum cardiomyopathy was found to be significant in the 50 sPE patients (p = .0005). Conclusions Placentas from parturients of African ancestry express higher levels of metabolism ( LEP ) and hypoxia/angiogenesis ( FLT1 ) genes, as well as allograft rejection/adaptive immune response genes, including IL3RA . High placental expression of IL3RA may predict worse maternal cardiovascular outcomes, including peripartum cardiomyopathy. Studies evaluating placental IL3RA levels in peripartum cardiomyopathy cohorts are therefore warranted, as are broader studies evaluating placental factors in maternal cardiovascular outcomes postpartum.
2022-09-22 | Pregnancy-induced Physiological Hypertrophic Preconditioning Attenuates Pathological Myocardial Hypertrophy by Mnemonic Activation of FoxO3a/GSK3β Pathway
Abstract Previous studies show a woman’s age at final pregnancy is correlated with post-reproductive longevity and nulliparity is associated with higher risk of incident heart failure, and we previously reported a cardioprotective phenomenon termed myocardial hypertrophic preconditioning, but it is unknown whether pregnancy-induced physiological hypertrophic preconditioning can also protect the heart against subsequent pathological hypertrophic stress. Here, we found that compared with nulliparous mice, pathological cardiac hypertrophy induced by Ang Ⅱ infusion or TAC was significantly attenuated and heart failure induced by TAC was markedly improved in mice with pregnant preconditioning. Activation of FoxO3a was significantly enhanced in the hearts of postpartum mice. FoxO3a inhibited myocardial hypertrophy by suppressing signaling pathway of phosphorylated glycogen synthase kinase-3β (p-GSK3β)/β-catenin/Cyclin D1. Silencing or overexpression of FoxO3a attenuated or enhanced the anti-hypertrophic effect of pregnant preconditioning in mice with pathological stimulation. Our findings demonstrate that pregnancy-induced myocardial hypertrophic preconditioning confers resistance to subsequent hypertrophic stress and slows progression to heart failure through activation of FoxO3a/GSK3β pathway.
2021-06-07 | The HGR motif is the antiangiogenic determinant of vasoinhibin: implications for a therapeutic orally active oligopeptide
The hormone prolactin acquires antiangiogenic and antivasopermeability properties after undergoing proteolytic cleavage to vasoinhibin, an endogenous prolactin fragment of 123 or more amino acids that inhibits the action of multiple proangiogenic factors. Preclinical and clinical evidence supports the therapeutic potential of vasoinhibin against angiogenesis-related diseases including diabetic retinopathy, peripartum cardiomyopathy, rheumatoid arthritis, and cancer. However, the use of vasoinhibin in the clinic has been limited by difficulties in its production. Here, we removed this barrier to using vasoinhibin as a therapeutic agent by showing that a short linear motif of just three residues (His46-Gly47-Arg48) (HGR) is the functional determinant of vasoinhibin. The HGR motif is conserved throughout evolution, its mutation led to vasoinhibin loss of function, and oligopeptides containing this sequence inhibited angiogenesis and vasopermeability with the same potency as whole vasoinhibin. Furthermore, the oral administration of an optimized cyclic retro-inverse vasoinhibin heptapeptide containing HGR inhibited melanoma tumor growth and vascularization in mice and exhibited equal or higher antiangiogenic potency than other antiangiogenic molecules currently used as anti-cancer drugs in the clinic. Finally, by unveiling the mechanism that obscures the HGR motif in prolactin, we anticipate the development of vasoinhibin-specific antibodies to solve the on-going challenge of measuring endogenous vasoinhibin levels for diagnostic and interventional purposes, the design of vasoinhibin antagonists for managing insufficient angiogenesis, and the identification of putative therapeutic proteins containing HGR.
cell therapies
2026-09-19 | Venoarterial extracorporeal membrane oxygenation for peripartum cardiomyopathy complicated by severe preeclampsia: a case report with 5-year follow-up.
Peripartum cardiomyopathy (PPCM) coexisting with severe preeclampsia is uncommon and diagnostically challenging because dyspnea, pulmonary edema, and cardiac dysfunction may be attributed to either condition. Long-term outcomes after rescue mechanical support remain poorly documented. A 28-year-old primigravida at 37 + 6 weeks presented with 2 days of worsening orthopnea, dyspnea, and cough. At 15 + 3 weeks, electrocardiography had shown complete left bundle branch block, although left ventricular ejection fraction (LVEF) was 61%. On admission, blood pressure was 159/120 mmHg, heart rate 157 beats/min, urine protein was positive, N-terminal pro-B-type natriuretic peptide (NT-proBNP) was 5,660 pg/ml, and echocardiography showed an LVEF of 26%. Severe preeclampsia and acute heart failure due to PPCM were diagnosed. Labetalol, magnesium sulfate, and furosemide were administered, followed by emergency cesarean delivery of a 2,880-g male infant (Apgar scores, 8 and 10). Persistent postoperative hemodynamic instability despite mechanical ventilation and pharmacotherapy prompted multidisciplinary initiation of venoarterial extracorporeal membrane oxygenation (VA-ECMO). She was successfully decannulated on day 4 and discharged on day 21 with an LVEF of 44%. NT-proBNP normalized by 6 months, LVEF exceeded 50% by 9 months, and at 5 years LVEF was 59% and NT-proBNP was 20.9 pg/ml. This case provides rare 5-year documentation of sustained myocardial recovery after VA-ECMO in PPCM with severe preeclampsia. In peripartum patients with severe hypertension and respiratory symptoms, an LVEF below 45% should prompt evaluation for PPCM; timely echocardiography, multidisciplinary care, and early VA-ECMO may bridge refractory hemodynamic instability to recovery, followed by prolonged cardiac surveillance.
2026-08-14 | The spectrum of pregnancy-induced cardiac remodeling: transitioning from healthy adaptive hypertrophy to peripartum cardiomyopathy.
Pregnancy imposes profound hemodynamic, metabolic, and biomechanical stresses on the heart, requiring coordinated structural and molecular adaptations to preserve cardiac function. To compensate, the cardiovascular system undergoes significant reversible adaptations, such as increased blood volume and elevated cardiac output. Such alterations induce physiological left ventricular hypertrophy that is regulated, in part, by mechanotransduction, a process by which cells convert mechanical stimuli such as stretch and pressure into biochemical pathways. Integrin-mediated complexes link cardiomyocytes with the extracellular matrix (ECM), allowing the myocardium to sense increased wall stress/stretch and activate cardioprotective signaling cascades. Together, these pathways preserve cytoskeletal integrity, sustain cardiomyocyte viability, and promote adaptive hypertrophic growth that regresses post-partum as hemodynamic load returns to pre-pregnancy levels. However, within a subset of pregnant women, this healthy adaptive response becomes dysregulated and adaptive hypertrophy transitions into maladaptive, leading to peripartum cardiomyopathy (PPCM) with heart failure (HF). PPCM has a mortality rate between 7% and 15%, establishing it as a significant cause of maternal death globally. Here, we discuss integration of mechanotransduction and cell survival pathways to support cardiac adaptation during pregnancy. Elucidating the role of gene variants and mechanotransduction in the pregnant heart may lead to improved patient outcomes in PPCM and HF.
2026-01-10 | Successful use of immunoadsorption therapy in advanced dilated cardiomyopathy: A case report.
Dilated cardiomyopathy (DCM) is a major cause of chronic heart failure, and some patients continue to deteriorate despite guideline-directed medical therapy. Immunoadsorption (IA), which removes pathogenic autoantibodies, has been proposed as a potential adjunctive therapy, but its clinical use remains limited. This case illustrates the potential benefits of IA in advanced, treatment-refractory DCM. A 53-year-old woman with a 9-year history of DCM presented with recurrent chest tightness and dyspnea. Despite long-term guideline-directed medical therapy, her symptoms progressively worsened. The patient had chronic DCM initially diagnosed in the peripartum period, with a left ventricular ejection fraction (LVEF) of 11% at onset. Before IA, echocardiography demonstrated severe systolic dysfunction (LVEF 22%-24%) with significant mitral regurgitation, and laboratory evaluation showed markedly elevated pro-BNP (4454 pg/mL). The patient underwent two sessions of immunoadsorption in September 2024, followed by high-dose intravenous immunoglobulin (IVIG) as per standard protocols. Following treatment, her symptoms improved, pro-BNP decreased to 2109 pg/mL, and repeat echocardiography showed an increase in LVEF to 29.2%. This case suggests that immunoadsorption may offer clinical benefit in patients with advanced, refractory DCM. While promising, IA remains experimental and requires further investigation in larger, controlled studies.
2025-09-27 | A CASE OF ORTHOTOPIC BICAVAL HEART TRANSPLANTATION IN A PATIENT WITH PERIPARTUM CARDIOMYOPATHY
This paper presents a clinical case of orthotopic bicaval heart transplantation in a patient with end-stage chronic heart failure that developed against the background of peripartum cardiomyopathy. The disease manifested itself in the second trimester of pregnancy, complicated by severe preeclampsia and progressive heart failure. In the absence of an available donor organ, the patient was implanted with a left ventricular assist device HeartMate 3 as a «bridge to transplantation». Four years after left ventricular assist device implantation, when a donor appeared, orthotopic heart transplantation was successfully performed. The case demonstrates the effectiveness of a multidisciplinary approach in conditions of a limited donor resource and emphasizes the need for early diagnosis, systemic prevention and development of transplantation services to improve outcomes in patients with peripartum cardiomyopathy.
2025-08-16 | Cardiac Transplantation for Peripartum Cardiomyopathy in a Patient With Sickle Cell Disease.
Cardiac surgery, particularly cardiac transplantation, is considered high risk in patients with sickle cell hemoglobinopathies and rarely reported in the literature. We present a case of a 33-year-old woman with sickle cell β+ thalassemia and peripartum cardiomyopathy, who presented with sickling crisis and cardiogenic shock requiring temporary mechanical support. The patient ultimately successfully underwent heart transplantation. This case illustrates how careful use of mechanical circulatory support, appropriate perisurgical planning including preoperative exchange transfusion and avoidance of hypothermia, allowed for successful orthotopic heart transplantation in a woman with sickle cell hemoglobinopathy and cardiogenic shock in the postpartum setting. Cardiac transplantation in patients with hemoglobinopathies is rare but achievable. A tailored perioperative approach, developed by a collaborative multidisciplinary team, can optimize outcomes and lead to successful transplantation in these complex cases.
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2025-02-23 | Polygenic susceptibility to dilated cardiomyopathy underlies peripartum, alcohol-induced, and cancer therapy-related cardiomyopathies
ABSTRACT Background Rare (monogenic) variants linked to non-ischemic dilated cardiomyopathy (DCM) are enriched among individuals with peripartum (PPCM), alcohol-induced (ALCM), and cancer therapy-related (CCM) cardiomyopathies, but are present in less than 15% of cases. Whether a common variant (polygenic) predisposition to DCM also pervades these secondary cardiomyopathies remains unclear. Methods We evaluated the association of a DCM polygenic score with PPCM, ALCM, and CCM in the Mass General Brigham (MGB) Biobank (n = 42,137), with replication in the UK Biobank (n = 295,160) and FinnGen (n = 417,950). We then assessed the proportion of cases with a monogenic variant and/or a high polygenic score (defined as > 80 th percentile of the score distribution). Finally, we queried medical charts to ascertain whether cardiomyopathy onset in those at high polygenic risk might have been heralded by relevant clinical risk factors. Results We identified 415 individuals with a secondary cardiomyopathy (30 with PPCM, 275 with ALCM, and 110 for CCM) across the three cohorts. The DCM polygenic score associated with PPCM (OR = 1.88 per 1 standard deviation (SD) increase in polygenic score, p= 0.001), ALCM (OR per SD = 1.38, p = 1.46E-07), and CCM (OR per SD = 1.58, p = 2.97E-06). Monogenic DCM variants were strongly associated with PPCM, ALCM, and CCM, but were present in less than 10% of cases. Roughly 40% of all secondary cardiomyopathy cases had a high polygenic score, which conferred ∼3-fold odds of cardiomyopathy (p <0.001). Most secondary cardiomyopathy cases lacked known antecedent clinical risk factors. Conclusion Cases of PPCM, ALCM, and CCM are enriched for monogenic DCM variants and a high DCM polygenic score, further supporting a shared genetic susceptibility influenced by distinct environmental precipitants. Considering both monogenic and polygenic risk for DCM may improve identification of individuals predisposed to secondary cardiomyopathies, particularly among those lacking established clinical risk factors.
2003-07-15 | Uncoupling Protein-2 Overexpression Inhibits Mitochondrial Death Pathway in Cardiomyocytes
Uncoupling proteins (UCPs) are located in the mitochondrial inner membrane and partially dissipate the transmembrane proton electrochemical gradient. UCP2 is expressed in various human and rodent tissues, including the heart, where its functional role is unknown. In the present study, we tested the hypothesis that UCP2 overexpression could protect cardiomyocytes from oxidative stress–induced cell death by reducing reactive oxygen species (ROS) production in mitochondria. Using an adenoviral vector containing human UCP2, we investigated the effects of UCP2 overexpression on the mitochondrial death pathway induced by oxidative stress (100 μmol/L H 2 O 2 ) in cultured neonatal cardiomyocytes. UCP2 overexpression significantly suppressed markers of cell death, including TUNEL positivity, phosphatidylserine exposure, propidium iodide uptake, and caspase-3 cleavage. Furthermore, UCP2 remarkably prevented the catastrophic loss of mitochondrial inner membrane potential induced by H 2 O 2 , which is a critical early event in cell death. Ca 2+ overload and the production of ROS in mitochondria, both of which contribute to mitochondrial inner membrane potential loss, were dramatically attenuated by UCP2 overexpression. Thus, overexpression of UCP2 attenuates ROS generation and prevents mitochondrial Ca 2+ overload, revealing a novel mechanism of cardioprotection.
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