RARE DISEASE
Peripartum cardiomyopathy
Peripartum cardiomyopathy
Peripartum cardiomyopathy
Synonyms: Postpartum cardiomyopathy
Synonyms: Postpartum cardiomyopathy
Synonyms: Postpartum cardiomyopathy
Drug discovery
0
drugs
With orphan designations
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
620 drug discovery papers about Peripartum cardiomyopathy, with 2 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
620 drug discovery papers about Peripartum cardiomyopathy, with 2 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
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.
2026-08-14 | 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.
2026-08-01 | 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.
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.
2026-08-14 | 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.
2026-08-01 | 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.
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