Bromocriptine for the treatment of peripartum cardiomyopathy: a multicentre randomized study.

AIMS: An anti-angiogenic cleaved prolactin fragment is considered causal for peripartum cardiomyopathy (PPCM). Experimental and first clinical observations suggested beneficial effects of the prolactin release inhibitor bromocriptine in PPCM. METHODS AND RESULTS: In this multicentre trial, 63 PPCM patients with left ventricular ejection fraction (LVEF) ≤35% were randomly assigned to short-term (1W: bromocriptine, 2.5 mg, 7 days) or long-term bromocriptine treatment (8W: 5 mg for 2 weeks followed by 2.5 mg for 6 weeks) in addition to standard heart failure therapy. Primary end point was LVEF change (delta) from baseline to 6 months assessed by magnetic resonance imaging. Bromocriptine was well tolerated. Left ventricular ejection fraction increased from 28 ± 10% to 49 ± 12% with a delta-LVEF of + 21 ± 11% in the 1W-group, and from 27 ± 10% to 51 ± 10% with a delta-LVEF of + 24 ± 11% in the 8W-group (delta-LVEF: P = 0.381). Full-recovery (LVEF ≥ 50%) was present in 52% of the 1W- and in 68% of the 8W-group with no differences in secondary end points between both groups (hospitalizations for heart failure: 1W: 9.7% vs. 8W: 6.5%, P = 0.651). The risk within the 8W-group to fail full-recovery after 6 months tended to be lower. No patient in the study needed heart transplantation, LV assist device or died. CONCLUSION: Bromocriptine treatment was associated with high rate of full LV-recovery and low morbidity and mortality in PPCM patients compared with other PPCM cohorts not treated with bromocriptine. No significant differences were observed between 1W and 8W treatment suggesting that 1-week addition of bromocriptine to standard heart failure treatment is already beneficial with a trend for better full-recovery in the 8W group. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, study number: NCT00998556.

16-kDa prolactin and bromocriptine in postpartum cardiomyopathy.

Peripartum cardiomyopathy (PPCM) is a potentially life-threatening heart disease emerging toward the end of pregnancy or in the first postpartal months in previously healthy women. Recent data suggest a central role of unbalanced peri-/postpartum oxidative stress that triggers the proteolytic cleavage of the nursing hormone prolactin (PRL) into a potent antiangiogenic, proapoptotic, and proinflammatory 16-kDa PRL fragment. This notion is supported by the observation that inhibition of PRL secretion by bromocriptine, a dopamine D2-receptor agonist, prevented the onset of disease in an animal model of PPCM and by first clinical experiences where bromocriptine seem to exert positive effects with respect to prevention or treatment of PPCM patients. Here, we highlight the current state of knowledge on diagnosis of PPCM, provide insights into the biology and pathophysiology of 16-kDa PRL and bromocriptine, and outline potential consequences for the clinical management and treatment options for PPCM patients.

Bromocriptine treatment in patients with peripartum cardiomyopathy and right ventricular dysfunction.

BACKGROUND: Right ventricular (RV) dysfunction predicts adverse outcome in peripartum cardiomyopathy (PPCM). We recently demonstrated beneficial effects associated with the prolactin release inhibitor bromocriptine at different doses when added to standard heart failure therapy in PPCM. Here, we evaluated for the first time the therapeutic potential of bromocriptine particularly in PPCM patients with RV involvement. METHODS: In this study, 40 patients with PPCM were included, of whom 24 patients had reduced RV ejection fraction (RVEF < 45%). We examined the effect of short-term (1W: bromocriptine, 2.5 mg, 7 days, n = 10) compared with long-term bromocriptine treatment (8W: 5 mg for 2 weeks followed by 2.5 mg for another 6 weeks, n = 14) in addition to guideline-based heart failure therapy in patients with an initial RVEF < 45% on the following outcomes: (1) change from baseline (Δ delta) in RVEF, (2) change from baseline in left ventricular EF (LVEF), and (3) rate of patients with full LV recovery (LVEF ≥ 50%) and (4) rate of patients with full RV recovery (RVEF ≥ 55%) at 6-month follow-up as assessed by cardiac magnetic resonance imaging. RESULTS: Reduced RVEF at initial presentation was associated with a lower rate of full cardiac recovery at 6-month follow-up (patients with RV dysfunction: 58% vs. patients with normal RV function: 81%; p = 0.027). RVEF increased from 38 ± 7 to 53 ± 11% with a delta-RVEF of + 15 ± 12% in the 1W group, and from 35 ± 9 to 58 ± 7% with a Δ RVEF of + 23 ± 10% in the 8W group (Δ RVEF 1W vs 8W: p = 0.118). LVEF increased from 25 ± 8 to 46 ± 12% with a Δ LVEF of + 21 ± 11% in the 1W group, and from 22 ± 6 to 49 ± 10% with a Δ LVEF of + 27 ± 9% in the 8W group (Δ LVEF 1W vs 8W: p = 0.211). Full LV recovery was present in 50% of the 1W group and in 64% of the 8W group (p = 0.678). Full RV recovery was observed in 40% of the 1W group and in 79% of the 8W group (p = 0.092). CONCLUSIONS: Despite overall worse outcome in patients with RV dysfunction at baseline, bromocriptine treatment in PPCM patients with RV involvement was associated with a high rate of full RV and LV recovery, although no significant differences were observed between the short-term and long-term bromocriptine treatment regime. These findings suggest that bromocriptine in addition to standard heart failure therapy may be also effective in PPCM patients with biventricular impairment.

Outcome of subsequent pregnancies in patients with a history of peripartum cardiomyopathy.

AIMS: Subsequent pregnancies (SSPs) in patients with peripartum cardiomyopathy (PPCM) have a high risk of heart failure relapse. We report on outcome of SSPs in PPCM patients in Germany, Scotland, and South Africa. METHODS AND RESULTS: Among 34 PPCM patients with a SSP, pregnancy ended prematurely in four patients while it was full-term in 30. Overall relapse rate [left ventricular ejection fraction, (LVEF) <50% or death after at least 6-month follow-up] was 56% with 12% (4/34) mortality. Relapse of PPCM after SSP was not associated with differences in parity, twin pregnancy, gestational hypertension, or smoking. Persistently reduced LVEF (<50%) before entering SSP was present in 47% of patients while full recovery (LVEF ≥50%) was present in 53%. The majority of patients entering SSP with persistently reduced LVEF were of African ethnicity (75%). Persistently reduced LVEF before SSP was associated with higher mortality (25% vs. 0%) and lower rate of full recovery at follow-up. Patients obtaining standard therapy for heart failure and bromocriptine immediately after delivery displayed significantly better LVEF at follow-up and a higher rate of full recovery with no patient dying compared with patients obtaining standard therapy for heart failure alone. This was independent of African or Caucasian race. CONCLUSION: Full recovery of LVEF before SSP was associated with lower mortality and better cardiac function at follow-up. Addition of bromocriptine to standard therapy for heart failure immediately after delivery was safe and seemed to be associated with a better outcome of SSP in African and Caucasian patients.

Signal transducer and activator of transcription 3 is required for myocardial capillary growth, control of interstitial matrix deposition, and heart protection from ischemic injury.

The transcription factor signal transducer and activator of transcription 3 (STAT3) participates in a wide variety of physiological processes and directs seemingly contradictory responses such as proliferation and apoptosis. To elucidate its role in the heart, we generated mice harboring a cardiomyocyte-restricted knockout of STAT3 using Cre/loxP-mediated recombination. STAT3-deficient mice developed reduced myocardial capillary density and increased interstitial fibrosis within the first 4 postnatal months, followed by dilated cardiomyopathy with impaired cardiac function and premature death. Conditioned medium from STAT3-deficient cardiomyocytes inhibited endothelial cell proliferation and increased fibroblast proliferation, suggesting the presence of paracrine factors attenuating angiogenesis and promoting fibrosis in vitro. STAT3-deficient mice showed enhanced susceptibility to myocardial ischemia/reperfusion injury and infarction with increased cardiac apoptosis, increased infarct sizes, and reduced cardiac function and survival. Our study establishes a novel role for STAT3 in controlling paracrine circuits in the heart essential for postnatal capillary vasculature maintenance, interstitial matrix deposition balance, and protection from ischemic injury and heart failure.

Alterations in Janus kinase (JAK)-signal transducers and activators of transcription (STAT) signaling in patients with end-stage dilated cardiomyopathy.

BACKGROUND: Experimental studies indicate that interleukin-6 (IL-6)-related cytokines, signaling via the shared receptor gp130, Janus kinases (JAKs), and signal transducers and activators of transcription (STATs), provide a critical cardiomyocyte survival pathway in vivo. Little is known about the activation of this signaling pathway in the myocardia of patients with end-stage dilated cardiomyopathy (DCM). METHODS AND RESULTS: We performed a comprehensive expression and activation analysis of IL-6-related cytokines, receptors, signal transducers, and signal transduction inhibitors in left ventricular (LV) myocardia from patients with DCM (n=10) and non-failing (NF) donor hearts (n=5). Differential expression (DCM versus NF) was observed by immunoblotting at each level of the signaling cascade, including receptor ligands (IL-6: -59%, P<0.01; leukemia inhibitory factor [LIF]: +54%, P<0.05), receptor subunits (LIF receptor: -16%, P<0.05), signaling molecules (the Janus kinase TYK2: -48%, P<0.01; STAT3: -47%, P<0.01), and suppressors of cytokine signaling (SOCS1: +97%, P<0.05; SOCS3: -49%, P<0.01). Tyrosine-phosphorylation status of gp130 was increased (+60%, P<0.05), whereas tyrosine-phosphorylation status of JAK2 was reduced in DCM (-72%, P<0.01). Moreover, as shown by immunohistochemistry, the number of STAT3-positive cardiomyocytes was reduced in DCM (-42%, P<0.01). CONCLUSION: Signaling via gp130 and JAK-STAT is profoundly altered in DCM. Importantly, tyrosine-phosphorylation of JAK2 is reduced in the face of increased gp130 phosphorylation, indicating impaired downstream activation of this critical pathway in DCM.

Regulation of proangiogenic factor CCN1 in cardiac muscle: impact of ischemia, pressure overload, and neurohumoral activation.

BACKGROUND: CCN1, a potent proangiogenic factor, is induced in the vasculature by tissue injury, angiotensin II (Ang II), and growth factor stimulation. Because these conditions occur in myocardial ischemia and pressure overload, we investigated the regulation of CCN1 in cardiomyocytes in vitro and in the heart in vivo. METHODS AND RESULTS: Ang II, signaling via the angiotensin type 1 (AT1) receptor, and alpha1-adrenergic stimulation with phenylephrine induced CCN1 expression in ventricular cardiomyocytes isolated from 1- to 3-day-old rats. Cell culture supernatant of Ang II-treated cardiomyocytes induced migration of smooth muscle cells, which was abolished by neutralizing antibody to CCN1. Ang II- and phenylephrine-mediated induction of CCN1 expression in cardiomyocytes was completely abolished by inhibition of MEK/extracellular signal-regulated kinases (ERK) or protein kinase C (PKC). Likewise, mechanical stretch induced CCN1 expression in cardiomyocytes, an effect that was prevented by AT1 receptor blockade or PKC inhibition. Similarly, pressure overload in vivo upregulated myocardial CCN1 expression levels via AT1 receptor- and PKC-dependent mechanisms. After myocardial infarction in mice, CCN1 expression was strongly induced in both ischemic and remote left ventricular myocardium. Marked CCN1 protein expression was noted in cardiomyocytes of patients with end-stage ischemic cardiomyopathy but was almost absent in nonfailing human myocardium. CONCLUSIONS: Pressure overload, ischemia, and neurohormonal factors, such as Ang II or alpha1-adrenergic stimuli, induce myocardial expression of CCN1, a potent proangiogenic factor, supporting the notion that CCN1 may play an important role in the adaptation of the heart to cardiovascular stress.

Role of interleukin-6 for LV remodeling and survival after experimental myocardial infarction.

Circulating levels of interleukin (IL)-6 are elevated after myocardial infarction (MI) and associated with increased morbidity and mortality. Its myocardial expression post-MI suggests a pathophysiological role in this condition. To explore the role of endogenous IL-6, we analyzed MI size, left ventricular (LV) remodeling, and mortality after permanent coronary ligation in IL-6 knockout mice (IL-6-/-) and wild-type controls (WT). Six weeks after MI, IL-6-/- and WT had similar mortality rates, MI sizes, LV remodeling, and LV dysfunction in vivo, determined by catheterization. Infarct size 24 h post-MI, shown by 2,3,5-triphenyltetrazolium chloride (TTC) staining, was similar at 24 h. Treatment with exogenous IL-6 did not alter MI size in WT. Infarction resulted in marked phosphorylation of STAT3, without differences between genotypes. Leukemia inhibitory factor (LIF) protein was increased 48 h post-MI in IL-6-/-, and angiotensin II and AT1 receptor (AT1R) protein were strongly increased in IL-6-/- baseline and post-MI, suggesting compensatory up-regulation. Lack of IL-6 does not affect long-term MI size or LV function, remodeling, and survival. In mice lacking IL-6, other members of the IL-6 family such as LIF and other factors signaling via JAK/STAT such as angiotensin may act in a compensatory manner to activate the JAK/STAT pathway, thereby maintaining STAT3 phosphorylation, which is crucial for the cellular effects of IL-6 cytokines.

Rationale and design of a randomized, controlled multicentre clinical trial to evaluate the effect of bromocriptine on left ventricular function in women with peripartum cardiomyopathy.

BACKGROUND: Peripartum cardiomyopathy (PPCM) is an idiopathic heart disease that develops in the last month of pregnancy and/or the first months following delivery in previously healthy women and may lead to acute heart failure. A cleaved fragment of the nursing hormone prolactin is considered essential in the pathophysiology of PPCM. To date, no specific therapy has been tested for PPCM in a randomized controlled trial of adequate size. AIMS: The purpose of this trial is to investigate the safety of the dopamin-D2-receptor agonist bromocriptine and its effects on left ventricular (LV) function in women with PPCM. METHODS: This is an 11 center German trial with a prospective randomized controlled open-label design. The trial enrolls females with newly diagnosed PPCM according to European Society of Cardiology criteria with a LV ejection fraction (LVEF) <35 %. Patients are randomized 1:1 to either best supportive care (BSC) including standard heart failure therapy plus 8 weeks of bromocriptine therapy (2.5 mg b.i.d. for 14 days and 2.5 mg q.d. from day 15 to 56) or to BSC plus 1 week of low-dose bromocriptine (2.5 mg q.d.) with anticoagulant therapy at a prophylactic dose administered during the period of bromocriptine treatment in both groups. The primary endpoint is change in LVEF from baseline to 6 months follow-up as assessed by cardiac magnetic resonance imaging (or echocardiography if CMR is not tolerated). The secondary endpoints are hospitalization for worsening heart failure, heart transplantation, and all-cause mortality during follow-up or a combination of these endpoints. A total of 60 patients will be recruited (including 6 potential dropouts) giving a power of 0.9 for an expected LVEF change of 10.8 % between treatment groups at 6 months. PERSPECTIVE: This trial will provide important knowledge on potential benefits and safety of prolonged inhibition of prolactin release with bromocriptine in addition to standard heart failure therapy in newly diagnosed PPCM. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00998556.

Prognostic implication of right ventricular involvement in peripartum cardiomyopathy: a cardiovascular magnetic resonance study.

AIMS: Peripartum cardiomyopathy (PPCM) is a major cause of acute heart failure in the peripartum period and considered potentially life threatening. While many aspects of its clinical profiles have been frequently reported, functional analysis, in particular of the right ventricle, and tissue characterization by cardiovascular magnetic resonance (CMR) imaging have been only sporadically described. The aim of the present study was to analyse pathological alterations and their prognostic relevance found in CMR imaging of patients newly diagnosed with PPCM. METHODS AND RESULTS: In this multicenter study 34 patients with confirmed PPCM underwent CMR imaging at the time of diagnosis and at 5 ± 1 months follow-up. Cine imaging of PPCM patients showed moderate to severe reduction of systolic left ventricular (LV) function (mean LVEF: 29.7 ± 12.8%). In 35% of the patients right ventricular (RV) systolic function was also reduced with a mean RVEF of 42.9 ± 13.9%. Dilatation of the LV was observed in 91% (mean LV-EDV/BSA 128.5 ± 32.1 mL/m2), and dilatation of the RV was present in 24% (mean RV-EDV/BSA 87.4 ± 18.5 mL/m2) of the patients. Focal non-ischemic late gadolinium enhancement (LGE) was visible in 71%, and regional wall motion abnormalities were evident in 88% of the patients. LGE and wall motion abnormalities were predominantly located in the anteroseptal and basal to midventricular segments. RV dysfunction at baseline was associated with reduced probability of full cardiac recovery at 5 ± 1 months follow-up. CONCLUSIONS: Besides LV systolic dysfunction, RV dysfunction and dilatation are observed in about one third of PPCM patients at the time of diagnosis. RV dysfunction is associated with unfavourable outcome. A distinct pattern of LV wall motion abnormalities and myocardial scar is evident in most PPCM patients. The present study may help to establish a set of CMR criteria suitable for diagnosis in patients with suspected PPCM and may add further knowledge to the pathology of the disease.

Cardiovascular disorders in pregnancy: diagnosis and management.

Cardiovascular diseases (CVDs) are a major cause of complications in pregnancy worldwide and the number of patients who develop cardiac problems during pregnancy is increasing. This review summarises recent literature on the aetiology and the underlying pathophysiology, diagnostic tools, risk stratification and prognosis in women who develop heart failure during pregnancy and in the peri-partum phase as well as in patients with pre-existing cardiomyopathies undergoing pregnancy. We specifically highlight peri-partum cardiomyopathy, valvular disease and Marfan's syndrome. Furthermore, we provide overviews on established treatment concepts and novel therapeutic strategies for these different disease types, stressing the point that pregnancy-associated cardiac disease requires interdisciplinary concepts for diagnosis, management and treatment.

Prognostic value of NT-proBNP in patients with systemic morphological right ventricles: a single-centre experience.

UNLABELLED: In systemic morphological right ventricles after atrial redirection surgery, NT-proBNP is correlated with NYHA-class, ventricular function and subaortic AV-valve regurgitation (TR). The impact of NT-proBNP on adverse clinical outcomes is, however, unknown. METHODS: This prospectively designed, longitudinal, observational study evaluated NT-proBNP in 116 patients (24.9 ± 4.2 years old, NYHA class I/II/III=97/18/1, 71 men) relative to all cardiac causes of hospitalisation, heart failure, transplantation and death. RESULTS: The mean observation time was 7.3 ± 2.4 years. In univariate Cox proportion analysis, the predictors for all causes of hospitalisation (n=41; 35.5%) were NT-proBNP (HR: 5.99; 95%CI: 3.21-11.18), NYHA class (HR: 2.98; 95%CI: 1.62-5.5), ventricular function (HR: 1.96; 95%CI: 1.27-3.02), TR (HR: 2.39; 95%CI: 1.48-3.59), ventricular septal defect repair (HR: 1.29; 95%CI: 1.08-1.53) and a history of supraventricular tachycardia (SVT) (HR: 7.13; 95%CI: 3.74-13.59). In multivariate Cox proportion analysis, NT-proBNP (HR: 3.71; 95%CI: 1.82-7.57), SVT (HR: 4.27; 95%CI: 2.03-8.94) and ventricular septal defect repair (HR: 1.41; 95%CI: 1.15-1.72) remained independently associated with all causes of hospitalisation. For heart failure, transplantation and death, the single predictors were NT-proBNP (HR: 20.67; 95%CI: 4.69-91.78), NYHA class (HR: 6.45; 95%CI: 2.75-15.14), ventricular function (HR: 2.70; 95%CI: 1.48-4.92), TR (HR: 4.11; 95%CI: 1.99-8.47), QRS duration (HR: 2.09; 95%CI: 1.06-4.12) and SVT (HR: 8.00; 95%CI: 2.82-22.69). Multivariate Cox proportion analysis identified NT-proBNP (HR: 6.82; 95%CI: 1.32-35.04) and NYHA class (HR: 6.79; 95%CI: 1.75-26.28). Using ROC curves, the ability of NT-proBNP to detect patients at risk was greater for heart failure, transplantation and death (AUC: 0.944; 95%CI: 0.900-0.988) than for all causes of hospitalisation (AUC: 0.8; 95%CI: 0.713-0.887). CONCLUSION: In systemic right ventricles, NT-proBNP is a useful risk predictor for all causes of hospitalisation and, in particular, for heart failure, transplantation and death. It therefore might be a useful tool for risk assessment in this patient population.

Bromocriptine treatment associated with recovery from peripartum cardiomyopathy in siblings: two case reports.

INTRODUCTION: Peripartum cardiomyopathy is a rare form of cardiomyopathy, with heterogeneous presentation occurring in women between one-month antepartum and six months postpartum. It carries a poor prognosis and a high risk of mortality. CASE PRESENTATION: We report the development of peripartum cardiomyopathy in two sisters, 27- and 35-year-old African women, one of whom presented with a large left ventricular thrombus. Subsequently, both patients were treated with bromocriptine, heparin and standard therapy for heart failure (angiotensin converting enzyme inhibitors, beta-blockers and diuretics). During follow-up, the left ventricular thrombus observed in one patient degraded. Neither patient experienced a thrombotic event, and both experienced continuous improvements in cardiac function and New York Heart Association stage. CONCLUSION: The development of peripartum cardiomyopathy in two sisters indicates that there may be a genetic basis for this type of cardiomyopathy, and that women with a positive family history for peripartum cardiomyopathy may have an increased risk of developing the disease. This is also the first report of a patient experiencing degradation of a large left ventricular thrombus under standard therapy for heart failure with bromocriptine. It suggests that the use of bromocriptine in association with adequate anti-coagulation and heart failure therapy may be beneficial and safe.

Postpartum cardiomyopathy: a cardiac emergency for gynecologists, general practitioners, internists, pulmonologists, and cardiologists.

INTRODUCTION: Peri- or postpartum cardiomyopathy (PPCM) is a rare, life-threatening heart disease of unclear origin and is characterized by heart failure of sudden onset between the final weeks of pregnancy and 6 months after delivery. METHODS: Selective literature search in the databases of the National Center for Biotechnology Information based on the key words "peri- and postpartum cardiomyopathy," "pregnancy" and "heart failure" and additional information from the authors' personal experience. RESULTS: PPCM is often not diagnosed until late in its course, because its clinical manifestations are highly variable and a heart disease may not be suspected at first. Frequent presenting symptoms of PPCM, such as prostration, shortness of breath on mild exertion, and coughing, are often initially misinterpreted as evidence of pneumonia or as physiological accompaniments of pregnancy and delivery. The clinical picture of PPCM corresponds to a dilated cardiomyopathy (DCM) with signs of severe heart failure. Therefore, treatment with ACE inhibitors, diuretics, aldosterone antagonists, and beta-blockers is required. Recent research findings suggest a possible new approach to the treatment of PPCM with bromocriptine, which inhibits the release of prolactin, a lactation-promoting hormone. To date, only the treatment of heart failure in PPCM is evidence-based, while all other treatments are "level C," i.e., based on expert opinion only. CONCLUSION: The early diagnosis and interdisciplinary management of PPCM can often lead to substantial recovery from heart failure and cardiomyopathy.

Inflammatory, abscess-forming foreign body reaction mimics a thrombus formation on an atrial septal defect closure device: A commented case report.

We are presenting a case of floating left and right atrial formations on an atrial septal defect occluder system (23mm StarFLEX)-Occluder) initially supposed to be thrombotic appositions in a 57-year-old man. The closure was performed on the background of left hemispheric stroke and atrial septal aneurysm (ASA) with patent foramen ovale (PFO). The suspect structures were detected in the 6-month follow-up by transesophageal echocardiography (TEE). The patient underwent a successful surgical explantation of the closure device and closure of the patent foramen ovale (PFO) using a pericardial patch. The pathological evaluation of the biatrial device associated appositions revealed hytrophic heart muscle tissue with perifocal scarring and purulent abscess-forming, granulating and foam-cell including inflammatory foreign body reaction instead of the expected thrombus formation.

A cathepsin D-cleaved 16 kDa form of prolactin mediates postpartum cardiomyopathy.

Postpartum cardiomyopathy (PPCM) is a disease of unknown etiology and exposes women to high risk of mortality after delivery. Here, we show that female mice with a cardiomyocyte-specific deletion of stat3 develop PPCM. In these mice, cardiac cathepsin D (CD) expression and activity is enhanced and associated with the generation of a cleaved antiangiogenic and proapoptotic 16 kDa form of the nursing hormone prolactin. Treatment with bromocriptine, an inhibitor of prolactin secretion, prevents the development of PPCM, whereas forced myocardial generation of 16 kDa prolactin impairs the cardiac capillary network and function, thereby recapitulating the cardiac phenotype of PPCM. Myocardial STAT3 protein levels are reduced and serum levels of activated CD and 16 kDa prolactin are elevated in PPCM patients. Thus, a biologically active derivative of the pregnancy hormone prolactin mediates PPCM, implying that inhibition of prolactin release may represent a novel therapeutic strategy for PPCM.