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.

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 2.5mg for 6weeks) 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.

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.

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.

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. 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. 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. 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.

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.

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. (C) 2013 Elsevier Ireland Ltd. All rights reserved.

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.

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.

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.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.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.The early diagnosis and interdisciplinary management of PPCM can often lead to substantial recovery from heart failure and cardiomyopathy.

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.

To the Editor: Postpartum cardiomyopathy (PPCM) is a disease of unknown origin and exposes women to a high risk of mortality after delivery despite optimal medical therapy ([1][1]). Prolactin is up-regulated postpartally where it induces lactation and promotes reshaping of the uterus. Prolactin

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 inhibitior 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.

1. Sliwa K, Fett J, Elkayam U. Peripartum cardiomyopathy. Lancet 2006;368:687–93. 2. Corbacho AM, Martinez De La Escalera G, Clapp C. Roles of prolactin and related members of the prolactin/growth hormone/ placental lactogen family in angiogenesis. J Endocrinol 2002;173: 219–38. 3. Hilfiker-Kleiner D, Kaminski K, Podewski E, et al. A cathepsin D-cleaved 16 kDa form of prolactin mediates postpartum cardiomyopathy. Cell 2007;128:589–600. 4. Francis GS, Parks R, Cohn JN. The effects of bromocriptine in patients with congestive heart failure. Am Heart J 1983;106:100–6. 5. Mejia-Rodriguez O, Alvarez-Aguilar C, Vega-Gomez HE, Belio-Caro F, Vargas-Espinosa JM, Paniagua-Sierra JR. Bromocriptine induces regression of left ventricular hypertrophy in peritoneal dialysis patients. Proc West Pharmacol Soc 2005;48:122–5. 6. Goldberg LI. The role of dopamine receptors in the treatment of congestive heart failure. J Cardiovasc Pharmacol 1989;14 Suppl 5: S19–27.