Peripartum cardiomyopathy (PPCM) is a cause of pregnancy-associated heart failure. It typically develops during the last month of, and up to 6 months after, pregnancy in women without known cardiovascular disease. The present position statement offers a state-of-the-art summary of what is known about risk factors for potential pathophysiological mechanisms, clinical presentation of, and diagnosis and management of PPCM. A high index of suspicion is required for the diagnosis, as shortness of breath and ankle swelling are common in the peripartum period. Peripartum cardiomyopathy is a distinct form of cardiomyopathy, associated with a high morbidity and mortality, but also with the possibility of full recovery. Oxidative stress and the generation of a cardiotoxic subfragment of prolactin may play key roles in the pathophysiology of PPCM. In this regard, pharmacological blockade of prolactin offers the possibility of a disease-specific therapy.--

Abstract-Heart failure remains a leading cause of morbidity and mortality. The cellular mechanism underlying the development of cardiac dysfunction is a decrease in the number of viable cardiomyocytes. Recent observations have suggested that the adult heart may contain a progenitor cell population. Side population (SP) cells, characterized by a distinct Hoechst dye efflux pattern, have been shown to exist in multiple tissues and are capable of tissue-specific differentiation. In this report, we confirm the existence of a cardiac SP cell population, immunophenotypically distinct from bone marrow SP cells. Moreover, we demonstrate that among cardiac SP cells, the greatest potential for cardiomyogenic differentiation is restricted to cells negative for CD31 expression and positive for stem cell antigen 1 (Sca1) expression (CD31 Ϫ /Sca1 ϩ ). Furthermore, we determine that CD31 Ϫ /Sca1 ϩ cardiac SP cells are capable of both biochemical and functional cardiomyogenic differentiation into mature cardiomyocytes, with expression of cardiomyocyte-specific transcription factors and contractile proteins, as well as stimulated cellular contraction and intracellular calcium transients indistinguishable from adult cardiomyocytes. We also determine the necessity of cell-extrinsic signaling through coupling, although not fusion, with adult cardiomyocytes in regulating cardiomyogenic differentiation of cardiac SP cells. We, therefore, conclude that CD31 Ϫ /Sca1 ϩ cardiac SP cells represent a distinct cardiac progenitor cell population, capable of cardiomyogenic differentiation into mature cardiomyocytes through a process mediated by cellular coupling with adult cardiomyocytes. (Circ Res. 2005;97:52-61.)

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Background The EURObservational Research Programme is a rolling programme of cardiovascular registries and surveys of the European Society of Cardiology (ESC). These registries will provide information on the nature of cardiovascular disease and its management. This manuscript provides an update on new literature on peripartum cardiomyopathy (PPCM), published since the 2010 Position Statement from the Heart Failure Association of the European Society of Cardiology Working Group on PPCM, and describes a new registry on this under‐recognized condition. Peripartum cardiomyopathy is an idiopathic cardiomyopathy presenting with heart failure secondary to left ventricular systolic dysfunction towards the end of the pregnancy, or in the months following delivery, where no other cause for heart failure is found. Aims The PPCM Registry aims to describe disease presentation, comorbidities, diagnostic and therapeutic management of patients with PPCM, as well as information on their offspring. Centres not only from ESC and ESC‐affiliated countries, but from around the world, are encouraged to participate. Methods A prospective registry on patients presenting with PPCM. At the time of writing, approximately 100 patients have been enrolled from 20 countries. All data entry is online via secure passwords and is supported by well‐trained information technology personnel. Conclusion The EURObservational Research Programme will allow a comparison of women from around the world, from different ethnic backgrounds, presenting with PPCM and will report on their 6 month and 12 month outcomes. The study aims to include 1000 patients and follow them for 1 year. New centres volunteering to participate in the study will be welcomed.

Tissue-specific progenitor cells contribute to local cellular regeneration and maintain organ function. Recently, we have determined that cardiac side-population (CSP) cells represent a distinct cardiac progenitor cell population, capable of in vitro differentiation into functional cardiomyocytes. The response of endogenous CSP to myocardial injury, however, and the cellular mechanisms that maintain this cardiac progenitor cell pool in vivo remain unknown. In this report we demonstrate that local progenitor cell proliferation maintains CSP under physiologic conditions, with little contribution from extracardiac stem cell sources. Following myocardial infarction in adult mice, however, CSP cells are acutely depleted, both within the infarct and noninfarct areas. CSP pools are subsequently reconstituted to baseline levels within 7 days after myocardial infarction, through both proliferation of resident CSP cells, as well as through homing of bone marrow-derived stem cells (BMC) to specific areas of myocardial injury and immunophenotypic conversion of BMC to adopt a CSP phenotype. We, therefore, conclude that following myocardial injury, cardiac progenitor cell populations are acutely depleted and are reconstituted to normal levels by both self-proliferation and selective homing of BMC. Understanding and enhancing such processes hold enormous potential for therapeutic myocardial regeneration.T issue-specific progenitor cell populations maintain the regenerative capacity of terminally differentiated organs, both under basal conditions and following local tissue injury. Side population (SP) cells, characterized by their intrinsic capacity to efflux Hoechst dye through ATP-binding cassette transporters, contribute to the long-term regenerative potential of hematopoietic and extrahematopoietic tissues. 1 Recently, we have demonstrated that cardiac SP (CSP) cells, immunophenotypically distinct from bone marrow (BM)-derived stem cells (BMC), are present in the adult heart and are capable of both biochemical and functional cardiomyogenic differentiation into mature cardiomyocytes, thereby identifying CSP as a distinct cardiac progenitor cell population. 2 Supplementation of cardiac progenitor cell pools after myocardial infarction (MI) with exogenous cells has been shown to improve ventricular function by regenerating myocardium and cardiac vasculature. [3][4][5] The response of endogenous CSP cells to myocardial injury, however, and the cellular mechanisms that maintain this endogenous cardiac progenitor cell pool under basal and after injury conditions remain unknown. We, therefore, serially assessed CSP pools in hearts following MI and determined the role of selfproliferation and BMC in reconstituting cardiac progenitor pools. Methods and MaterialsCSP were isolated from mouse hearts as described previously. 2 MI was performed in mice via permanent coronary ligation. 6 BM transplantation was performed in lethally irradiated mice using marrow isolated from C57bl/6-Tg(ACTbEGFP) mice. 7 All animals were obtained from The ...

Aims  We sought to describe the clinical presentation, management, and 6-month outcomes in women with peripartum cardiomyopathy (PPCM) globally. Methods and results  In 2011, >100 national and affiliated member cardiac societies of the European Society of Cardiology (ESC) were contacted to contribute to a global registry on PPCM, under the auspices of the ESC EURObservational Research Programme. These societies were tasked with identifying centres who could participate in this registry. In low-income countries, e.g. Mozambique or Burkina Faso, where there are no national societies due to a shortage of cardiologists, we identified potential participants through abstracts and publications and encouraged participation into the study. Seven hundred and thirty-nine women were enrolled in 49 countries in Europe (33%), Africa (29%), Asia-Pacific (15%), and the Middle East (22%). Mean age was 31 ± 6 years, mean left ventricular ejection fraction (LVEF) was 31 ± 10%, and 10% had a previous pregnancy complicated by PPCM. Symptom-onset occurred most often within 1 month of delivery (44%). At diagnosis, 67% of patients had severe (NYHA III/IV) symptoms and 67% had a LVEF ≤35%. Fifteen percent received bromocriptine with significant regional variation (Europe 15%, Africa 26%, Asia-Pacific 8%, the Middle East 4%, P < 0.001). Follow-up was available for 598 (81%) women. Six-month mortality was 6% overall, lowest in Europe (4%), and highest in the Middle East (10%). Most deaths were due to heart failure (42%) or sudden (30%). Re-admission for any reason occurred in 10% (with just over half of these for heart failure) and thromboembolic events in 7%. Myocardial recovery (LVEF > 50%) occurred only in 46%, most commonly in Asia-Pacific (62%), and least commonly in the Middle East (25%). Neonatal death occurred in 5% with marked regional variation (Europe 2%, the Middle East 9%). Conclusion  Peripartum cardiomyopathy is a global disease, but clinical presentation and outcomes vary by region. Just under half of women experience myocardial recovery. Peripartum cardiomyopathy is a disease with substantial maternal and neonatal morbidity and mortality.

Abstract-Recently, the side population (SP) phenotype has been introduced as a reliable marker to identify subpopulations of cells with stem/progenitor cell properties in various tissues. We and others have identified SP cells from postmitotic tissues, including adult myocardium, in which they have been suggested to contribute to cellular regeneration following injury. SP cells are identified and characterized by a unique efflux of Hoechst 33342 dye. Key Words: Abcg2 Ⅲ Mdr1 Ⅲ progenitor cells Ⅲ proliferation Ⅲ SP cells R ecently, the side population (SP) phenotype has been introduced as a reliable marker to identify subpopulations of cells with stem/progenitor cell properties in various tissues including the heart. 1 On the molecular level, the SP phenotype is linked to the presence of ATP-binding cassette (ABC) transporters with the ability to efficiently efflux the DNA binding dye Hoechst 33342. 2 This ABC transporterdependent Hoechst efflux phenomenon confers the characteristic fluorescent-activated cell sorting (FACS) profile of SP cells as a Hoechst-low "side population" located to the periphery of the Hoechst-high main population. 2 Among the various members of the ABC transporter superfamily, Abcg2 (also referred to as breast cancer resistance protein 1 [Bcrp1]) and Mdr1 (also referred to as P-glycoprotein [p-gp] or Abcb1) have been shown to efficiently efflux Hoechst 33342 and thereby confer the SP phenotype. 3 Although both transporters are highly expressed in bone marrow (BM)SP cells, studies performed in mice with targeted disruption of the Mdr1a and Mdr1b genes, the murine homologs of the human Abcb1/Mdr1 gene, demonstrated that Abcg2 is the sole molecular determinant of the SP phenotype in hematopoietic stem cells. 4 Moreover, Abcg2 expression is conserved in SP cells from a wide range of tissues including blood, gonad, lung, skeletal muscle and the retina, suggesting an important role of Abcg2 in stem cells. 4 -7 We and others have characterized SP cells isolated from adult myocardium. 8 -11 These cardiac (c)SP cells are phenotypically distinct from BMSP cells, in that they are not hematopoietic but exhibit the potential to differentiate into functional cardiomyocytes. 10 As in SP cells from the bone marrow, Abcg2 is expressed in SP cells from the heart. 9 The contribution of Abcg2 to the cSP phenotype and its biological significance in cSP progenitor cells, however, remain unknown. In this study, we find that the contribution of Abcg2 to the SP phenotype in the heart exists in an age-dependent manner, with Abcg2 as the molecular determinant of the SP phenotype in the neonatal heart and Mdr1 as the basis for the SP phenotype in the adult heart. In addition, we demonstrate Original

The presence of HMW-multimer defects and a high value for a point-of-care hemostatic test, the CT-ADP, were each predictive of the presence of aortic regurgitation after TAVR and were associated with higher mortality 1 year after the procedure. (Funded by Lille 2 University and others; ClinicalTrials.gov number, NCT02628509.).