Metabolic changes in hypertrophic cardiomyopathies : Scientific update from the Working Group of Myocardial Function of the European Society of Cardiology

JV is supported by the Netherlands Cardiovascular Research Initiative, an initiative with support of the Dutch Heart Foundation, CVON2014-40 DOSIS. SH has received funding from the European Union Commission’s Seventh Framework programme under grant agreement N° 305507 (HOMAGE), N° 602904 (FIBROTARGETS) and FP7-Health-2013- Innovations-1 N° 602156 (HECATOS). . We acknowledge the support from the Netherlands Cardiovascular Research Initiative, an initiative with support of the Dutch Heart Foundation, CVON2011-ARENA, CVON2016-Early HFPEF, and ShePREDICTS. This research is cofinanced as a PPP-allowance Research and Innovation by the Ministry of Economic Affairs within Top Sector Life sciences & Health. This research was co-funded by the C3 project “Vision Core Leuven” of the Leuven UniversityPeer reviewedPublisher PD

In peripartum cardiomyopathy plasminogen activator inhibitor-1 is a potential new biomarker with controversial roles

Aims Peripartum cardiomyopathy (PPCM) is a life-threatening heart disease occurring in previously heart-healthy women. A common pathomechanism in PPCM involves the angiostatic 16 kDa-prolactin (16 kDa-PRL) fragment, which via NF-kappa B-mediated up-regulation of microRNA-(miR)-146a induces vascular damage and heart failure. We analyse whether the plasminogen activator inhibitor-1 (PAI-1) is involved in the pathophysiology of PPCM. Methods and results In healthy age-matched postpartum women (PP-Ctrl, n = 53, left ventricular ejection fraction, LVEF > 55%), PAI-1 plasma levels were within the normal range (21 +/- 10 ng/mL), but significantly elevated (64 +/- 38 ng/mL, P <0.01) in postpartum PPCM patients at baseline (BL, n = 64, mean LVEF: 23 +/- 8%). At 6-month follow-up (n = 23), PAI-1 levels decreased (36 +/- 14 ng/mL, P <0.01 vs. BL) and LVEF (49 +/- 11%) improved. Increased N-terminal pro-brain natriuretic peptide and Troponin T did not correlate with PAI-1. C-reactive protein, interleukin (IL)-6 and IL-1 beta did not differ between PPCM patients and PP-Ctrl. MiR-146a was 3.6-fold (P <0.001) higher in BL-PPCM plasma compared with PP-Ctrl and correlated positively with PAI-1. In BL-PPCM serum, 16 kDa-PRL coprecipitated with PAI-1, which was associated with higher (P <0.05) uPAR-mediated NF-kappa B activation in endothelial cells compared with PP-Ctrl serum. Cardiac biopsies and dermal fibroblasts from PPCM patients displayed higher PAI-1 mRNA levels (P <0.05) than healthy controls. In PPCM mice (due to a cardiomyocyte-specific-knockout for STAT3, CKO), cardiac PAI-1 expression was higher than in postpartum wild-type controls, whereas a systemic PAI-1-knockout in CKO mice accelerated peripartum cardiac fibrosis, inflammation, heart failure, and mortality. Conclusion In PPCM patients, circulating and cardiac PAI-1 expression are up-regulated. While circulating PAI-1 may add 16 kDa-PRL to induce vascular impairment via the uPAR/NF-kappa B/miR-146a pathway, experimental data suggest that cardiac PAI-1 expression seems to protect the PPCM heart from fibrosis. Thus, measuring circulating PAI-1 and miR-146a, together with an uPAR/NF-kappa B-activity assay could be developed into a specific diagnostic marker assay for PPCM, but unrestricted reduction of PAI-1 for therapy may not be advised

The innate immune system in chronic cardiomyopathy : a European Society of Cardiology (ESC) scientific statement from the Working Group on Myocardial Function of the ESC

Funded by Regione Campania CISI-Lab European Union Commission's Seventh Framework . Grant Number: 305507, 602904 FP7-Health-2013-Innovations-1. Grant Number: 602156 FWO Flanders, Belgium. Grant Number: FWO G080014 N European Union Horizon2020. Grant Number: UE LSHM-CT-05-018833, FNRS PDR T.0144.13 Bundesministerium für Bildung und Forschung. Grant Number: BMBF01 EO1004 Deutsche Forschungsgemeinschaft. Grant Number: SFB688 TP A10Peer reviewedPublisher PD

Complex roads from genotype to phenotype in dilated cardiomyopathy : scientific update from the Working Group of Myocardial Function of the European Society of Cardiology

The authors acknowledge the support from the Netherlands Cardiovascular Research Initiative, with support of the Dutch Heart Foundation, CVON2011-ARENA, CVON2018-ARENA PRIME, CVON2016-Early HFPEF, and CVON 2017-ShePREDICTS to S.H.Peer reviewedPostprin

Risk stratification and management of women with cardiomyopathy/heart failure planning pregnancy or presenting during/after pregnancy: a position statement from the Heart Failure Association of the European Society of Cardiology Study Group on Peripartum Cardiomyopathy.

This position paper focusses on the pathophysiology, diagnosis and management of women diagnosed with a cardiomyopathy, or at risk of heart failure (HF), who are planning to conceive or present with (de novo or previously unknown) HF during or after pregnancy. This includes the heterogeneous group of heart muscle diseases such as hypertrophic, dilated, arrhythmogenic right ventricular and non-classified cardiomyopathies, left ventricular non-compaction, peripartum cardiomyopathy, Takotsubo syndrome, adult congenital heart disease with HF, and patients with right HF. Also, patients with a history of chemo-/radiotherapy for cancer or haematological malignancies need specific pre-, during and post-pregnancy assessment and counselling. We summarize the current knowledge about pathophysiological mechanisms, including gene mutations, clinical presentation, diagnosis, and medical and device management, as well as risk stratification. Women with a known diagnosis of a cardiomyopathy will often require continuation of drug therapy, which has the potential to exert negative effects on the foetus. This position paper assists in balancing benefits and detrimental effects

Continuity of midwifery care and gestational weight gain in obese women: a randomised controlled trial

Background: The increased prevalence of obesity in pregnant women in Australia and other developed countries is a significant public health concern. Obese women are at increased risk of serious perinatal complications and guidelines recommend weight gain restriction and additional care. There is limited evidence to support the effectiveness of dietary and physical activity lifestyle interventions in preventing adverse perinatal outcomes and new strategies need to be evaluated. The primary aim of this project is to evaluate the effect of continuity of midwifery care on restricting gestational weight gain in obese women to the recommended range. The secondary aims of the study are to assess the impact of continuity of midwifery care on: women&rsquo;s experience of pregnancy care; women&rsquo;s satisfaction with care and a range of psychological factors.Methods/Design: A two arm randomised controlled trial (RCT) will be conducted with primigravid women recruited from maternity services in Victoria, Australia. Participants will be primigravid women, with a BMI&ge;30 who are less than 17 weeks gestation. Women allocated to the intervention arm will be cared for in a midwifery continuity of care model and receive an informational leaflet on managing weight gain in pregnancy. Women allocated to the control group will receive routine care in addition to the same informational leaflet. Weight gain during pregnancy, standards of care, medical and obstetric information will be extracted from medical records. Data collected at recruitment (self administered survey) and at 36 weeks by postal survey will include sociodemographic information and the use of validated scales to measure secondary outcomes.Discussion: Continuity of midwifery care models are well aligned with current Victorian, Australian and many international government policies on maternity care. Increasingly, midwifery continuity models of care are being introduced in low risk maternity care, and information on their application in high risk populations is required. There is an identified need to trial alternative antenatal interventions to reduce perinatal risk factors for women who are obese and the findings from this project may have application in other maternity services. In addition this study will inform a larger trial that will focus on birth and postnatal outcomes.<br /

Reversal learning in Drosophila larvae

Adjusting behavior to changed environmental contingencies is critical for survival, and reversal learning provides an experimental handle on such cognitive flexibility. Here, we investigate reversal learning in larval Drosophila Using odor-taste associations, we establish olfactory reversal learning in the appetitive and the aversive domain, using either fructose as a reward or high-concentration sodium chloride as a punishment, respectively. Reversal learning is demonstrated both in differential and in absolute conditioning, in either valence domain. In differential conditioning, the animals are first trained such that an odor A is paired, for example, with the reward whereas odor B is not (A+/B); this is followed by a second training phase with reversed contingencies (A/B+). In absolute conditioning, odor B is omitted, such that the animals are first trained with paired presentations of A and reward, followed by unpaired training in the second training phase. Our results reveal "true" reversal learning in that the opposite associative effects of both the first and the second training phase are detectable after reversed-contingency training. In what is a surprisingly quick, one-trial contingency adjustment in the Drosophila larva, the present study establishes a simple and genetically easy accessible study case of cognitive flexibility