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Backgound. The existence of a “placental clock” which determines the duration of gestation has been previously proposed. It is related to placental CRH secretion and is active from an early phase in human pregnancy. Urocortin is a specific ligand for the corticotropin-releasing factor (CRF) receptor expressed by human trophoblast and fetal membranes. The purpose of this study was to evaluate whether urocortin concentrations in the early second trimester amniotic fluid might serve to predict preterm delivery. Method. The urocortin concentrations in early second trimester amniotic fluid were measured in 41 pregnancies with term delivery and in 41 pregnancies with preterm delivery by using an immunoradiometric assay. Conditional logistic regression analysis was used for statistical analysis. Results. Mean amniotic fluid urocortin concentrations in women with preterm labor were 1.55±0.63 ng/mL while those in women with term labor were 1.6±0.49 ng/mL (p: NS). No statistical significant results were found when comparing amniotic fluid urocortin concentrations in women with preterm premature rupture of membranes leading to preterm labor (𝑛=19) to women with term delivery without premature rupture of membranes. Conclusion. These results suggest that urocortin concentrations in the amniotic fluid of genetic amniocentesis are not predictive of preterm labor and birth.

Background and Objectives : congenital heart disease (CHD), cyanotic and, to a lesser degree, acyanotic, often are accompanied by coagulation abnormalities, impacting substantially morbidity and mortality. Until now, no consistent hemostatic patterns have been demonstrated in neonates and children with CHD because they represent a variable and heterogenous population. The aim of the present study is to investigate the hemostatic profile, as well as the role of ADAMTS-13 (a disintegrin and metalloprotease with thrombospondin type-1 motives), the cleaving protein of von Willebrand factor (VWF) in neonates with CHD and compare them to healthy age-matched controls. Materials and Methods : twenty neonates with a mean gestational age of 37.1 ± 2.5 weeks were included in the CHD group, and 18 healthy neonates with a mean gestational age of 38.2 ± 1.5 weeks were in the control group. Results: prothrombin time was significantly prolonged, and accordingly, factor VII (FVII) levels were significantly decreased in the CHD group in comparison to controls. Factor VIII (FVIII), VWF, and ristocetin cofactor activity (Rcof) levels were significantly higher in the study vs. control group. Concentrations of ADAMTS-13 were decreased in the CHD vs. control group, but the difference was not statistically significant. Our results, in combination, indicate a balanced hemostatic mechanism, although with greater variability in neonates with CHD, while developmental aspects of coagulation are evident in the specific patient population. Conclusions: the coagulation profile is moderately impaired early in the course of CHD, though increased thrombogenicity is already present and should not be ignored.

Neonatal sepsis is a life-threatening condition associated with significant morbidity and mortality. Sepsis-induced coagulopathy is a well-recognized entity, signifying the strong cross-talk between inflammation and coagulation. The aim of the present study was to compare the coagulation profile between the acute phase of sepsis and recovery in term and preterm neonates. Additional comparisons to healthy neonates were undertaken. Levels of clotting, anti-clotting factors and ADAMTS-13 (A disintegrin and metalloprotease with thrombospondin type-1 motives), the cleaving protein of von Willebrand factor (VWF), were measured in 16 term and preterm neonates in the acute phase of infection and following recovery, as well as in 18 healthy neonates. Clotting times were prolonged, while levels of particular clotting factors were lower in the acute phase of infection compared to controls and recovery. On the other hand, levels of fibrinogen, factor VIII (FVIII) and VWF were significantly higher in the acute phase in comparison to controls and recovery, while they remained persistently higher in the infection group compared to controls. In regard to the anticlotting mechanism, a clear suppression was observed in septic neonates. ADAMTS-13 levels were significantly lower in the acute phase of infection in comparison to controls and recovery ( p = 0.015 and 0.004, respectively), while a trend toward superimposed normalization was demonstrated post infection, as higher ADAMTS-13 levels were measured in recovered neonates compared to controls ( p = 0.002). The coagulation profile is considerably deranged in neonatal sepsis. ADAMTS-13 deficiency in septic neonates is a novel finding with promising future implications, as ADAMTS-13 substitution may serve as a useful therapeutic option in neonatal sepsis, prompting further investigation in future studies.

Background: Platelet function of fetal growth restricted (FGR) neonates remains a field of debate. Platelet function analyzer (PFA-100) offers a quantitative in vitro assessment of primary, platelet-related hemostasis. Our aim was to examine platelet function using PFA-100 in FGR neonates and associate our results with perinatal parameters., Methods: PFA-100 was applied on 74 FGR neonates, 48 full-term (>37 weeks' gestation) and 26 preterm neonates (<37 weeks). The control group consisted of 118 healthy neonates. Two closure times (CTs) with COL/EPI and COL/ADP cartridges were determined on cord blood samples for each subject. Statistical analysis was performed by SAS 9.4. The statistical significance level was set at 0.05 and all tests were two-tailed., Results: COL/EPI CTs were prolonged in FGR (median 132 s, IQR 95-181 s) compared with control neonates (median 112.5 s, IQR 93-145 s), p = 0.04. Median COL/EPI CT for term and preterm FGR neonates was 126 s (IQR 90-157 s) and 137 s (IQR 104-203), respectively ( p = 0.001), and COL/ADP CT was 70 s (IQR 62-80 s) for term and 75 s (IQR 68-82 s) for preterm FGR neonates ( p = 0.08). Among FGR neonates, COL/EPI CT was related with delivery time (with preterm neonates exhibiting prolonged COL/EPI CTs), p = 0.05. No correlation was proved between both CTs and hematological parameters in FGR neonates., Conclusion: FGR neonates showed impaired platelet function via PFA-100, with preterm FGR neonates confronting the greatest risk. Prolonged COL/EPI CTs in FGR neonates seemed to be independent of hematological parameters and could warn for closer evaluation during the first days of their lives., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Kollia, Iacovidou, Iliodromiti, Pouliakis, Sokou, Mougiou, Boutsikou, Politou, Boutsikou and Valsami.)

The majority of patients with congenital heart disease (CHD) who have undergone open heart surgery during childhood are possible candidates for additional transcatheter or surgical interventions. One fifth of these conditions usually involve the right ventricular outflow tract (RVOT). Percutaneous pulmonary valve replacement (PPVR) has been widely established as an alternative, less invasive option to surgical pulmonary valve replacement (SPVR). The variability of RVOT anatomy and size, the relative course of the coronary arteries, and the anatomy of the pulmonary artery branches are factors that determine the success of the intervention and the complication rates. Careful and reliable pre-interventional imaging warrants the selection of suitable candidates and minimizes the risk of complications. 2D and 3D fluoroscopy have been extensively used during pre- and peri-interventional assessment. Established imaging techniques such as cardiovascular magnetic resonance (CMR) and computed tomography (CT) and newer techniques such as fusion imaging have proved to be efficient and reliable tools during pre-procedural planning in patients assessed for PPVR., (Copyright © 2022 Hellenic Society of Cardiology. Published by Elsevier B.V. All rights reserved.)

Neonatal platelet hemostasis, although it has been well described over the recent years, remains elusive in specific patient populations, including neonates from high-risk pregnancies, such as those complicated with gestational diabetes mellitus (GDM). We aimed at evaluating the platelet function of neonates born to mothers with GDM using the platelet function analyzer (PFA-100). Cord blood samples were drawn from each subject and tested with two different agonists to provide two closure time (CT) values (collagen with epinephrine (COL/EPI) and collagen with adenosine diphosphate (COL/ADP)). A total of 84 and 118 neonates formed the GDM and the control group (neonates from uncomplicated pregnancies), respectively. COL/EPI CTs were prolonged in neonates from the GDM group compared to neonates from the control group, while no statistically significant difference of COL/ADP CTs was noted between the two groups, GDM and the control. Higher COL/ADP CTs were demonstrated in neonates born via cesarean section and in neonates with blood group O. A negative correlation between COL/ADP CT and gestational age, white blood cells (WBCs) and von Willebrand factor (VWF) activity was noted in neonates from the GDM group. In conclusion, neonates from the GDM group demonstrate a more hyporesponsive phenotype of their platelets, in comparison to the control neonates.

Whereas younger female patients were diagnosed with idiopathic pulmonary arterial hypertension (IPAH) in 1980s, it is now frequently encountered in elderly patients with cardiovascular comorbidities (CVCs) associated with increased risk for left heart disease. We present data until November 2019 regarding specific features and clinical outcomes of IPAH population from the Hellenic Pulmonary Hypertension Registry (HOPE). Patients were divided into two groups based on the presence of ≥ or <3 CVCs, arterial hypertension, diabetes mellitus, obesity, presence of coronary artery disease, or atrial fibrillation. Overall, 77 patients with IPAH (55.1 [interquartile range, IQR: 24.1] years, 62.8% women) have been recorded. Fifteen patients (19.2%) had ≥3 CVCs, while 25 (32%) were over 65 years old. Patients with ≥3 CVCs were older, presented an almost equal female to male ratio, walked less in 6-min walk test, and had lower mean arterial pulmonary pressure and pulmonary vascular resistance at baseline than patients with less CVCs. Fewer patients with ≥3 CVCs received PAH-specific treatment compared to patients with less comorbidities ( n  = 11 [73.3%] versus n  = 58 [95.5%], p  = 0.02). During a median follow-up period of 3.8 (IQR: 2.7) years, 18 patients died (all-cause mortality 24.3%). Male sex and older age were independent predictors of mortality and/or lung transplantation, while CVCs did not have a significant impact on clinical outcomes. In this nationwide, register-based study, the epidemiology of IPAH involves older patients with CVCs, who seem to have less hemodynamic compromise, but worse functional impairment and are treated less aggressively with PAH pharmacotherapy., Competing Interests: Alexandra Arvanitaki has been the recipient of the International Training and Research Fellowship EMAH Stiftung Karla Voellm, Krefeld, Germany. Anastasia Anthi reports receiving honoraria and consultancy fees from Actelion Pharmaceuticals Hellas, Bayer, ELPEN, GSK, MSD, Lilly, and United Therapeutics. Eftychia Demerouti has been an advisory board member for Actelion Pharmaceuticals Hellas, MSD Hellas, and GlaxoSmithKline and an honorarium speaker for Actelion Pharmaceutical Hellas and MSD Hellas. Ioanna Mitrouska reports receiving honoraria and consultancy fees from Actelion Pharmaceuticals Hellas, Bayer, ELPEN, MSD, and GSK. Katerina K. Naka reports lecture fees from Novartis, Medtronic, and Abbott, while she serves as an investigator in randomized clinical trials and/or registries sponsored by Novartis, Merck, Amgen, BMS, Boehringer Ingelheim, Pfizer, and Actelion Pharmaceutical Hellas, outside the submitted work. Stylianos E. Orfanos reports has been receiving research grants and/or honoraria and/or consultancy fees from Actelion Pharmaceutical Hellas, Bayer, ELPEN, Galenica‐Ferrer, GSK, MSD, Pharmaserve Lilly, PharmaSwiss, Pfizer, and United Therapeutics. Georgia Pitsiou reports receiving honoraria and consultancy fees from Actelion Pharmaceutical Hellas, Bayer, ELPEN, MSD, and GSK. Ioannis Stanopoulos reports receiving honoraria and consultancy fees from Actelion Pharmaceuticals Hellas. Iraklis Tsangaris reports has been receiving honoraria and consultancy fees from Actelion Pharmaceuticals Hellas, Bayer, ELPEN, GSK, Pfizer, Lilly, and United Therapeutics. Athanasios Manginas reports consultation fees from Astra Zeneca, Bayer, ELPEN, Actelion Pharmaceuticals Hellas, and MSD. George Giannakoulas reports has been receiving honoraria and consultancy fees from Actelion Pharmaceuticals Hellas, Bayer, ELPEN, Galenica‐Ferrer, GSK, Pfizer, Lilly, MSD, and United Therapeutics. The remaining authors declare no conflicts of interest. The remaining authors declare no conflicts of interest., (© 2022 The Authors. Pulmonary Circulation published by John Wiley & Sons Ltd on behalf of Pulmonary Vascular Research Institute.)

We explored whether radiomic features from T1 maps by cardiac magnetic resonance (CMR) could enhance the diagnostic value of T1 mapping in distinguishing health from disease and classifying cardiac disease phenotypes. A total of 149 patients (n = 30 with no heart disease, n = 30 with LVH, n = 61 with hypertrophic cardiomyopathy (HCM) and n = 28 with cardiac amyloidosis) undergoing a CMR scan were included in this study. We extracted a total of 850 radiomic features and explored their value in disease classification. We applied principal component analysis and unsupervised clustering in exploratory analysis, and then machine learning for feature selection of the best radiomic features that maximized the diagnostic value for cardiac disease classification. The first three principal components of the T1 radiomics were distinctively correlated with cardiac disease type. Unsupervised hierarchical clustering of the population by myocardial T1 radiomics was significantly associated with myocardial disease type (chi 2  = 55.98, p < 0.0001). After feature selection, internal validation and external testing, a model of T1 radiomics had good diagnostic performance (AUC 0.753) for multinomial classification of disease phenotype (normal vs. LVH vs. HCM vs. cardiac amyloid). A subset of six radiomic features outperformed mean native T1 values for classification between myocardial health vs. disease and HCM phenocopies (AUC of T1 vs. radiomics model, for normal: 0.549 vs. 0.888; for LVH: 0.645 vs. 0.790; for HCM 0.541 vs. 0.638; and for cardiac amyloid 0.769 vs. 0.840). We show that myocardial texture assessed by native T1 maps is linked to features of cardiac disease. Myocardial radiomic phenotyping could enhance the diagnostic yield of T1 mapping for myocardial disease detection and classification., (© 2021. The Author(s).)

Chronic Thromboembolic Pulmonary Hypertension (CTEPH) is a rare disease with poor prognosis if left untreated, characterized by pulmonary vascular bed obstruction due to unresolving thromboembolic material. The Hellenic pulmonary hypertension registry (HOPE) was launched in Greece in early 2015 and enrolls patients from all pulmonary hypertension subgroups in Greece. In total, 98 patients with CTEPH were enrolled from January 2015 until November 2019. Of these patients, 55.1% represented incident population, 50% were classified in the World Health Organization functional class II and 49% had a history of acute pulmonary embolism. The median values of pulmonary vascular resistance (PVR) and cardiac index were 7.4 (4.8) WU and 2.4 (1.0) L/min/m 2 , respectively, the mean diffusing capacity for carbon monoxide was 74.8 ± 20.6%, the median 6-minute walk distance was 347 (220) meters and the median value of N Terminal-pro brain natriuretic peptide was 506.0 (1450.0) pg/mL. In total, 60.2% of the patients were under pulmonary arterial hypertension-targeted therapy at the time of enrolment; specifically, riociguat was received by 35.7% of the patients and combination therapy was the preferred strategy for 16% of the patients. In total, 74 patients were evaluated for pulmonary endarterectomy (PEA), 34 (45.9%) were assessed as operable but only 23 of those (31.1%) finally underwent PEA. The remaining 40 patients were ineligible for PEA according to the operability assessment and 13 (17.6%) of them underwent balloon pulmonary angioplasty. The age of the non-operable patients was significantly higher than the operable patients ( p < 0.001), while there was no significant difference with regard to the history of coagulopathies between the operable and non-operable patients ( p = 0.33).

(1) Background: There has been various reports on the potential impact of anesthetic agents used during oocyte retrieval (OR) on the impairment of the capacity of the oocyte for fertilization and subsequent embryo quality; results have been conflicting; (2) Methods: The effects of two different sedation protocols during OR in two groups of patients undergoing In Vitro Fertilization/Intra-Cytoplasmic Sperm Injection IVF/ICSI, were compared on propofol consumption and on in vitro fertilization (IVF)/ICSI success. The study group received dexmedetomidine and fentanyl, while the control remifentanil and midazolam. In a prospective cohort study, we encompassed 72 cycles/patients. The administered dose of propofol per patient and fertilization rates were the primary outcomes, while anesthesiological parameters and IVF/ICSI outcomes were the secondary endpoints; (3) Results: We found a significant increase in propofol consumption in the study compared to the control group (77.0 ± 10.6 mg vs. 12.1 ± 6.1; p < 0.001), but fertilization rates were similar ( p = 0.469). From the secondary anesthesiological outcomes, the post anesthesia discharge scores were better in the control group (15.0 (13.5 min) vs. 5.0 (10.0 min), p = 0.028). From the IVF/ICSI secondary outcome parameters, we found a higher quality of embryos on day three in the study compared to the control group ( p = 0.040). The comparison of the other secondary outcomes yielded non-significant differences; (4) Conclusions: The use of dexmedetomidine, as an alternative agent during OR, was associated with higher propofol consumption as a rescue dose compared to remifentanil but was linked with similar fertilization rates and higher quality of embryos produced.

The perception that women represent a low-risk population for cardiovascular (CV) disease (CVD) needs to be reconsidered. Starting from risk factors, women are more likely to be susceptible to unhealthy behaviors and risk factors that have different impact on CV morbidity and mortality as compared to men. Despite the large body of evidence as regards the effect of lifestyle factors on the CVD onset, the gender-specific effect of traditional and non-traditional risk factors on the prognosis of patients with already established CVD has not been well investigated and understood. Furthermore, CVD in women is often misdiagnosed, underestimated, and undertreated. Women also experience hormonal changes from adolescence till elder life that affect CV physiology. Unfortunately, in most of the clinical trials women are underrepresented, leading to the limited knowledge of CV and systemic impact effects of several treatment modalities on women's health. Thus, in this consensus, a group of female cardiologists from the Hellenic Society of Cardiology presents the special features of CVD in women: the different needs in primary and secondary prevention, as well as therapeutic strategies that may be implemented in daily clinical practice to eliminate underestimation and undertreatment of CVD in the female population., (Copyright © 2020 Hellenic Society of Cardiology. Published by Elsevier B.V. All rights reserved.)

Background: Adults with repaired tetralogy of Fallot die prematurely from ventricular tachycardia (VT) and sudden cardiac death. Inducible VT predicts mortality. Ventricular scar, the key substrate for VT, can be noninvasively defined with late gadolinium enhancement (LGE) cardiovascular magnetic resonance but whether this relates to inducible VT is unknown., Methods: Sixty-nine consecutive repaired tetralogy of Fallot patients (43 male, mean 40±15 years) clinically scheduled for invasive programmed VT-stimulation were prospectively recruited for prior 3-dimensional LGE cardiovascular magnetic resonance. Ventricular LGE was segmented and merged with reconstructed cardiac chambers and LGE volume measured., Results: VT was induced in 22 (31%) patients. Univariable predictors of inducible VT included increased RV LGE (odds ratio [OR], 1.15; P =0.001 per cm 3 ), increased nonapical vent LV LGE (OR, 1.09; P =0.008 per cm 3 ), older age (OR, 1.6; P =0.01 per decile), QRS duration ≥180 ms (OR, 3.5; P =0.02), history of nonsustained VT (OR, 3.5; P =0.02), and previous clinical sustained VT (OR, 12.8; P =0.003); only prior sustained VT (OR, 8.02; P =0.02) remained independent in bivariable analyses after controlling for RV LGE volume (OR, 1.14; P =0.003). An RV LGE volume of 25 cm 3 had 72% sensitivity and 81% specificity for predicting inducible VT (area under the curve, 0.81; P <0.001). At the extreme cutoffs for ruling-out and ruling-in inducible VT, RV LGE >10 cm 3 was 100% sensitive and >36 cm 3 was 100% specific for predicting inducible VT., Conclusions: Three-dimensional LGE cardiovascular magnetic resonance-defined scar burden is independently associated with inducible VT and may help refine patient selection for programmed VT-stimulation when applied to an at least intermediate clinical risk cohort.

Objectives: Cardiac surgery or catheter interventions are nowadays commonly performed to reduce volume loading of the right ventricle in adults with congenital heart disease. However, little is known, on the effect of such procedures on pre-existing tricuspid regurgitation (TR). We assessed the potential reduction in the severity of TR after atrial septal defect (ASD) closure and pulmonic valve replacement (PVR)., Methods: Demographics, clinical and echocardiographic characteristics of consecutive patients undergoing ASD closure or PVR between 2005 and 2014 at a single centre who had at least mild preoperative TR were collected and analysed., Results: Overall, 162 patients (mean age at intervention 41.6±16.1 years, 38.3% male) were included: 101 after ASD closure (61 transcatheter vs 40 surgical) and 61 after PVR (3 transcatheter vs 58 surgical). Only 11.1% received concomitant tricuspid valve surgery (repair). There was significant reduction in the severity of TR in the overall population, from 38 (23.5%) patients having moderate or severe TR preoperatively to only 11 (6.8%) and 20 (12.3%) at 6 months and 12 months of follow-up, respectively (McNemar p<0.0001). There was a significant reduction in tricuspid valve annular diameter (p<0.0001), coaptation distance (p<0.0001) and systolic tenting area (p<0.0001). The reduction in TR was also observed in patients who did not have concomitant tricuspid valve (TV) repair (from 15.3% to 6.9% and 11.8% at 6 and 12 months, respectively, p<0.0001). On multivariable logistic regression including all univariable predictors of residual TR at 12 months, only RA area remained in the model (OR 1.2, 95% CI 1.04 to 1.37, p=0.01)., Conclusions: ASD closure and PVR are associated with a significant reduction in tricuspid regurgitation, even among patients who do not undergo concomitant tricuspid valve surgery., Competing Interests: Competing interests: ACM-G has received support from the Instituto de Investigacion Biomedica de Salamanca (IBSAL). KD, AK and AM-G from the Royal Brompton Hospital have received unrestricted educational and research grants and acted as consultants for Bayer, Pfizer, Actelion and GSK. SVB-N was supported by the British Heart Foundation (FS/11/38/28864)., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Pulmonary arterial hypertension (PAH) is a heterogenous clinical entity with poor prognosis, despite recent major pharmacological advances. To increase awareness about the pathophysiology, epidemiology, and management of the disease, large national registries are required. The Hellenic pulmOnary hyPertension rEgistry (HOPE) was launched in early 2015 and enrolls patients from all pulmonary hypertension subgroups in Greece. Baseline epidemiologic, diagnostic, and initial treatment data of consecutive patients with PAH are presented in this article. In total, 231 patients with PAH were enrolled from January 2015 until April 2018. At baseline, about half of patients with PAH were in World Health Organization functional class II. The majority of patients with PAH (56.7%) were at intermediate 1-year mortality risk, while more than one-third were low-risk patients, according to an abbreviated risk stratification score. Half of patients with PAH were on monotherapy, 38.9% received combination therapy, while prostanoids were used only in 12.1% of patients. In conclusion, baseline data of the Greek PAH population share common characteristics, but also have some differences with other registries, the most prominent being a better functional capacity. This may reflect earlier diagnosis of PAH that in conjunction with the increased proportion of patients with atypical PAH could partially explain the preference for monotherapy and the limited use of prostanoids in Greece. Nevertheless, early, advanced specific therapy is strongly recommended., (© The Author(s) 2019.)

In patients with CHD after Fontan palliation, there is a lack of a pumping chamber in the pulmonary circulation; thus, pulmonary blood flow and cardiac output are sensitive to increased pulmonary vascular resistance; if obstructive sleep apnoea is present, there are legitimate concerns from continuous positive airway pressure ventilation, which may hinder pulmonary blood flow.

Objective: To prospectively evaluate maternal and cord blood concentrations of sclerostin - an osteocyte-secreted factor, inhibiting osteoblast differentiation and bone formation and associated with adverse metabolism - in pregnancies with normal and abnormal fetal growth., Methods: Plasma sclerostin concentrations were determined by ELISA in 80 maternal and 80 cord blood samples from asymmetric intrauterine-growth-restricted (IUGR, n = 30), large-for-gestational-age (LGA, n = 30), and appropriate-for-gestational-age (AGA, n = 20) singleton full-term pregnancies. Fourteen out of 30 mothers with LGA offspring presented with gestational diabetes mellitus (GDM)., Results: Maternal and fetal sclerostin concentrations did not differ among LGA, IUGR, and AGA groups. Fetal concentrations were higher than maternal. In LGA group, maternal concentrations were elevated in cases of GDM (b = 13.009, 95%CI 1.425-24.593, p = .029). In a combined group and the IUGR group, maternal concentrations were elevated in older mothers (b = 0.788, 95%CI 0.190-1.385, p = .010, and b = 0.740, 95%CI 0.042-1.438, p = .039, respectively)., Conclusions: Maternal and fetal sclerostin concentrations may not be differentially regulated in pregnancies complicated by abnormal fetal growth. Circulating maternal levels are higher in cases of GDM, probably implying reduced bone formation. Sclerostin up-regulation with aging may be one of the molecular pathways responsible for the observed age-related decline in bone synthesis, leading to accelerated bone loss in humans.

Pulmonary atresia with intact ventricular septum may be complicated by coronary aneurysms and myocardial ischaemia. We report a case of an acquired postoperative right ventricular outflow tract aneurysm with communication to the left ventricular outflow tract. Multimodality imaging helped in the characterisation of this structural abnormality, which led to treatment modification of the patient.

Background: Personalized external aortic root support (PEARS) was introduced in 2004 for prevention of aortic root dilatation in Marfan patients. The individual's aortic root is replicated by 3-dimensional printing. A polymer mesh sleeve is manufactured, which is implanted with the aim to support and stabilize the aortic wall., Objectives: The aim of this study was to assess effectiveness of PEARS for prevention of aortic root dilatation in Marfan patients., Methods: A total of 24 consecutive Marfan patients operated 2004 to 2012 were prospectively monitored with magnetic resonance imaging. Following a pre-defined protocol, baseline and follow-up aorta measurements were made in a blinded random sequence., Results: The mean age of the patients was 33 ± 13.3 years (range: 16 to 58 years), and the mean aortic root diameter was 45 ± 2.8 mm (range: 41 to 52 mm). Follow-up was 6.3 ± 2.6 years. There was no increase in the aortic root and ascending aorta diameters, but there was a tendency toward reduction: annulus diameter 28.9 ± 2.3 mm to 28.5 ± 2.4 mm (change -0.39 mm, 95% confidence interval [CI]: -1.05 to 0.27 mm), sinus of Valsalva diameter 44.9 ± 2.9 mm to 44.5 ± 3.0 mm (change -0.37 mm, 95% CI: -1.23 to 0.51 mm), and ascending aorta diameter 32.4 ± 3.6 mm to 32.3 ± 3.7 mm (change -0.10 mm, 95% CI: -0.92 to 0.74 mm). In the same period, the descending aorta diameter increased from 22.9 ± 2.4 mm to 24.2 ± 3.0 mm (change 1.32 mm, 95% CI: 0.70 to 1.94 mm; p < 0.001) with a tendency toward increase in aortic arch diameter 24.1 ± 2.0 mm to 24.5 ± 2.8 mm (change 0.41 mm, 95% CI: -0.56 to 1.37 mm)., Conclusions: PEARS is effective in stabilizing the aortic root and preventing its dilatation. It is a viable alternative for prevention of aortic root dissection in Marfan patients., (Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Introduction: The diagnosis of ALCAPA syndrome is sporadic in adulthood, of the limited cases in the literature most are incidental or without symptoms. There is a broad spectrum of clinical manifestations of ALCAPA syndrome however, including sudden cardiac death., Cases: We present herewith a series of 12 consecutive patients with ALCAPA, all diagnosed in adulthood (between 18 and 73 years of age). Five patients developed symptoms (breathlessness) after the fourth decade of life, 3 were undiagnosed despite a history of previous mitral valve repair, one presented with heart failure, one with resuscitated cardiac arrest, whereas two patients were asymptomatic. We review in this paper, the clinical history, diagnostic approach and therapeutic choices of ALCAPA syndrome., Conclusion: ALCAPA syndrome is not confined to childhood, late diagnosis in adulthood has a varied clinical presentation. ALCAPA syndrome should be particularly considered as a potential, albeit uncommon cause of mitral regurgitation and/or dilated cardiomyopathy., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objective: Fetal macrosomia is associated with cardiac hypertrophy and increased cardiovascular risk. Cardiac biomarkers may play diagnostic/prognostic role in cardiovascular disease. We tested whether cardiac biomarkers are differentially expressed in cord blood samples of full-term singleton large-for-gestational-age (LGA), as compared to appropriate-for-gestational-age (AGA) pregnancies., Methods: Cardiotrophin-1 (CT-1), Titin, pentraxin (PTX-3) and soluble CD36 (sCD36) concentrations were determined in 80 cord blood samples from a) LGA pregnancies due to maternal diabetes (n = 8), overweight/obese (n = 11), excessive weight gain (n = 7), without specific pathology (n = 14), b) AGA normal pregnancies (controls, n = 40). Neonates were classified as LGA or AGA based on customized birth weight (BW) standards., Results: CT-1 and Titin concentrations were higher in LGA than AGA pregnancies (p < .001 and p = .023, respectively). A subgroup analysis (in the LGA group) showed increased CT-1 concentrations only in diabetic pregnancies. PTX-3 and sCD36 concentrations were similar in LGA and AGA fetuses. In the LGA group, PTX-3 concentrations positively correlated with birth-weight (r = .416, p = .008) and respective sCD36 concentrations (r = .443, p = .004)., Conclusion: Higher Titin concentrations in LGAs possibly represent a candidate molecular mechanism underlying the association between fetal macrosomia and cardiomyocyte/diastolic dysfunction. CT-1 is up-regulated only in LGAs exposed to maternal diabetes. PTX-3 and sCD36 are probably not affected by excessive fetal growth.

Objective: Gestational diabetes mellitus (GDM) may induce fetal macrosomia or growth restriction and is associated with later offspring neurodevelopmental disorders. We aimed to determine whether neurotrophins brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF) and neurotrophin-4 (NT-4) are differentially expressed in cord blood samples at birth in large-for-gestational-age (LGA), intrauterine-growth-restricted (IUGR) and appropriate-for-gestational-age (AGA) offspring of diabetic mothers, as compared to AGA controls from non-diabetic mothers., Methods: BDNF, NGF and NT-4 concentrations were prospectively determined in 80 cord blood samples from LGA (n = 15), IUGR (n = 12) and AGA (n = 33) diabetic, as well as from AGA normal (controls, n = 20) singleton full-term pregnancies., Results: Fetal BDNF concentrations considerably decreased in GDM, as compared with normal pregnancies [(b = -2.836, 95%CI -5.067 to (-0.604), p = 0.013)] and were higher in females (b = 2.298, 95%CI 0.357-4.238, p = 0.021). Cord blood NGF concentrations were lower in IUGR than AGA infants (p = 0.038)., Conclusions: BDNF is down-regulated in the fetus exposed to GDM, independently of the fetal growth pattern, probably representing a candidate mechanism underlying the association between maternal diabetes and later psychopathology. IUGR fetuses born to diabetic mothers present with NGF deficiency, which may contribute to their long-term neurodevelopmental sequelae. Gender-dependent differences in fetal BDNF may partly explain the higher prevalence of adverse neurodevelopmental outcomes following brain insults in male infants.

Treatment of acute emergencies in patients with pulmonary arterial hypertension (PAH) can be challenging. In the UK and Ireland, management of adult patients with PAH is centred in eight nationally designated pulmonary hypertension (PH) centres. However, many patients live far from these centres and physicians in local hospitals are often required to manage PAH emergencies. A committee of physicians from nationally designated PH centres identified the 'most common' emergency clinical scenarios encountered in patients with PAH. Thereafter, a review of the literature was performed centred on these specified topics and a management approach was developed based on best available evidence and expert consensus. Management protocols were developed on the following PAH emergencies: chest pain (including myocardial ischaemia), right ventricular failure, arrhythmias, sepsis, haemoptysis ('CRASH'), as well as considerations relevant to surgery, anaesthesia and pregnancy. Emergencies are not uncommon in PAH. While expertise in PAH management is essential, all physicians involved in acute care should be aware of the principles of acute management of PAH emergencies. A multidisciplinary approach is necessary, with physicians from tertiary PH centres supporting care locally and planning safe transfer of patients to PH centres when appropriate., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Introduction: Genetic factors contribute to the variation of human life span which is believed to be more profound after 85 years of age. The aim of the present study was to evaluate the frequency of 5 gene polymorphisms between nonagenarians, centenarians and average individuals., Material and Methods: Single nucleotide polymorphisms (SNPs) of telomerase reverse transcriptase ( TERT ; rs2736098), insulin-like growth factor-1 binding protein-3 ( IGFBP3 ; A-202C, rs2857744), fork-head box O3A ( FOXO3A ; rs13217795 and rs2764264) factor and adiponectin ( ADIPOQ ; rs2241766) were evaluated in 405 individuals: n = 256 nonagenarians and centenarians (study group) and n = 149 average lifespan individuals (control group aged 18 - < 80 years)., Results: The frequency of women was significantly higher in the study group than the control group (64.5 vs. 49.7%, p = 0.004). Genotypic and allele frequencies did not differ between groups according to gender. However, in men, the frequency of TT genotype of FOXO3A ; rs2764264 was higher in the study group than the control group (45.6 vs. 28.0%, p = 0.05). Overall, the frequency of the C allele of FOXO3A ; rs2764264 was significantly lower in the study group than the control group (3.9 vs. 9.5%, respectively, p = 0.023). Furthermore, in the study group, the T allele was significantly more frequent in the nonagenarians ( n = 239) than the centenarians ( n = 17) in both FOXO3A ; rs13217795 and rs2764264 (64.4 vs. 44.1%, p = 0.018 and 69.7 vs. 50.0%, p = 0.017, respectively)., Conclusions: According to survival status, there is differentiation in the prevalence of both studied FOXO3A gene polymorphisms. The study group had half of the C alleles compared with the control group and centenarians less frequently had the T allele of both FOXO3A gene polymorphisms compared with nonagenarians. No difference was found between groups according to TERT , IGFBP3 and ADIPOQ gene polymorphisms. It seems that some polymorphisms may be significant in prolonging our lifespan. Nevertheless, confirmation in additional study populations is needed.

Isolated right superior caval vein drainage into the left atrium is a rare congenital cardiac anomaly usually presenting with hypoxaemia and cyanosis. Surgical repair is the definitive treatment for this condition. In this report, we present the case of a 72-year-old patient with uncorrected anomalous drainage of a right superior caval vein into the left atrium, first diagnosed in the 1960s. To the best of our knowledge, this is the oldest reported unrepaired case.

Objective: To determine maternal colostrum/serum concentrations of the bioactive substances irisin, adropin and copeptin and investigate their association with several perinatal parameters and pathologic conditions during pregnancy., Methods: In a cohort of 81 mothers with full-term deliveries, colostrum/serum concentrations of irisin, adropin and copeptin were prospectively evaluated by ELISA on Day 3-4 postpartum., Results: Copeptin and adropin were detectable in human colostrum at higher, while irisin at lower concentrations than in maternal serum (p < 0.001 in all cases). Colostrum adropin and copeptin concentrations positively correlated with maternal serum ones (r = 0.421, p < 0.001 and r = 0.304, p = 0.006, respectively)., Conclusions: Irisin, adropin and copeptin are present in colostrum and we speculate that they may be implicated in postnatal adaptation with respect to thermoregulation, vascular adaptation, glucose metabolism, lung function and fluid homeostasis. These findings may possibly enhance the necessity for early breastfeeding, particularly of infants born by cesarean section, who are prone to hypothermia, breathing disorders and dehydration.

Objective: Intrauterine-growth-restriction-(IUGR) is associated with chronic fetal stress, as well as a phase of enhanced fetal/early postnatal insulin sensitivity, followed by a later emergence of insulin resistance. We aimed to prospectively investigate concentrations of copeptin, a sensitive marker of stress and insulin resistance, in IUGR versus appropriate-for-gestational-age-(AGA) fetuses., Methods: Cord blood copeptin concentrations were determined by ELISA in well-defined, non-distressed at birth, asymmetric IUGR (n = 30) and AGA (n = 20) full-term pregnancies. Doppler studies were indicative of placental insufficiency., Results: Cord blood copeptin concentrations were similar in IUGR cases and AGA controls, after controlling for delivery mode. Copeptin concentrations were markedly elevated in vaginally delivered fetuses (p = 0.001). No association was recorded between fetal copeptin concentrations and maternal age, parity, gestational age, or fetal gender., Conclusions: Cord blood copeptin concentrations are probably not affected by IUGR at term, in the absence of fetal distress, possibly due to a balance between copeptin up-regulation by chronic fetal stress, on one hand, and copeptin down-regulation in the presence of increased insulin sensitivity, on the other hand; thus, copeptin may not be a sensitive marker of chronic perinatal stress in healthy asymmetric IUGR infants. Cord blood copeptin seems to primarily reflect perinatal stress associated with delivery mode.

Aims: Specialized nurses estimated the HeartScore in an urban Greek population by recognizing cardiovascular disease (CVD) risk factors in the setting of the Onassis Cardiovascular Prevention Program (OCPP). They also provided nursing consultation and assessed the clinical and biochemical characteristics of the studied population., Methods and Results: Individuals were recruited through TV announcements and via the website of the Onassis Cardiac Surgery Centre. All participants visited the Onassis Cardiac Centre from 20 September to 30 October 2011. Overall, 2,145 individuals were included in the study. CVD risk was calculated by the HeartScore and serum total cholesterol was measured (mean: 193±43 mg/dl). Although 33% of the participants reported dyslipidaemia, only 17% were on hypolipidaemic treatment. Hypertension and dyslipidaemia frequency increased with age., Conclusion: In the present study, specialized nurses estimated the HeartScore in a Greek urban population. The majority of the studied population was undiagnosed and untreated. These results highlight the necessity for both primary and secondary prevention programs that can be carried out by specialized nurses. Such programs may improve the diagnosis and treatment of CVD risk factors; early initiation and optimization of therapy as well as management of drug intolerance (e.g. statins) can contribute to CVD risk reduction.

Objective: The present study is on line with our previous studies evaluating the influence of ATP-binding cassette transporter A1 ( ABCA1 ) gene polymorphisms on the lipid variables of Greek student-nurses. The current study was undertaken to (1) estimate the influence of variant(s) such as rs2066715 (V825I), R219K, R1587K, I883M of ABCA1 gene on lipid variables and (2) evaluate the effect of all four ABCA1 polymorphisms on common demographic parameters., Methods: The study population involved 432 unrelated nurses (86 men) who were genotyped for ABCA1 polymorphisms and correlated according to lipid variables [total cholesterol (TC), triglycerides (TGs), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C) and apolipoprotein (apo) A] and demographic parameters (age, gender, BMI, waist circumference)., Results: According to lipid variables concentration there was no difference between genotypes and alleles of V825I, R219K and I883M polymorphisms. The LDL-C concentration was 13% lower in RR compared with RK genotype (100.7 vs . 113.9 mg/dl, p=0.013) of R1587K gene polymorphism. In regression analysis the effects of age, gender and only R1587K gene polymorphism on LDL-C concentrations were proved significant. Additionally, LDL-C was increased (by 1.29 mg/dl on average) by every year of increase of age. Moreover, females had lower LDL-C concentrations as compared with males., Conclusion: Findings suggested that only R1587K polymorphism of ABCA1 gene was associated with lipid variables, age, and gender of Greek nurses. These findings may be helpful in assessing the risk factors for premature coronary heart disease and distinct individuals with lower/higher atherosclerotic burden.

Objective: To prospectively investigate maternal concentrations of the myokine irisin in large for gestational age (LGA) and intrauterine growth restricted (IUGR) versus appropriate for gestational age (AGA) normal pregnancies and associate them with various perinatal parameters., Methods: Plasma irisin and insulin concentrations were measured by enzyme-linked immunosorbent assay (ELISA) and immunoradiometric assay (IRMA), respectively, in a cohort of 80 mothers delivering LGA (n = 30), IUGR (n = 30) and AGA (n = 20) singleton full-term infants., Results: Maternal irisin concentrations were similar among LGA, IUGR and AGA groups and did not correlate with respective insulin ones or maternal body mass index. In a combined group, maternal irisin concentrations decreased with advancing gestational age (p < 0.001) and were lower in multi-, compared to nulliparous women (p = 0.004). In the IUGR group, maternal irisin concentrations were higher in cases of smoking (p = 0.006)., Conclusions: Irisin may not be differentially regulated in insulin resistance-associated pregnancy disorders resulting in fetal macrosomia and IUGR. Maternal irisin down-regulation with advancing gestation could possibly contribute to the observed maternal fat accumulation and progressive insulin resistance towards term. Similarly, lower maternal irisin concentrations in multiparous women may reflect the documented positive association between parity and fat deposition. Irisin up-regulation in cases of smoking may indicate the need for enhanced oxygen consumption to maintain energy production under conditions of hypoxia.

Objective: To determine levels of adropin (implicated in insulin resistance and endothelial dysfunction) in intrauterine growth restricted (IUGR), large (LGA) and appropriate for gestational age (AGA) pregnancies., Methods: Cord-blood (UC) adropin and insulin concentrations were measured in 30 IUGR, 30 LGA and 20 AGA full-term infants and their mothers (MS)., Results: No significant differences in adropin concentrations were observed between the three groups. In the IUGR group MS adropin was significantly decreased when neonates had higher birth weights [b = -0.003, 95% CI -0.006 to 0.0, p = 0.043]. In all groups, MS adropin levels were positively correlated with UC ones (r = 0.282, p = 0.011) and were significantly increased in female neonates [b = 0.977, 95% CI 0.122-1.832, p = 0.026]. In the LGA group, MS insulin was negatively correlated with UC adropin (r =  -0.362 p = 0.049)., Conclusions: Increased maternal adropin levels in severe IUGR cases might represent a regulatory feedback mechanism against endothelial placental dysfunction. The positive correlation between maternal and umbilical cord adropin levels implies its transplacental transfer. Increased maternal adropin levels in female neonates could be attributed to interaction of adropin with fetal estrogens through vascular endothelial growth factor (VEGF). The negative correlation between maternal insulin and fetal adropin levels in the LGA group is probably attributed to their respective insulin resistance.