bluuebunny/crossref_metadata_2025_split huggingface dataset:
P4489Morphological changes in the EGDE-treated bioprosthetic heart valves
Authors: Ovcharenko E , Klyshnikov K Y U , Glushkova T , Rogulina N , Barbarash L S 
Published: October 2019

Abstract

Background
Prosthetic heart valves fabricated from pericardium preserved in EGDE (ethylene glycol diglycidyl ether) may be a promising option for patients with valvular heart disease.

Purpose
To assess morphological changes in the failed PeriCor and UniLine bioprostheses and to determine the underlying mechanisms contributing to their dysfunction.

Methods
17 patients with EGDE-treated mitral bioprosthetic valves (PeriCor group, n=11, UniLine group= 6). undergoing repeat mitral valve replacement were included in the study. The median age of patients at the time of the primary replacement was 59 (54; 64) and 57 (55, 65) years, respectively. All cases of calcifications, spontaneous perforations, leaflet tears and ruptures, pannus growth, bioprosthetic leaflet fusion were assessed using microscopy and micro-computed tomography. The contribution of degenerative changes leading to the failure of bioprostheses was estimated with the Chi-square test.

Results
Pannus growth was observed in 53.8% of all explanted bioprostheses. Its overgrowth was abundant covering the leaflets and the stent struts and resulted in decreased effective orifice area and subsequent stenosis. Bioprosthetic leaflet fusion was observed only in the PeriCor group and accounts for 70%. Of them, 93% of cases of leaflet fusion was accompanied by the ruptures in the opposite commissural zones and subsequent leaflet perforations. The signs of calcification were reported in 57.6% of cases. Of them, 50% of cases had calcified stent frame tissue covering and 35% - pannus. Interestingly, calcification was not the main cause leading to the valve failure in 53.3% of cases.

Conclusion
Modes of bioprosthetic valve dysfunction include primary tissue degeneration, calcification and pannus growth. Primary tissue degeneration, pannus growth and commissural fusions account for a larger percentage in the modes of dysfunctions for EGDE-treated xenoaortic bioprostheses rather than calcification. Our findings suggest that preservation methods play one of the key roles in the dysfunction pattern.
P4499Development of a hydrogel-based pre-vascularized 3D cardiac patch displaying capillary network
Authors: Kitasato L , Atlas Y , Joanne P , Germain S , Agbulut O , Muller L 
Published: October 2019

Abstract

Purpose
Stem cell-based attempts at regenerating chronically failing heart have not met the clinical outcomes expected by experimental studies. The efficacy of cell transplant is largely dependent on the engraftment rate, which requires cells to receive an adequate blood supply. To address this issue, we propose to develop a composite tissue engineering construct made of biocompatible pre-vascularized fibrin hydrogel. The objectives of this study are to determine co-culture conditions and to optimize fabrication of fibrin hydrogels supporting generation of capillaries and cardiomyocyte activity at the same time.

Materials and methods
Rat primary cardiomyocytes were co-seeded with human umbilical vein endothelial cells (HUVECs) in fibrin hydrogels. Cultures were performed in 96 well plates. Cells were cultured in a mixture of medium conditioned with human dermal fibroblasts and of cardiomyocyte medium (1:1) for 8 days. To improve co-culture of the two cell types, insulin (1 μg/mL) and/or VEGF (5 ng/mL) were added 24 hours after the initial day of culture and maintained for 24 hours. The cells treated with VEGF were also treated 5 days after initial seeding with insulin and VEGF (insulin at 1 μg/mL and VEGF at 1 or 5 ng/mL). After culture, cardiomyocytes were immuno-stained for Troponin T or Connexin-43, endothelial cells for CD31, basement membrane for collagen IV. From spinning disk images, cardiomyocyte volume, contraction and total length/ branches of capillaries were measured.

Results
: We first determine the best conditions allowing the generation of active cardiomyocytes and the formation of a network of mature capillaries into fibrin hydrogels. We showed that cardiomyocytes volume and contraction were not influenced by the addition of VEGF or insulin. For cells treated with VEGF for 24 hours, total length and total branches of capillaries were significantly increased over other conditions without supplements (control), or with insulin alone or with VEGF. We also observed lumen formation and basement membrane deposition.

Conclusions
These results may provide a new model of vascularized human heart tissue for in vitro studies, displaying cardiomyocyte contractility together with lumenized capillary formation. Furthermore, our data may help overcome current obstacles toward the success of cardiac cell therapy for damaged myocardium. In such approach, endothelial capillaries will serve as structural and trophic support through inosculation with the host cardiac vasculature after epicardial graft. As a perspective of this work, and in order to improve the cardiomyocyte alignment and the development of capillaries, we will design specific PDMS mold to allow the formation of a micro-tissue. Application of human cardiac cells and implantation in in vivo model is expected.

Acknowledgement/Funding
ESC research grant, Fondation de l'avenir, Societe Francaise de Cardiologie, Institut Servier
P4500Cellular senescence of endothelial cells impairs angiogenesis by altering energy metabolism through p53-tigar axis
Authors: Urata R , Ikeda K , Nakagawa T , Hoshino A , Honda S , Yagi N , Emoto N , Matoba S 
Published: October 2019

Abstract

Background
Ischemic disease is prevalent in elderly population due to impaired angiogenesis. Endothelial cell (EC) generates energy largely via glycolysis, which is further activated when angiogenesis actively occurs. PFK-1 is one of the most important regulatory enzymes for glycolysis, which is activated by PFKFB3. On the other hand, TIGAR inhibits PFK-1 under the control of p53. Crucial roles of PFKFB3 in EC functions under physiological and pathological conditions have been reported; however, a role of TIGAR in EC angiogenic functions remains to be elucidated. Furthermore, it remains unknown whether and how cellular senescence affect the energy metabolism in EC.

Purpose
The purpose of this study is to investigate molecular mechanisms underlying EC dysfunction associated with ageing, especially by focusing on endothelial energy metabolism.

Method and result
Senescent EC showed reduced glucose consumption assessed by [U-13C]-glucose tracer assay in association with increased expression of p53 and TIGAR. Angiogenic capacity assessed by tube-formation assay was reduced in senescent EC. Of note, either silencing of TIGAR by siRNA or lentivirus-mediated overexpression of PFKFB3 improved angiogenic capacity in senescent EC. These results collectively suggest that senescence impairs glycolysis in EC by activating p53-TIGAR axis, which leads to senescence-associated endothelial dysfunction. To analyze an impact of EC senescence in angiogenesis in vivo, we generated EC-specific progeroid mice in which dominant negative form of telomere repeat-binding factor 2 (TRF2) was overexpressed in EC under the control of the TIE2 promoter. After confirming EC-specific senescence in these endothelial progeroid mice, we generated hind-limb ischemia model. Recovery of blood flow assessed by laser doppler velocimeter was significantly impaired in endothelial progeroid mice, indicating that EC senescence is directly and causally implicated in age-related angiogenic dysfunction. Of note, genetic inactivation of TIGAR completely rescued the impaired ischemia-induced neovessel formation in EC-specific progeroid mice.

Conclusion
Using unique endothelial progeroid mice, we revealed that EC senescence is a bona fide risk for ischemic disease, largely by reducing glycolysis in EC through p53-TIGAR axis. Our data suggest that endothelial energy metabolism is an attracting therapeutic target for the prevention and/or treatment of ischemic diseases, especially in elderly population.
P4505VECTOR-HF: The first human experience with the V-LAP, a wireless left atrial pressure monitoring system for patients with heart failure
Authors: Sievert H , Di Mario C , Perl L , Meerkin D , Abraham W T 
Published: October 2019

Abstract

Background/Introduction
Invasive pressure-guided therapy has been shown to improve outcomes in patients with heart failure (HF). Thus far, only right-sided pressure sensors have shown clinical efficacy and safety. The Vectorious Medical Technologies V-LAP™ is a novel battery-less and wireless left-sided pressure monitoring system, directly assessing left-atrial pressure (LAP) in an ambulatory setting. In pre-clinical studies, it was shown to enable accurate and safe measurement of LAP. We hereby describe the first human experience with the device.

Methods
The V-LAP left atrial monitoring systEm for patients with Chronic sysTOlic and diastolic congestive heart failuRe first-in-human (VECTOR) study is a prospective, multicenter, single arm, open-label clinical trial to assess the safety, performance and usability of the V-LAP system in patients with heart failure. The V-LAP™ wireless sensor is implanted using a trans-septal access, under angiographic and echocardiographic guidance. The system includes an external unit, which both powers the implant and collects data via radio frequency communication upon activation, designed to be operated on a daily basis. We hereby describe the first cases, implanted in the CardioVascular Center, in Frankfurt, Germany.

Results
At this point in time, there have been two successful implantations of the V-LAP™, performed in two NYHA Class III patients. Both were admitted repeatedly for exacerbations of HF, and demonstrated elevated NT-ProBNP levels. They were therefore considered appropriate candidates for the monitoring system, to enable optimal medical therapy. The procedure was performed in a trans-femoral, trans-septal fashion, under mild sedation, with a successful implantation of a V-LAP™, and calibration for pressure measurement. There were no complications, data showed accurate LAP reading (Figure 1).

Conclusions
In the first-in-human cases, the implantation of the novel wireless left atrial pressure sensor V-LAP™ was feasible, safe, and showed good accuracy and precision. We now await both short and long-term efficacy and safety outcomes of the device, with the hopes of optimizing care according to ambulatory LAP data for patients with HF.

Acknowledgement/Funding
Vectorious Medical Technologies
P4515The aging heart failure patient: frailty and cognitive impairment more common than you would expect - baseline data of the heart-brain clinic
Authors: Kleipool E E F , Handoko M L , Van Rossum A C , Hornstra J M , Peters M J L , Liem S S , Muller M 
Published: October 2019

Abstract

Background
Heart failure (HF) is a cardiovascular disease that is increasing by epidemic proportions, largely due to an aging society and therapeutic advances in disease management. Because heart failure is largely a cardiogeriatric syndrome, age-related syndromes such as frailty and cognitive impairment are common in heart failure patients.

Purpose
To assess the prevalence and determinants of frailty and cognitive impairment in a HF population ≥60 years of age.

Methods
Data from n=236 patients with HF (77±9 years; 43% female) visiting the heart-brain clinic in Amsterdam in 2018–2019. HF severity was evaluated by NT-proBNP and NYHA-classification. Frailty was assessed using Fried's frailty criteria, cognition using the Montreal cognitive assessment (MoCa). Logistic regression analyses were performed to evaluate which variables were associated with frailty and cognitive impairment.

Results
Median (IQR) NT-proBNP was 2000 (876–3469) pmol/L, 38% of patients had NYHA III-IV. 51% of patients were pre-frail and 28% frail. 77% of the patients were (mildly) cognitive impaired. Age, NYHA-classification III-IV, NT-proBNP>2000 pmol/L and use of ≥10 drugs were associated with frailty; HR (95% CI): 2.0 (1.4–3.0) per 10 years, 3.4 (1.9–6.2), 1.8 (1.0–3.2) and 1.8 (1.4–3.3) respectively. Age was associated with cognitive impairment; HR (95% CI) 2.2 (1.4–3.6) per 10 years.
Figure 1

Conclusion(s)
Frailty affects almost a third of the patients with HF and is more prevalent in older patients and those with more severe HF. Screening for frailty and cognitive impairment should be part of the standard workup in older HF patients as frail and/or cognitively impaired HF patients are less likely to adhere to their HF treatment and more likely to be (re)admitted to hospital for HF.
P4532PR interval prolongation, still a marker of worse outcome in patients treated with cardiac resynchronization therapy
Authors: Van Stipdonk A M W , Dural M , Salden F , Ter Horst I A H , Crijns H J G M , Prinzen F W , Meine M , Maass A H , Vernooy K 
Published: October 2019

Abstract

Background
Patients without left bundle branch block (non-LBBB) generally derive little benefit from CRT. Recently, CRT has been suggested to be beneficial in patients with prolonged PR interval. However in the general HF population, the presence of prolonged PR interval is associated with worse outcome.

Purpose
To evaluate the association of a prolonged PR interval with clinical outcome in CRT-treated LBBB and non-LBBB patients.

Methods
Pre-implantation 12-lead ECGs from 1.245 consecutive CRT patients without atrial fibrillation from 3 implanting centres in the Netherlands were evaluated for the presence of LBBB QRS morphology and PR interval prolongation (≥230ms). The primary endpoint was the combination of left ventricular assist device implantation, cardiac transplantation and all-cause mortality.

Results
Patients with LBBB (n=620) showed a significantly shorter mean PR interval than non-LBBB patients (n=625) (187ms vs 198ms, p<0.001). Prolonged PR interval was found in 12.6% of patients with LBBB and 19.2% of non-LBBB patients (P<0.001). In non-LBBB patients with PR prolongation event rate was significantly higher (54 vs 34%, p<0.001). In LBBB patients there was a non-significant difference (28 vs 20%, p=0.1). Regression analyses (figure 1) showed similar results, with a significantly higher odds of experiencing an event in non-LBBB patients with PR prolongation (HR 2.24 [1.68, 2.99], p<0.001), and a trend to significantly higher odds in LBBB patients with PR prolongation (HR 1.61 [1.02, 2.56], p=0.04)
Figure 1

Conclusion
In HF patients treated with CRT, PR prolongation is negatively associated with long term clinical outcome. The association seems to be stronger in non-LBBB patients than in LBBB patients.

Acknowledgement/Funding
None
P4538Effect of risk of malnutrition on 30-day mortality among older patients with acute heart failure in emergency departments
Authors: Martin Sanchez F J , Llopis Garcia G , Cuesta Triana F , Matia Martin P , Llorens P , Miro O 
Published: October 2019

Abstract

Introduction
There is a need to explore the risk of malnutrition as a modifiable prognostic factor in order to establish routine screening of malnutrition in the emergency setting among older patients with acute heart failure (AH.

Objectives
To determine the impact of risk of malnutrition on 30-day mortality risk among older patients attended for AHF in the Emergency Department (ED).

Methodology
We performed a secondary analysis of the OAK-3 Registry including all consecutive patients ≥65 years attended with AHF in 16 Spanish EDs over a 2-month period (January-February 2016). Risk of malnutrition was defined by the Mini Nutritional Assessment Short Form (MNA-SF) <12 points. Unadjusted and adjusted logistic regression models were used to assess the association between risk of malnutrition and 30-day mortality.

Results
We included 749 patients (mean age: 85 (SD 6); 55.8% females). Risk of malnutrition was observed in 594 (79.3%) patients. The rate of 30-day mortality was 8.8%. After adjusting for MEESSI-AHF risk score clinical categories (model 1) and after adding all variables showing a significantly different distribution among groups (model 2), the risk of malnutrition was an independent factor associated with 30-day mortality (adjusted OR by model 1=3.4; 95% CI 1.2–9.7; p=0.020 and adjusted OR by model 2=3.2; 95% CI 1.1–9.2; p=0.030) compared to normal nutritional status.

Conclusions
The risk of malnutrition assessed by the MNA-SF is associated with 30-day mortality in older patients attended with AHF in EDs. Routine screening of risk of malnutrition may help emergency physicians in decision-making and establishing a care plan.

Acknowledgement/Funding
Spanish Ministry of Health and FEDER (PI 18/00456, PI 18/00393, PI 17/00972, PI17/1732, PI15/00773, PI15/01019, and PI11/01021)
P4545ACUTE HF score: a new multi-parametric score for the prognostication of acute heart failure
Authors: Mandoli G E , De Carli G , Pastore M C , Rizzo L , Nannelli C , Lunghetti S , D'Ascenzi F , Focardi M , Valente S , Mondillo S , Cameli M 
Published: October 2019

Abstract

Background
Prognosis of patients with acute heart failure (AHF) and different etiologies remains a challenging issue for the Cardiologist.

Purpose
We aimed to evaluate clinical and echocardiographic indexes and blood tests values of patients admitted to Intensive Care Unit (ICU) for AHF to test their capability to predict events at short-, medium- and long-term follow-up.

Methods
We retrospectively enrolled 830 patients who entered the ICU of our third-level hospital between 2010 and 2013 for AHF. Exclusion criteria included: active malignances, heart transplantation, patients with left ventricular assist device. We evaluated in each subject: cause of admission, medical history, chest congestion severity at admission, blood tests, echocardiographic parameters and administered drugs during in-hospital stay. Primary endpoints included: mortality rate at 30 days, 6 months and 5 years after dismission, days of ICU stay and cardiology ward stay. Indexes with statistical significance at univariate analysis, were then tested by multivariate analysis.

Results
The study population (average age 72.2±13 y) had an ejection fraction (EF) 36±12% at ICU admission. Best predictors of prognosis in the populations, after multivariate analysis, resulted to be: renal failure, EF, age, mitral regurgitation (MR) more than mild, use of non-invasive ventilation support during ICU stay, previous stroke or transient ischemic attack (TIA). With these indexes, we created a multi-parametric prognostic score composed by: 0.7*[age >76 years] + 1.4*[plasmatic creatinine >2mg/dl] + 0.8*[non-invasive mechanical ventilation] + 0.9*[previous stroke/TIA] + 0.8*[EF <30%] + + 0.7*[previous hospitalization for AHF] + 0.5*[moderate/severe MR]. According to the score, we stratified the population in 3 tertiles with increasing mortality risk: low if <1.5, medium if 1.5–3, high risk if >3 (Figure 1). At ROC curve analysis, the score showed a greater prognostic accuracy than each parameter (30 days AUC 0.75, 6 months AUC 0.78, 5 years AUC 0.79).
Figure 1

Conclusions
A combined clinical, humoral and echocardiographic score could represent a new tool in the prognostication of patients with AHF since the admission in ICU.
P4551Prognostic utility of Palliative Prognostic Index for prediction of 30-day and 1-year outcome in patients with acute decompensated heart failure
Authors: Sumi T , Umemoto N , Kajiura H , Inoue S , Iio Y , Shibata N , Sugiura T , Taniguchi T , Asai T , Yamada M , Shimizu K , Murohara T 
Published: October 2019

Abstract

Background
The prognosis of heart failure remains poor similar to the terminal cancer patients, although recent progress in medical treatment. Palliative Prognostic Index (PPI) is a widely used prognostic index for terminal cancer patients (PPI includes: Palliative Performance Scale, oral intake, oedema, dyspnea at rest and delirium), suggesting the short-term prognostic marker of terminal cancer patients.

Purpose
The purpose of this study was to evaluate the impact of PPI on 30-day mortality, 1-year mortality and 1-year events (including all-cause mortality, readmission due to heart failure and new onset of cerebral infarction after hospital discharge) among acute decompensated heart failure (ADHF) patients.

Method
Study subjects comprised of consecutive 764 patients who admitted due to ADHF and followed up for 1-year. PPI were calculated at the time of hospital admission. Study subjects were divided into two groups based on the PPI: L-PPI (PPI<6) and H-PPI (6≤PPI). We calculated the C-index, net reclassification improvement (NRI) and the integrated discrimination improvement (IDI) to evaluate the improvement of prediction ability on 30-day mortality.

Result
H-PPI showed significantly higher 30-day mortality than L-PPI [7.9% vs 2.0%, log rank p<0.001, Hazard retio (HR): 1.26, 95% confidential interval(CI): 1.14–1.37, p<0.001], 1-year mortality [20.0% vs 12.7%, log rank p=0.022, HR 1.15, 95% CI 1.09–1.21, p<0.001]and 1-year events [45.5% vs 31.1%, log rank p<0.001, HR 1.13, 95% CI 1.09–1.17, p<0.001]. Multivariate cox proportional hazard models adjusted with several covariates revealed that PPI was an independent predictor of 30-day mortality (HR: 1.23, 95% CI: 1.10–1.36, p<0.001), 1-year mortality (HR: 1.10, 95% CI: 1.04–1.16, p<0.001) and 1-year events (HR: 1.11, 95% CI: 1.07–1.15, p<0.001), respectively.
A reference model for prediction of 30-day mortality was determined including left ventricular ejection fraction and serum albumin concentration by multivariable logistic regression analysis. (P<0.05) (C-index: 0.720) Adding PPI to the reference model (C-index: 0.773) significantly improved both NRI (0.458, p=0.038) and IDI (0.046, p=0.007), respectively.

Conclusion
We suggest that assessment of PPI showed good prognostic ability for 30-day and 1-year outcome, while PPI provided additional prognostic information in patients with ADHF.