bluuebunny/crossref_metadata_2025_split huggingface dataset:
P3445Subclinical myocardial dysfunction in pediatric kidney transplant recipients: a two-dimensional speckle-tracking echocardiography study
Authors: Lakatos B K , Barczi A , Cseprakal O , Szilagyi M , Kis E , Tokodi M , Szabo A , Reusz G Y , Kovacs A , Merkely B 
Published: October 2019

Abstract
Chronic kidney disease is associated with increased risk of cardiovascular mortality and morbidity in pediatric patients as well. Renal transplantation results in improved survival, however, several factors contribute to markedly elevated cardiovascular complication rate compared to the healthy population. While major cardiac events occur rarely in pediatric population, detection of subclinical changes in cardiac morphology and function may be of high interest to effectively identify high-risk patients.
Accordingly, our aim was to investigate left (LV)- and right ventricular (RV) morphology and function using conventional and two-dimensional (2D) speckle-tracking echocardiography (STE) in pediatric renal transplant recipients.
Our study group consisted of 41 kidney transplanted children (RTX; mean age: 14±3 years, m/f: 25/16) and 39 age- and gender matched healthy controls. Using 2D echocardiography, LV and RV focused apical loops were obtained and LV end-diastolic volume index (EDVi), ejection fraction (EF), mass index (Mi), RV end-diastolic area index (EDAi) and fractional area change (FAC) were measured. Using STE, we have determined LV global longitudinal (GLS) and circumferential strain (GCS), RV GLS, and LV and RV early diastolic longitudinal strain rate (LSrE).
LV EDVi did not differ between RTX and controls (51±13 vs. 52±10 mL/m2, p=NS), while LVMi was markedly higher in RTX patients (36±8 vs. 28±6 g/m2, p<0.0001). LVEF was comparable between the two groups (62±5 vs. 62±3%; p=NS), while LV GLS was significantly lower in RTX (−20.6±2.1 vs. −21.8±2.1%, p=0.01) along with a tendential increase in LV GCS (−31.6±4.3 vs. −29.7±4.6%, p=0.06). LV LSrE was significantly lower in RTX patients (1.29±0.29 vs. 1.45±0.27 1/s, p<0.05). RV EDAi did not differ between the two groups (11.2±2.3 vs. 11.6±2.0 cm2/m2, p=NS). Interestingly however, RTX patients had significantly higher RV FAC and RV GLS (FAC: 46±7 vs. 42±4%, GLS: −24.6±3.7 vs. −22.4±2.6%, both p<0.01) along with lower RV LSrE (1.32±0.57 vs. 1.60±0.43, p<0.05).
Cardiac morphology and function shows distinct changes after RTX. Along with comparable ventricular dimensions, LV hypertrophy and subclinical systolic and diastolic dysfunction is present. RV systolic function is relatively increased accompanied by subclinical diastolic dysfunction of the chamber, which may refer to previous RV overload. STE may be a useful tool to reveal early myocardial dysfunction in pediatric kidney transplant recipients.
P3451Female gender is an independent predictor of one-year mortality following primary angioplasty for ST-segment elevation myocardial infarction, regardless of age, clinical severity and frailty
Authors: Viana-Llamas M C , Silva-Obregon A , Arroyo Espliguero R , Estrella-Alonso A , Saboya-Sanchez S , Uribe-Heredia G , Garcia-Magallon B , Toran-Martinez C , Castillo-Sandoval A , Eguileor-Marin Z , Arriero-Fernandez N , Marian-Crespo C 
Published: October 2019

Abstract

Background
Gender-based differences in mortality of patients with ST-segment elevation myocardial infarction (STEMI) have been reported. However, controversy exists about the impact of female gender on mortality after correcting for baseline risk differences.

Purpose
Assess gender-based mortality in a cohort of STEMI patients following primary angioplasty.

Methods
Retrospective cohort of 427 consecutive STEMI patients (64 years [55–75]; 78% men) admitted to a general ICU between November-2013 and February-2017. We used Kaplan-Meier and Cox regression models for survival analysis. The Clinical Frailty Scale (CFS) was used to assess frailty.

Results
Women were older and had a higher GRACE 2.0 and frailty (CFS≥4). Women had lower creatine-phosphokinase and albumin levels and higher B-natriuretic peptide levels, despite the lack of gender-based differences in left ventricular ejection fraction (LVEF) and MI size and location. One-year mortality rate was higher in women, most often from cardiogenic shock during admission and at 30-day follow-up (Table). After Cox regression analysis, women had a 2.23-fold higher risk of one-year mortality compared with men (Figure), independently of age, frailty, GRACE 2.0, LVEF and inotropic agents requirements.
Baseline characteristics Women (n=93) Men (n=334) P value One-year mortality, n (%) 15 (16.1) 15 (4.5) <0.001 Cardiogenic shock, n (%) 10 (62.5) 6 (37.5) <0.001 Age (years) 70.8 [51.2–80.3] 61.9 [54.2–71.8] <0.001 Hypertension, n (%) 54 (58.1) 149 (44.6) 0.022 GRACE 2.0 129 [104.5–156] 112 [94–139] 0.001 Clinical Frailty Scale≥4, n (%) 28 (30.1) 32 (9.6) <0.001 MI location (anterior), n (%) 42 (45.2) 152 (45.5) 0.953 Creatin-phosphokinase (UI/L) 1040 [300.5–2134] 1517 [620.5–2852.8] 0.004 High-sensitivity troponin I (pg/mL) 4003 [62.1–48526.6] 9070 [65.8–65893] 0.473 Left ventricular ejection fraction (%) 52 [40–60] 55 [45–60] 0.465 B-natriuretic peptide (pg/mL) 241.1 [99.9–896.9] 103.6 [28.3–259.2] <0.001 Albumin (g/L) 36.1 [34.3–38.5] 38.4 [35.6–40.5] <0.001 Inotropic agents, n (%) 14 (15.1) 26 (7.8) 0.033
Kaplan-Meier and Cox survival curves.

Conclusions
Female gender is an independent predictor of one-year mortality in STEMI patients, regardless of age, clinical severity and frailty. A potential myocardial disfunction probably mediated by an increased frailty, may play a role in the high mortality rate among women after STEMI.
P3465Inducible left ventricular outflow tract obstruction is associated with a higher incidence of perioperative cardiac arrest in liver transplantation
Authors: Cailes B , Koshy A N , Han H , Sajeev J K , Ko J , Weinberg L , Gow P , Testro A , Srivastava P , Lim H , Teh A , Farouque O 
Published: October 2019

Abstract

Background
Inducible left ventricular outflow tract obstruction (LVOTO) is not infrequently encountered in liver transplant (LT) candidates undergoing cardiac workup. While the impact of LVOTO on adverse cardiovascular haemodynamics is well reported, it is unclear whether it predisposes to perioperative cardiovascular complications following LT.

Purpose
To investigate the effect of inducible left ventricular outflow tract obstruction on perioperative cardiovascular complications in a modern cohort of liver transplant patients.

Methods
Consecutive patients undergoing dobutamine stress echocardiography (DSE) were evaluated from a quaternary LT centre between 2010 and 2017. Inducible LVOTO was defined as LVOT gradient ≥36mmHg. Perioperative major adverse cardiovascular events (MACE) at 30 days and all-cause death were recorded from a prospectively maintained transplantation database and augmented by electronic medical record review.

Results
We evaluated 560 patients who underwent DSE as part of a workup for LT. Of these, 319 progressed to transplant. Inducible LVOTO was observed in 68 patients (21.3%). A higher baseline cardiac output (7.7 L/min vs 7.0 L/min, p=0.002) predicted for development of inducible LVOTO. Seventy-seven patients (4.1%) experienced a MACE including five deaths, 19 cases of heart failure, 11 cardiac arrests, 10 acute coronary syndromes and 46 cases of arrhythmias (VT/AF). Overall MACE occurred in 17/68 patients (25.0%) with LVOTO and 60/251 patients (23.9%) without LVOTO (p=0.85). However, there was a significantly increased risk of resuscitated perioperative cardiac arrest in patients with LVOTO (7.4% vs 2.4%, p=0.04). Patients with LVOTO also required significantly greater volumes of fluid intra-operatively (8.37L vs. 6.71L, p=0.043).
Cardiac Arrest in LT Patients with LVOTO

Conclusions
Inducible LVOTO is a frequent finding occurring in 21.3% of LT candidates. Despite higher intraoperative fluid resuscitation, LVOTO increased the risk of a perioperative cardiac arrest. Further studies are required to confirm these findings and to assess whether patients with LVOTO undergoing liver transplantation may benefit from heightened perioperative surveillance.
P3470Comparative effectiveness and safety of non-vitamin K oral anticoagulants and warfarin in non-valvular atrial fibrillation - a cohort study in 3 Nordic countries
Authors: Johnsen S , Madsen M , Linder M , Sulo G , Ghanima W , Gislason G , Halvorsen S , Hohnloser S H , Jenkins A , Al-Khalili F , Tell G S , Ehrenstein V 
Published: October 2019

Abstract

Background
Non-vitamin K oral anticoagulants (NOACs) are an alternative to warfarin in the prevention of stroke in non-valvular atrial fibrillation (NVAF). Nordic countries have high quality of warfarin treatment, making them an especially suitable setting for assessing effectiveness and safety of NOACs against warfarin.

Purpose
The BEYOND Pooled (BEnefit of NOACs studY of nOn-valvular AF patieNts in NorDic countries) study compared risks of ischaemic or haemorrhagic stroke/systemic embolism (S/SE), and risk of bleeding with acute hospitalisation with an overnight stay (bleeding) in NVAF patients treated with apixaban, dabigatran or rivaroxaban, each compared with warfarin treatment.

Methods
A cohort study of treatment-naïve adult NVAF patients dispensed apixaban, dabigatran, rivaroxaban or warfarin was identified from 01 Jan 2013 to 31 Dec 2016. The population and study variables were identified from national registries in Denmark, Norway and Sweden. After 1:1 propensity score (PS) matching for each NOAC-warfarin comparison, individual-level data were pooled across the countries. Cox proportional-hazards regression was used to estimate adjusted hazard ratios (aHRs) of the endpoints.

Results
PS matched NOAC cohort sizes were: apixaban (55,696) dabigatran (28,526) and rivaroxaban (30,701), and the total follow-up in the PS-matched population was 291,171 years (mean 1.3 years). During the follow-up, 35,450 oral anticoagulation (OAC) patients had a S/SE and 38,620 OAC patients had bleeding. Adjusted HRs for the two endpoints are presented in the table. PH assumption has not been formally tested but cum incidence curves did not indicate substantial differences in the effects over time.
Table 1. Adjusted hazard ratios (aHR) of stroke/systemic embolism and bleeding for non-vitamin K oral anticoagulants versus warfarin Endpoint Apixaban vs Warfarin: aHR (95% CI) Dabigatran vs Warfarin: aHR (95% CI) Rivaroxaban vs Warfarin: aHR (95% CI) Stroke/SE 0.93 (0.85–1.03) 0.89 (0.80–1.00) 0.97 (0.88–1.08) Bleeding 0.72 (0.67–0.77) 0.87 (0.80–0.95) 1.12 (1.04–1.20)

Conclusions
Relative to warfarin, apixaban and dabigatran were associated with lower rates of bleeding whereas rivaroxaban was associated with a higher rate. The three NOACs had comparable rates of stroke and systemic embolism relative to warfarin.

Acknowledgement/Funding
This study was funded by the Pfizer/Bristol-Myers Squibb Alliance.
P3483Diet governs metabolic and electrical properties of the atrial myocardium in mice
Authors: Baptista E , Doisne N , Piquereau J , Ichou F , Lhomme M , Pichard C , Galand V , Mougeneot N , Suffee-Mosbah N , Le Goff W , Meriskay M , Hatem S N 
Published: October 2019

Abstract

Background
Obesity is associated with an increased risk of atrial fibrillation. This epidemiologic observation may not only be due to shared co-morbidities but also from direct impacts of metabolic disorders on myocardium Here, we examined the impact of high fat diet (HFD) induced obesity on atrial properties in mice.

Methods
Eight weeks old C57Bl/6J mice were subjected to 2 or 4 months of HFD (60% fat) or normal diet (ND, 4% fat). Rapid burst atrial pacing were delivered using a trans-esophageal probe to induced AF in anesthetized animals. Action potential (AP) were recorded in left atrial trabeculae using glass microelectrode technique. Potassium currents were recorded in isolated atrial myocytes using the whole cell or perforated patch clamp configurations. Metabolomic and lipidomic analysis were performed on whole left atria. Mitochondrial respiration was studied in situ in saponin-permeabilized atrial muscle fibres using a Clarke electrode and oxygen consumption was measured after successive addition of ADP (2 mM), malate (4 mM), palmitoyl-CoA and carnitine (pCoA-Ca) (100 μM and 2 mM), pyruvate (1 mM), glutamate (10 mM), succinate (15 mM), amytal (1 mM) and tetramethyl-paraphenylenediamine (TMPD)/ascorbate (0.5/0.5 mM).

Results
HFD mice showed a higher atrial vulnerability to AF as indicated by longer AF episodes compared to ND mice. APs were shorter in HFD versus ND mice (AP duration measured at 90% of repolarization: 47.9±2.4 msec in HFD vs 58.2±1.4 msec in ND, P<0.001 after 2 months of HFD) and more sensitive to the K ATP channel blocker, glibenclamide. In perforated but not whole cell, patch clamped atrial myocytes, the K-ATP component of the potassium current was enhanced in HFD mice (at +70 mV: 0.41±0.12 pA/pF in HFD vs 0.13±0.08 pA/pF in ND, P<0.05). Metabolomic analysis indicated an increased consumption of free fatty acid by the beta-oxidation and an accumulation of long chain fatty acid. Although the mitochondrial respiration measurements showed a trend towards a lower complex IV-driven respiration in HFD mice, no significant difference between ND and HFD was noted regarding complex I and complex II-driven respiration. However, the ability of fatty acids (pCoA-Car) to support mitochondrial respiration was higher in HFD

Conclusions
High fat diet induces a shift from carbon hydrate to a beta oxidation of the atrial myocardium metabolism together with an enhanced use of fatty acids by mitochondria. These metabolic changes could result in an enhanced activity of K-ATP channels and AP shortening that might contribute to AF vulnerability in this clinical setting.

Acknowledgement/Funding
ANR-10-IAHU-05
P3485Autophagy insufficiency participates in hyperhomocysteinemia-induced cardiac aging
Authors: Wang W , Zhou Y , Xu J , Zhang S , Meng Y 
Published: October 2019

Abstract

Background
The elevated plasma homocysteine (Hcy) level can lead to severe cardiovascular injuries, which participates in the progression of atherosclerosis, heart failure and so on. Except cardiovascular diseases, accumulated researches further revealed that hyperhomocystenemia (HHcy) can also induce aging-related diseases, including Alzheimer's disease, Parkinson's disease, diabetic cardiomyopathy, etc. Though some researches had revealed that Hcy stimulation would lead to endothelial cells senescence, whether cardiac aging could be induced by HHcy still remain unknown.

Purpose
This study aimed to reveal whether HHcy can induce cardiac aging and the underlying mechanisms.

Methods
SD rats were utilized to establish HHcy rat model and natural aging rat model. The cardiac function were determined by Echocardiography. Transmission electron microscope were used to detect mitochondria injuries of myocardium. 18F-FDG PET/CT was used to detect the state of glucose metabolism in myocardial cells. Agilent mRNA Array was used to detect possible altered pathways in myocardium of HHcy rats. The autophagy level was determined by detection of both autophagy-related proteins expressions with Western Blot and autophagic flux with mRFP-GFP-LC3.

Results
HHcy rats showed overall aging phenotypes, which were consistent with natural aging rats. The impaired cardiac function and severely injured myocardium morphology were observed in HHcy rats. Aging-related markers were increased significantly in HHcy rats and Hcy-treated cells, presented as increased p16, p21 and p53 expressions and increased senescence-associated beta-galactosidase (SA-β-gal) activity. Mitochondria dysfunction and morphology injuries were also detected in HHcy rats. Moreover, decreased serum Beclin-1 level was tested in CHD patients with HHcy. The decreased autophagy level was further verified in HHcy rats and Hcy-treated cells. Furthermore, the over-expression of Atg5 could attenuate Hcy induced cellular senescence.

Conclusion
HHcy can reduce autophagy level, which leading to severe mitochondria injuries, and resulted in cardiac aging eventually.

Acknowledgement/Funding
Natural Science Foundation of China (81671382,91839107)
P3487Pre-ischemic succinate dehydrogenase inhibition is protective against ischemia-reperfusion injury in rat and human myocardium with and without diabetes mellitus
Authors: Jespersen N R , Hjortbak M V , Lassen T R , Stoettrup N B , Johnsen J , Tonnesen P T , Larsen S , Kimose H H , Boetker H E 
Published: October 2019

Abstract

Background
Ischemia-reperfusion (IR) injury can be attenuated through modulation of mitochondrial metabolism with succinate dehydrogenase (SDH) inhibition by dimethyl malonate (DiMAL). However, it is unknown whether SDH inhibition yields protection in aged, diabetic individuals and whether protection translate into human cardiac tissue.

Purpose
We wished to evaluate if SDH inhibition can be protective in aged, diabetic rat hearts and could be translated to the human myocardium.

Methods
We studied infarct size in aged non-diabetic and diabetic rat hearts subjected to isolated, retrograde perfusion and global ischemia and reperfusion. The hearts were randomized to: Sham hearts, IR injured hearts and IR injured hearts co-perfused with 0.1 mM or 0.6 mM DiMAL. Infarct size and mitochondrial respiratory capacity were evaluated post-ischemic. To translate our findings into human cardiac tissue, we tested the efficacy of DiMAL treatment in human atrial trabeculae from patients with and without diabetes mellitus undergoing cardiac surgery. We randomized atrial trabeculae to: IR injury, IR injury treated with ischemic preconditioning (IPC) and IR injury treated with 5 mM DiMAL. Contractile force recovery and mitochondrial respiratory capacity were evaluated post-ischemic.

Results
In non-diabetic rat hearts, DiMAL 0.1 mM reduced infarct size/area-at-risk (IS/AAR) compared to IR hearts (53±7% vs. 69±6% of IS/AAR; p<0.05). In diabetic hearts, an increased concentration of 0.6 mM DiMAL was required to confer protection (62±13% vs. 80±8% of IS/AAR; p<0.05). Mitochondrial complex I linked respiratory capacity was higher in both Sham and DiMAL 0.1 mM groups than with DiMAL 0.6 mM in non-diabetic hearts (157.4±26.5 and 140.0±35.3 vs. 81.8±42.4 pmol O2/(s*mg); p<0.01 and p<0.05). In trabeculae from humans without diabetes mellitus, IPC and DiMAL improved contractile force recovery compared to IR (43±12% and 43±13% vs. 23±13%, p<0.05). In trabeculae from patients with diabetes, IPC but not DiMAL administration improved contractile force recovery compared to IR (48±16% and 19±7% vs. 25±13%, p<0.01 and p>0.99). Mitochondrial complex I linked respiration capacity did not improve by IPC or DiMAL compared to IR in non-diabetic trabeculae (p>0.99).

Conclusion
Inhibition of the SDH by DiMAL protects the aged non-diabetic and diabetic heart from IR injury but the threshold for cardioprotection is increased in diabetic rat hearts. DiMAL provides cardioprotection similar to IPC in non-diabetic trabeculae but does not protect the human diabetic myocardium when given in identical concentrations. SDH inhibition can provide protection in both animal and human tissue and may provide a new target for pharmacologic conditioning in patients.
P3489Endothelial adenosine-to-inosine RNA editing is indispensable for vascular integrity
Authors: Tual-Chalot S , Bonini F , Vlachogiannis N I , Doddaballapur A , Shook K , Gatsiou A , Stellos K 
Published: October 2019

Abstract

Background
Adenosine (A)-to-inosine (I) RNA editing is a powerful upstream regulator of double-stranded RNA (dsRNA) metabolism, its role however in tissue homeostasis remains poorly understood. We have recently reported that RNA editing is dysregulated in human atherosclerotic heart disease, although its role in the maintenance of endothelial cell (EC) function is unknown.

Purpose
The goal of the present study is to evaluate the role of EC-specific ADAR1 in vascular homeostasis in vivo.

Methods
Constitutional or inducible EC restricted ADAR1 ablation was achieved by crossing mice carrying a conditional (floxed) ADAR1 allele with either a Tie2-Cre or with a tamoxifen-inducible Cdh5-CreERT2 mouse line. EC function was assessed by the postnatal retinal angiogenesis model and barrier function assays and immunohistochemistry of lung and liver tissues. Cell culture assays, gene-silencing techniques, RT-qPCR, western blot and confocal microscopy were utilized to assess the ADAR1 effects in intracellular endothelial signalling.

Results
Constitutive endothelial ADAR1 ablation caused prenatal lethality at embryonic stage E13.5, demonstrating an essential role for endothelial ADAR1 in development. Postnatal ADAR1 ablation resulted in reduced vascular outgrowth, reduced vessel branching in the central vascular plexus and decreased filopodial protrusions from ECs at the angiogenic front of the vascular plexus compared with littermate control mice at P5. Furthermore, endothelial ADAR1 ablation in adult mice resulted in sudden death within 6–8 days after activation of Cre recombinase due to development of severe pleural effusions caused by widespread vascular leakage, indicating a disturbance of EC barrier function in lung microvasculature. Mechanistically, ADAR1-mediated RNA editing is essential for the metabolism of endogenous long-to-short dsRNAs, while silencing of endothelial ADAR1 resulted in accumulation of cytoplasmic long dsRNAs. Long dsRNAs are recognised as a danger-associated molecular pattern by the cytosolic innate immune sensing and signalling sensors. Consequently, the cytoplasmic accumulation of endogenous long dsRNAs resulted in activation of innate immune system in ECs, as assessed by the induction of interferon-β. Concomitantly, activation of the cytoplasmic dsRNA sensors resulted in dissociation of beta-catenin from VE-cadherin in EC junctions and endocytosis of VE-cadherin.

Conclusion
ADAR1-mediated RNA editing of long dsRNAs is essential for the long-to-short dsRNA metabolism and thus suppression of endogenous innate immune sensing and signalling. EC-restricted ADAR1 ablation results in embryonic lethality, impaired retinal angiogenesis at P5 and sudden death in adult mice due to pleural effusions, which all indicate that ADAR1-mediated RNA editing is indispensable for maintenance of vascular barrier integrity.