bluuebunny/crossref_metadata_2025_split huggingface dataset:
P4647Next generation sequencing in 83 fetal left-sided CHDs reveals the entire genetic architecture of left-sided CHDs in fetal population
Authors: Sun H R , Hao X Y , Yi T , Gu X Y , He Y H 
Published: October 2019

Abstract

Background
No data is available for the contribution of single gene disorders (SGDs) to left-sided congenital heart defects (LSCHDs) in the fetal population.

Purpose
The aim of this study was to explore the entire genetic architecture of LSCHDs, especially the contribution of SGDs in a cohort of fetal LSCHDs.

Methods
Low-pass whole genome sequencing (WGS) and whole exome sequencing (WES) were performed on specimens from 83 deceased fetuses with lSCHDs, including 48 HLHS, 22 CoA, 5 AS, 3 AAH, 2 AS+CoA and 1 case of AA, AS+MS, MA. Sequencing was predominantly performed in fetus-parent trios (n=63, 75.9%), or in fetus only (n=20, 24.1%).

Results
34.9% (n=29) of the 83 fetal left-sided CHDs were identified with related genetic abnormalities. WGS analysis identified 14 (16.9%) with chromosomal abnormalities, including 6 (7.2%) aneuploidies and 8 (9.6%) pathogenic copy number variants (CNVs). WES analysis of the remaining 69 cases without chromosomal abnormalities identified 15 (15/69, 21.7%) with pathogenic/likely pathogenic variants. Of these 15 cases, KMT2D was the most frequently mutated gene (7/69, 10.1%), followed by NOTCH1 (4/69, 2.5%). Compound heterozygosity was identified in 3 genes (DNAH11, POFUT1, CRB2) that are not yet well established as CHD genes. Finally, we also observed a LOF variant in NONO (X-linked) that was maternally transmitted to an affected male case.
The genetic results of this cohort Aneuploidies Trisomy 18 4 Turner syndrome 2 CNVs 11q terminal deletion 3 1p36 deletion 1 15q terminal deletion 1 7q11.23 deletion 1 4p terminal deletion 1 12q complex internal duplication 1 SGDs AD (KMT2D = 7; NOTCH1 = 4) 11 AR (DNAH11, POFUT1, CRB2) 3 X-recessive (NONO) 1 AD: autosomal dominant; AR: autosomal recessive.

Conclusions
Our experience supports that SGDs contribute a significant part to the pathogenesis of fetal CHDs, WES has the potential to provide molecular diagnoses in fetal left-sided CHDs without chromosomal abnormalities. KMT2D mutations accounted for a large fraction of left-sided CHDs in fetal population. If the KMT2D mutation is detected, further diagnosis of Kabuki syndrome should be considered.
P4730Underweight is associated with unfavourable short- and long-term outcomes after MitraClip therapy: a body mass index derived subgroup analysis of the German Transcatheter Mitral Valve Interventions (
Authors: Kalbacher D , Tigges E P , Boekstegers P , Puls M , Plicht B , Eggebrecht H , Nickenig G , Von Bardeleben R S , Zuern C S , Franke J , Sievert H , Ouarrak T , Senges J , Lubos E 
Published: October 2019

Abstract

Background
Underweight and obesity represent classical risk factors for patients undergoing cardiac surgery or interventional treatment. The multicentre German Transcatheter Mitral Valve Interventions (TRAMI) registry comprises a large and prospectively enrolled real-world cohort of patients treated by MitraClip implantation.

Aims
The current analysis examines the impact of underweight, overweight and obesity on intra-hospital, short and long-term outcomes in patients treated by MitraClip therapy.

Methods and results
From 08/2010 until 07/2013, 799 patients (age 75.3±8.6 years, male gender 60.7%, median logistic EuroSCORE 20% [12; 31], functional mitral regurgitation (MR): 69.3%) were prospectively enrolled into the multicentre, industry-independent German Transcatheter Mitral Valve Interventions registry. Patients were stratified according to body mass index (BMI) into four groups: BMI<20 kg/m2 (underweight, n=49), BMI 20.0 to <25.0 kg/m2 (normal weight, n=293), BMI 25.0 to <30.0 kg/m2 (overweight, n=296) and BMI≥30 kg/m2 (obese, n=132). Procedure and radiation time were comparable among all groups. Significant increased rates of procedural failure (12.2% vs. 2.1 [normal weight], p<0.001), transfusion/bleeding (20.8% vs. normal weight: 5.6%, obesity: 7.0%, p<0.01), sepsis or multiorgan failure and low cardiac output failure were found for underweight patients only. Kaplan-Meier survival curves demonstrated inferior survival for underweight patients, but comparable outcomes for all other patients (global log rank test, p<0.01). Multivariable Cox-regression analysis (adjusted for age, gender, creatinine≥1.5mg/dl, diabetes, left ventricular ejection fraction<30% and chronic obstructive pulmonary disease) confirmed underweight (as compared to normal weight) as an independent risk factor of death (hazard ratio [HR]: 1.58, 95%-confidence interval (CI): 1.01–2.46, p=0.044) and overweight as protective against death (HR: 0.71; 95%-CI: 0.55–0.93; p=0.011).

Conclusion
Underweight patients are exposed to increased rates of procedural failure, bleeding and low cardiac output as well as increased short- and long-term mortality rates when undergoing MitraClip implantation and should therefore be carefully discussed within the heart team.

Acknowledgement/Funding
The TRAMI registry has been supported by proprietary means of IHF. Additional funding is provided by “Deutsche Herzstiftung” and a grant from Abbott.
P4735Preoperative frailty is a predictor of worse in-hospital outcomes after coronary artery bypass graft surgery and improves the predictive accuracy of EUROSCORE I and II
Authors: Rosler A , Constantin G , Nectoux P R , Borges D , Fraportti J , Pontes M R N , Dal Lago P , Lucchese F A 
Published: October 2019

Abstract

Introduction
Although coronary artery bypass grafting (CABG) is the most widely performed cardiovascular procedure in the world and is the standard treatment for complex coronary artery disease, the risk prediction for the procedure has major gaps. In this context, preoperative frailty may have a relevant role in the prediction of surgical risk.

Purpose
Our goal was to evaluate the impact of frailty on in-hospital outcomes after CABG and verify if any other comorbidity enhances the effects of fragility.

Methods
Prospective cohort of patients submitted consecutively to isolated CABG between Jan/2013 and Dec/2017. Frailty was defined as any deficiency in the Katz Index. Of the 1508 patients, 126 (8.4%) were classified as frail. Baseline characteristics and outcomes were compared by univariate analysis. Multivariate regression models were applied for the adjusted analysis of outcomes. The predictive accuracy of the regression models were analyzed using ROC curves. The additional predictive accuracy of the frailty and other risk variables were evaluated by comparing the ROC curves with the DeLong test.

Results
The frail patients presented more advanced age, more comorbidities and the majority were female. Frailty was an independent predictor for in-hospital mortality (OR 5.55, p=0.002) and MACCE (OR 5.60, p=0.001). In addition, by means of an adjusted analysis, we identified that the frailty was associated with a longer time of hospitalization (B 4.61, 95% CI 2.12–7.10, p<0.001). We also identified that preoperative anemia was classified as an independent predictor for hospital mortality and MACCE and improved the effect of frailty on outcomes. In this way, we could verify that when associated with surgical risk scores, frailty and anemia significantly improved the predictive accuracy of EuroScore 1 and EuroScore 2 for in-hospital mortality.
Predictive accuracies

Conclusions
Frailty and preoperative anemia are independent predictors of hospital mortality and MACCE after CABG. Frailty was also a predictor of longer hospitalization time. The association of frailty and anemia with surgical risk scores resulted in a significant improvement in the predictive accuracy of the scores. Frailty screening by Katz Index improved the risk assessment for isolated CABG and, when associated with anemia, demonstrated that frail and anemic patients had worse surgical outcomes.

Acknowledgement/Funding
The development of the present study was funded entirely by the Institution itself.
P4739Novel tissue-engineered heart valve without any foreign materials
Authors: Takewa Y , Nakayama Y , Shimamura J , Katagiri N , Tatsumi E 
Published: October 2019

Abstract

Background
We are developing a novel autologous tissue-engineered heart valve with a unique in-body tissue engineering. This is expected to be a viable bioprosthesis keeping better biocompatibility.

Purpose
We developed a conduit-type valve without any foreign materials and tested the feasibility and long-term availability in large animal experiments.

Methods
We created plastic molds for Biovalves with 3D printer easily and quickly considering the recipient character. We embedded them in the subcutaneous spaces of adult goats about 2 months. After extracting the molds with the tissue en-block and removing the plastic molds only, Biovalve with tri-leaflets similar to those of the native valves were constituted from completely autologous connective tissues and fibroblasts. Total 21 conduit-type Biovalves were implanted in the apico-aortic bypass or the pulmonary artery of goats, (8 and 13, respectively). No anticoagurants were used after implantation.

Results
The valves were successfully implanted and showed smooth movement of the leaflets with a little regurgitation in angiogram, and the maximum duration reached to 3 years 7 months. Histological examination of the Biovalves showed the autologous cells covering the laminar surface of the valve leaflets as the endothelium and also getting inside to construct characteristic tissues like native leaflets.

Conclusion
The valves have a potential to be used for viable bioprosthetic valves and to keep better function and biocompatibility longer than current ones.
P4740Clinical predictors of graft occlusion after coronary artery bypass grafting: a case-control study
Authors: Cheng Y J , Ma X T , Zhou Y J , Zhao Y X , Liu X L , Ma Y , Liu F , Sun Y , Zhang D 
Published: October 2019

Abstract

Objective
Coronary artery bypass grafting (CABG) is still one of the most common surgical procedures aimed at improving blood circulation in atherosclerotic coronary arteries.Graft occlusion influences outcome CABG. The risk factors of long-term graft occlusion remain uncertain.The aim of the present study was to investigate the clinical predictors of graft occlusion after CABG.

Methods
All patients with prior CABG in our center who underwent coronary computed tomography angiography (CTA) and/or percutaneous coronary angiography for follow-up between Aug 2013 and Dec 2017 were included in the present study. We excluded patients who underwent multiple CABG surgeries or percutaneous coronary intervention after index CABG. With regard to one patient with two or more different angiography results, we selected the angiography result which showed graft occlusion for the first time or the last angiography result. The baseline clinical data at index CABG was analyzed for their independent impact on graft occlusion in a case-control study using multivariate logistic regression.

Results
1178 (27.5%) of 4289 patients experienced at least one graft occlusion. The mean age was 63.23±9.02 years, 1004 (23.4%) patients were female. From all the occlusion cases, artery occlusion occurred in 337 (28.6%) patients and saphenous vein graft occlusion occurred in 875 (74.3%) patients.Complete baseline data was available for evaluation from 1178 of them (case group). We matched these patients through gender, age and time interval between the index CABG and angiography/CTA to another 1178 patients who did not have graft occlusion (control group). After multivariate logistic regression, chronic renal dysfunction (OR=1.008; 95% CI, 1.001–1.021; P=0.038) hyperuricemia (OR=1.89; 95% CI, 1.101–3.876; P=0.040) and hyperlipemia (with low density lipoprotein increased) (OR=1.377; 95% CI, 1.021–1.926; P=0.042) significantly increased the risk of long-term graft occlusion.

Conclusions
Chronic renal dysfunction hyperurcemia and hyperlipemia were independent risk factors of long-term graft occlusion.

Acknowledgement/Funding
National Key Research and Development Program of China (2017YFC0908800)
P4765Men who live alone have poor anticoagulation control: results from Danish registries
Authors: Bonde A N , Bjerre J , Proietti M , Gislason G , Lip G Y H , Hlatky M 
Published: October 2019

Abstract

Background
Efficacy and safety of vitamin K antagonists (VKAs) depend on quality of anticoagulation control, usually measured as time in therapeutic range (TTR). Factors that predict low TTR on VKAs could be used to identify patients who might benefit from interventions, or who would be better treated with a non-VKA oral anticoagulant (NOAC). Patients living alone may have difficulties in taking their medications, managing their diets, or coming to clinic for monitoring.

Purpose
To assess influence of cohabitation status on TTR with VKA among men and women.

Methods
We identified all Danish patients with atrial fibrillation (AF) who initiated VKA between 1997 and 2012, and studied patients who had 6 months of continuous VKA use and international normalized ratio (INR) monitoring. Patients were divided according to sex and whether they lived alone or with others. We calculated TTR using the Rosendaal method, and INR variability using Fihns method. We used a linear regression model to test for associations between TTR and covariates, and adjusted for age, income, medications and comorbidities.

Results
We identified 4,772 AF patients with 6 months of continuous VKA use and INR monitoring. 713 (15%) were men living alone, 1,073 (23%) were women living alone, 2,164 (45%) were men not living alone and 822 (17%) were women not living alone. INR was measured a median of 11 (interquartile range 8–15) times during the 180 days of VKA use, but men who lived alone had 0.6 (95% confidence interval (CI): 0.2 to 1.2) fewer INR measurements during the period. Median TTR was lowest among men living alone (57.2%), followed by women living alone (58.8%), women not living alone (61.0%) and men not living alone (62.5%). After multivariable adjustment, men who lived alone had a 3.6% (CI −5.6 to −1.6) lower TTR compared with men not living alone, but women who lived alone did not have significantly lower TTR (P=0.80) compared with women not living alone. Living alone had significantly greater effect on TTR among men than among women (interaction P=0.02). Men living alone also had higher adjusted INR variability (0.2, CI 0.0 to 0.4) compared with men not living alone.

Conclusion
Living alone was significantly related to low quality of anticoagulation control among men, but not among women.

Acknowledgement/Funding
this study was funded by an unrestricted grant from the Capital Region of Denmark, Foundation for Health Research
P4780Effectiveness and safety of non-vitamin k antagonist oral anticoagulants in patients with atrial fibrillation and valvular heart disease
Authors: Moon I K , Lee S R , Choi E K , Lee E J , Jung J H , Han K D , Cha M J , Oh S I , Lip G Y H 
Published: October 2019

Abstract

Background
Patients with atrial fibrillation (AF) often have concomitant valvular heart disease (VHD), especially in Asia. There are limited data on non-vitamin K antagonist oral anticoagulants (NOAC) impact on outcomes for stroke prevention and bleeding for these patients in real world clinical practice.

Purpose
To investigate the effectiveness and safety of NOACs compared with warfarin in patients with AF and associated Evaluated Heartvalves, Rheumatic or Artificial (EHRA) type 2 VHD.

Methods
We identified oral anticoagulants naive patients with AF and EHRA type 2 VHD from the Korean National Health Insurance Service database between 2014 and 2016 (n=2,671 taking warfarin; n=3,058 taking NOAC). Six clinical outcomes including ischemic stroke, intracranial hemorrhage (ICH), gastrointestinal bleeding (GI), major bleeding, all-cause death, and their composite outcome and fatal clinical events (any events that led to death within 30-day of its occurrence) were evaluated. Inverse probability of treatment weighting (IPTW) method was used to balance covariates between the two groups.

Results
After weighted using 5% trimmed IPTW method (n=2371 taking warfarin; n=2792 taking NOAC), the mean age was 71.2 years, male was 57% and CHA2DS2-VASc score was 3.9. During a mean 1.4-year follow-up, weighted incidence rate of ischemic stroke, ICH, GI bleeding, and all-cause death were lower in the NOAC group than in the warfarin group. Compared to warfarin, NOACs were associated with lower risks of ischemic stroke (hazard ratio [HR] 0.71, 95% confidence interval [CI] 0.53–0.96), GI bleeding (HR 0.50, 95% CI 0.35–0.72) and major bleeding (HR 0.61, 95% CI 0.45–0.80). Although NOAC and warfarin groups showed similar incidence rate of ICH, NOAC group was associated with a significantly lower risk of fatal ICH compared to warfarin group (HR 0.28, 95% CI 0.07–0.83). Overall, NOACs were associated with a lower risk of the composite outcome (HR 0.68, 95% CI 0.58–0.80). For an exploratory analysis, patients with EHRA type 1 VHD (n=366 taking warfarin; n=345 taking NOAC) was evaluated. In multivariable Cox regression analysis, NOAC group showed a comparable risk of ischemic stroke, ICH, all-cause death and composite outcome.
Clinical outcome in AF patients with VHD

Conclusion
In this nationwide Asian AF population with EHRA type 2 VHD, NOAC use was associated with lower risks of ischemic stroke, major bleeding, all-cause death, and the composite outcome compared to warfarin.
P4799Long-term thromboembolic risk in patients with postoperative atrial fibrillation after left-sided heart valve surgery
Authors: Butt J H , Olesen J B , Gundlund A , Olsen P S , Havers-Borgersen E , Aagaard D T , Gislason G H , Torp-Pedersen C , Kober L , Fosbol E L 
Published: October 2019

Abstract

Background
New-onset postoperative atrial fibrillation (POAF) is a common complication of cardiac surgery. However, data on the long-term risk of thromboembolism in patients who develop POAF after heart valve surgery are sparse. In addition, data on stroke prophylaxis in this setting are lacking.

Objective
To assess the long-term risk of thromboembolism in patients developing new-onset POAF following isolated left-sided heart valve surgery relative to patients with nonsurgical, nonvalvular atrial fibrillation (NVAF).

Methods
Using data from the Eastern Danish Heart Surgery Database and Danish nationwide registries, we identified patients who developed POAF following isolated left-sided heart valve surgery (i.e. biologic aortic/mitral valve replacement or aortic/mitral valve repair) from 2000 through 2015. These patients were matched with patients with nonsurgical NVAF in a 1:4 ratio by age, sex, heart failure, hypertension, diabetes, a history of thromboembolism, ischemic heart disease, and year of diagnosis. Long-term risk of thromboembolism was examined by the Aalen-Johansen estimator and cause-specific Cox regression models adjusted for comorbidities, concomitant pharmacotherapy, and oral anticoagulation therapy as a time-dependent covariate.

Results
A total of 1,539 patients undergoing isolated left-sided heart valve surgery were identified. Of these, 716 (46.5%) patients developed POAF after surgery. A total of 630 patients with POAF were matched with 2,520 patients with NVAF. In the matched study population, the median age was 71 years (25th-75th percentile 66–77 years) and 59.5% were men. Oral anticoagulation therapy was initiated within 30 days post-discharge in 62.7% and 51.4% of these patients, respectively. Compared with NVAF, POAF was not associated with a significantly different 5-year absolute risk of thromboembolism (10.7% [95% confidence interval [CI], 8.0%-13.9%] versus 8.9% [95% CI, 7.6%-10.2%] in the POAF and NVAF group, respectively) (Figure). In the adjusted analysis, the long-term risk of thromboembolism was similar in patients with POAF and NVAF (hazard ratio [HR] 1.01 [95% CI, 0.71–1.44]). Anticoagulation therapy during follow-up was associated with a lower risk of thromboembolic events in patients with POAF (HR 0.45 [95% CI, 0.18–0.99]) as well as NVAF (HR 0.58 [95% CI, 0.42–0.80]) compared with no anticoagulation therapy.

Conclusions
New-onset POAF following isolated left-sided heart valve surgery was associated with a similar long-term risk of thromboembolism compared with NVAF. Future studies addressing the role of oral anticoagulation therapy in POAF after heart valve surgery are warranted to examine the efficacy and safety as well as the timing and duration of anticoagulation therapy.
5164New risk prediction score for life-threatening ventricular tachyarrhythmias in laminopathies
Authors: Wahbi K , Ben Yaou R , Gandjbakhch E , Anselme F , Gossios T , Lakdawala N , Stalens C , Sacher F , Babuty D , Charron P , Vigouroux C , Bonne G , Kumar S , Elliott P , Duboc D 
Published: October 2019

Abstract

Background
An accurate estimation of the risk of life-threatening (LT) ventricular tachyarrhythmia (VTA) in patients with LMNA mutations is crucial to select candidates for implantable cardioverter defibrillator (ICD) implantation.

Methods
We included 839 adult patients with LMNA mutations, including 660 from a French nationwide registry in the development sample, and 179 from other countries, referred to 5 tertiary centers for cardiomyopathies, in the validation sample. LTVTA was defined as a) sudden cardiac death or b) ICD-treated or hemodynamically unstable VTA. The prognostic model was derived using Fine-Gray's regression model. The net reclassification was compared with current clinical practice guidelines. The results are presented as means (standard deviation) or medians [interquartile range].

Results
We included 444 patients 40.6 (14.1) years of age in the derivation sample and 145 patients 38.2 (15.0) years in the validation sample, of whom 86 (19.3%) and 34 (23.4%) suffered LTVTA over 3.6 [1.0–7.2] and 5.1 [2.0–9.3] years of follow-up, respectively. Predictors of LTVTA in the derivation sample were: male sex, non-missense LMNA mutation, 1st degree and higher atrioventricular block, non-sustained ventricular tachycardia, and left ventricular ejection fraction. In the derivation sample, C-index (95% CI) of the model was 0.776 (0.711–0.842). In the external validation sample, the C-index was 0.800 (0.642–0.959) and calibration slope 1.082 (95% CI, 0.643–1.522). A 5-year estimated risk threshold ≥7% predicted 96.2% of LTVTA and net reclassified 28.8% of patients with LTVTA compared with the guidelines-based approach.

Conclusions
Compared to the current standard of care, this risk prediction model for LTVTA in laminopathies facilitated significantly the choice of ICD candidates.

Acknowledgement/Funding
AFM Téléthon