bluuebunny/crossref_metadata_2025_split huggingface dataset:
P6497Loeys-Dietz syndrome-5: phenotypic spectrum of TGFB3 mutations in an international cohort and first report of a homozygous patient
Authors: Marsili L , Overwater E , Hanna N , Baujat G , Baars M J H , Brehin A C , Gerard M , Gouya L , Houweling A C , Vanlerberghe C , Voorhoeve E , Van Tintelen J P , Maugeri A , Arnaud P 
Published: October 2019

Abstract

Background
Mutations in TGFB3 cause Loeys-Dietz syndrome-5 (LDS5), an autosomal dominantly inherited connective tissue disorder. LDS5 is characterized by aortic aneurysms and dissections associated with systemic features mainly involving the ocular and skeletal systems. Precise delineation of LDS5 phenotype is difficult because of the small number of identified cases.

Purpose
The purpose of this study was to further define LDS5 with an emphasis on cardiologic features by describing the genotype and phenotype in an international cohort of patients.

Methods
We performed a retrospective cross-sectional multicentre study. Genetic testing was performed as a part of standard medical care. Clinical data were collected by means of an anonymized questionnaire, which was sent to the referent physicians.

Results
Ten (7 novel) TGFB3 mutations were identified in 31 patients (16 index patients). The mean age at last evaluation was 32 years (range 4–60 years). Aortic root dilatation, varices, and mitral valve insufficiency were the most common cardiovascular findings, reported in 28%, 22%, and 21% of patients, respectively. Higher incidences (40%, 29%, and 25%) of these findings were observed in the index patients. Four patients (8%) underwent aortic surgery, all after age 40. Abdominal aortic aneurysms were reported in 2/26 (8%) patients. Extra aortic artery disease included iliac artery aneurysm (one index patient) and tortuosity of the internal carotid and vertebral arteries (one index patient and one relative). The most frequently reported systemic features were high-arched palate, arachnodactyly, pes planus, pectus deformity, and joint hypermobility. Interestingly, we identified an homozygous TGFB3 mutation in a patient who presented with aortic dilatation at age 17, splenic torsion, severe myopia, cleft palate, and other skeletal features. Her heterozygous parents, brother, and sister displayed signs of the disease, but to a milder degree. To the best of our knowledge, this is the first identification of homozygous TGFB3 mutation.

Conclusions
Our data are in line with previous research, showing that aortic root dilatation is the main cardiovascular feature of LDS5. No deaths related to cardiovascular events were reported in any of the presented families. The cardiovascular phenotype of LDS5 appears to be milder compared to other vascular connective tissue disorder, such as Marfan syndrome, although our findings suggest that homozygosity is associated with a more severe and early-onset phenotype.
P6499Genetic screening in 109 adult Chinese patients with thoracic aortic aneurysm and dissection
Authors: Li J , Wu B , Wang Y , Sun Y P , Liu D , Zhai J , Lai H , Sun Y X , Wang C 
Published: October 2019

Abstract

Background
Thoracic aortic aneurysm and dissection (TAAD) comprises a heterogenous group of cardiovascular urgencies, which could be further categorized into syndromic and non-syndromic entities. The accurate and timely identification of culprit genetic variants is of grave importance for TAAD patients, since different genetic defects have been associated with different risks for aortic dissection, thus different thresholds for preventive aortic intervention.

Purpose
With the advent of next-generation sequencing (NGS) techniques, accumulating records of rare variants have been found in TAAD patients, while inadequate functional validation also makes it difficult to give proper counsel for individual TAAD patients. Therefore, it is necessary for us to start re-evaluating clinical applications of genetic screening strategies in specific patient populations.

Methods
From June 2016 to July 2017, genetic screening using an NGS-based panel of 18 candidate genes (FBN1, FBN2, TGFBR1, TGFBR2, TGFB2, TGFB3, SMAD3, COL1A1, COL3A1, COL5A2, COL5A1, PLOD1, ACTA2, MYH11, MYLK, PRKG1, MFAP5, and SKI) was applied in 109 adult TAAD patients from our institution. Patients with bicuspid aortic valve disease, complex congenital cardiac defect, aortic root infection, aortitis, pregnancy, and an age older than 70 years were excluded from the present study.

Results
Among 109 TAAD patients, 36 harboured an FBN1 variant, including 2 splicing site, 6 frame shift, 5 non-sense, and 23 mis-sense variants. The pathogenicity of mis-sense variants was further categorized into 10 disease-causing variants via database survey, 5 disease-causing variants via family survey, and 8 variants of uncertain significance (VUS). On the other hand, 25 patients harboured a non-FBN1 variant, including 3 established pathogenic variants on TGFBR1, TGFB2, and ACTA2 genes, as well as 22 VUS. Patients with an FBN1 variant displayed younger age, lower rate of hypertension, higher rate of aortic root aneurysm, and more frequent mitral valve prolapse, while an extreme male predominance (24/25) was observed in patients with a non-FBN1 variant.

Conclusion
In an adult Chinese TAAD cohort, disease-causing genetic variants were found in 28.4% (31/109) of patients, with FBN1 mutations still being the single leading cause of disease. The present study advocated a genetic screening strategy emphasizing the detection of FBN1 mutations in adult Chinese TAAD patients, and further studies should address the pathogenicity and clinical relevance of non-FBN1 VUS in TAAD patients.
P6509Plasma trimethylamine n-oxide level is associated with neoatherosclerosis in patients with very late stent thrombosis
Authors: Tan Y , Yan H B 
Published: October 2019

Abstract

Background
Trimethylamine N-oxide (TMAO) has been demonstrated to promote the pathogenesis of atherosclerosis. It is unknown whether plasma TMAO is associated with neoatherosclerosis, an important underlying mechanism of very late stent thrombosis (VLST). We investigated the relationship between the culprit plaque morphology and plasma TMAO concentration in patients with ST-segment elevation myocardial infarction caused by VLST.

Methods
Optical coherence tomography (OCT) was used to evaluate the culprit lesion morphology. Thirty consecutive patients with VLST were enrolled; 17 patients were identified as neoatherosclerosis and 13 without neoatherosclerosis. Patients with neoatheroslcerosis were further divided into two subgroups, including 11 patients with plaque rupture and 6 without plaque rupture, respectively.

Results
The plasma TMAO levels were significantly higher in patients with VLST than in healthy individuals (3.64 μM [2.08–4.58] vs. 1.47 μM [0.89–2.75], p<0.001). Within VLST patients, plasma TMAO levels were significantly higher in patients with neoatherosclerosis than in those without neoathersclerosis (4.35 μM [3.43–5.37] vs. 2.02 μM [1.30–3.59]; p<0.001). The logistic analysis revealed that plasma TMAO was a predictor of neoatherosclerosis (odds ratio: 3.35, 95% confidence interval: 1.40–8.03; p=0.007). In addition, patients with neoatherosclerosis with plaque rupture had significantly elevated plasma TMAO concentration than those without plaque rupture (5.29 μM [4.35–7.21] vs. 3.63 μM [3.02–3.92]; p=0.012). The area under receiver operating characteristic curve for patients with neoatherosclerosis versus those without neoatherosclerosis was 0.87, the corresponding sensitivity and specificity was 0.77 and 0.88, respectively.
The comparison of plasma TMAO level

Conclusions
High plasma TMAO was associated with neoatherosclerosis and plaque rupture in patients with VLST.

Acknowledgement/Funding
This study was supported by the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences (2016-I2M-1-009)
P6511CABG was associated with higher risk of periprocedural stroke than PCI in patients with complex coronary artery disease
Authors: Watanabe H , Shiomi H S , Kimura T K 
Published: October 2019

Abstract

Background
Periprocedural stroke was believed to occur more frequently after coronary artery bypass grafting (CABG) than percutaneous coronary intervention (PCI). However, few clinical data have endorsed it.

Methods
The CREDO-Kyoto registry Cohort-1 and Cohort-2 are large-scale registries enrolling consecutive patients undergoing first coronary revascularization in the BMS era (2000–2002) for Cohort-1, or in the DES era (2005–2007) for Cohort-2 in Japan. Using the pooled individual patient-level data, the current study population consisted of 7774 patients who received PCI (PCI group) and 4392 patients who received CABG (CABG group).

Results
The cumulative 30-day incidence of stroke was significantly lower in the PCI group than in the CABG group (0.5% versus 1.7%, P<0.0001). Even after adjusting for baseline characteristics, the excess 30-day risk of the PCI group relative to the CABG group for stroke remained significant (hazard ratio [HR]: 0.34, 95% confidence interval [CI]: 0.23–0.52, P<0.0001). Similarly, the cumulative 10-year incidence of stroke was significantly lower in the PCI group than in the CABG group (13.2% versus 14.8%, P=0.046). However, after adjusting for confoundings, the excess 10-year risk of the PCI group relative to the CABG group for stroke was not higher than that of CABG (hazard ratio [HR]: 0.84, 95% confidence interval [CI]: 0.68–1.04, P=0.11).

Conclusions
CABG was associated with higher risk of periprocedural stroke than PCI in patients with complex coronary artery disease. However, the risk of stroke during 10-year follow-up was similar between the groups.
P65217.5-Fr sheathless guides versus 7-Fr glidesheath slender sheath/7-Fr guiding catheter combination for acute myocardial infarction: a propensity-matched analysis
Authors: Isawa T , Horie K , Taguri M , Ootomo T 
Published: October 2019

Abstract

Purpose
To investigate the differences between a 7.5-Fr sheathless guides and a 7-Fr Glidesheath slender sheath (GSS) /7-Fr guiding catheter combination regarding access-site complications and process time metrics in percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI).

Methods
We enrolled 609 patients undergoing PCI for AMI at our hospital using either a 7.5-Fr sheathless guides or a 7-Fr GSS/7-Fr guiding catheter combination; 1:1 propensity score matching was performed. A propensity score was estimated using a multivariate logistic regression model. Variables included were age, gender, weight, hypertension, diabetes, smoking, statin, estimated glomerular filtration rate, end-procedural activated clotting time, oral anticoagulants, SYNTAX score I, previous PCI, history of MI, Killip class, prior ipsilateral transradial intervention, and radial artery diameter.

Results
A total of 336 subjects were included in the propensity-matched sample. Compared with the GSS group, the sheathless group had significantly less frequent severe radial spasm (Sheathless: 0.6% vs. GSS: 4.8%, p=0.037) and Bleeding Academic Research Consortium type 2, 3, or 5 bleeding events (Sheathless: 12.5% vs. GSS: 21.4%, p=0.041).
Procedure outcomes Variables Total population Propensity-matched population Sheathless (n=368) Glidesheath (n=241) OR (95% CI) p Sheathless (n=168) Glidesheath (n=168) OR (95% CI) p Primary outcomes   RAO at 30 days 10 (2.7) 3 (1.2) 0.45 (0.08–1.77) 0.26 4 (2.4) 1 (0.6) 0.25 (0.03–2.22) 0.37   Severe radial spasm (grade 3 or 4) 5 (1.4) 12 (5.0) 3.78 (1.22–13.87) 0.011 1 (0.6) 8 (4.8) 8.35 (1.03–67.52) 0.037   BARC type 2, 3, or 5 bleeding within 30 days 40 (10.9) 45 (18.7) 1.87 (1.15–3.05) 0.008 21 (12.5) 36 (21.4) 1.91 (1.06–3.43) 0.041   Procedural success 361 (98.6) 238 (98.8) 1.10 (0.21–7.14) 0.54 167 (99.4) 166 (98.8) 0.50 (0.05–5.53) 1.0 Secondary outcomes   Coronary ostial dissection 7 (1.9) 3 (1.2) 0.65 (0.11–2.87) 0.75 4 (2.4) 3 (1.8) 0.75 (0.16–3.38) 1.0   MACCEs within 30 days 4 (1.1) 7 (2.9) 2.70 (0.68–12.73) 0.12 4 (2.4) 0 (0) n/a 0.12   Puncture to balloon time, min 26.0 (21.0–35.0) 27.0 (20.0–38.0) n/a 0.52 26.5 (21.0–37.0) 27.0 (20.0–38.0) n/a 0.77 Data are presented as median (interquartile range) or n (%), unless otherwise indicated. Bleeding Academic Research Consortium; CI, confidence interval; MACCEs, major adverse cardiac and cerebrovascular events; OR, odds ratio; RAO, radial artery occlusion. MACCEs include all-cause death, myocardial infarction, target-vessel revascularization, and cerebrovascular accident.

Conclusions
These data demonstrate a clear advantage of sheathless guides over GSS/guiding catheter combination for decreased risk of severe radial spasm and bleeding.
P6539Automated detection of atrial fibrillationb based on vocal features analysis
Authors: Golovchiner G , Abelow A , Swissa M , Morelli O , Beker A 
Published: October 2019

Abstract

Background
Early identification of atrial fibrillation (AF) has been a long-standing clinical challenge and an unmet need. AF may be present without the patient being aware of any symptoms, leading to a delay in or failure of diagnosis. ESC guidelines recommend opportunistically screening patients >65 years of age using pulse palpation or an ECG rhythm strip, however these methods have limited effectivity. Analysis of natural speech signals has been used as a monitoring tool for various medical conditions and has recently been reported to enable estimation of heart rate. In this study we evaluated the efficacy of vocal features analysis in the detection of AF and in discriminating between sinus rhythm (SR) and episodes of AF.

Methods
In this prospective multicenter study, patients with persistent AF admitted for cardioversion were enrolled. A total of 86 patients in 2 centers were included. Prior to cardioversion, the patients spoke specific vowels and words according to a pre-specified protocol; an ECG tracing was simultaneously recorded. Following successful cardioversion and recovery from sedation, these recordings were repeated in SR. The recordings of the first 34 patients were used to develop an algorithm of AF detection based on analysis of acoustic features in SR and AF conditions. The algorithm was then validated in all of the patients (n=86) in the following manner: 25% of SR recordings were used to train the algorithm while the remaining 75% of SR and 100% of AF data from every patient were tested with the algorithm to distinguish between AF and SR.

Results
A total of 513 recordings from 86 patients were analyzed. Classification of the recordings as AF or SR was performed using varying cutoff values of the separation parameter. The resulting curve showing the specificity and sensitivity of the developed algorithm for distinguishing AF from SR is presented. Two specific examples of working points are a specificity of 92% and sensitivity of 83%, and a specificity of 82% and sensitivity of 92%.

Conclusions
This study demonstrates the feasibility of detecting AF and discriminating it from SR using analysis of acoustic features extracted from spoken vowels. The potential use of this method for wider population screening should be further evaluated.
P6552Is it possible to recognize free-wall implantation of leadless pacemakers from an ECG?
Authors: Kajiyama T , Kondo Y , Nakano M A , Nakano M I , Hayashi T , Ito R , Takahira H , Kobayashi Y 
Published: October 2019

Abstract

Background
Leadless pacemaker (Micra, Medtronic, US) is a effective treatment for bradycardia and eliminates any malfunctions related to intravenous leads. However, some cases exhibit pericardial effusion, presumably associated to device implantation to right ventricular free-wall.

Objectives
The present study was carried out to find ECG features during ventricular pacing by Micra, which enabled to distinguish free-wall implantation from septal implantation without imaging modalities.

Methods
Consecutive 21 patients who received implantation of Micra in our facility were enrolled. Location of device in the right ventricle was evaluated using echocardiography or computed tomography in order to determine whether the device was implanted on the septum or the freewall. The difference of 12-lead ECG during ventricular pacing from Micra were analyzed between the septum group and the free wall group.

Results
According to the imaging investigation, body of Micra was clearly identifiable in 17 patients. The locations of device were classified into septum in 11 patients, free-wall in 4 patients, and indeterminate but apex in 2 patients. Further analysis regarding ECG was performed exclusively between the septum group and the free-wall group. In lead V1, peak deflection index (PDI) was significantly larger in free-wall group than septum group (0.64±0.06 vs. 0.45±0.10, P=0.005), whereas there was no difference of QRS duration, transitional zone and QRS pattern.
PDI of V1 and Location of LPM

Conclusion
PDI of V1 could be useful to predict implantation of Micra to free-wall and may potentially stratify the risk of postprocedural pericardial effusion.
P6557Permanent atrial fibrillation development in patients with DDD pacemaker -Rrisk factors and association with mortality in long-term
Authors: Debski M , Ulman M , Zabek A , Boczar K , Haberka K , Kuniewicz M , Lelakowski J , Malecka B 
Published: October 2019

Abstract

Background
In patients undergoing permanent DDD cardiac pacing, the maintenance of atrial contractility is important to ensure adequate ventricular filling and to guarantee an optimal ventricular ejection capacity. Atrial fibrillation (AF) is a major risk factor for thromboembolic events and is associated with increased cardiovascular and all-cause mortality.

Purpose
To analyse the risk factors for development of permanent AF in patients with DDD pacemaker and determine its association with all-cause mortality in long-term follow-up.

Methods
Retrospectively collected records comprised all consecutive patients who underwent primary DDD pacemaker implantation at single-centre between 1984–2014. Patients who were lost to follow-up after hospital discharge were excluded from analysis. Follow-up was completed on 31st August 2016. Definition of permanent AF was the occurence of AF which persisted until the end of follow-up. Data on patients' survival status and deceased patients' dates of death were collected from the national death registration system. Information of death date was available as of 31st August 2016. The endpoint was all-cause mortality.

Results
We included a total of 3771 patients and 24,432 patient-years of follow-up and exluded 157 (4%) patients who were lost to follow-up after hospital discharge. Mean follow-up was 78±62 months (max. 370 months), 1761 (47%) were female. Paroxysmal AF prior to DDD pacemaker implantation was detected in 1276 patients (34%). During entire follow-up 717 (19%) patients developed permanent AF in a mean period of 55±50 months. Analysis of risk factors for development of permanent AF is presented in Figure. Cox proportional hazards model with time-dependent covariate showed that development of permanent AF significantly increased mortality during follow-up (HR = 1.885, 95% CI, 1.654–2.148, P<0.001; with adjustment for age at implantation and sex: HR = 1.475, 95% CI, 1.294–1.682, P<0.001).
Permanent AF risk factors

Conclusions
Female sex protected against permanent AF development, whereas age at implantation, history of paroxysmal AF and apical position of RV lead increased the risk. Permanent AF was significantly increasing the all-cause mortality, even after adjustment for age at implant and gender.

Acknowledgement/Funding
None
P6564Prediction of the progression from paroxysmal to persistent or permanent atrial fibrillation using different scores. Is AF progression mainly atrial aging?
Authors: Fauchier L , Martins R , Bisson A , Bodin A , Clementy N , Pierre B , Babuty D 
Published: October 2019

Abstract

Reliable prediction of atrial fibrillation (AF) progression from paroxysmal to non-paroxysmal form of AF could help in optimizing follow-up and decision-making regarding the rate and rhythm control management. The HATCH score and others have been proposed to identify AF patients likely to progress to sustained forms of AF, but external validation is limited. We aimed at evaluating these scores in a large series of AF patients and to identify possible factors leading to persistent/permanent AF.

Methods
All patients with AF seen over a period of 10 years were identified in a database and followed up for AF progression and mortality. Predictors of outcomes were identified using Cox regression model. The values of HATCH, CHA2DS2-VASc, ALARMEc, APPLE, MB-LATER scores and CHARLSON comorbidity index were evaluated with C statistics for prediction of AF progression.

Results
Among 8962 patients (71±14 years), 4991, 476 and 3495 had paroxysmal, persistent AF, and permanent AF, respectively. During a follow-up of 927±1084 days, 404 paroxysmal AF patients progressed to persistent or permanent AF (yearly rate of 3.0%). Progression was associated with a trend toward increased cardiovascular mortality. Independent predictors of AF progression were heart failure (hazard ratio (HR) 2.07; 95% CI 1.50–2.85, p<0.0001), valvular disease (HR=1.87, 95% CI=1.35–2.58, p=0.0002) and the use of digoxin (HR=2.39, 95% CI=1.75–3.29, p<0.001). Conversely, a history of stroke was associated with a lower rate of progression (HR=0.50, 95% CI=0.28–0.88, p=0.02). Overall, most of the score, particularly the HATCH score, were modest predictors of progression (table). The best score was actually the CHARLSON comorbidity index. The predictive values of all scores were better on patients not treated with antiarrhythmic agent.
C-statistics for AF progression All patients (n=4,991) p value* HATCH 0.576 (0.562–0.590) <0.0001 CHA2DS2-VASc 0.532 (0.503–0.560) <0.0001 ALARMEc 0.634 (0.607–0.660) 0.03 APPLE 0.631 (0.605–0.658) 0.03 MB-LATER 0.612 (0.587–0.638) 0.001 CHARLSON 0.667 (0.640–0.693) – *DeLong test vs CHARLSON comorbidity index.

Conclusion
Most of scores have a modest predictive value to identify the risk of evolution to permanent AF. Among them, the CHARLSON comorbidity index had the best predictive value and outperformed other tools. This suggests that AF progression may actually reflect global aging both at the individual and local atrial level.