bluuebunny/crossref_metadata_2025_split huggingface dataset:
2214Prevalence and severity of coronary disease in patients with familial hypercholesterolemia hospitalized for an acute myocardial infarction: data from the RICO survey
Authors: Farnier M , Mouhat B , Pommier T , Yao H , Maza M , Chague F , Bichat F , Cottin Y , Zeller M 
Published: October 2019

Abstract

Aim
Individuals with heterozygous familial hypercholesterolemia (FH) are at high risk of early myocardial infarction (MI). However, coronary artery disease (CAD) burden of FH remains not well described. From a large database of a regional registry of acute MI, we aimed to address prevalence of FH and severity of CAD.

Methods
Consecutive patients hospitalized with MI in a multicentre database from 2001–2017 were considered. An algorithm, adapted from Dutch Lipid Clinic Network criteria, was built upon 4 variables (LDL-cholesterol (LDL-C) and lipid lowering agents, premature and family history of CAD) to identify FH probabilities.

Results
Among the 11624 patients included in the survey, 249 (2.1%) had probable/definite FH (score ≥6), and 2405 (20.7%) had possible FH (score 3–5). When compared with patients without FH (score 0–2), FH patients (score ≥6) were 20y younger (51 (46–57) vs 71 (61–80) y, p<0.001), with a lower rate of hypertension (47 vs 59%, p<0.001), diabetes (17 vs 25%, p<0.001) and prior stroke (4 vs 8%, p=0.016), but a higher prevalence of smokers (56 vs 23%, p<0.001), personal (20 vs 15%, p=0.02) or familial history of CAD (78 vs 18%, p<0.001). Chronic statin treatment was only used in 48% of FH patients and ezetimibe in 8%. After adjustment for age, sex and diabetes, FH patients were characterized by increased extent of CAD (syntax score 11 (4–19) vs 7 (1–13), p<0.001) and multivessel disease (55 vs 40%, p<0.001).

Conclusion
In this large real world population of acute MI, a high prevalence of FH was found. FH patients were characterized by their young age associated with the severity of CAD burden and limited use of preventive lipid lowering therapy.

Acknowledgement/Funding
University Hospital Center Dijon Bourgogne, Agence Régionale de Santé Bourgogne Franche Comté, France
2401Cardiac resinchronization therapy for the systemic right ventricle: a single center experience
Authors: Barracano R , Guarguagli S , Kavouras C , Brida M , Griffith S , Wong T , Gatzoulis M A 
Published: October 2019

Abstract

Introduction
Cardiac resynchronization therapy (CRT) has become a treatment of choice in patients with chronic heart failure (HF). About 25% of patients with systemic right ventricle (SRV) progress to symptomatic HF, which may be refractory to drug therapy and is commonly associated with significant morbidity and mortality. For these reasons, CRT has been emerging as an effective treatment strategy for patients with SRV failure and electrocardiographic signs of ventricular dyssynchrony. Few studies have reported the acute and long - term effects of CRT in SRV subjects, with different findings. Our study aimed to describe the experience with CRT in SRV patients in a single tertiary centre.

Purpose
Assess the long term efficacy of CRT in patient with SRV

Materials and methods
All consecutive SRV patients who underwent CRT implantation and/or upgrading between 1994 and 2018 at our tertiary centre were included. Clinical and echocardiographic parameters before and after CRT implantation were collected and analyzed.

Results
A total of 21 patients (mean age 47.8±14.8 years, 13 M) were implanted with CRT-P (12, 57%) or CRT-D (9,43%) during the study period. 90% of patients showed an anatomy of congenitally corrected transposition of the great arteries (CCTGA), whereas 9.5% underwent Mustard procedure for transposition of the great arteries (TGA). Among CCTGAs, 11 (52.5%) subjects underwent previous surgical procedures, including implant of a conduit between the left ventricle (LV) and the pulmonary artery (PA) in 8 (38%) patients, tricuspid valve repair in 2 (9.5%) and surgical closure of atrial septal defect in 1 (5%). Before CRT implant/upgrading, 10 (48%) patients had a moderate to severe reduction in the SRV ejection fraction (EF) and 7 (33%) had a moderate to severe tricuspid regurgitation (TR). Overall, 15 (71%) patients referred a NYHA II or III. After a median follow up of 57 months (IQR 35–83), 43% of patients showed an improvement in their functional status, which was associated with an improvement of SRV EF and TR only in 22% and 33% of these patients. On the contrary, no patient reported a worsening in NYHA class, while SRV EF decreased in 28.5% and the grade of TR worsen in 23.8% of patients.

Conclusions
CRT is emerging as an effective treatment for SRV dysfunction. However, criteria for implantation are not well defined and the deterioration of SRV function related to subpulmonary univentricular pacing should be considered. Moreover, TR did not improve in this study, suggesting that concurrent tricuspid valve interventions may be necessary in patients with severe TR and may facilitate the improvement in RV function achieved with CRT. Proper planning, tertiary expertise and international collaborations are all paramount in this field.
P1222Intensification of lipid lowering therapy before and after publication of the IMPROVE-IT trial: A temporal analysis from the SPUM-ACS cohort
Authors: Gencer B , Carballo D , Nanchen D , Koskinas K , Klingenberg R , Raeber L , Auer R , Carballo S , Heg D , Windecker S , Luscher T F , Matter C M , Rodondi N , Mach F 
Published: October 2019

Abstract

Background
The gradual implementation of evidence-based treatment strategies has improved outcomes in patients with acute coronary syndromes (ACS). The Improved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT) was published on June 3rd, 2015, but its relevance on real life practice has not been explored.

Methods
We analyzed a prospective Swiss cohort of 6266 patients hospitalized for ACS between 2009 and 2017. The primary endpoints were the ezetimibe use overall or in combination with high-intensity statin at discharge and at one year after ACS. Secondary endpoint was LDL-C target achievement at one year in a subsample of 2984 patients. Relative Ratios (RR) were used to assess changes in primary endpoints before and after the publication of IMPROVE-IT, adjusting for age, sex, pre-existing diabetes, history of myocardial infarction, baseline low-density lipoprotein cholesterol (LDL-C) and attendance to cardiac rehabilitation.

Results
The period following the publication of the IMPROVE-IT trial was associated with an overall increase in the use of ezetimibe at discharge (from 1.8% to 3.8%, P<0.001, adjusted RR 2.85, 95% CI 1.90–4.25) and at one year (from 5.0% to 13.8%, P<0.001, adjusted RR 3.00, 95% CI 2.40–3.75). Before IMPROVE-IT trial, ezetimibe use at one year was stable around 5%, then steadily increased after its publication until 20% for patients included in 2017. The combination of high-intensity statin and ezetimibe increased from 0.9% to 2.1% at discharge (P<0.001, adjusted RR 3.35, 95% CI 1.90–5.89) and from 2.1% to 7.8% at one year (P<0.001, adjusted RR 3.98, 95% CI 2.90–5.47). The period following the publication of the IMPROVE-IT trial was associated with an improvement of LDL-C target <1.8 mmol/L (adjusted RR 1.37, 95% CI 1.12–1.68).

Conclusion
After the publication of the IMPROVE-IT trial, the use of ezetimibe was increased by three-fold in a large contemporary cohort of ACS patients, concomitant with an improved LDL-C target achievement.
P1231Loss of function in cytoskeletal genes associates with early onset atrial fibrillation
Authors: Vad O , Ahlberg G , Refsgaard L , Svendsen J H , Tveit A , Christophersen I E , Olesen M S 
Published: October 2019

Abstract

Introduction
Atrial fibrillation (AF) is the most common cardiac arrhythmia. It carries an increased risk of serious complications and an increased mortality. Genome Wide Association Studies have demonstrated that variants in several structural genes are associated with AF, and recently two landmark papers have implicated loss of function (LoF) variants in titin (TTN), a gene associated with dilated cardiomyopathy (DCM), in patients with early onset AF. An atrial cardiomyopathy syndrome has been proposed as a mechanism in the development of AF.

Purpose
We hypothesized that genes encoding structural proteins that were associated with DCM, could also be involved in atrial cardiomyopathy and contribute to AF.

Materials and methods
We performed targeted deep sequencing of structural genes associated with DCM. The genes were grouped by cellular function, and the burden of LoF variants was examined in a cohort of 540 early onset AF patients and compared to a control group (n=383). The patients were below age 49 with normal echo, and no other cardiovascular disease at onset of AF. Patient inclusion in the cohort is still ongoing, and we are working on obtaining a CRISPR/CAS9 modified zebra fish model with LoF variants in cytoskeletal proteins.

Results
We identified a total of 6 carriers of LoF variants in 3 genes thought to encode cytoskeletal proteins (DMD, PDLIM3 and FKTN). The burden of variants in cytoskeletal genes was significantly increased in patients with early onset AF compared with controls (p=0.0385). Four carriers had LoF variants in the dystrophin gene (DMD), while there was 1 carrier of LoF variants in PDLIM3 and FKTN respectively. All carriers with LoF variants in DMD developed persistent AF before age 30.

Conclusion
Our data suggest that rare mutations in cytoskeletal genes previously associated with DCM, may also play a role in the development of early onset AF. The data supports that AF is a part of an atrial cardiomyopathy syndrome.

Acknowledgement/Funding
Novo Nordisk Fonden Pre-Graduate Scholarships
P1236Revealing cardiac mechanics with CMR whilst CRT is active: the first step
Authors: Koshy A , Gierula J , Paton M , Swoboda P , Toms A , Saunderson C , Shelley D , Plein D , Cubbon R , Kearney M , Witte K 
Published: October 2019

Abstract

Introduction
Cardiac resynchronisation therapy (CRT) is a routine treatment for heart failure with reduced ejection fraction and conduction delay to improve symptoms and prognosis. Technological advancements both in cardiac magnetic resonance (CMR) and devices (MRI-conditional modes) now enable investigation of the haemodynamic response to CRT over a range of heart rates.

Methods
Patients with a CRT-D device were enrolled from heart failure clinics at a single tertiary centre. A complete device system assessment and baseline device check was conducted to ensure MRI compatibility and suitability. Left ventricular (LV) volumes and systolic blood pressure were measured at baseline and heart rates of 75, 90, 100, 115, 125, and 140 bpm (randomised order) with CRT active and intrinsic conduction (AOO). MRI conditional mode parameters were replicated through standard parameter modification to ensure biventricular pacing during CRT active scans. All scans were conducted using a 3.0 T Siemens Prisma MRI scanner with analysis on commercially available software. Contractility was derived from the systolic blood pressure and left ventricular end systolic volume. A post scan device and lead assessment was conducted to assess for scanning safety.

Results
Scanning was conducted in 22 patients (safety cohort). Post scan battery voltage reduced by 2.9±1.0%. Mean change in atrial, right ventricular and left ventricular lead impedance was 0.5±0.06%, 3.0±0.04% and −1.7±0.05% respectively. Mean change in atrial, right ventricular and left ventricular pacing threshold was 0.0±0.3%, 8.3±0.3% and 5.6±0.3%. No patient experienced symptoms related to scanning or device failure.
Preliminary data for patients with CRT on and off have been analysed (paired analysis cohort, n=8, 6 men). Mean age was 71.1±8.2, aetiology was primarily ischaemic (62.5%) with the remainder dilated cardiomyopathy. The mean LV ejection fraction at baseline was 29.4±12.9%. Biventricular pacing led to acute improvements in ejection fraction (p=0.005), left ventricular cardiac output (p<0.0001) and contractility (p=0.05) over the entire range of heart rates studied. We also noted an improvement in the force frequency relationship during biventricular pacing with a higher peak contractility (p=0.05), a higher heart rate at which this occurred (HR=130) and a generally up sloping relationship when compared with intrinsic conduction.

Conclusion
We have demonstrated for the first time, the mechanistic improvements in cardiac contractility consequent to CRT using CMR and also that MRI scans of conditional devices can be safe with CRT active.

Acknowledgement/Funding
Dr A Koshy is conducting a PhD supported by grant from Medtronic. Dr Klaus Witte has received honoraria from Medtronic
P1240Is resynchronization therapy really efficient in laminopathy?
Authors: Burdeau J , Viart G , Gandjbakhch E , Savoure A , Godin B , Maury P , Pasquie J L , Wahbi K , Eltchaninoff H , Anselme F 
Published: October 2019

Abstract

Introduction
Laminopathy (LMNA) is a group of rare disease caused by a mutation of lamin A/C genes. Heart transplantation (HT) is often required. Cardiac resynchronization therapy (CRT) may be an option to postpone HT.

Purpose
To describe characteristics and outcome of LMNA patients receiving CRT.

Methods
All consecutive LMNA patients implanted with a CRT device for conventional indications were included in the study. Clinical and echocardiographic (TTE) data were collected during the follow-up period.

Results
From 2002 to 2017, 68 LMNA patients had CRT implantation. Despite CRT, 30/68 patients (44%) had HT. Population divided into two groups according to response to CRT. Patients were considered without benefit (WHOB-CRT group) if they experienced severe events (inscription on heart transplantation list or death) within two years after CRT implantation. Other patients were in the WB-CRT group. TTE and clinical parameters are described in Table 1.
Table 1 Parameters WB-CRT (n=33) WHOB-CRT (n=35) P-value At implantation   Age (years) 52.3±9.7 50.6±9.5 0.27   Women 9 (27%) 13 (37%) 0.45   NYHA class 2.7±0.6 2.8±0.7 0.45   LVEF (%) 33.2±8.8 31.3±7 0.64   LVEDD (mm) 60±6.9 60±6.9 0.96   TAPSE (mm) 23±3.7 14±4.8 0.002 At last follow up   NYHA class 2.2±0.6 2.9±0.7 <0.001   LVEF (%) 36.4±11 27±9 <0.001   LVEDD (mm) 59±5.5 59±7.7 0.98   TAPSE (mm) 19.9±5.5 12.3±3.3 0.003 Left ventricular ejection fraction (LVEF); Left ventricular end diastolic diameter (LVEDD); Tricuspid annular plane systolic excursion (TAPSE).

Conclusion
Cardiac resynchronization therapy is less efficient in LMNA patients. An impaired right ventricular stroke function seems to be the only predictive factor leading to poor response to CRT.
P1242ECG predictors of outcome in non-left bundle branch block cardiac resynchronization therapy patients
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
The effectiveness of cardiac resynchronization therapy (CRT) in patients without left bundle branch block (non-LBBB) QRS morphology is limited, compared to those with LBBB. Still, a substantial part of these patients can benefit from therapy and additional selection criteria are needed to identify these patients.

Purpose
To evaluate the association of additional baseline 12-lead ECG features; with clinical and echocardiographic outcomes in CRT-treated non-LBBB patients.

Methods
Pre-implantation 12-lead ECGs from 790 consecutive non-LBBB CRT patients from 3 implanting centres in the Netherlands were evaluated for the presence of predefined ECG parameters. QRS morphology (right bundle branch block and intraventricular conduction delay), QRS duration (≥/<150ms), QRS area (≥/<109μVs), left ventricular activation time ((≥/<125ms), and the presence of fragmented QRS (fQRS). The association with the primary endpoint, the combination of left ventricular assist device implantation, cardiac transplantation and all-cause mortality, was evaluated.

Results
There was a significantly lower occurrence of the primary endpoint in non-LBBB patients with QRS area ≥109 μVs (p<0.001) and in those without fQRS present (p=0.004) (figure 1).
Figure 1

Conclusion
A large QRS area and the absence of fQRS are positively associated to event free survival in non-LBBB patients treated with CRT. Whereas currently used patient selection cut-off QRS duration is not associated to outcome in these patients. These data may provide additional value for the non-LBBB patient selection for CRT and warrant prospective evaluation of these ECG features.

Acknowledgement/Funding
None
P1248Characteristics and clinical significance of right ventricular involvement in patients with hypertrophic cardiomyopathy
Authors: Seo J W , Choi K U , Choi J Y , Lkhagvasuren P J , Shim C Y , Hong G R , Ha J W 
Published: October 2019

Abstract

Background
A few studies have demonstrated bi-ventricular hypertrophy in hypertrophic cardiomyopathy (HCM). However, clinical significance of HCM with right ventricular (RV) involvement has not been fully established. Therefore, we aimed to investigate the structural characteristics and clinical significance of RV hypertrophy in patients with HCM.

Methods
In a single center, large HCM registry, 256 patients with HCM who underwent both cardiac magnetic resonance (CMR) and transthoracic echocardiography within 6 months were retrospectively analyzed. RV involvement was defined as increased RV wall thickness >7 mm on CMR in any segments of RV free wall and apex. Patients who had evidence of significant RV pressure overload (RV systolic pressure >50mmHg) or had undergone septal myectomy were excluded. Cardiovascular outcomes were defined as the composite of cardiovascular death and hospitalization for cardiovascular disease.

Results
Among 256 patients, 41 (16%) showed RV involvement. During follow-up period (median 1099 days), 32 cardiovascular outcomes (3 cardiovascular death and 29 cardiovascular hospitalization) were occurred. Patients with RV involvement showed a significantly higher left ventricular (LV) thickness (23.8±5.8 vs. 21.2±5.0 mm, p=0.004), more advanced diastolic dysfunction, and larger left atrial volume index (LAVI, 48.5±20.3 vs. 40.2±14.9 mm/m2, p=0.016) compared to those without RV involvement. In multivariate cox regression analysis, presence of RV involvement (HR: 4.21, 95% CI: 1.99–8.90, p<0.001) and LV ejection fraction <50% (HR: 4.29, 95% CI: 1.37–13.43, p=0.012) were independently associated with cardiovascular outcomes. The Kapan-Meier curve showed that there was a significant decrease in probability of cardiovascular outcomes-free survival in patients with RV involvement (p=0.007) after using 1:1 propensity score matching (n=82) to adjust for age, sex, LV ejection fraction, LV maximal wall thickness, LAVI, and RV systolic pressure than patients without RV involvement (Figure 1).
Figure 1

Conclusion
RV involvement in patients with HCM were not rare (16%). Patients with RV involvement showed more advanced LV structure and dysfunction, suggesting an indicator of severe HCM. RV involvement in HCM has clinical significance related to cardiovascular outcomes.
P1255Comparative safety and effectiveness of standard doses of apixaban versus dabigatran, rivaroxaban, and VKAs in non-valvular atrial fibrillation patients in France: the NAXOS study
Authors: Danchin N , Steg P G , Hanon O , Mahe I , Belhassen M , Jacoud F , Nolin M , Ginoux M , Dalon F , Lefevre C , Cotte F E , Gollety S , Falissard B , Van Ganse E 
Published: October 2019

Abstract

Background
Real-world data comparing all available oral anticoagulants (OAC) on a nationwide scale (i.e. in France: apixaban, rivaroxaban, dabigatran and vitamin K antagonists – VKAs) are lacking. In everyday practice, oral anticoagulants are often underdosed, which may render comparisons between agents difficult.

Purpose and methods
NAXOS is a French real-world study comparing the safety (major bleeding), effectiveness (stroke, systemic thromboembolic events (STE)) and all-cause mortality for apixaban, dabigatran, rivaroxaban, and VKAs, in adult patients with non-valvular atrial fibrillation (NVAF) initiating a given OAC between 2014 and 2016. The French national health insurance data (SNIIRAM) were used. Analyses were performed with adjustment on propensity scores. To avoid bias potentially related to underdosing, the present analysis included only patients receiving standard doses of apixaban (5mg bid), rivaroxaban (20mg od), and dabigatran (150 mg bid), or VKAs. Only OAC naïve patients were included.

Results
In the OAC-naive cohorts treated with apixaban, rivaroxaban, and dabigatran, 54,575 (62.3%), 65,208 (65.2%), and 9,000 (42.4%), respectively, had the standard dose at the index dispensation, and 112,628 patients received VKAs. After adjustment on propensity scores, apixaban 5 mg was associated with a lower risk of major bleeding, compared to VKAs (Hazard Ratio: 0.47; 95% CI: 0.43–0.51) and rivaroxaban 20mg (HR: 0.64; 0.59–0.71), but not to dabigatran 150 mg (HR: 0.97; 0.79–1.18). Apixaban was associated with a lower risk of stroke and STE, compared to VKAs (HR: 0.62; 0.56–0.69) but not to rivaroxaban (HR: 1.03; 0.92–1.16), and dabigatran (HR: 0.96; 0.76–1.21). Apixaban showed a lower risk of all-cause mortality compared to VKAs (HR: 0.44; 0.41–0.47) and rivaroxaban (HR: 0.87; 0.81–0.94) but not to dabigatran (HR: 1.10; 0.92–1.32).
Figure 1. Forest plot presenting the results of the standard dose analysis (PS adjusted).

Conclusions
The NAXOS population-based country-wide observational study shows that 42% to 65% of patients were treated with standard doses of OACs. Analyses of standard doses confirmed the superiority of apixaban compared with VKAs for the three studied outcomes and suggests better safety profile of apixaban compared to rivaroxaban but similar to dabigatran.

Acknowledgement/Funding
The Alliance Bristol-Myers Squibb/Pfizer