bluuebunny/crossref_metadata_2025_split huggingface dataset:
P4716One-year outcomes of the tri-repair study assessing cardioband tricuspid valve reconstruction system for patients with severe tricuspid regurgitation
Authors: Nickenig G , Von Bardeleben R S , Schaefer U , Kuck K H , Vahanian A , Juliard J M , Latib A , Baldus S , Maisano F , Hausleiter J 
Published: October 2019

Abstract

Background
Severe tricuspid regurgitation (TR) is associated with high morbidity and mortality rates with limited treatment options.

Objectives
We report the one-year outcomes of the Cardioband™ Tricuspid Valve Reconstruction System in the treatment of severe functional TR in 30 patients enrolled in the TRI-REPAIR study.

Methods
Between October 2016 and July 2017, 30 patients were enrolled in this single-arm, multicenter, prospective study. Patients were diagnosed with severe, symptomatic TR in the absence of untreated left-heart disease and deemed inoperable because of unacceptable risk for open-heart surgery by the local heart team. Clinical, functional, and echocardiographic data were prospectively collected before and up to one year post-procedure. An independent core lab assessed all echocardiographic data and an independent clinical event committee adjudicated the safety events.

Results
Mean patient age was 75 years, 73% were females, 23% had ischemic heart disease, and 93% had atrial fibrillation. At baseline, 83% were in NYHA Class III-IV, 63% had edema, and LVEF was 58%. Technical success was 100%. Through one year, one patient had a reintervention and exited the study. Five patients died of which one was device-related. Between baseline and one year (paired analyses), echocardiography showed average reductions of annular septolateral diameter of 16% (44mm vs. 37mm; p<0.0001), PISA EROA of 49% (0.73cm2 vs. 0.37cm2, p=0.0037), and mean vena contracta of 30% (1.2cm vs. 0.9cm, p=0.0046). Clinical assessment showed that at one year 78% of patients were in NYHA Class I-II (p=0.0003). Six minute walk distance improved by 42m (p=0.0525). Kansas City Cardiomyopathy Questionnaire score improved by 19 points (p=0.0009). Edema was absent in 70% of the patients.

Conclusions
These results show that the Cardioband tricuspid system performs as intended and appears to be safe in patients with symptomatic and severe functional TR. At one year significant reduction of TR through a sustained decrease of annular dimensions, improvements in heart failure symptoms, quality of life, and exercise capacity were observed. Further studies are warranted to validate these initial promising results.

Acknowledgement/Funding
Edwards Lifescieinces
P4726Functional mitral regurgitation treated with percutaneous repair: a relative survival analysis of a national Swiss cohort
Authors: Biasco L , Klersy C , Corti R , Moccetti T , Pedrazzini G 
Published: October 2019

Abstract

Introduction
Percutaneous treatment of functional mitral regurgitation (FMR) with MitraClip (MC) has led to discordant results in recent randomized clinical trials. We aimed at estimating excess mortality (EM) and to evaluate its predictors in a large Swiss FMR population treated with MC.

Methods
FMR patients enrolled in the MitraSwiss Registry (479 pts) with a mean age of 74.7±9.42 years were evaluated. We computed and plotted EM up to 5 years after implant using the Swiss 2008–20013 mortality tables, stratified by age and sex. A Poisson regression was used to model EM as a function of age, sex, pre-implant RV/RA gradient, calendar period (2011–2013; 2014–2015,2016–2017), ischemic vs non ischemic aetiology, acute procedural success and residual MR.

Results
Patient's survival at 1,2,3,4 and 5 years were respectively 0.84, 0.72, 0.59, 0.53 and 0.48. FMR patients treated with MC showed excess mortality of +13% (95% CI,10%-18%), +22% (95% CI,17%-28%), +34% (95% CI,27%-41%), +37% (95% CI,28%-46%) and +39% (95% CI,28%-50%) at each time point as compared to the Swiss population, with not differences over the entire follow up (p=0.481). Age group, sex, RV/RA gradient calendar period, ischemic vs non ischemic and residual MR were not associated with excess mortality while a clear association was recognized with acute procedural success (p=0.011).

Conclusions
In FMR patients treated with MC a persistent EM was observed at a 5 years follow up. Acute procedural success is the only determinant of EM with a 65% lower EM as compared to procedural failures.
P4751Underdosing fragile patients - Are we helping or harming?
Authors: De Almeida J P L , Martinho S , Girao A , Barreiro I , Baptista R , Ferreira J , Goncalves V , Milner J , Ferreira C , Alves P , Azul A , Goncalves L 
Published: October 2019

Abstract

Background
An individualized approach should be taken regarding the utilization of direct oral anticoagulants (DOAC) in frail and elderly populations with atrial fibrillation (AF). We hypothesized that among an elderly and frail population, where the risk of bleeding, both real and perceived, is very high, the proportion of patients with a dose regimen different from the formal indication would be particularly high due to potential underdosing.

Methods
We conducted a retrospective, observational study enrolling 327 patients with AF admitted to an Internal Medicine ward during a 1-year period and discharged with a DOAC prescription. We divided the population in 2 groups: patients prescribed a reduced dose without formal dose reduction criteria (underdosed, n=170) and the rest of the population (n=157), which included adequately dosed patients, both with normal dose (n=99) and correctly reduced dose (n=43) and overdosed patients (n=15). A 1-year follow-up was completed for all patients, assessing the following outcomes: all-cause mortality, stroke, systemic embolism and major bleeding.

Results
Patients were elderly (81.9±7.68) and frail (Katz index 3.35±2.36). Apixaban was the most commonly prescribed NOAC (38.8%), followed by rivaroxaban (36.4%) and dabigatran (24.8%). Among underdosed patients, apixaban was prescribed in 45.3% of patients, dabigatran in 29.4% and rivaroxaban 25.3%. Although only 18.3% of patients had clinical criteria for dose reduction, 65.4% were discharged with reduced dose and thus 52% were underdosed.
Regarding 1-year outcomes, mortality (40.8% vs 25.5%, RR=1.6, p=0.003) and the combined stroke, systemic embolism and major bleeding event rate (10.1% vs 3.2%, RR=3.16, p=0.015) were higher for underdosed patients.
Among underdosed patients, comparing with the rest of the population, the increased ischemic events rate (ischemic stroke and systemic embolism) did not reached statistical significance (3.7% vs. 1.9%, p=0.5), but it did for hemorrhagic events (major bleeding and hemorrhagic stroke) (6.1% vs 0.6%, p=0.01)
On multivariate analysis, even after considering adjustment for age, Katz and CHAD2VAS2C scores, renal function and DOAC prescribed, DOAC underdosing was associated with a higher risk of both ischemic and hemorrhagic events (HR = 3.51, 95% CI 1.08–11.38). However, it lost its independent negative effect regarding mortality (HR 1.32, 95% CI 0.87–1.99).
Survival and event rate in underdosed

Conclusions
There is a significant proportion of frail and elderly patients with AF that are underdosed. This subset has a significant survival disadvantage, eventually reflecting prescription bias. However, underdosed patients have also a higher event rate of both ischemic and hemorrhagic events, suggesting that underdosing fragile patients is not an effective strategy and that instead it may be hazardous.
P4763High power radiofrequency ablation with fixed short duration is rapid, efficient and safe for circumferential pulmonary vein isolation
Authors: Schreieck J , Duckheim M , Yurtbil U , Flassak J , Scheckenbach C , Stimpfle F , Heinzmann D , Gawaz M , Seizer P 
Published: October 2019

Abstract

Background
Short duration 50 Watt radiofrequency (RF) ablation has been shown to be feasible for atrial fibrillation (AF) ablation with short procedure times.

Purpose
We evaluated 50 Watt RF power with a different fixed short application duration at the anterior and posterior left atrial wall using contact force (CF) sensing catheters for circumferential pulmonary vein isolation (PVI).

Methods
Consecutive patients (pts) with indication for de novo AF ablation (n=40, age 64±12 years) with paroxysmal (n=23) or persistent (n=17) AF underwent high density 3D mapping of the left atrium. Low voltage areas of more than 5% of the left atrium were only found in 20% of pts. Thereafter, circumferential PVI using CF sensing catheters was performed. For each RF application (50 Watt, RF duration 11–13s at the anterior wall, 9–11s at the posterior wall) a stable catheter tip position with minimal mean CF of 3g was required and application was stopped in case of CF more than 30g. Esophageal temperature measurement was performed with temperature cut off 39.0°C. In case of temperature rise, ablation protocol was switched to conventional 20 Watt RF applications for ablation adjacent to the esophagus.

Results
Complete PVI was achieved in all pts with 81±29 short RF applications resulting in cumulative RF applications duration of 13.1±4.2min and an ablation duration of 59±17min for complete PVI. Even RF application with low CF (3–5g) were effective. Due to esophageal temperature rise, switch to conventional RF application with 20 Watt was performed in 43% of pts at least at one posterior PV entrance. After a waiting period of 20 min only in 33% of pts any PV conduction recurs, in 28% of pts only at a single spot and reconnected fibers were not associated with low CF application at that spot, but clearly associated with low energy application at the posterior wall. All PV were successfully re-isolated in most of pts with a single spot high energy RF application. No serious complications occurred in association with PVI. Follow up will be available at presentation time.

Conclusion
RF ablation with 50 Watt fixed short duration is efficient and safe for circumferential PVI. Ablation procedure durations are shorter and early recurrence rates are lower compared to reported conventional ablation procedures. The importance of CF titration seems to be diminished by 50 Watt RF applications in the left atrium. Further follow up have to be waited.
P4782Direct comparison of dabigatran, apixaban, rivaroxaban and edoxaban for effectiveness and safety among patients with non-valvular atrial fibrillation
Authors: Choi E.-K , Lee S R , Lee S R , Kwon S , Kwon S , Han K D , Han K D , Jung J H , Jung J H , Oh S , Oh S , Lip G Y H , Lip G Y H 
Published: October 2019

Abstract

Background
Although the prescription of non-vitamin K antagonist oral anticoagulants (NOACs) in patients with non-valvular atrial fibrillation (AF) has been rapidly increasing in Asian countries since their introduction, limited evidence exists on the effectiveness and safety of warfarin and all 4 available NOACs from current clinical practice in the Asian population. We aimed to evaluate comparative effectiveness and safety of warfarin and all 4 available NOACs

Methods
We studied a retrospective observational cohort of oral anticoagulant (OAC) naïve non-valvular AF patients treated with warfarin or NOACs (rivaroxaban, dabigatran, apixaban, or edoxaban) from January 2015 to December 2017, based on the Korean Health Insurance Review and Assessment database. For the comparisons, warfarin to 4 NOACs and NOAC to NOAC comparison cohorts were balanced using inverse probability of treatment weighting (IPTW). Ischemic stroke, intracranial hemorrhage (ICH), gastrointestinal bleeding (GIB), major bleeding (MB) and a composite clinical outcome were evaluated.

Results
A total of 116,804 patients were included (25,420 with warfarin, 35,965 with rivaroxaban, 17,745 with dabigatran, 22,177 with apixaban, and 15,496 with edoxaban). Patients treated with warfarin were younger (mean age 67 years) compared to NOAC users (71 to 73 years) and had lower mean CHA2DS2-VASc score (3.18) than the NOAC groups (3.58 to 3.76). Among the NOAC users, patients prescribed apixaban were older (mean age 73 years) than other NOAC groups (71 to 72 years), had higher mean CHA2DS2-VASc score (3.76) than others (3.55 to 3.63) and higher burden of comorbidities. More than half of patients were prescribed reduced dose regimes. After IPTW, all baseline covariates were well balanced across 5 treatment groups. Compared with warfarin, all NOACs were associated with lower risks of ischemic stroke, ICH, GIB, MB and composite outcome (Figure A). Apixaban and edoxaban showed a lower rate of ischemic stroke compared with rivaroxaban and dabigatran (Figure B). Apixaban, dabigatran and edoxaban had a lower rate of GIB and MB compared with rivaroxaban. The composite clinical outcome was non-significantly different for apixaban vs edoxaban.

Conclusions
In this large contemporary observational Asian cohort, all 4 NOACs were associated with lower rates of ischemic stroke and major bleeding compared to warfarin. Differences in clinical outcomes between NOACs may give useful guidance for physicians to choose drugs to fit their particular patient clinical profile.
P4787Use of direct oral anticoagulants in patients with atrial fibrillation having a history of intracranial hemorrhage
Authors: Chao T F , Chen S A 
Published: October 2019

Abstract

Background
Patients with atrial fibrillation (AF) having a history of intracranial hemorrhage (ICH) were excluded from the pivotal randomized trials comparing direct oral anticoagulants (DOACs) and warfarin. We aimed to compare the effectiveness and safety of DOACs and warfarin among AF patients having a history of ICH.

Method
A total of 4,540 AF patients having a CHA2DS2-VASc score ≥1 for males and ≥2 for females who had a history of ICH and received oral anticoagulants (DOACs in 3,493 and warfarin in 1,047) were identified from the Taiwan National Health Insurance Research Database. A propensity matching analysis was performed to balance the baseline differences, and 973 patients were finally identified in each groups.

Results
The risk of ischemic stroke did not differ significantly between warfarin and DOACs (4.41%/yr vs 4.87%/yr; HR 0.985, p=0.927). The risks of bleeding events were lower with DOACs compared to warfarin with a HR (95% CI) of 0.752 (0.573–0.986, p=0.040) for major bleeding and 0.614 (0.379–0.995, p 0.048) for ICH. The risk of mortality was also lower in patients treated with DOACs (HR = 0.539; 95% CI = 0.453–0.642, p<0.001). The cumulative incidence curves of each events for 2 groups are shown in Figure.

Conclusion
Compared to warfarin, DOACs were associated with a similar risk of ischemic stroke and better safety profiles among AF patient with a history of ICH.
P4789Comparisons of direct oral anticoagulants and warfarin in patients with atrial fibrillation and liver cirrhosis
Authors: Chao T F , Lip G Y H , Chen S A 
Published: October 2019

Abstract

Background
Patients with atrial fibrillation (AF) and severe liver cirrhosis were excluded from the pivotal randomized trials comparing direct oral anticoagulants (DOACs) and warfarin. In the present study, we compared the effectiveness and safety of DOACs and warfarin among AF patients with liver cirrhosis.

Method
A total of 3,691 AF patients with liver cirrhosis having a CHA2DS2-VASc score ≥1 for males and ≥2 for females and received oral anticoagulants (DOACs in 2,548 and warfarin in 1,143) were identified from the Taiwan National Health Insurance Research Database. The effectiveness and safety were compared between DOACs and warfarin groups.

Results
There was a trend suggesting a lower risk of ischemic stroke with DOACs compared to warfarin (2.91%/yr vs 3.41%/yr; HR 0.743, p=0.060). The risks of bleeding events were lower with DOACs compared to warfarin with a HR (95% CI) of 0.718 (0.573–0.899, p=0.004) for major bleeding and 0.509 (0.292–0.889, p=0.018) for ICH. The risk of mortality was also lower in patients treated with DOACs (HR=0.483; 95% CI: 0.424–0.551, p<0.001). The cumulative incidence curves of each events for 2 groups are shown in Figure. The results were essentially similar after the propensity matching analysis of 2 groups.

Conclusion
Compared to warfarin, DOACs were associated with a lower risk of ICH, major bleeding and mortality among AF patient with liver cirrhosis.
4935Prognostic influence of MDCT-derived global left ventricular longitudinal strain in patients with aortic stenosis treated with transcatheter aortic valve implantation
Authors: Gegenava T , Bijl P , Vollema M , Kley F , Weger A , Hautemann D , Reiber J , Ajmone-Marsan N , Bax J , Delgado V 
Published: October 2019

Abstract

Introduction
Transcatheter aortic valve implantation (TAVI) is an effective treatment for patients with severe aortic stenosis (AS), It can lead to an improvement in symptoms and quality of life but there is also an increasing recognition that some patients simply fail to derive a functional, morbidity, or mortality benefit post-TAVI. Left ventricular (LV) ejection fraction is the LV systolic function parameter to risk stratify patients with severe AS. However, LV global longitudinal strain (GLS) provides incremental prognostic value to LVEF. Computed tomography plays an essential role in the evaluation of TAVI candidates. Novel software permits analysis of LV GLS from dynamic Multi-detector row computed tomography (MDCT) data.

Purpose
The present study aimed at investigating the prognostic value of MDCT-derived LV GLS in patients undergoing TAVI.

Methods
LV GLS was measured on dynamic MDCT using novel CT-software (Figure, panel A) at baseline. Patients were followed up for all-cause mortality and cumulative event rates were analyzed with Kaplan-Meier method.

Results
A total 214 patients (51% male, 80±7 years) were analysed retrospectively. Mean value of MDCT-derived LV GLS was −12.5±4%. During a median follow-up of 1378 days (interquartile range: 881–1895 days), 67 (31%) patients died. The Kaplan-Meier curve shows, that TAVI recipients with MDCT-derived LV GL S>−14% experienced higher cumulative rates of all-cause mortality, compared to patients with MDCT-derived LV GLS ≤−14% (Chi-square 10.549; Log rank p=0.001) (Figure, panel B). On uni- and multivariate Cox-regression models, MDCT-derived LV GLS demonstrated significant association with all-cause mortality (hazard ratio [HR]: 0.851; 95% confidence interval [CI]: 0.772–0.937; p=0.001).
MDCT LV GLS and survival

Conclusions
MDCT-derived LV GLS is independently associated with all-cause mortality in patients treated with TAVI.
4964Loss-of-spen disturbs cardiac conduction in zebrafish mediated by impaired connexin43 function
Authors: Rattka M , Westphal S , Pott A , Kessler M , Weinmann K , Just S , Rottbauer W 
Published: October 2019

Abstract

Introduction
Genome-wide association studies identified SPLIT ENDS (SPEN) gene as an interesting candidate in the pathogenesis of heart failure. SPEN is known to be of importance in transcriptional regulation in several pathways and knockout in mice results in severe cardiac structural abnormalities and premature intrauterine lethality. Moreover, SPEN was associated with human 1.36 syndrome and is located in the critical region for congenital heart defects. Hence, spen seems to be of importance in cardiac physiology, but not much is known about its biologic function in the heart.

Purpose
The aim of our study was to further deepen the insights on spen's role in cardiac pathology.

Methods
Morpholino-mediated gene knockdown is an excellent method to approach in vivo function of cardiac candidate genes in zebrafish. We conducted spen-specific knockdown experiments and first analyzed the emerging heart failure and arrhythmia phenotype. Next, we assessed possible target genes of the transcriptional regulator spen by gene expression profiling and verified our results by quantitative real-time PCR (qPCR), Western Blot, in situ hybridization and further knockdown- and rescue-experiments.

Results
Spen-deficiency results in severe heart failure and arrhythmia in zebrafish. While in the first 24 hpf (hours post fertilization) spen-morphant embryos develop normally, they exhibit reduced contractility and bradycardia at 48 hpf. From 60 hpf onwards impaired spen function is associated with electrophysiological abnormalities, closely resembling human second grade av block as well as atrial and ventricular fibrillation. Transcriptional profiling of pooled spen-morphant hearts revealed connexin43 (cx43) to be severely downregulated. This finding was verified by qPCR, Western Blot analysis and in situ hybridization experiments. Consequently, we hypothesized cx43 to be transcriptionally controlled by spen and that inadequate function of spen lowers cx43 levels, thereby causing cardiac conduction abnormalities. Subsequently, we performed cx43-knockdown, which phenocopied the spen-morphants phenotype. Importantly, all loss-of function experiments could be rescued by overexpression of wild type cx43 mRNA. Moreover, sensitizing via double injection of sub-phenotypic concentrations of spen- and cx43-morpholinos resulted in a supra-additive effect, validating molecular crosstalk between spen and cx43 on the signaling level. Compared to unaffected controls, over 90% of sensitized embryos display the arrhythmia phenotype and show atrial- and ventricular fibrillation already at 48 hpf.

Conclusion
Our results demonstrate that the transcriptional regulator spen controls the transcription of connexin43 and that impairment of this mechanism leads to severe cardiac arrhythmia in zebrafish.
4972Upfront triple combination therapy with ambrisentan, tadalafil and subcutaneous treprostinil in incident patients with severe pulmonary arterial hypertension
Authors: D'Alto M , Romeo E , Argiento P , Badagliacca R , Papa S , Farro A , Sarubbi B , Russo M G , Vizza C D , Golino P 
Published: October 2019

Abstract

Aim
Current treatments strategies for high-risk patients with pulmonary arterial hypertension (PAH) are based on the use of parenteral prostanoids. The evidence to support triple upfront combination therapy remains largely based on expert consensus or small studies. Aim of this study was to evaluate the efficacy and safety of an upfront triple combination therapy with ambrisentan, tadalafil and subcutaneous (sc) treprostinil in patients with severe PAH.

Methods
This is a multi-center retrospective analysis of patients with newly diagnosed severe PAH treated with upfront triple combination therapy with ambrisentan, tadalafil and sc treprostinil between 2014 and 2018. Clinical evaluations, WHO functional class (FC), 6-min walk distance, biomarkers and right heart catheterization were collected from the patients' medical records at baseline and during the follow-up.

Results
Overall, 20 patients (mean age 44±15 years, 15 female) were included.
Over a median follow-up of 12 months, all patients were still alive on triple combination therapy. At baseline 11 patients were in WHO-FC 3 and 9 patients in WHO-FC 4. At follow-up, WHO-FC (2.0±0.5 vs 3.5±0.5, p<0.001, improved in all: 2, 16, and 2 patients in FC 1, 2 and 3, respectively), exercise capacity (431±67 vs 152±130 m, p<0.001), NT-proBNP (423±260 vs 3492±1864 pg/ml; p<0.001), and haemodynamics (right atrial pressure 5±2 vs 13±3 mmHg, p<0.001; mean pulmonary artery pressure 42±5 vs 60±9 mmHg, p<0.001; cardiac index 3.5±0.8 vs 1.8±0.3 l/min/m2, p<0.001; pulmonary vascular resistance 5.5±1.3 vs 16.4±4.4 Wood units, p<0.001; pulmonary arterial compliance 2.5±0.9 vs 0.8±0.3 ml/mmHg, p<0.001) significantly improved compared with baseline. No patient discontinued the therapy due to serious adverse events.

Conclusions
Triple upfront combination therapy with ambrisentan, tadalafil and sc treprostinil is safe and offers clinical and heamodynamics benefits in incident patients with severe PAH.