bluuebunny/crossref_metadata_2025_split huggingface dataset:
P3642Predictive value of soluble urokinase-type plasminogen activator receptor for cardiovascular death and non-fatal myocardial infarction in patients with coronary artery disease
Authors: Nikorowitsch J , Borchardt T , Appelbaum S , Ojeda F , Lackner K J , Schnabel R B , Blankenberg S , Zeller T , Karakas M 
Published: October 2019

Abstract

Introduction
Stratification for subsequent coronary events among patients with coronary artery disease (CAD) is of considerable interest due to the potential to guide secondary preventive therapies. Soluble urokinase-type plasminogen activator receptor (suPAR) is expressed on various cells involved in atherogenesis and plaque instability, and has been associated with poor clinical outcomes in patients with various conditions.

Purpose
In this study we investigated the potential role of suPAR as a prognostic biomarker for adverse outcome in patients with CAD, and acute coronary syndrome (ACS) in particular.

Methods
Plasma levels of suPAR were measured in a cohort of 1,703 patients (AtheroGene Study) with documented coronary artery disease –including 626 patients with ACS and 1077 patients with stable angina pectoris (SAP). The main outcome measures were defined as cardiovascular death and non-fatal myocardial infarction (MI). Survival curves for the endpoints considered were computed according to thirds of the suPAR distribution. The equality of survival curves was tested using the log-rank test. Multivariable models adjusted for common cardiovascular risk factors and the biomarkers CRP, NT-proBNP and high-sensitivity troponin I (hs-TnI) in particular were also computed.

Results
The prognostic utility of suPAR was evidenced by survival curves stratified for tertiles of circulating suPAR levels –both, in the overall cohort (p=0.00062), and in the ACS cohort (p=0.00099) with a median follow-up of 3,5 years. In multivariable-adjusted Cox regression analyses the hazard ratio (HR) for the prediction of cardiovascular death was 3.60 for log-transformed suPAR levels (p<0.001) in the overall CAD cohort, whereas it was 3.34 (p=0.003) in the ACS cohort. The HR regarding prediction of the combined outcome cardiovascular death and/or non-fatal MI during follow-up was 2.19 (p<0.001) in the overall cohort, and 2.56 (p<0.001) in the ACS cohort. After multivariate adjustment, including conventional cardiovascular risk factors and hs-TnI, suPAR, after log transformation, still enabled a reliable and strong prediction of future cardiovascular death with a HR of 3.17 (p<0.001) in the overall CAD cohort, and a HR of 2.85 (p=0.014) in the ACS cohort.

Conclusions
Our study demonstrates that suPAR has a strong prognostic value independent of hs-TnI in secondary prevention settings, and thereby might represent a valuable biomarker for risk estimation in CAD.

Acknowledgement/Funding
Stiftung Rheinland-Pfalz für Innovation, European Union 7th Framework Programme, DZHK e.V., ERA-Net, Abbott Diagnostics
P3668In non-critically ill patients suffering from endocarditis partial oral antibiotic therapy is non-inferior to intravenous therapy
Authors: Wernly B , Rezar R , Lichtenauer M , Navarese E P , Alushi B , Hoppe U C , Jung C , Lauten A 
Published: October 2019

Abstract

Introduction
Antibiotic treatment for infective endocarditis is paramount typically consisting of intravenous therapy for up to eight weeks leading to long hospital stays. This often is associated with reduced quality of life for patients and might heighten complication rates. Recently, several trials evaluating the efficacy of partial oral treatment (switching to an oral antibiotic after an initial intravenous therapy for stabilization) versus an intravenous therapy were published. We here meta-analyze all available data.

Methods and results
Overall after screening 1848 studies at title and abstract level four studies including a total of 788 patients were included. Heterogeneity was assessed using the I2 statistic. Primary endpoint was all-cause mortality, secondary endpoint endocarditis relapse. Pooled event rates were obtained for each subset of studies and combined in a fixed-effect meta-analysis, and odds ratios were calculated using a fixed-effects model (Mantel-Haenszel).
A total of 765 patients suffered from primary left-sided endocarditis. From right-sided endocarditis suffered 72 patients. All treatment regimes were adjusted to susceptibility testing. Included patients were evaluated clinically and non-critically ill.
Rate of mortality was lower in partial oral versus intravenous strategy (OR 0.34 95% CI 0.17–0.68; p=0.003; I2 30%): In partial oral group, 11 of 379 patients died, whereas in the intravenous group, 33 of 409 patients died. Endocarditis relapse rates were not dissimilar between intravenous versus oral group (OR 0.55 95% CI 0.26–1.20; p=0.13; I2 0%) with, 10 of 459 patients in the partial oral group and 18 of 456 patients in the intravenous group evidencing a relapse.

Conclusion
Partial oral therapy is non-inferior to intravenous therapy with regards to endocarditis relapse in non-critically-ill patients suffering from both left- and right-sided endocarditis. In this meta-analysis, partial oral therapy was associated with lower mortality rates. This finding certainly needs validation in further future randomized trials comparing partial oral versus intravenous antibiotic treatment in non-critically-ill patients. As partial oral therapy allows shorter hospitalization it might be preferable and improve both quality of care and patients quality of life.
P3671Selexipag dosing and titration in the first 500 patients enrolled in SPHERE (SelexiPag: tHe UsErs dRug rEgistry)
Authors: McLaughlin V , Kim N H , Hemnes A R , Highland K B , Chin K M , Farber H W , Zhao C , Narayan V , Shah M , Chakinala M M 
Published: October 2019

Abstract

Introduction
SPHERE is an ongoing US-based, multicentre, prospective, registry collecting data on use of the oral selective IP prostacyclin receptor agonist selexipag in real-world settings. Here, we report selexipag dosing and titration in the first 500 patients.

Methods
SPHERE, initiated in November 2016, will enrol 800 patients newly initiated on or already treated with selexipag at enrolment who have a documented titration regimen. Patients are followed for up to 18 months. Patients were considered “newly initiated” on selexipag if they were enrolled in SPHERE ≤60 days after starting selexipag and were considered “previously initiated” if they enrolled >60 days after starting selexipag. The highest dose is the maximum dose reached during up-titration within 6 months since initiation. Selexipag “maintenance dose” is defined as the first dose received for ≥14 days without interruption or change; “titration speed” is defined as the highest dose reached within the first 6 months after initiation divided by the time (in weeks) to reach it.

Results
The data cut-off for this analysis was December 20, 2018. Most patients had Group 1 pulmonary hypertension (PH) (95.4%), which was primarily idiopathic (49.6%) or connective tissue disease associated (26.0%). At selexipag initiation 49.8% of patients had functional class III symptoms. At the time of selexipag initiation, 19.2% of patients were on PH therapy containing a prostacyclin pathway agent (PPA) (8.5% with a parenteral PPA). The median maintenance dose of selexipag was 1200 μg BID (IQR: 800–1600 μg BID) and the median time to reach it was 8.1 wks (IQR: 5.3–11.0 wks). Low (≤400 μg BID), medium (600–1000 μg BID), and high (≥1200 μg BID) maintenance doses were attained by 15.1%, 30.8%, and 49.5% of patients, respectively (and in 23.2%, 31.2%, and 36.2%, respectively, in GRIPHON). The median titration speed was 175 μg BID/wk (IQR: 110.5–195.3 μg BID/wk), slower than the protocol-outlined 200 μg BID/wk in GRIPHON. In SPHERE, most patients titrated at speeds <200 μg BID/wk, regardless of whether they were newly (175 μg BID/wk; IQR 118.6, 195.3) or previously (175 μg BID/wk; IQR 109.8, 195.3) initiated. As expected, more patients discontinued due to adverse events in the newly (29.0%) versus previously (14.1%) initiated groups. The most common adverse events leading to selexipag discontinuation were worsening pulmonary hypertension (2.2%), headache (2.0%), myalgia (1.4%), and nausea (1.0%).

Conclusion
The median maintenance selexipag dose in SPHERE was 1200 μg BID. While the median titration speed was 175 μg BID/wk, there was marked variation and the vast majority of patients titrated slower than 200 μg BID/wk. No new safety signals were observed.

Acknowledgement/Funding
Actelion Pharmaceuticals US, Inc.
P3727Left atrial appendage closure in patients with a reduced left ventricular ejection fraction: results from the prospective multicenter German LAARGE registry
Authors: Fastner C , Brachmann J , Lewalter T , Zeymer U , Sievert H , Borggrefe M , Weiss C , Geist V , Krapivsky A , Kaeunicke M , Mudra H , Hochadel M , Schneider S , Senges J , Akin I 
Published: October 2019

Abstract

Background and purpose
Atrial fibrillation (AF) patients with increased thromboembolic risk and contraindications for standard oral anticoagulation (OAC) can profit from an interventional left atrial appendage closure (LAAC). While impaired left ventricular ejection fraction (LVEF) is associated with an increased thromboembolic risk in AF patients, cardiac interventions are often associated with an increase in complications in this patient population, and, therefore, the LAAC procedure's success and benefit has yet to be investigated in this subgroup.

Methods
This prospective, observational LAAC registry included 622 patients with documented LVEF from 37 German centers between April 2014 and January 2016. Patients were categorized into one of three groups: LVEF >55% (preserved; p), LVEF 35–55% (mid-range; mr) and LVEF <35% (reduced; r). Procedure was conducted in a standard fashion, and baseline characteristics, imaging as well as procedural data, intra-hospital and one-year follow-up outcome were registered for each group.

Results
55.3% of patients had a pLVEF, 38.7% a mrLVEF and 5.9% a rLVEF. Patients with rLVEF were more often affected by coronary artery disease (p<0.001 for trend), and had an elevated CHA2DS2-VASc (4.3±1.5 vs. 4.8±1.5 vs. 5.3±1.6; p<0.001) and HAS-BLED score (3.7±1.1 vs. 4.1±1.2 vs. 4.3±0.9; p<0.001). Percentage of prior cerebrovascular events and major bleedings was comparable at baseline (each p=n.s.). Procedural success was high (97.9%), while rates of intra-hospital MACCE (0.5%) and other major complications (4.2%) were low, with no significant difference between the groups (each p=n.s.). MACCE during follow-up was more frequent in rLVEF patients (11.0 vs. 11.3 vs. 27.8%; p=0.013), which was mainly driven by myocardial infarctions and all-cause deaths in this high risk collective. Likewise, Kaplan-Meier estimation showed a lower overall survival in this group (89.7 vs. 89.3 vs. 74.6%; p<0.01). On the contrary, rates of stroke were extremely low across all groups and statistically similar (0.3 vs. 1.0 vs. 0%; p=n.s.). This was 93.4, 82.7 and 100.0% less in comparison to the estimated risk calculated from the CHA2DS2-VASc score

Conclusions
The LVEF had no influence on the procedural success as well as the intra-hospital complications after LAAC. Annual rate of stroke was low across all groups, and risk reduction was substantial especially in this high risk collective, as compared to the estimated risk.

Acknowledgement/Funding
Stiftung Institut für Herzinfarktforschung, Ludwigshafen, Germany
P3783A higher habitual flavonoid intake is associated with a lower risk of atrial fibrillation
Authors: Bondonno N , Murray K , Bondonno C P , Lewis J R , Croft K D , Kyro C , Gislason G , Tjonneland A , Scalbert A , Cassidy A , Piccini J P , Overvad K , Dalgaard F 
Published: October 2019

Abstract

Background
Our understanding of how diet affects future risk of atrial fibrillation (AF) is limited. Evidence suggests that higher habitual intakes of flavonoids, bio-active compounds found in plant-based foods and beverages, lower cardiovascular disease risk, attenuate inflammation, and may have anti-arrhythmic properties.

Purpose
To investigate the association between flavonoid intake and clinically apparent AF in a large cohort of Danish men and women.

Methods
Baseline data from 55 634 participants without AF of the Danish Diet, Cancer and Health Study, recruited from 1993 to 1997, were cross-linked with Danish nationwide registries. Flavonoid intake was calculated from validated food frequency questionnaires using the Phenol-Explorer database. Associations between flavonoid intake and AF hospitalisation were examined using restricted cubic splines based on Cox proportional hazards models with adjustments for age, sex, BMI, smoking status, physical activity, alcohol intake, income, and hyperthyroidism.

Results
After a median [IQR] follow-up of 21 [18–22] years, 6 301 participants were hospitalised with AF. Non-linear associations were observed for total flavonoid intake and for all flavonoid sub-classes. For total flavonoid intake, after adjusting for potential lifestyle confounders and compared to participants in quintile 1 (median intake: 173 mg/day), those in quintile 3 (median intake: 320 mg/day) and quintile 4 (median intake: 494 mg/day) had a significantly lower risk of AF, with hazard ratios (95% CI) of 0.93 (0.87, 0.99) and 0.92 (0.86, 0.98), respectively. Compared to median intake in the lowest quintile, a total flavonoid intake of 1000 mg/day was associated with a lower risk of AF in smokers [0.86 (0.77, 0.96)] but not in non-smokers [0.96 (0.88, 1.05)], a lower risk of AF in high alcohol consumers [>20 g/d: 0.84 (0.75, 0.94)] but not in low-to-moderate alcohol consumers [<20 g/d: 0.97 (0.89, 1.06], a trending lower risk of AF in diabetics [0.76 (0.51, 1.14)] but not in non-diabetics [0.95 (0.89, 1.02)], and a trending lower risk of AF in those with ischaemic heart disease [0.84 (0.65, 1.09)] but not in those without [0.96 (0.89, 1.03), Figure 1].
Figure 1

Conclusion
We observed an inverse association between total flavonoid intake and AF, most notably in sub-populations with known lifestyle and disease risk factors for AF. This finding warrants investigation in randomised controlled trials. If confirmed, ensuring the adequate consumption of flavonoid-rich foods, particularly in individuals “at risk”, may be an important strategy to mitigate AF risk.

Acknowledgement/Funding
The Danish Diet, Cancer, and Health Study was funded by the Danish Cancer Society.
P3793Spironolactone in patients with permanent atrial fibrillation, possible heart failure protective potential
Authors: Dabrowski R , Chwyczko T , Kowalik I , Smolis-Bak E , Borowiec A , Maczynska J , Dobrowolski M , Szwed H 
Published: October 2019

Abstract

Background
Atrial fibrillation (AF) promotes electrical, neurohormonal and structural remodeling of atria and ventricles. Long lasting AF leads to atrial interstitial fibrosis, apoptosis, loss of myofibrils and finally to heart failure (HF).

Purpose
The aim of the study was impact of aldosterone antagonist, spironolactone, on exercise tolerance and neurohormonal activity in patients with permanent AF without symptoms of HF.

Methods
In prospective, randomized study patients with permanent AF at least for 1 year, no signs and symptoms of HF and stable clinical condition were included. Patients were randomized to: beta-blocker plus spironolactone (dose: 25 mg) treatment and rate-control treatment with only beta-blocker. Propranolol, metoprolol and bisoprolol were used, doses were adjusted to achieve resting heart rate 60–80/min. Ergospirometry (CPX) and 6-minute walk (6-MWT) tests were performed during separate days.

Results
Study group consisted of 49 patients, 69% men, mean age 62.1±9.6 without structural and chronic active diseases, mean time of arrhythmia was 5.5 years, Q1: 2, Q3: 8 years. Follow-up was 11.2 months. All patients were treated with beta-blockers, 27 patients were treated with 25 mg spironolactone. Surprisingly physical capacity in 6-minute walk test (6-MWT) in studied patients was not significantly reduced in comparison with values ranges for healthy volunteers. After 11.2 months follow-up significantly longer exercise time (433±113 vs. 367±162 sec, p<0.05) and lower maximal HR (159±25 vs. 165±22 beats/min, p<0.0550) were observed in spironolactone treated group. Other CPX variables did not differ significantly between groups after 11,2 months: VO2: 20.7±5.1 vs. 20.1±4.8 [ml/kg/min]; VO2 as % of normal value: 78.4±15.2 vs. 76.8±15.2; O2 pulse: 12±2.8 vs. 12.7±3.6 [ml/beat]; AT: 1.4±0.3, 1.6±0.5 [L/min]; VE: 74.9±20.0, 72.6±17.9 [L/min]. All spirometric variables worsened after 11.2 months: VC: 4.3±1.1 vs. 3.8±0.8 [L], p<0.0005, FVC: 4.2±1.1 vs. 3.8±1.0 p<0.005 [L], FEV1: 3.1±0.8 vs. 2.8±0.7 [L], p<0.01. In spironolactone treated group after 11.2 months BNP concentrations were significantly lower: Q1: 54, Q2: 83, Q3: 100 vs. Q1: 42, Q2: 93; Q3: 184 ng/L (p=0.025) and aldosterone levels were markedly increased: Q1: 216, Q2: 266; Q3:443 vs. Q1: 169; Q2: 228; Q3:294 ng/dL (p=0.0007).

Conclusions
In patients with permanent atrial fibrillation cardiopulmonary exercise responses were markedly abnormal, but exercise capacity was increased after spironolactone treatment. Deterioration of spirometry results might be due to beta-blocker treatment. In spironolactone treated group BNP levels were significantly lower what may correspond to its heart failure protective activity.
P3804Left ventricular wall thickness measured with computed tomography predicts mitral regurgitation improvement in patients implanted with cardiac resynchronization therapy
Authors: Galand V , Ghoshhajra B , Szymonifka J , Das S , Orencole M , Leclercq C , Truong Q A , Singh J P 
Published: October 2019

Abstract

Background
Secondary mitral regurgitation (MR) is common in heart failure (HF) patients and results in progressive left ventricular (LV) dilatation, papillary muscle (PM) displacement and mitral valve leaflet tethering. In selected HF patients, cardiac resynchronization therapy (CRT) has been proved to reduce MR by LV reverse remodeling, resynchronization of PM insertion site contraction and reduction in MV tenting area and inter PM distance. However, data regarding the impact of LV wall thickness (WT) on MR improvement are scarce.

Methods
In this prospective study, a total 54 patients scheduled for CRT, underwent pre procedural CT. Reduced LV WT was defined as WT<6mm and was quantified as a percentage of total LV area. LV was segmented in 17 segments to assess the number of LV segments with reduced WT. End point was 6-month echocardiographic MR improvement by ≥1 class. For this analysis, we focused on patient with mild (class 2) to severe (class 4) MR.

Results
Among the 54 patients, 38 (70.4%) had mild to severe MR at baseline and a total of 16 (42.1%) experienced MR improvement by ≥1 class at 6 months. there was no difference regarding the co-morbidities, electrocardiogram and echocardiographic parameters between patients with or without MR improvement. However, patients without MR improvement had significant higher NT-pro BNP level at baseline. Interestingly, patients without MR improvement had larger LVWT <6mm area (41.541.5±19.4 vs. 22.4±16.1%, p=0.003) associated with higher number of papillary muscle (PM) inserted in reduced LV WT area. In multivariate analysis, an area ≥25% of LVWT<6mm including at least 1 PM insertion was the only predictor of no MR improvement at 6 months (HR 18.4 (1.25–271.75), p=0.034). Lastly, patients with MR improvement had significant lower rate of basal segments with reduced WT, especially in the lateral location. Of note, patients with MR improvement exhibited fewer rate of postero-lateral WT <6mm segments.
Left ventriculat segmentation

Conclusion
LV WT evaluated using CT is a strong predictor of no MR improvement in HF patients with mild to severe MR and who scheduled for CRT implantation.
P3816Cost-effectiveness of ventricular tachycardia catheter ablation: limitations in the current trial evidence base
Authors: Chen Y , Gomes M , Garcia J V , Lambiase P D 
Published: October 2019

Abstract

Introduction
Randomised clinical trials (RCTs) have suffered from criticisms including a lack of generalisability as well as a lack of cost-effectiveness analysis of the different interventions being studied. Such analyses are used by organisations including the UK's National institute for Health and Care Excellence (NICE) to inform system-level decisions regarding which treatments are funded. There is the potential for a growing chasm to exist between what is the latest innovation in cardiology and what can be afforded.

Purpose
To evaluate the cost-effectiveness of ventricular tachycardia (VT) catheter ablation versus anti-arrhythmic drug (AAD) therapy in ischemic heart disease.

Methods
A decision-analytic Markov model was used to calculate the costs and health outcomes of catheter ablation or AAD treatment of VT for a hypothetical cohort of patients with ischaemic cardiomyopathy andan implantable cardioverter defibrillator (ICD). Model inputs where informed using RCT-level evidence [Table 1] wherever possible. Costs were calculated from a UK perspective.

Results
Catheter ablation vs. AAD therapy had an incremental cost-effectiveness ratio (ICER) of £144,150 (€161,448) per quality adjusted life year (QALY) gained, over a five-year time horizon. The ICER for a ten-year time horizon was £75,074 (€84,083) and £69,986 (€78,384) over the cohort's lifetime. Using probabilistic sensitivity analyses to account for model parameter uncertainty, the likelihood of catheter ablation being cost-effective was only 11%, assuming a willingness to pay threshold of £30,000 used by the NICE [Figure 1].
Table 1. Summary of RCT level source data used to inform Markov model inputs Name of trial SMASH VT VTACH SMS CALYPSO VANISH VISTA Sample size 128 110 111 27 259 118 Mean age 67 66 67 64 68 66 Control AAD AAD AAD AAD AAD Clinical ablation Intervention Ablation Ablation Ablation Ablation Ablation Substrate ablation Length of follow up 22 months 24 months 28 months 6 months 28 months 12 months Mortality (%) 11% [AAD] 7% [AAD] 19% [AAD] 14% [AAD] 28% [AAD] 15% [C-ablation] vs. vs. vs. vs. vs. vs. 9% [Ablation] 10% [Ablation] 17% [Ablation] 15% [Ablation] 27% [Ablation] 9% [S-Ablation] Readmission (%) 19% [AAD] 55% [AAD] 44% [AAD] 50% [AAD] 31% [AAD] 32% [C-ablation] vs. vs. vs. vs. vs. vs. 12% [S-ablation] 6% [Ablation] 33% [Ablation] 39% [Ablation] 38% [Ablation] 25% [Ablation]
Cost-effectiveness acceptability curve

Conclusion
Catheter ablation of VT is unlikely to be cost-effective compared with AAD therapy alone in patients with ischaemic cardiomyopathy implanted with an ICD based on pooled trial evidence. However, better designed studies incorporating detailed and more frequent quality of life assessment are needed to advise health policy in this field and to provide more informed cost-effectiveness analyses.

Acknowledgement/Funding
NIHR Academic Clinical Fellowship