bluuebunny/crossref_metadata_2025_split huggingface dataset:
P654Effectiveness of evolocumab for patients with familial hypercholesteraemia (FH) in European clinical practice
Authors: Ray K K , Schoonen M , Annemans L , Van Hout B A , Sibartie M , Bridges I , Bruckert E 
Published: October 2019

Abstract

Background
FH is a genetic disorder which causes lifelong elevations in LDL-C from birth, resulting in a significantly increased risk of premature atherosclerotic cardiovascular disease (ASCVD). In clinical trials among patients with heterozygous FH (HeFH) and homozygous FH (HoFH), evolocumab significantly reduced LDL-C by approximately 40–60% from baseline. Few data are available on evolocumab use among FH patients treated in a real-world setting.

Purpose
Describe the characteristics of FH patients receiving evolocumab in routine clinical practice and their response to therapy.

Methods
This observational study across 10 European countries follows subjects from the date of evolocumab initiation (baseline) for up to 2.5 years, with relevant clinical data abstracted from medical charts (for subjects on apheresis, LDL-C measures included those obtained directly following apheresis). We analysed a cohort of FH subjects from an interim analysis which included subjects initiating evolocumab from Aug 2015 through Jun 2018. FH was diagnosed by the treating physician using standard criteria.

Results
A total of 502 FH subjects were included, 477 had HeFH (95%) and 25 HoFH (5%). The main diagnostic methods used included: the Dutch Lipid Clinic Network criteria (39% of HeFH, 28% of HoFH), genetic testing (27% of HeFH, 36% of HoFH), LDL-C values alone (23% HeFH, 16% HoFH). Mean (95% Confidence Interval [CI]) age was 58 (57–59) years for HeFH and 56 (50–61) for HoFH; 71% and 84% <65 years, respectively. 60% of HeFH subjects were male (HoFH: 40% male). In the overall FH cohort, additional CV risk factors were common (59% hypertension, 15% diabetes, 6% chronic kidney disease ≥ stage 2, 17% current smoker, 22% BMI≥30), with the majority having experienced a prior CV event (77% of HeFH, 80% of HoFH). Among HeFH subjects, 40% were receiving a high intensity statin at baseline, 11% medium intensity, 2% low intensity and 47% no statins. For HoFH, the corresponding values were 36%, 16%, 0 and 40%, respectively. Baseline ezetimibe use was 53% in HeFH and 48% in HoFH. Among HeFH patients, median (IQR) baseline LDL-C was 4.30 (3.41, 5.50) mmol/L; this dropped to 1.73 (1.03, 2.97) mmol/L within 3 months of evolocumab initiation, median LDL-C reduction 56% (Figure 1). Only 20 HoFH patients had a baseline LDL-C value; median (IQR), 4.07 (2.68, 6.17) mmol/L which dropped to 2.59 (1.63, 3.40) by month 3 [n=16]. No serious and no fatal adverse reactions were observed.
Figure 1

Conclusions
In this real-world study of evolocumab use in clinical practice, a large proportion of FH patients were not on statins and had LDL-C levels >4 mmol/L. After initiation of evolocumab median LDL-C fell by about one half in HeFH and by about one third in HoFH. Evolocumab was well-tolerated.

Acknowledgement/Funding
This study was fully funded by Amgen Inc
P657Anticoagulation strategies based on warfarin or direct oral anticoagulants compared to major hemorrhagic events: the relevance of patients aged 75 years or older
Authors: Conti A , Bini G , Renzi N , Bogazzi I C , Mazzucchelli M , Covelli A , Catarzi S , Lencioni A M , Genovesi M , Pisani N , Cipriano A , Ghiadoni L 
Published: October 2019

Abstract

Objective
To evaluate rates of major bleeding (mBleed) associated with anticoagulant treatments in patients (pts) with age ≥75 years (y), referred to hospital in northwest Tuscany.

Methods
We analysed 4-y survey; 302,687 visits; catchment area 197,722 inhabitants, of whom 15,267 on Warfarin (W) and 10,397 on direct oral anticoagulants (DOACs). DOACs were available in the catchment area since 4 y (dabigatran and rivaroxaban), 3 y (apixaban), and 2 y (edoxaban). Overall, 3,373 pts received dabigatran, 4,046 rivaroxaban, 2,141 apixaban, and 839 edoxaban. Pts with hemorrhage were submitted to propensity score matching for mBleed and stratified according to age ≥75 y, and W or DOACs. Primary endpoint was one-month death in pts with age ≥75 y.

Results
Out of 1,919 mBleed enrolled, those of pts aged ≥75 y were 1,127 (59%) versus (vs) 792 (41%) aged <75 y, with 77 (4.0%) one-month death vs 20 (1.0%), respectively; p<0.0001.
Patients on W showed higher rate of mBleed (n=175; 9.1%) compared to DOACs (n=53; 2.8%); p<0.0001. One-month death accounted for 14 (0.7%) vs 1 (0.1%), respectively; p=0.0019. Pts aged ≥75 years were more likely to show female gender and comorbidities including atrial fibrillation; p<0.01. Among DOACs, edoxaban presented the lowest absolute rate of hospital admission for mBleed and dabigatran the highest, although without statistical differences within DOACs (p=0.6454). Interestingly, in the subset of pts aged ≥75 y, within DOACs, we found no statistical difference in one-month mortality, although edoxaban showed one death due to brain mBleed; conversely, we found statistical significance in rate of mBleed. Indeed, edoxaban vs dabigatran showed p=0.0008, edoxaban vs apixaban p=0.0242, edoxaban vs rivaroxaban p=0.0058, apixaban vs rivaroxaban p=0.7093, apixaban vs dabigatran p=0.2279, rivaroxaban vs dabigatran p=0.5087.
Warfarin or DOACs and outcomes Major Bleeding (pts ≥75 y) p value versus pts <75 y p value within group One-month death (pts ≥75 y) p value versus pts <75 y p value within group n=1,127 n=77 Warfarin 175 (9.1%) 0.0001 <0.0001 14 (1.2%) 0.514 0.0019 DOACS 53 (2.8%) 0.0001 1 (0.1%) 0.256 Dabigatran 21 (1.1%) 0.026 0.0088 0 (0%) 0.391 0.8012 Rivaroxaban 16 (0.8%) 0.121 0 (0%) 0.619 Apixaban 13 (0.7%) 0.033 0 (0%) 1 Edoxaban 3 (0.2%) 0.647 1 (0.1%) 0.191 Patients: pts; direct oral anticoagulants: DOACs; p value Yates' correction: p value.
Patients with age >75 years and bleeding

Conclusion
In pts with age ≥75 y, rate of mBleed and short-term mortality were significantly higher than in pts aged <75 y In those pts, DOACs showed significantly lower rate of mBleed, and short-term death. Within DOACs, edoxaban was more likely to show lower rate of mBleed.
P661Nocturnal hypoxemic burden in ambulatory patients with atrial fibrillation: a disease-orientated assessment of sleep-disordered breathing severity
Authors: Linz D , Nalliah C , Baumert M , Kadhim K , Middeldorp M , Elliott A , Lau D , McEvoy D , Kalman J , Sanders P 
Published: October 2019

Abstract

Background
Studies investigating the relationship between sleep-disordered breathing (SDB) and atrial fibrillation (AF) have largely assessed SDB-severity by the apnea–hypopnea index (AHI). However, the AHI does not incorporate nocturnal hypoxemic burden, which may increase the risk of non-paroxysmal AF (nPAF) as the clinical manifestation of more progressed AF substrates. This investigation sought to systematically characterize and compare the composition of AHI and hypoxemic burden with the aim to defining a disease-orientated metric for SDB-severity best associated with prevalent nPAF.

Methods
Polysomnography including overnight oximetry data were obtained in 435 consecutive ambulatory AF patients to determine the composition of AHI (apneas vs. hypopneas), the number of acute episodic desaturations per hour (oxygen desaturation index, ODI) and the composition of total time spent below 90% oxygen saturation (T90Total) attributed to acute desaturations (T90Desaturation). Logistic regression analysis was used to characterize the association with prevalent nPAF.

Results
One hundred sixty-nine AF patients (38%) had nPAF and one third (n=149, 34%) had moderate-to-severe SDB (AHI>15). 82% of the median total AHI (9.4 [3.6–20.1]) could be attributed to hypopneas. Only 29% of events were associated with episodic desaturations, which contributed to 96% (T90Desaturation) of the variation in T90Total. The high variability in durations and nadirs of distinct desaturation events can expose patients to long T90Total, even if the AHI is low. Not AHI, but T90Total and ODI were associated with nPAF independent of gender and age. However, diabetes, hypertension and body mass index contributed more significantly to the overall risk of nPAF.

Conclusions
In AF patients, hypopneas constitute a majority of respiratory events during sleep. Patients with low AHI can still be exposed to high nocturnal hypoxemic burden, which is mainly a cumulative consequence of episodic desaturations. T90Total and ODI, but not AHI, were associated with nPAF independent of gender and age, but concomitant modifiable risk factors made a more significant contribution to the overall risk of nPAF versus PAF.
P662Association of baseline disability and major adverse outcomes in patients with atrial fibrillation: an analysis from the SPORTIF trials
Authors: Proietti M , Lip G Y H 
Published: October 2019

Abstract

Introduction
The modified Rankin Scale (mRS) is usually used to evaluate the degree of disability in patients who have suffered a stroke. Some data suggest that pre-stroke mRS may be associated with clinical outcomes. No data exist about atrial fibrillation (AF) patients.

Purpose
To evaluate if baseline level of disability, evaluated as mRS, is associated with major adverse outcomes in patients with AF

Methods
Data from the SPORTIF III and V trials were used to evaluate study aims. mRS was categorized as follows: i) mRS 0 = No Disability; ii) mRS 1 = Operational Limitation; iii) mRS ≥2 = Disability. Stroke/systemic embolism (SE), death and composite of stroke/SE/acute myocardial infarction (AMI)/death were considered as major adverse outcomes.

Results
Among 7329 patients enrolled in SPORTIF trials, 7325 (99.9%) had data about baseline mRS, with 5587 (76.3%) with mRS 0, 1156 (15.8%) with mRS 1 and 582 (7.9%) with mRS ≥2. Mean (SD) and median [IQR] CHA2DS2-VASc was progressively higher across the three mRS categories (both p<0.001). An adjusted linear regression analysis confirmed that mRS was associated with an increasing CHA2DS2-VASc (unstandardized B: 0.354, 95% confidence interval [CI]: 0.317–0.390, p<0.001]. After a mean (SD) 1.55 (0.40) years of follow-up 184 (2.5%) stroke/SE, 392 (5.4%) death and 597 (8.2%) composite events were recorded. Log-rank test showed that cumulative risk of stroke/SE (p=0.005), death (p<0.001) and composite outcome (p<0.001) was progressively higher across the mRS categories [Figure]. Cox adjusted regression analysis found no independent association between mRS categories and stroke/SE occurrence, but baseline disability (mRS ≥2) was independently associated with death (hazard ratio [HR]: 2.17, 95% CI: 1.65–2.86 compared with no disability). Both operational limitation (mRS 1) and disability (mRS ≥2) were associated with the composite outcome (HR: 1.28, 95% CI: 1.04–1.59 and HR: 1.91, 95% CI: 1.51–2.42, respectively) compared to no disability.
Kaplan-Meier curves

Conclusions
In a large cohort of AF patients derived from a randomized controlled trial, baseline disability was associated with an increased risk of death and composite outcome of stroke/SEAMI/death.

Acknowledgement/Funding
None
P663Identifying patients at risk for atrial fibrillation in the community: a systematic review and meta-analysis of prediction models
Authors: Himmelreich J C L , Veelers L , Lucassen W A M , Van Weert H C P M , Harskamp R E 
Published: October 2019

Abstract

Background
Atrial fibrillation (AF) presents a considerable burden on our health care systems. Early detection of AF may prevent AF-associated complications, such as stroke and heart failure. Given our aging populations, the number of new AF cases is expected to double over the next decades. As such, there is renewed interest to screen for AF in the community. To optimise screening efforts, risk prediction models may help us identify at-risk patients.

Purpose
To identify and evaluate the performance of prediction models for AF that may be applicable for screening in community settings.

Methods
We searched PubMed, Embase, and CINAHL databases for studies that derived and/or validated AF risk models from population-based cohorts. Three investigators independently assessed risk of bias (CHARMS checklist), and performed data extraction and evidence synthesis. The primary expression of associations in meta-analysis was the C-statistic for discrimination between AF and non-AF cases during follow-up, using a random effects model. We calculated 95% prediction intervals (PI) due to high heterogeneity (I2 >30%) in all analyses.

Results
We identified 23 studies that presented data on 8 risk models derived from 18 cohorts with a total of 1,4 million participants from across the globe. Average age in these cohorts ranged from 43–76 years and follow-up ranged from 3 to 20 years. Two of the 8 risk models had a sufficient number of validation studies to be included in the meta-analysis. The CHARGE-AF (Cohorts for Heart and Aging Research in Genomic Epidemiology) score had a summary C-statistic of 0.72 (95%-PI: 0.67–0.77; n=7 cohorts, n=53.040 patients). The FHS (Framingham Heart Study) score for AF had a summary C-statistic of 0.71 (95%-PI: 0.59–0.83; n=4 cohorts, n=19.300 patients). Both models include age, height and weight, blood pressure, prevalent heart failure, and antihypertensive medication use as variables. CHARGE-AF additionally includes race, current smoking, and history of diabetes and myocardial infarction. FHS additionally includes sex, PR interval, and significant murmur.

Conclusions
Currently two risk scores, CHARGE-AF and FHS, have been rigorously tested for predicting atrial fibrillation in general populations. The CHARGE-AF score may present the more promising, user-friendly score for future community screening efforts, as it solely relies on readily available clinical parameters.

Acknowledgement/Funding
This work was supported by the Netherlands Organisation for Health Research and Development (ZonMw) [80-83910-98-13046]
P668Aspirin for primary prevention of cardiovascular disease
Authors: Gelbenegger G , Postula M , Pecen L , Halvorsen S , Lesiak M , Schoergenhofer C , Jilma B , Hengstenberg C , Siller-Matula J M 
Published: October 2019

Abstract

Background
Platelet inhibition by aspirin reduces ischemic events but increases the risk of bleeding events. Yet, the role of aspirin in primary prevention of cardiovascular disease remains unclear.

Purpose
To produce a clinically relevant benefit-risk assessment of aspirin for primary prevention of cardiovascular disease.

Methods
We performed a meta-analysis of aspirin effects in primary prevention of cardiovascular disease comprising 13 randomized-controlled trials in 164.225 patients comparing aspirin versus placebo/control during a mean follow-up period of 6.4 years. Using a random effect model, relative risks and 95% confidence intervals were calculated for each outcome.

Results
Aspirin reduced the relative risk of ischemic stroke by 10% (RR: 0.90; 95% CI: 0.82–0.99), myocardial infarction by 14% (RR: 0.86; 95% CI: 0.77–0.95) and the major adverse cardiovascular events by 9% (RR: 0.91; 95% CI: 0.86–0.95) but was associated with a 46% relative risk increase of major bleeding events (RR: 1.46; 95% CI: 1.30–1.64). Aspirin did not reduce the risk of cardiovascular mortality (RR: 0.99; 95% CI: 0.90–1.08), all-cause mortality (RR: 0.98; 95% CI: 0.93–1.02) or cancer (RR 1.05; 95% CI, 0.87–1.26). Aspirin use did not translate into a net clinical benefit adjusted for event-associated mortality risk (mean 0.034%; 95% CI: −0.18 to 0.25%).
Forest plot of major outcomes.

Conclusions
Aspirin use in primary prevention is associated with a reduced risk of stroke and myocardial infarction, but at a cost of an increased risk of major bleeding.

Acknowledgement/Funding
None
P675Current status of anticoagulation in patients with breast cancer and atrial fibrillation
Authors: Pardo Sanz A , Rincon L M , Guedes Ramallo P , Belarte L , De Lara G , Tamayo A , Cruz A , Contreras H , Martinez A , Huertas S , Portero J J , Monteagudo J M , Marco A , Del Prado S , Zamorano J L 
Published: October 2019

Abstract

Aims
Balance between embolic and bleeding risk is challenging in patients with cancer. There is a lack of specific recommendations for the use of antithrombotic therapy in oncologic patients with atrial fibrillation (AF). We compared the embolic and bleeding risk, the preventive management and the incidence of events between patients with and without cancer. We further evaluated the effectiveness and safety of direct oral anticoagulants (DOACs) and vitamin K antagonists (VKAs) within patients with cancer.

Methods
The AMBER-AF registry is an observational multicentre study that analysed patients with non-valvular AF treated in Oncology and Cardiology Departments in Spain. 1237 female patients with AF were enrolled: 637 with breast cancer and 599 without cancer. Mean follow-up was 3.1 years.

Results
Both groups were similar in age, CHA2DS2-VASc and HASB-LED scores. Lack of guidelines recommended therapies was more frequent among patients with cancer. Compared with patients without cancer, adjusted rates of stroke (hazard ratio [95% confidence interval]) in cancer patients were higher (1.56 [1.04–2.35]), whereas bleeding rates remained similar (1.25 [0.95–1.64]). Within the group of patients with cancer, the use of DOACs vs VKAs did not entail differences in the adjusted rates of stroke (0.91 [0.42–1.99]) or severe bleedings (1.53 [0.93–2.53]).
Follow-up events

Conclusions
Antithrombotic management of AF frequently differs in patients with breast cancer. While breast cancer is associated with a higher risk of incident stroke, bleeding events remained similar. Patients with cancer treated with DOACs experienced similar rates of stroke and bleeding as those with VKAs.
P682Radiotherapy-induced malfunction in cancer patients with cardiac implantable electronic devices
Authors: Imberti J F , Placentino F , Malavasi V L , Demarco G , Lohr F , Boriani G 
Published: October 2019

Abstract

Background
The number of patients with cardiac implantable electronic devices (CIED) requiring a radiation therapy (RT) for cancer treatment is increasing over time. Nevertheless, the rate and predictors of CIED malfunctions are still controversial.

Purpose
The aim of our study is to estimate the prevalence and possible predictors of RT-related CIED malfunctions and to describe malfunction characteristics.

Methods
We retrospectively reviewed medical records of all pacemaker (PM)/implantable cardioverter defibrillator (ICD) patients who underwent RT at our centre between January 2004 and July 2018. We included data from the CIED interrogation performed before the RT course to the first interrogation after the end of the RT course. As a safety measure, during RT a magnet was applied to every ICD and, in all PM-dependent patients, the device was temporarily reprogrammed in V00. Device relocation from the RT field was performed in 2/150 (1.3%) RT courses.

Results
One hundred twenty-seven patients were included, who underwent 150 separate RT courses. Eighty one percent of patients had a PM, while 19% had an ICD. Of note 17.4% of patients were PM-dependent. Neutron producing RT was used in 37/139 (26.6%) patients, whereas marginal neutron producing and non-neutron producing RT was used in 9/139 (6.4%) and 93/139 (67%) patients respectively. The cumulative dose (Dmax) delivered to the CIED exceeded 5Gy only in 2/132 (1.5%) cases. Three device-related malfunctions were found (2%). None of them were life-threatening or lead to a clinical event. All dysfunctions were resolved by reprogramming the device and did not require CIED substitution or leads extraction. Details of dysfunctions included: 1) a partial reset of an ICD, leading to self-reprogramming in safety mode, 2) full reset of a PM, which required the re-initialisation of the device and 3) programming change of the magnetic PM frequency to 30bpm (instead of 90 bpm). In all cases the Dmax delivered to the CIED was <1Gy. A neutron producing RT was used in the first two cases, whereas a non-neutron producing RT was used in the last case.

Conclusions
In accordance with the current literature, our results show that RT in patients with CIED is substantially safe. Malfunctions are uncommon and do not result in clinical events, but can develop even if the Dmax delivered to the CIED is <1 Gy. Device interrogation on a regular basis is advisable to promptly recognise CIED malfunctions.
P6893D echocardiography, arterial stiffness, and biomarkers for detection and prediction of late cardiotoxicity in non-Hodgkin lymphoma
Authors: Mihalcea D , Memis H , Balinisteanu A , Vladareanu A M , Vinereanu D 
Published: October 2019

Abstract

CHOP chemotherapy (cyclophosphamide, doxorubicin, vincristine, prednisone) in non-Hodgkin lymphoma (NHL) is limited by risk of cardiotoxicity. Aim. To define new parameters to detect late cardiotoxicity.

Methods
64 patients (27 men, 59±11 years) with NHL, scheduled for CHOP, with LVEF>50%, were assessed at baseline, after chemotherapy ended and 1 year later, by 3D echo for LVEF and deformation (longitudinal, radial, circumferential, area strain: LS, RS, CS, AS), by echo-tracking for pulse wave velocity (PWV) and wave intensity (WI), and by troponin I and NTproBNP. Cardiotoxicity was defined as LVEF decrease<50%, with >10% from baseline.

Results
10 patients (group I) developed late cardiotoxicity, while 54 patients did not (group II). There was a reduction of LS, CS, AS, and increase of PWV and WI, with greater changes in group I (table). LVEF decrease correlated with LS, CS, AS, PWV, WI, troponin changes (r=0.57, r=0.37, r=0.41, r=−0.53, r=−0.43, r=−0.34 p<0.05). LS reduction after chemotherapy ended was the best independent predictor for LVEF decrease 1 year after therapy completion (R2=0.42 p=0.001). Decrease of LS >22% at the end of treatment predicted late cardiotoxicity with 85% sensitivity and 74% specificity.
Late cardiovascular toxicity parametrs CHOP Group I Group II LS (-%) Baseline 22±2 21±2 Final 14±2† 18±2† After 1 year 11±1† 16±2† CS (-%) Baseline 21±2 21±2 Final 16±2† 19±2† After 1 year 13±2† 15±1† AS (%) Baseline 39±3 40±2 Final 33±2† 37±2† After 1 year 28±2† 35±1 PWV (m/s) Baseline 3.4±1.2 3.3±0.7 Final 6.9±1.5† 4.3±1.4† After 1 year 8.9±2.1† 5.5±1.3† WI (m/s) Baseline 4.2±0.8 4.4±0.6 Final 7.7±1.4† 5.1±0.8† After 1 year 9.4±0.9† 6.1±0.9† Abbreviations in text. †p<0.001.

Conclusion
Assessment of 3D myocardial deformation is able to detect late cardiovascular toxicity, and to predict further LVEF decline in NHL patients.

Acknowledgement/Funding
Grant PCCDI 83/2018 (BIOVEA)