bluuebunny/crossref_metadata_2025 huggingface dataset:
P4783Treatment persistence of patients with atrial fibrillation on VKA or NOAC: Data from GLORIA-AF Phase III 1-year interim analysis
Authors: Lip G Y H , Diener H.-C , Dubner S J , Halperin J L , Rothman K J , Ma C.-S , Lu S , Paquette M , Riou Franca L , Zint K , Teutsch C , Huisman M V
Published: October 2019

Background

Oral anticoagulation (OAC) persistence is important for optimizing stroke prevention in patients with atrial fibrillation (AF); non-vitamin K oral anticoagulants (NOACs) generally show better persistence than vitamin K antagonists (VKAs), while the impact of dosing regimens remains unclear. We compared treatment persistence of NOACs and VKAs, and of NOAC dosing regimens in the prospective GLORIA-AF registry program.

Methods

Patients newly diagnosed with AF were enrolled in Phase III of GLORIA-AF (2014–2016) from 4 geographical regions (North America [NA], Europe, Asia and Latin America). Treatment persistence after 1 year for i) NOAC (dabigatran, rivaroxaban, apixaban, edoxaban) vs VKA, and ii) twice daily (bid, dabigatran, apixaban) vs once daily (od; rivaroxaban, edoxaban) NOAC treatment was analysed using multivariable Cox analysis; propensity score trimming was used to reduce bias due to unmeasured confounders. Missing data was handled by multiple imputation.

Results

Overall, 21,592 patients were enrolled (4970 [23%] patients on VKAs, 12,797 [59%] on NOACs, 2391 [11%] on antiplatelets, and 1426 [6.6%] received no therapy; 8 [0.04%] received other treatment). After trimming, 11,935 and 4484 patients treated with NOACs and VKAs, respectively, were compared. NOACs had better treatment persistence than VKAs (discontinuation hazard ratio [HR]=0.75, 95% confidence interval [CI] 0.69–0.81). Other relevant associations were decreased OAC persistence for symptomatic AF, NA and Asia regions (Table). There was no difference in treatment persistence for patients on a bid (N=7842) vs od (N=4098) NOAC (discontinuation HR=0.94, 95% CI 0.86–1.02).

Conclusion

In this 1-year interim analysis of GLORIA-AF Phase III, treatment persistence was improved with NOACs vs VKAs, whereas for NOACs, dosing regimen (bid vs od) had no impact on treatment persistence.

Acknowledgement/Funding

The GLORIA-AF Registry program was funded by Boehringer-Ingelheim
P4785Clinical characteristics and 1-year outcomes in atrial fibrillation patients with or without history of intracranial haemorrhage treated with edoxaban: snapshot analysis of the Global ETNA-AF program
Authors: Kirchhof P , Unverdorben M , Koretsune Y , Wang C C , Kim Y H , Brueggenjuergen B , Lee B C , Levy P , Rauer H , Reimitz P E , Yamashita T , De Caterina R
Published: October 2019

Background

Patients with atrial fibrillation (AF) who survive an intracranial haemorrhage (ICH) are at high risk of stroke, death, and recurrent haemorrhage. Effectiveness and safety of the nonvitamin K antagonist oral anticoagulant (NOAC) edoxaban in this patient population has not been reported.

Purpose

This snapshot analysis from the global ETNA-AF program compared 1-year outcomes in AF patients with and without history of ICH treated with edoxaban from Europe, Japan, and Korea/Taiwan.

Methods

Global ETNA-AF (EU: NCT02944019, Japan: UMINehz745.116117011, Korea/Taiwan: NCT02951039) is a multinational, multicentre, prospective, noninterventional program of AF patients receiving edoxaban in regular clinical care. Demographics, baseline characteristics, and outcomes at 1-year follow-up were reported for 19416 patients with and without a history of ICH.

Results

Of the 19416 patients, 297 had a history of ICH. At 1-year follow-up, incidences of International Society on Thrombosis and Haemostasis (ISTH) major bleeding (including ICH) and clinically relevant nonmajor bleeding (CRNMB) were generally low. The rate of ischaemic stroke was higher in patients with a history of ICH than in those without prior ICH.

Europe (N=7672) Korea/Taiwan (N=1701) Japan (N=10043) History of ICH, n (%) Yes No Yes No Yes No 36 (0.5) 636 (99.5) 27 (1.6) 1674 (98.4) 234 (2.3) 9809 (97.7) Age, median (IQR) 75 (69, 78) 74 (68, 80) 70 (66, 76) 72 (66, 77) 76 (71, 82) 75 (68, 81) Gender, male % 72.2 57.4 70.4 59.9 60.7 59.3 Weight, median (IQR) kg 80.0 (75.0, 88.0) 80.0 (70.0, 92.0) 68.0 (54.0, 77.0) 65.0 (58.0, 73.0) 57.0 (50.0, 65.0) 59.0 (51.0, 68.0) CHA2DS2-VASc, mean (SD) 4.2 (1.44) 3.1 (1.38) 3.9 (1.63) 3.0 (1.43) 4.0 (1.56) 3.4 (1.64) HAS-BLED, mean (SD) 4.3 (1.23) 2.6 (1.12) 3.9 (1.55) 2.4 (10.7) 3.7 (1.07) 2.3 (1.12) CrCl [mL/min], median (IQR) 70.5 (58.8, 85.1) 70.4 (53.8, 90.1) 63.7 (45.8, 84.2) 61.6 (48.4, 78.1) 58.5 (46.0, 73.2) 60.2 (46.1, 77.0) Edoxaban 60/30 mg, % 83.3 / 16.7 77.1 / 22.9 55.6 / 44.4 50.2 / 49.8 21.8 / 78.2 27.8 / 72.2 1-year outcome, n (%/year)   Major bleeding (ISTH) 2 (5.94) 66 (0.92) 0 (0) 13 (0.82) 3 (1.92) 66 (0.96)   Intracranial haemorrhage 1 (2.91) 19 (0.26) 0 (0) 5 (0.32) 1 (0.64) 18 (0.26)   Major GI* bleeding 0 (0.00) 20 (0.28) 0 (0) 2 (0.13) 2 (1.28) 30 (0.43)   CRNMB 0 (0.00) 102 (1.43) 0 (0) 11 (0.70) 6 (3.82) 219 (3.20)   Ischaemic stroke 1 (2.93) 41 (0.57) 1 (4.04) 11 (0.70) 4 (2.57) 78 (1.13) *Gastrointestinal.

Conclusion

Our data underpin the need for effective stroke prevention. In AF patients with a history of ICH, data suggest that edoxaban can be safely and effectively administered in patients with and without prior ICH in regular clinical care.

Acknowledgement/Funding

Daiichi Sankyo
P4788One-year outcomes of elderly patients with atrial fibrillation: snapshot data from the global noninterventional program on edoxaban treatment in routine clinical practice in atrial fibrillation
Authors: Wang C C , Kim Y H , Brueggenjuergen B , De Caterina R , Kirchhof P , Lee B C , Levy P , Rauer H , Reimitz P E , Unverdorben M , Yamashita T , Koretsune Y
Published: October 2019

Background

As populations age, prevalence of atrial fibrillation (AF) and ensuing need for oral anticoagulation increase. Benefits and risks of nonvitamin K antagonist oral anticoagulants such as edoxaban in the frail, elderly population with AF in regular clinical care is of special interest.

Purpose

Data from Global ETNA-AF capturing almost 2ehz745.1164 patients treated with edoxaban in Europe, Japan, and Korea/Taiwan, was analyzed to compare outcomes in patients <75 years, elderly (≥75 years), and very elderly (≥85 years) patients.

Methods

Global ETNA-AF is a multinational, multicentre, prospective, noninterventional program (EU: NCT02944019, Japan: UMINehz745.116417011, Korea/Taiwan: NCT02951039). Demographics, baseline characteristics, and 1-year outcome data were reported for 19416 patients classified into 3 age categories.

Results

At 1-year follow-up, rates of major bleeding (including intracranial haemorrhage [ICH]) and ischaemic stroke were generally low. All-cause and CV mortality increased with age; CV mortality was a minor proportion of all-cause mortality in all age groups. Rates of major bleeding and ischaemic stroke increased slightly with age, but to a lesser extent than all-cause and CV mortality. There was no increase in the rate of ICH with age.

<75 yrs (N=9725) ≥75 yrs (N=9687) ≥85 yrs (N=2186) Age, median (IQR) 68.0 (63.0, 72.0) 80.0 (77.0, 84.0) 87.0 (86.0, 89.0) Gender, male % 65.8 51.5 41.4 BMI, median (IQR) 25.6 (22.9, 29.0) 24.5 (21.9, 27.5) 23.4 (20.8, 26.1) Weight, median (IQR) kg 71.0 (60.0, 84.5) 62.5 (52.9, 75.0) 55.4 (47.6, 67.0) CHA2DS2-VASc, mean (SD) 2.4 (1.28) 4.1 (1.27) 4.4 (1.34) CrCl [mL/min], median (IQR) 78.4 (63.6, 95.9) 52.0 (41.1, 64.5) 40.3 (32.2, 49.4) Edoxaban 60/30 mg, % 64.0/36.0 34.3/65.7 15.8/84.2 1-year outcome, n (%/year)   Major bleeding (ISTH) 57 (0.71) 93 (1.19) 25 (1.53)   Intracranial hemorrhage 22 (0.27) 22 (0.28) 3 (0.18)   Major GI* bleeding 18 (0.22) 36 (0.46) 16 (0.98)   CRNMB** 126 (1.57) 212 (2.73) 56 (3.45)   Ischaemic stroke 53 (0.66) 83 (1.06) 23 (1.41)   All-cause/CV mortality 95 (1.18)/25 (0.31) 224 (2.86)/55 (0.70) 89 (5.44)/23 (1.41) *Gastrointestinal. **Clinically relevant nonmajor bleeding.

Conclusion

Global data from this set of unselected patients support the use of edoxaban as a safe and effective treatment in elderly and very elderly patients with AF in regular clinical care.

Acknowledgement/Funding

Daiichi Sankyo
P4792Dabigatran versus vitamin K antagonists in patients with atrial fibrillation and valvular heart disease
Authors: Strange J E , Sindet-Pedersen C , Staerk L , Grove E L , Gerds T A , Torp-Pedersen C , Gislason G H , Butt J H , Fosboel E L , Olesen J B
Published: October 2019

Background

Atrial fibrillation (AF) and valvular heart disease (VHD) are both associated with an increased risk of stroke. Outside post-hoc analyses of randomized controlled trials, knowledge on the effectiveness and safety of dabigatran in patients with AF and VHD is scarce.

Objectives

To compare the risk of all-cause mortality, stroke, and bleeding in patients with AF and VHD treated with dabigatran or a vitamin K antagonist (VKA).

Methods

All Danish residents are provided a unique personal identification number enabling cross-linking of data from Danish nationwide registries. We identified all patients with AF and VHD initiating treatment with dabigatran or VKA between the 22nd of August 2011 and the 31st of December 2014. We defined VHD as aortic stenosis/regurgitation, mitral regurgitation, bioprosthetic heart valves, mitral-, and aortic valve repair. Outcomes were all-cause mortality, stroke, and bleeding. 2-year standardized absolute risks were calculated from cause-specific Cox regression models with death as competing risk.

Results

In total, 599 (27.3%) and 1,596 (72.7%) patients initiated treatment with dabigatran and VKA. The 2-year standardized absolute risk of all-cause mortality (95% CI) for VKA was 27.6% (25.1% to 30.1%) and 25.4% (21.8% to 29.0%) for dabigatran with a corresponding absolute risk difference of −2.2% (−6.3% to 1.9%) (Figure 1). The 2-year standardized absolute risk of stroke for VKA was 3.4% (2.3% to 4.5%) and 3.9% (2.2% to 5.5%) for dabigatran with a corresponding absolute risk difference of 0.5% (−1.6% to 2.5%). Lastly, the 2-year standardized absolute risk of bleeding for VKA was 8.2% (6.6% to 9.7%) and 7.6% (5.1% to 10.1%) for dabigatran with a corresponding absolute risk difference of −0.5% (−3.4% to 2.4%).

Figure 1

Conclusions

In this nationwide cohort study, we found no significant difference in the risk of all-cause mortality, stroke, or bleeding in patients with AF and VHD when comparing VKA to dabigatran.
P4800Estimated effect of NOACs compared to Vitamin K Antagonists in real-world atrial fibrillation patients: Data from FANTASIA Registry
Authors: Esteve Pastor M A , Rivera-Caravaca J M , Roldan V , Roldan Rabadan I , Muniz J , Cequier A , Bertomeu-Martinez V , Badimon L , Rana-Miguez P , Ruiz-Ortiz M , Anguita M , Lip G Y H , Marin F
Published: October 2019

Background

Despite of the effectiveness and safety profile of Non-vitamin K Antagonists Oral Anticoagulants (NOACs) even in real-world (RW) Atrial Fibrillation (AF) patients, Vitamin K Antagonists (VKAs) have remained widely used in clinical practice worldwide but the comparison with acenocoumarol therapy in RW is unknown.

Purpose

To estimate the potential absolute benefit in clinical adverse events if the AF patients anticoagulated with VKA therapy had been treated with NOACs.

Methods

We analyzed anticoagulated AF patients who were prospectively recruited into the multicentre FANTASIIA registry. Patients were treated with VKAs for at least 6 months prior to inclusion. The estimation of clinical adverse events avoided was calculated applying absolute risk reductions, relative risk reductions and hazard ratios from the meta-analysis of RW use of NOACs relative to VKAs.

Results

We analyzed 1,470 patients under VKA therapy (mean age 74.1±9.5 years; 56.4% male). Stroke rate with acenocoumarol treatment was 0.88%/year. The estimated rates for stroke using NOACs would be 0.80%/year for Dabigatran 150 mg; 0.76%/year for Rivaroxaban and 0.74%/year for Apixaban instead of VKA. No significant differences were observed between the different NOACs and VKA in stroke rate. Major bleeding with acenocoumarol was 3.40%/year. The estimated rates for major bleeding using NOACs would be 2.75%/year for Dabigatran 150 mg; 3.37%/year for Rivaroxaban and 2.18%/year for Apixaban instead of VKA. Apixaban was the only NOAC that showed a significant estimated reduction rates (p=0.046). Finally, the all-cause mortality rate with acenocoumarol was 4.69%/year. The estimated rates of all-cause mortality using NOACs would be 3.28%/year for Dabigatran 150mg; 4.88%/year for Rivaroxaban and 2.67%/year for Apixaban. Dabigatran and Apixaban showed significant estimated reduction rates with the highest reduction with Apixaban (Table).

Annual Rate reduction of adverse events

Conclusion

The absolute estimated effect of NOACs in the AF patients anticoagulated with VKA showed a significant reduction in adverse clinical events. Apixaban performed the highest estimated reduction in major bleeding and all-cause mortality in comparison with acenocoumarol.
4938Left ventricular global longitudinal strain recovery predicts scar size reduction and systolic remodelling post ST-elevation myocardial infarction
Authors: Vo T , Nguyen T , Chen A , French J , Otton J , Mussap C , Richards D , Dimitri H , Thomas L
Published: October 2019

Background

Left ventricular (LV) strain has prognostic utility following ST-elevation myocardial infarction (STEMI); however, serial changes in LV strain has not been evaluated post-infarct. We sought to determine the relationship between post-STEMI transthoracic echocardiographic (TTE) LV global longitudinal strain (GLS) and cardiac magnetic resonance (CMR) imaging derived scar size and LV systolic remodelling.

Methods

Following revascularisation, 172 first STEMI patients (85% male, 56.9±10.7 years) had paired TTE for GLS, and CMR to evaluate scar size and LV systolic function at baseline (2–7 days) and follow-up (8–10 weeks). Patients were divided into 3 groups according to absolute baseline GLS: group 1 (GLS ≥16%), group 2 (12%< GLS <16%), group 3 (GLS ≤12%). GLS recovery was defined as ≥10% increase in GLS at follow-up, excluding patients with normal baseline GLS. LV systolic adverse remodelling was defined as ≥15% increase in LVESV. LV systolic reverse remodelling was defined as ≥15% decrease in LVESV. Scar reduction was defined as ≥30% decrease in scar size.

Results

Group 1 and 2 had smaller follow-up scar size and higher LVEF compared to group 3 (p<0.0001 for both, see table). There was no difference in scar size reduction or systolic reverse remodeling among the baseline GLS groups (p>0.05 for both). Importantly, no patients from group 1 demonstrated systolic adverse remodelling. Relative change in GLS is significantly correlated with changes in LVEF (r=0.354, p<0.0001) and scar size (r=−0.262, p<0.0001), see figure. On multivariate binary logistic analysis, patients who demonstrated GLS recovery had greater reduction in scar size (OR=2.77 (1.09–7.01), p=0.032) and LV systolic reverse remodelling (OR=9.63 (1.21–76.41), p=0.032).

Follow-up parameters within GLS groups All patients (n=172) Group 1 (n=47) Group 2 (n=72) Group 3 (n=53) Follow-up GLS, % 16.02±3.44 19.38±1.90 16.36±2.09 12.57±2.69 GLS recovery, n 110 (64%) 19 (40%) 53 (74%) 38 (72%) Follow-up scar size, % 7.67±5.40 5.01±3.38 6.27±3.73 12.02±6.24 Follow-up LVEF, % 51.80±10.20 57.83±6.95 54.14±8.02 43.26±9.83 Data presented as mean ± SD or n (%).

Correlation graphs for change in GLS

Conclusion

Stratification of STEMI patients by baseline GLS was a determinant of CMR scar size as well as LV systolic function. However, the evaluation of GLS recovery could provide additional insights into reduction in scar size and LV systolic remodelling, both important prognostic markers. Thus, echocardiographic serial GLS evaluation may be a relevant non-invasive parameter, that is cheaper and more widely available for monitoring STEMI patients and guiding therapy.
4942Automated recognition of regional wall motion abnormalities by deep neural network interpretation of echocardiography
Authors: Huang M S , Tsai M R
Published: October 2019

Background

The deep neural network assisted in automated echocardiography interpretation joint to cardiologist final confirmation has now been gradually emerging. There were applications applied in echocardiography views classification, chamber size and myocardium mass evaluation, and certain disease detections already published. Our aim, instead of frame-by-frame “image-level” interpretation in previous studies, is to apply deep neural network in echocardiography temporal relationship analysis – “video-level” – and applied in automated left ventricle myocardium regional wall motion abnormalities recognition.

Methods

We collected all echocardiography performed in 2017, and preprocessed them into numeric arrays for matrix computations. Regional wall motion abnormalities were approved by authorized cardiologists, and processed into labels whether regional wall motion abnormalities presented in anterior, inferior, septal, or lateral walls of the left ventricle, as the ground truth. We then first developed a convolutional neural network (CNN) model to do view selection, and gathered parasternal long/short views, and apical four/two chamber views from each exam, as well as developing view prediction confidence for strict image quality control. Within these images, we annotated part of images to develop the second CNN model, known as U-net, for image segmentation and mark each regional wall. Finally, we developed the major three-dimensional CNN model with the inputs composed of four views of echocardiography videos and then output the final label for motion abnormalities in each wall.

Results

In total we collected 13,984 series of echocardiography, and gathered four main views with quality confidence level above 90%, which resulted in 9,323 series for training. Within these images, we annotated 2,736 frames for U-net model and resulted in dice score of segmentation 73%. With the join of segmentation model, the final three-dimensional CNN model predict regional wall motion with accuracy of 83%.

Conclusions

Deep neural network application in regional wall motion recognition is feasible and should mandate further investigation for promoting performance.

Acknowledgement/Funding

None
4946The effects of climate and air pollutants on heart failure hospitalizations and mortality (CLIMATE-HF Study)
Authors: Ngampongpan W , Yingchonchareon T , Aekplakorn W , Boonhat H , Pattanaprateep O , Sritara P , Yamwong S , Vathesatogkit P , Janwanishstaporn S
Published: October 2019

Background

The data on the effects of air pollution on acute heart failure (HF) in tropical countries is limited. Particulate matter air pollution in Thailand is comparably higher than in other countries in Southeast Asia. The existence of climate and air pollution seasonal variation in our country has never been studied before.

Purposes

We sought to explore the effects of air pollution on HF hospitalizations and in-hospital mortality, including the effects of seasonal variation on HF negative outcomes and the association between air pollutants and hospitalizations of acute heart failure across geographical areas.

Methods

We undertook a retrospective analysis of longitudinal collected clinical data. The Data from 258,539 patients with primary HF admissions and daily pollutant parameters between 2011 and 2015 were collected. Data in daily pollutant parameters including respirable suspended particulates with diameter ≤10 μm (PM10), total suspended particles, ozone, carbon monoxide, nitric oxide, sulfur dioxide, air quality index were obtained. Generalized additive regression models and non-linear distributed lag functions were performed.

Results

440,988 hospital admissions occurred with strong seasonal variation and peaked in winter. Particulate matter ≤10 μm (PM10) 2 days prior to admission date was associated with relative risk (RR) (95% confidence interval (CI)) of 1.02 (1.00–1.04, p-value <0.001) for HF hospitalizations after adjusting with age, sex, respiratory tract infection, acute coronary syndrome and other HF comorbidities (diabetes, hypertension, chronic kidney disease). The association of HF hospitalizations and seasonal PM10 variations was strongest in the Northeastern part of Thailand with RR (95% CI) of 1.04 (1.01–1.05), p-value = 0.005.

Conclusion

HF hospitalizations were associated with preceding PM10 exposure, especially in the area with greater seasonal PM10 variations. Reducing exposure to particulate matter air pollution among those at risk for HF may be the potential prevention of HF hospitalizations.

Acknowledgement/Funding

Research grant from Heart Failure Foundation, Ramathibodi Hospital
4948Irregular eating behavior and incidence of cardiovascular disease: results from a Swedish 60-year-old cohort of men and women
Authors: Laguzzi F , Salleber S , Gigante B , De Faire U , Hellenius M L , Leander K
Published: October 2019

Background

Irregular meals may increase the risk of cardiovascular disease (CVD) but knowledge is limited. We aimed to investigate this association in men and in women, respectively, in a Swedish cohort followed-up for 11 years for incident CVD.

Methods

4,232 participants (54% women) aged 60, randomly selected from Stockholm County in 1997–1998 were followed regarding incident CVD (coronary heart disease or ischemic stroke) up to 2009. Using national registers, 375 incident CVD cases (135 in women) were identified in subjects free from prior CVD events. Self-reported habit of seldom or sometimes having regular meals was compared to reports of often or always having regular meals. Cox proportional models were employed to estimate hazard ratios (HR) with 95% confidence interval (CI).

Results

The habit of having irregular meals was associated with increased risk of CVD in men (HR: 1.70 95% CI: 1.19; 2.43) but not in women (HR: 0.64 95% CI: 0.33; 1.22) in a model adjusted for civil status. Adjustments for smoking, physical activity, obesity and occasional intake of fruits and vegetables did not affect these relationships.

Conclusions

Our results show a clear association between irregular meal patterns and increased risk of CVD in men but not in women. Further studies are needed to confirm these gender specific results and elucidate the underlying biological mechanisms.

Acknowledgement/Funding

The Stockholm County Council, The Swedish Heart-Lung Foundation, The Swedish Research Council for Longitudinal Research, The Swedish Research Council
5163Predictors of adverse cardiovascular events in patients with truncating variants in the filamin c (flnc) gene
Authors: Akhtar M , Rangel-Sousa D , Palomino-Doza J , Arana Achaga X , Bilinska Z , Zamarreno Golvano E , Climent V , Navarro Penalver M , Barriales-Villa R , Charron P , Yotti R , Zorio E , Jimenez-Jaimez J , Garcia-Pavia P , Elliott P M
Published: October 2019

Background

Truncating variants in Filamin C (FLNCtv) are associated with arrhythmogenic (AC) and dilated cardiomyopathies (DCM). Affected patients are reported to demonstrate a high incidence of arrhythmic and heart-failure related cardiovascular events. The aim of this study was to determine factors that predict adverse events in mutation carriers.

Methods

The study cohort comprised 168 FLNCtv carriers followed at 19 European centres. Baseline and longitudinal follow-up clinical data were collected. The primary endpoint was a composite of sudden cardiac death (SCD), aborted SCD, appropriate implantable cardioverter-defibrillator (ICD) shock, cardiac transplantation (HTx) and mortality from end-stage heart failure (ESHF).

Results

47 different pathogenic or likely-pathogenic FLNCtv were identified in 60 unrelated probands. In those with baseline and longitudinal data (160 patients; 57 probands), 114 (71.3%) patients exhibited evidence of cardiac disease at initial evaluation. Gene penetrance was 85% by the age of 40 years. During a median follow-up of 1.5 years (IQR 4.1), 24 individuals (15%) reached the primary endpoint – 16 arrhythmic (SCD/aborted SCD/ICD shock) and 8 heart failure (ESHF/HTx) related-events. Univariable predictors at baseline evaluation of the composite primary endpoint included proband status (HR 4.0, 95% CI: 1.5–10.9, p=0.01), symptoms of dyspnoea (HR 2.8, 95% CI: 1.2–6.4, p=0.02), LV systolic dysfunction (LVSD) (HR 12.4, 95% CI: 2.9–53.2, p=0.001), frequent ventricular ectopy (VE>500) on 24-hour Holter (HR 9.3, 95% CI: 1.2–74.7, p=0.04) and the presence of late gadolinium enhancement on CMR (HR 8.9, 95% CI: 1.2–68.5, p=0.04).

Multivariable analysis identified LVSD (LVEF <50%) at baseline as an independent predictor of the primary endpoint with a hazard ratio of 8.6 (95% CI: 1.8–41.5, p=0.007). ROC analysis using LV systolic dysfunction to predict the primary endpoint demonstrated an area under the curve of 0.84 (95% CI: 0.76–0.91, p<0.001) and identified an optimal LVEF “cut-off” of 47% for predicting adverse events with a Youden's index of 0.61 (sensitivity 0.91; specificity 0.70).

Kaplan-Meier plot to demonstrate freedom

Conclusions

LVSD is associated with an over 8-fold increase in the hazard of a primary endpoint event in FLNCtv gene carriers indicating that these patients should be considered for implantable cardioverter-defibrillator (ICD) implantation, optimal heart failure medical therapy and close clinical follow-up.

Acknowledgement/Funding

NIHR Biomedical Research Centre; Instituto de Salud Carlos III; DETECTIN-HF project; Wellcome Trust;CIBERCV; EU Regional Development Fund; FEDER.
5191Recurrent coronary heart disease in the year following myocardial infarction among US men and women between 2008 and 2015
Authors: Peters S A E , Colantonio L D , Zhao H , Bittner V , Farkouh M E , Dluzniewski P J , Poudel B , Muntner P , Woodward M
Published: October 2019

Background

Although the risk of recurrent events among adults with coronary heart disease (CHD) has declined considerably from the 1970's in the US and many Western countries, studies from the 2000's show that rates remain high. Women have lower rates of incident CHD but little is known about sex differences in recurrent events in adults with CHD.

Purpose

To examine trends in rates of recurrent myocardial infarction (MI), recurrent CHD, and all-cause mortality following a MI hospitalization between 2008 and 2015 among US men and women. Also, we compared sex differences in event rates among individuals with a MI hospitalization versus their counterparts without a history of CHD.

Methods

Data were used from 1,232,024 (53% women) US adults <65 years of age with commercial health insurance in the MarketScan database and US adults ≥66 years of age with government health insurance through Medicare who had a MI hospitalization between January 1, 2008 and December 31, 2015. For each calendar year, age-standardized sex-specific rates of recurrent MI, recurrent CHD (i.e., recurrent MI or coronary revascularization), and all-cause mortality (in Medicare only) were calculated through 365 days following the hospital discharge date for MI. In a secondary analyses, we assessed the rate of recurrent MI, CHD events and all-cause mortality among women versus men with a history of MI (n=324,283) and without a history of CHD (n=1,297,132) in 2014–2015. For these analyses, adjusted hazard ratios (95% confidence intervals) were calculated using follow-up through December 31, 2016.

Results

From 2008 to 2015, age-standardized rates over 365 days of follow-up for recurrent MI declined by 15%, from 94 to 80 per 1000 person-years, in men and by 14%, from 89 to 77 per 1000 person-years, in women. Age-standardized recurrent CHD rates decreased by 16%, from 163 to 138 per 1000 person-years, in men and by 17%, from 142 to 118 per 1000 person-years, in women. In the Medicare population, age-standardized all-cause mortality rates following MI decreased by 6%, from 446 to 421 per 1000 person-years, in men and by 3%, from 412 to 398 per 1000 person-years, in women. In the secondary analyses, the women-to-men hazard ratios for those with a history of MI and those without prior CHD were 0.97 (0.94–0.99) and 0.67 (0.65–0.69), respectively, for MI, 0.89 (0.87–0.91) and 0.52 (0.51–0.54), respectively, for CHD, and 0.84 (0.83–0.85) and 0.74 (0.73–0.75) respectively, for all-cause mortality.

Conclusion

Reductions in rates of recurrent MI, recurrent CHD, and all-cause mortality within 365 days after hospitalization for MI have been similar for US women and men. The lower risk for events comparing women versus men without prior CHD is attenuated after a MI.

Acknowledgement/Funding

The design and conduct of the study was supported through a research grant from Amgen, Inc.
5196Coronary artery calcification predicts MACE and all-cause mortality in individuals undergoing non-cardiac computed tomography for non-cardiovascular indications
Authors: Banerji D , Alvi R M , Ivanov A , Sootodeh R , Olalere D , Will E , Aluru J S , Bogdan S , Osborne M T , Lu M T , Hoffmann U
Published: October 2019

Introduction

Coronary artery calcification (CAC) measured on ECG-gated cardiac CT is a strong predictor of cardiovascular (CV) risk in asymptomatic individuals in a primary prevention setting. However, the prognostic value of CAC in an unselected population referred for non-gated non-cardiac chest CT (NCCT) is unknown.

Purpose

To determine whether CAC predicts major adverse cardiovascular events (MACE) and all-cause mortality in patients referred for NCCT for non-CV indications.

Methods

A random sample of 741 individuals, without prior known history of coronary artery disease (CAD) who underwent NCCT for non-CV indications at a tertiary care hospital in 2008 were included in this study. NCCT was assessed qualitatively for the presence and extent of CAC by two experienced physicians. Data abstraction was performed by electronic medical record (EMR) review. Our primary endpoint of MACE, defined as CV mortality, MI, PCI, CABG, heart failure and stroke as well as secondary endpoint of all-cause mortality, over a median follow up of 8 (IQR 4–10) years, was adjudicated per independent review.

Results

Among 741 individuals (mean age 61.1±15.5 years, 60% female, 91% Caucasian), 57% were hypertensive, 30% had hyperlipidemia, 14% were diabetic and the mean ASCVD score was 12.2±11.6. CAC was present in 425/741 (57.4%) individuals. Among those with CAC, it was mild in 172/425 (40%), moderate in 143/425 (34%) and severe in 110/425 (26%) individuals. Overall, MACE occurred in 115/741 (15.5%) patients. Compared to those without MACE, CAC was more prevalent (83% vs. 53%, p<0.001) and extensive (at least moderate: 67% vs. 28%, p<0.001) in those with MACE. Over a median follow up of 8 (IQR 3–10) years, the presence of any CAC was associated with a 4-fold higher risk of MACE (HR 4.22, 95% CI (1.4–8.9), p<0.001), after adjustment for age and gender. On stratification, severe CAC had a near 9-fold increased risk of MACE (HR 8.8, 95% CI (5.1–15.2), p<0.001), followed by moderate CAC with a near 6-fold increased risk of MACE (HR 5.7, 95% CI (2.8–9.8), p<0.001), and a near doubling of MACE risk with mild CAC (HR 1.99, 95% CI (1.1–4.3), p=0.034). Similar results were observed with all-cause mortality (Figure 1).

Conclusions

CAC is an independent predictor of MACE and all-cause mortality in an unselected patient population referred for NCCT for non-CV indications, which may provide an opportunity to improve population health without the need for additional imaging.

Acknowledgement/Funding

Dr. Banerji and Dr. Alvi were supported by NIH/NHLBI 5T32HL076136.
5203Ablation of scar-related ventricular tachycardia: paced electrogram feature analysis (PEFA) is a novel and effective substrate based strategy
Authors: Crinion D , Hassan Shariat M H S , Gupta D G , Gul E E G , Glover B G , Hashemi J H , Abdollah H A , Simpson C S , Michael K A M , Baranchuk A B , Redfearn D R
Published: October 2019

Background

Ablation of scar related ventricular tachycardia (VT) has been shown to be superior to escalation of drug therapy. However, the incremental benefit remains modest, with 42% experiencing recurrent shocks and 64% appropriate anti-tachycardia pacing (ATP) in the VANISH study. Improved ablation strategies are needed. Paced electrogram feature analysis (PEFA) is a novel substrate based ablation technique.

Purpose

To investigate the effectiveness of the PEFA based VT ablation technique.

Methods

A single centre, prospective study. Consecutive cases of scar related VT that had an implantable cardiac defibrillator (ICD) and no prior ablations were recruited. Close coupled pacing was performed at the right ventricular apex and the VT isthmus(es) identified on high density mapping catheters by increased electrogram (EGM) duration and latency. A algorithm was developed to identify the latest EGM component after the S2 pacing artefact,. This millisecond value was displayed on the geometry as a colour (PEFA map) (St Jude Ensite Precision Electroanatomic Mapping). PEFA identified VT isthmus sites were targeted for ablation (Figure 1). Follow up ICD interrogation data was utilized to assess for VT recurrence.

Results

A total of 20 patients were recruited. These comprised ischaemic cardiomyopathy (CM) (17/20), dilated CM (2/20), and arrhythmogenic CM (1/20), male (18/20), and endocardial only approach (19/20). Mean age was 64.3±11.3 years, ejection fraction 24.4% ± 14.4, and ablation time was 1989.9±1078.1 seconds. Non-inducibility was demonstrated at the end of the case in 18/20. A class I or III anti-arrhythmic drug was continued in 50%. VT recurred in three cases (Day 28,30,55). One death occurred following a stroke on day 181. Mean follow up was 437.5±231.7 days.

Figure 1

Conclusion

This is the largest study to date on PEFA based VT ablation, the first to include non-ischaemic aetiologies, and reports a longer mean follow up. A high proportion of cases were non-inducible, and low VT recurrence rates were observed. PEFA appears to be a promising tool to guide VT ablation targets.

Acknowledgement/Funding

This research was funded in part by the Canadian Institute for Health Research (139080) and a grant from St. Jude Medical.
5205Electrocardiographic predictors of appropriate implantable cardioverter defibrillator therapies in patients with tetralogy of Fallot
Authors: Waldmann V , Bouzeman A , Koutbi R , Bessiere F , Hermida A , Duthoit G , Elbaz N , Messali A , De Guillebon M , Mansourati J , Da Costa A , Martins R , Gourraud J B , Combes N , Marijon E
Published: October 2019

Background

The electrocardiogram (ECG) is widely available and may contribute to a better risk stratification for sudden cardiac death in patients with tetralogy of Fallot. QRS duration has been consistently associated with outcomes, with a lack of specificity for sudden mortality and a relatively low predictive value. New markers such as QRS fragmentation and vectocardiographic parameters have been recently suggested.

Purpose

To identify ECG predictors of appropriate therapies in patients with tetralogy of Fallot and implantable cardioverter defibrillator (ICD).

Methods

The DAI-T4F study is a large ongoing national French registry including all patients with tetralogy of Fallot and ICD (NCT03837574). Information have been collected prospectively since 2010 with annual update. Baseline patient characteristics and clinical events during the follow-up were analyzed with central adjudication. Cox proportional hazard models were used to identify factors associated with appropriate ICD therapies.

Results

A total of 134 patients (median age 41.7 years, 70.7% males) were enrolled. During a median (IQR) follow-up of 6.1 (2.7–10.2) years, 59 (44.0%) patients received at least one appropriate ICD therapy, giving annual incidence of 5.5% and 7.1% in primary and secondary prevention, respectively (p=0.058). Overall, QRSd ≥180ms (p=0.073), QRS fragmentation (p=0.052), and QRS vector magnitude (vm, p=0.327) were not significantly associated with appropriate ICD therapies, whereas QRS fragmentation in right leads (HR=1.7, 95% CI: 1.1–2.9, p=0.039) and the association of QRSd ≥180ms and overall QRS fragmentation (HR=1.9, 95% CI: 1.1–3.4, p=0.036) were associated with an increased risk of appropriates ICD therapies. In patients with ICD for primary prevention (47 patients, 35.1%), 53.8% had QRS fragmentation, 48.6% had decreased QRS vm, and 41.0% had QRSd ≥180ms. In this group, while non-sustained ventricular tachycardia (NSVT) considered isolated was not associated with ventricular events during follow-up (p=0.069), respective combinations with QRSd ≥180 ms (HR=7.2, 95% CI: 1.6–32.7, p=0.011), QRS fragmentation (HR=3.8, 95% CI: 1.2–12.4, p=0.025), or decreased QRS vm (HR=3.6, 95% CI: 1.1–12.1, p=0.042) were all associated with a higher incidence of appropriate ICD therapies. Positive predictive value and negative predictive value were 0.33 and 0.85, 0.58 and 0.74, and 0.36 and 0.84 in patients with NSVT and QRS ≥180ms, NSVT and QRS fragmentation, and NSVT and decreased QRS vm, respectively.

Conclusions

Our findings highlight that cumulative risk score derived from ECG may contribute to improve risk stratification in patients with tetralogy of Fallot, in particular QRS fragmentation and QRS vm in association with QRS duration and other traditional risk factors.
5219A novel senolytic drug, seno-7284 ameliorates age-related cardiometabolic diseases
Authors: Katsuumi G , Katsuumi I , Suda M , Yoshida Y , Hayashi Y , Ikegami R , Wakasugi T , Nakao M , Nagasawa A , Sugimoto M , Mikawa R , Minamino T
Published: October 2019

Background

Senescence at cellular level develops with various genotoxic stresses and it plays a pivotal role in aging and age-related disorders. Recently, it was shown that elimination of senescent cells, so called “senolysis” has potential to become a next generation therapy for age-related disorders including cardiovascular diseases, pulmonary emphysema, Alzheimer's diseases, etc. However, currently there is no senolytic agent available in clinical settings.

Purpose

Present study was aimed to identify a novel senolytic agent effective for cardiometabolic diseases in compounds already available in clinical settings. Here we demonstrate a compound called “seno-7284” exhibits senolytic effect in murine models of type 2 diabetes, atherosclerosis and progeroid.

Methods

We generated 1) diet-induced obase and diabetic model by imposing a high fat diet for two months, 2) atherosclerosis mice model by imposing western diet to ApoE homozygous knockout mice (ApoE-KO mice) for three months, and 3) Zmpste24 homozygous knockout mice (Zmpste24-KO mice) as a progeroid mice model. We administrated seno-7284 by mixing it into the diet (0.03% w/w). In one, two or four weeks after the administration of seno-7284 to each mice model, we collected tissue samples for further analyses.

Results

Seno-7284 reduced the accumulation of senescent cells in visceral adipose tissue of dietary obese mice as senescence-associated beta-galactosidase (SA-beta-gal) staining exhibits (Figure a). This effect was associated with the suppression in systemic glucose intolerance (Figure b), and adipose tissue inflammation in four weeks after the administration of seno-7284. Administrating seno-7284 for two weeks also reduced accumulation of senescent cells in atherosclerotic lesion in aorta of ApoE-KO mice (Figure c), and inhibited the progression of atherosclerosis (Figure d). Surprisingly, this drug significantly improved the lifespan of Zmpste24-KO mice by administering it from 12 weeks old. Further analysis including RNA-seq or metabolomic analysis suggested that seno-7284 stimulates endogenous senolytic function of NK cells and CD8+ T cells.

Conclusion

Our results indicate that seno-7284 mediates its biological effects by inducing senolysis in some murine aging models. Seno-7284 would become a promising therapeutic agent for age-related cardiometabolic diseases.
5948Circulating biomarkers of cell adhesion in relation to clinical outcomes in patients with chronic heart failure: the Bio-SHiFT study
Authors: Bouwens E , Van Den Berg V J , Akkerhuis K M , Baart S , Caliskan K , Brugts J J , Mouthaan H , Van Ramshorst J , Germans T , Umans V A , Boersma H , Kardys I
Published: October 2019

Background

Cardiovascular inflammation and vascular endothelial dysfunction are present in chronic heart failure (CHF), and cellular adhesion molecules are considered to play a key role in these mechanisms. The temporal patterns of the blood biomarkers involved could provide further insights into these processes.

Purpose

We aimed to evaluate the prognostic value of the temporal patterns of blood biomarkers of cell adhesion in stable patients with CHF.

Methods

In 263 patients, a median of 9 (IQR: 5–10) serial, tri-monthly blood samples were collected during a median follow-up of 2.2 (IQR: 1.4–2.5) years. The composite primary endpoint (PE) of cardiovascular mortality, HF-hospitalization, heart transplantation and LVAD was reached in 70 patients. For efficiency, we selected all baseline samples, the two samples closest to a PE, and the last sample available for event-free patients. Thus, in 567 samples we measured twelve biomarkers of cell adhesion using the Olink Proteomics Cardiovascular III multiplex assay. Associations between biomarkers and first PE were investigated by combining linear mixed effect models and Cox regression (so-called joint model).

Results

Median age was 68 (IQR: 59–76) years, with 72% men and 74% NYHA class I-II. Levels of CD93 (Complement component C1q receptor), CDH5 (VE cadherin), CHI3L1 (Chitinase-3-like protein 1), EPHB4 (Ephrin type-B receptor 4) and JAM-A (Junctional adhesion molecule A) differed at baseline already. The average biomarker evolutions of these markers, and additionally of ICAM-2 (Intercellular adhesion molecule-2), showed different patterns in patients approaching the PE versus those who remained event-free (Figure 1). Repeatedly measured levels of these biomarkers were independently associated with the PE. Corresponding HRs [95% CI] per 1SD increase in log2 level (arbitrary unit) were: CD93: 1.85 [1.29–2.70], CDH5: 1.72 [1.23–2.44], CHI3L1: 2.45 [1.73–3.56], EPHB4: 1.83 [1.33–2.55], ICAM2: 1.74 [1.24–2.46] and JAM-A: 2.07 [1.39–3.18], adjusted for clinical characteristics (age, sex, diabetes, atrial fibrillation, baseline NYHA class, diuretics, systolic blood pressure and eGFR).

Figure 1. Average temporal patterns of cell adhesion biomarkers during follow-up.

Conclusion

CD93, CDH5, CHI3L1, EPHB4, ICAM2 and JAM-A show different patterns as adverse events approach in CHF patients, and their temporal patterns strongly predict clinical outcome. These findings demonstrate the incremental value of repeated measurements of biomarkers of cell adhesion in stable patients with CHF.

Acknowledgement/Funding

This work was supported by the Jaap Schouten Foundation and the Noordwest Academie.
5969The experiences of women with a subcutaneous implantable cardioverter defibrillator
Authors: Van Der Stuijt W , Quast A B E , Baalman S W E , Wilde A A M , Knops R E
Published: October 2019

Introduction

The subcutaneous implantable cardioverter defibrillator (S-ICD) is positioned in close proximity of the left mamma. In female patients, this may result in issues, such as limitations in clothing, breastfeeding or self-perception. Moreover, female patients are underrepresented in most large S-ICD studies, thus underexposing these gender-specific issues which may impact their daily life substantially.

Objective

To assess the issues female S-ICD patients are experiencing and provide practical “tips and tricks” for cardiologists and implanters to minimalize gender-specific issues.

Methods

All female patients implanted with an S-ICD in a large tertiary center between February 2009 and November 2018 received a single questionnaire with questions on physical, esthetical and situational issues.

Results

Patients were categorized in three age groups, 18–39 years (n=32), 40–55 years (n=35) and >55 years (n=19). Eighty-four percent of the patients experienced pain after S-ICD implant, almost half (42.9%) of those patients reported extreme pain. After S-ICD implant, self-perception was altered in a small group (20%) and a third of the patients does not wear the same clothing as before. During sexual activity, many female patients actively avoid the touch of their partner on the lead and generator due to discomfort. While no-one reported problems with childbirth or breastfeeding, two patients did experience irritation from the lead during their pregnancies, possibly due to growth of the mammae. The majority of patients (64%) experiences daily discomfort while wearing a bra, specifically with the linings and the sideband (figure A and B). Women prefer a more cranial position of the S-ICD generator with the lower sideband supporting the device (figure C). A position of the S-ICD generator posterior from the lining of the left cup also reduces discomfort.

Conclusion

Female S-ICD patients experience a variety of gender-specific issues with a substantial impact on their daily life. Implanters should provide adequate counseling and use bra position during pre-implant marking to minimize daily discomfort of female patients.
6072Risk of stroke in hypertensive patients with atrial fibrillation treated with oral anticoagulants
Authors: Harskamp R E , Lucassen W A M , Lopes R D , Van Weert H C
Published: October 2019

Background

Hypertension is common in patients with atrial fibrillation (AF) and carries an additional risk for complications, most notably stroke and bleeding. We assessed the history of hypertension, level of blood pressure control, and an interaction with the choice of oral anticoagulants on clinical outcomes.

Purpose

To gain insights into the risks of hypertension in the setting of AF and explore possible interactions with the safety and efficacy of non-vitamin K oral anticoagulants (NOACs) versus vitamin K antagonists (VKAs).

Methods

We performed a systematic review and meta-analysis of studies that randomised patients to NOACs or VKAs and reported outcomes stratified by presence of hypertension. Collected outcomes included: ischaemic stroke or systemic embolism (SE), death from any cause, hemorrhagic stroke, major bleeding, and intracranial hemorrhage. Log adjusted hazard ratios (HR) and corresponding standard error were calculated, and HRs were compared using Mantel-Haenszel random effects. Quality of the evidence was assessed with Cochrane risk of bias tool.

Results

Five high-quality studies were eligible, including 71,602 participants who received NOACs (apixaban, dabigatran, edoxaban, rivaroxaban) or VKAs, with median follow-up of 1.8–2.8 years. 89.2% of participants had a history of hypertension. Compared with patients without hypertension, those with controlled and uncontrolled hypertension had higher risk for stroke/SE (HR: 1.21 [1.04–1.41] and HR: 1.50 [1.12–2.01], respectively) and haemorrhagic stroke (HR: 1.78 [1.06, 3.00] and HR: 1.66 [0.99–4.01], respectively). On a continuous scale, the risk of stroke increased 7% per 10mmHg increase in systolic blood pressure. As shown in the Table, no interactions were found between hypertension status and the efficacy or safety of NOACs versus VKAs.

Table 1. Interaction of presence of hypertension on the comparative efficacy and safety of NOAC versus VKA Hypertension (n=63,869) No hypertension (n=7,733) P-value (int) Adjusted HR, 95% CI Adjusted HR, 95% CI Stroke or systemic embolism 080, 0.72–0.89 0.79, 0.53–1.19 0.98 Haemorrhagic stroke 0.55, 0.41–0.74 0.24, 0.04–1.37 0.36 Death from any cause 0.91, 0.84–0.98 0.89, 0.76–1.04 0.82 Major bleeding 0.90, 0.76–1.07 0.84, 0.69–1.01 0.57 Intracranial haemorrhage 0.41, 0.24-.068 0.48, 0.14–1.69 0.81 Major or clinically relevant non-major bleed 0.90, 0.68–1.18 0.91, 0.55–1.53 0.96

Conclusions

Adequate blood pressure management is vital to optimally reduce the risk of stroke in patients with atrial fibrillation. The benefits of NOACs over VKAs, also apply to patients with elevated blood pressure.