bluuebunny/crossref_metadata_2025_split huggingface dataset:
2372Causes of death and effect of co-morbidities on mortality in young patients with heart failure. Data from the Swedish Heart Failure, Cause of Death and National Patient Registers
Authors: Basic C , Rosengren A , Dahlstrom U , Edner M , Zverkova Sandstrom T , Schaufelberger M 
Published: October 2019

Abstract

Background
The last two decades incidence and prevalence of heart failure (HF) among young patients have increased in Sweden. Up to the beginning of the 21st century mortality in patients with HF has decreased but causes of death and the effects of co-morbidity on mortality in young patients with HF are not well studied.

Purpose
To address causes of death and the effect of co-morbidity at baseline on mortality during the last decade in young patients with HF.

Methods
The Swedish Heart Failure Register (SwedeHF,) a nationwide quality register, was introduced in Sweden in 2003. All hospital discharge diagnoses are recorded in the National Patient Register (NPR) and deaths are registered in the Cause of Death Register. All patients ≥18 and <55 years with a HF diagnosis in SwedeHF were included and linked to the Cause of Death Register and NPR with the personal identification number. ICD 10-codes for all comorbidities and principal cause of death were identified during the observation period from 2003 to 2016. Besides, comorbidity and mortality data were compared with age and sex matched controls from the general population, database from Statistics Sweden (SCB).

Results
We identified 3752 (6.2%) patients <55 years from the total SwedeHF population (n=60,962) and added 7573 age and sex matched controls. There were 971 (25.9%) women and 2781 (74.1%) men mean age 44.9 (8.4) and 46.4 (7.3) years respectively. Among the young 604 (16.1%) patients died vs. 162 (2.2%) among matched controls (p<0.001) during the observation period. Principal cause of death was HF in 2.7% of the young patients (in men 3% vs. 1.4% in women (p=0.221)), other cardiovascular diseases 48.7% (27.7% in men vs. 20% in women (p=0.05)), congenital heart disease 4% (3% in men vs. 6.9% in women (p=0.077)), cancer 12.9% (9.6% in men vs. 23.6% in women (p=0.003)), neurologic disease 4.5% (5.4% in men vs. 1.4% in women (p=0.028)) suicide 0.8% (0.7% in men vs 1.4% in women (p=0.47)) and other causes 15.1% (15.9% in men vs 12.5% in women (p=0.179)) vs. 0, 26.5%, 1.2%, 32.7%, 1.2%, 9.9% and 18.5% in matched controls (all p<0.0001). The effect of co-morbidity at baseline on mortality in young patients with HF is presented in Figure 1.
Effect of co-morbidity on mortality

Conclusion
Compared to matched controls young patients with HF had worse survival. Almost one quarter of women with HF had cancer as a principal cause of death. Men with AF, obesity and depression at baseline had higher risk to die than women. Women with HF and hypertension, PAH or kidney disease at baseline had higher risk to die than men with HF and the same co-morbidities.

Acknowledgement/Funding
Swedish state under the agreement concerning research and education of doctors, The Swedish Heart and Lung Foundation, Västra Götaland Region grants
2410Oncologic radiotherapy-induced implantable cardioverter-defibrillator malfunctions: a real-time, in-vitro evaluation
Authors: Di Girolamo E , Faustino M , Furia N , Appignani M , Marini M , Genovesi D , Di Carlo C , Delana A , Barbareschi A , Falco M D 
Published: October 2019

Abstract

Background
Direct exposure of implantable cardioverter-defibrillators (ICDs) during radiotherapy is still considered not recommended, or even unsafe, by manufacturers and guidelines. The effects of photon beams on ICDs are unpredictable, depending on multiple factors, and malfunctions may occur during exposure.

Purpose
To evaluate transient ICD malfunctions by direct exposure to doses up to 10 Gy during low-energy radiotherapy, 33 contemporary wireless-enabled ICDs, with at least 4 months to elective replacement indicator (E.R.I.) were evaluated in a realtime in-vitro session.

Methods
All ICDs had baseline interrogation. Single chamber ICDs were programmed in the VVI/40 mode and dual or triple chamber ICDs were programmed in the DDD/40 mode. Rate response function and antitachycardia therapies were disabled, with the ventricular tachycardia (VT)/ventricular fibrillation (VF) detection windows still active. A centering computed tomography was performed to build the corresponding treatment plan and the ICDs were blinded randomized to receive either 2, 5 or 10 Gy exposure by a low photon-energy linear accelerator (6MV) in a homemade water phantom (600 MU/min). The effective dose received by the ICDs was assessed by an in-vivo dosimetry. During radiotherapy, the devices were observed in a real-time session using manufacturer specific programmer, and ICD function (pacing, sensing, programmed parameters, detection) was recorder by the video camera in the bunker throughout the entire photon exposure. All ICDs had an interrogation session immediately after exposure.

Results
During radiotherapy course, almost all ICDs (90.9%) recorded major or minor transient electromagnetic interferences. On detail, 13 ICDs (39.4%) reported atrial and/or ventricular oversensing, with base-rate-pacing inhibition and VT/VF detection. 16 ICDs (48.5%) recorded non clinically relevant noise, and no detections were observed. Only 4 ICDs (12.1%) reported neither transient malfunction nor minor noise, withstanding direct radiation exposure. At immediate post-exposure interrogation, the ICDs that recorded major real-time malfunctions had VT/VF detections stored in the device memory. In none of the ICDs spontaneous changes in parameter settings were reported. Malfunctions occurred regardless of either 2, 5 or 10 Gy photon beam exposure.

Conclusions
Transient electromagnetic interferences were observed in most of the contemporary ICDs during radiotherapy course, regardeless of photon dose. To avoid potentially life-threatening ICD malfunctions such as pacing inhibition or inappropriate shock delivery, magnet application on the pocket site or reprogramming devices in the asynchronous mode are still suggested in ICD patients ongoing even low energy radiotherapy exposure.

Acknowledgement/Funding
None
2417Elevated interleukin-6 and interleukin-18 concentrations predict residual inflammatory risk both before and after interleukin-1beta inhibition with canakinumab
Authors: Ridker P M , MacFadyen J , Thuren T , Libby P 
Published: October 2019

Abstract

Background
The Canakinumab Antiinflammatory Thrombosis Outcomes Study (CANTOS) established that targeting inflammation with interleukin-1b (IL-1b) inhibition can significantly reduce cardiovascular event rates in the absence of beneficial effects on cholesterol. Yet, CANTOS participants treated with both statins and canakinumab remain at considerable risk. Both interleukin-6 (IL-6, a central signaling cytokine) or interleukin-18 (IL-18, which like IL-1b requires the NLRP3 inflammasome for activation) may contribute to the recurrent events that occur even on canakinumab therapy, and thus represent novel targets for treating atherothrombosis.

Purpose
To assess the impact of canakinumab therapy on plasma levels of IL-6 and IL-18, and to assess the potential contributions of IL-6 and IL-18 to residual inflammatory risk both before and after treatment with canakinumab.

Methods
Plasma samples from 3,381 stable post-myocardial infarction patients assigned to active IL-1b inhibition within CANTOS underwent measurement of IL-6 and IL-18 both before and after initiation of canakinumab. All participants were followed over a 3.7 year period for major adverse cardiovascular events (MACE) and all-cause mortality.

Results
When compared to placebo, canakinumab significantly reduced IL-6 levels in a dose-dependent manner yielding placebo-subtracted median percent reductions in IL-6 at 3 months of 24.8, 36.3, and 43.2 percent for the 50mg, 150mg, and 300mg doses, respectively (all p-values <0.001). In marked contrast, no dose of canakinumab significantly altered IL-18 levels measured at 3 months (all effects less than 1 percent, all p-values >0.05). Yet, despite these differential plasma effects, both baseline and on-treatment levels of IL-6 and IL-18 associated with rates of future cardiovascular events and with all-cause mortality. For example, for MACE, each tertile increase in IL-6 measured 3 months after canakinumab initiation associated with a 42 percent increase in risk (95% CI 26–59%, P<0.0001) while each tertile increase in IL-18 measured 3 months after canakinumab initiation associated with a 15 percent increase in risk (95% CI 3–29% P=0.015). Similar effects were observed for MACE-plus, cardiovascular death, and all-cause mortality.

Conclusions
These randomized trial biomarker analyses from CANTOS demonstrate that interleukin-1b inhibition with canakinumab significantly reduces plasma levels of IL-6 but not IL-18, yet that there remains substantial residual inflammatory risk related to both IL-6 and IL-18. As such, our data support further pharmacologic development of potential anti-cytokine therapies for atherothrombosis that simultaneously inhibit IL-1b and IL-18 (such as NLRP3 inhibitors) as well as agents that directly target IL-6 signaling.

Acknowledgement/Funding
Novartis
P1217Zirconium-89 labelled probe for molecular imaging of inflammation in experimental atherosclerosis
Authors: Ahmed M , Tegnebratt T , Tran T , Damberg P , Bone D , Lu L , Gistera A , Tarnawski L , Hedin U , Eriksson P , Holmin S , Gustafsson B , Caidahl K 
Published: October 2019

Abstract

Background
Early detection of inflamed atherosclerotic lesions by molecular imaging might improve risk assessment beyond that of vascular stenosis and plaque morphology imaging, and improve the clinical management of high-risk patients.

Purpose
To target the key features of unstable atherosclerotic lesions, we studied the feasibility of our radiotracer, based on modified human serum albumin (HSA), to identify inflamed atherosclerotic lesions by in vivo molecular imaging.

Methods
We applied a maleylated HSA (Mal-HSA) probe, recognised by scavenger receptors on macrophages, in an experimental in vivo imaging study of atherosclerosis. Mal-HSA was coupled with a positron-emittingmetal ion, Zirconium-89 (89Zr). The targeting potential of this probe was evaluated and compared with unspecific 89Zr-HSA and 18F-FDG in a mouse model of atherosclerosis (Apoe−/−, n=22) and compared with wild-type (WT) mice (C57BL/6, n=21) as controls. Radiotracer accumulation in the aortic arch was analysed in vivo by the fusion of positron emission tomography–magnetic resonance imaging (PET-MRI), radiotracer bio-distribution was measured ex vivo by gamma counter, and plaque uptake was evaluated by phosphor imaging (PI) autoradiography (ARG).

Results
PET-MRI, gamma counter measurements, and PI-ARG showed the accumulation of 89Zr-Mal-HSA in the atherosclerotic lesions of Apoe−/− mice. The maximum standardised uptake value (SUVmax) for 89Zr-Mal-HSA at 16 and 20 weeks were 26% and 20% higher (P<0.05) in Apoe−/− mice than control WT mice, whereas no difference in SUVmax was found for 18F-FDG in the same animals. 89Zr-Mal-HSA uptake in the aorta as evaluated by gamma counter 48 h post-injection was 32% higher (P<0.01) for Apoe−/− mice compared to WT mice, and the aorta-to-blood ratio was 10-fold higher (P<0.001) for 89Zr-Mal-HSA compared with unspecific 89Zr-HSA. HSA probes were mainly distributed to the liver, spleen, kidneys, bone and lymph nodes. The PI-ARG results corroborated the PET and gamma counter measurements, showing higher accumulation of 89Zr-Mal-HSA in the aortas of Apoe−/− mice compared to WT mice; 9.4±1.4 vs 0.8±0.3% (P<0.001).

Conclusions
The modified HSA-based radiotracer showed in vivo targeting of inflamed atherosclerotic lesions of mouse aorta, which could also be verified ex vivo. 89Zr-Mal-HSA seems to be a promising diagnostic tool for the identification of vascular inflammation. Further methodological studies are needed to verify its applicability for detecting rupture-prone plaques.

Acknowledgement/Funding
Swedish Research Council (22036); the Swedish HLF (20150423, 20170669); ALF (20150517, 447561, 726481); Söderberg Foundations, VINNOVA and KI
P1221Effect of transcatheter aortic valve implantation on cardiac sympathetic nervous function assessed by 123I-metaiodobenzylguanidine scintigraphy in patients with severe aortic stenosis
Authors: Kadoya Y , Zen K , Tamaki N , Ito N , Kuwabara K , Yamano M , Yamano T , Nakamura T , Yaku H , Matoba S 
Published: October 2019

Abstract

Background
Cardiac sympathetic nervous (CSN) function assessed by 123I-metaiodobenzylguanidine (MIBG) scintigraphy is associated with poor prognosis in patients with heart failure.

Purpose
The aim of this study was to investigate the effects of transcatheter aortic valve implantation (TAVI) on CSN function in patients with severe aortic stenosis (AS) using MIBG scintigraphy.

Methods
This was a single-center prospective observational study that enrolled patients between July 2017 and July 2018. Among 77 registered patients who scheduled to undergo TAVI, 35 patients (7 men; mean age: 87 years) were evaluated. The MIBG scintigraphy was performed at baseline and 6 months after TAVI procedure to evaluate the heart-mediastinum ratio (H/M) and washout rate (WR). The MIBG parameter changes were compared with B-type natriuretic peptide (BNP) levels and echocardiographic parameters, including aortic valve area (AVA), peak velocity (Vmax), mean pressure gradient (PG), and left ventricular ejection fraction (LVEF).

Results
All patients successfully underwent TAVI with improved BNP level (388±341 pg/mL vs. 167±118 pg/mL, p<0.001). The AVA, Vmax, mean PG and LVEF improved after TAVI (0.6±0.2 cm2 vs. 1.6±0.5 cm2, p<0.001; 4.6±0.8 m/s vs. 2.1±0.3 m/s, p<0.001; 54±20 mmHg vs. 9±3 mmHg, p<0.001; 58±11% vs. 63±9%, p=0.01, respectively). In the MIBG imaging, the delayed H/M significantly increased (2.5±0.6 vs. 2.6±0.7, p=0.03), and the WR decreased (32±8% vs. 29±8%, p=0.047) after TAVI. There was a correlation between the changes in the MIBG parameters and the change in mean PG from baseline to 6 months (delayed H/M: r=0.391, p=0.02; WR: r=0.347, p=0.04). Multivariate logistic regression analysis showed that baseline mean PG was an independent predictor of improved both delayed H/M and WR (odds ratio=1.062; 95% confidence interval: 1.009–1.137; p=0.042).

Conclusions
TAVI can improve the CSN function in patients with AS. Such CSN improvement was related with hemodynamic changes.

Acknowledgement/Funding
None
P1228Impact of history of vascular disease on lipoprotein(a) associations with cardiovascular outcomes: a Mendelian randomisation study in 283,658 UK Biobank participants
Authors: Stiby A , Clarke R , Parish S , Hopewell J C 
Published: October 2019

Abstract

Background
Mendelian randomisation (MR) studies have been widely used to assess the causal relevance of risk factors for disease and to elucidate the likely effects of novel drug targets. MR studies have confirmed the causal relevance of lipoprotein(a) [Lp(a)] for risk of coronary heart disease (CHD), but the impact of prior vascular disease on these associations remains unclear, and is potentially important when testing the effects of Lp(a) lowering therapies.

Purpose
To examine the associations of LPA variants, as a proxy for Lp(a) levels, with risk of CHD, ischaemic stroke and peripheral vascular disease (PVD), by history of vascular disease in UK Biobank (UKB).

Methods
An LPA genotype score was constructed in 283,658 unrelated white British UKB participants, using 2 SNPs (rs3798220 and rs10455872) previously shown to be independently associated with, and explain ∼40% of the variance in, Lp(a) levels. The LPA score was tested for association with hospitalisation for CHD (n=23,165), presumed ischaemic stroke (n=2,579) and PVD (n=3,780) using Cox PH models. Estimated hazard ratios (per LPA variant) for cardiovascular outcomes are reported both overall and by history of vascular disease (CHD, ischaemic stroke or PVD) at baseline.

Results
As observed in previous studies, LPA was associated with a higher risk of CHD (Hazard ratio [HR] 1.27 per LPA variant; 95% CI: 1.24–1.31). However, the effect was substantially attenuated in participants with versus without prior vascular disease (p-interaction = 3x10–5; Figure). The effect of the LPA score on PVD was comparable to that for CHD (p-heterogeneity = 0.25), whilst the effect on ischaemic stroke was significantly weaker than that for CHD (p-heterogeneity = 6x10–3). As for CHD, the effects of the LPA score on both ischaemic stroke and PVD were weaker in those with versus those without prior vascular disease. Furthermore, the heterogeneity between the effects on cardiovascular outcomes was more extreme when stratified by history of CHD.

Conclusions
This MR study shows that the effects of LPA on risk of CHD, ischaemic stroke and PVD are weaker in individuals with a history of vascular disease, perhaps reflecting the effects of medications used in this setting. Therefore, MR studies in the general population may overestimate the anticipated effects of Lp(a)-lowering therapies in randomised trials, which are typically conducted in individuals with prior vascular disease.

Acknowledgement/Funding
British Heart Foundation
P1239His-bundle pacing in CHF-patients with narrow QRS and chronic AF using dual-chamber ICD
Authors: Slawuta A , Boczar K , Zabek A , Ciesielski A , Hiczkiewicz J , Vijayaraman P , Malecka B , Gajek J 
Published: October 2019

Abstract

The heart rate regularization is crucial for proper treatment of patients with atrial fibrillation and congestive heart failure. The standard resynchronization can be applied, but in patients with narrow QRS this procedure is of no use.
The aim of our study is to assess the efficacy of direct His-bundle pacing in patients with congestive heart failure and chronic atrial fibrillation using dual chamber ICD implanted for prevention of sudden cardiac death.

Methods
The study population included 78 patients with CHF and chronic AF: group A - 56 pts treated with direct His-bundle pacing using atrial port of dual chamber ICD and group B - 22 patients implanted with single chamber ICD as recommended by the guidelines. The patients in group B constituting clinical controls were derived from the Heart Failure Outpatients Clinic with established clinical status and pharmacotherapy.

Results
The demographic data, clinical characteristics and echocardiography measurements at baseline and during follow-up were presented in the table:
Table 1 Group A Group B P value Age (years) 69.7±6.9 66.7±11.3 n.s. Sex (% of male sex) 84.0 86.4 n.s. Ventricular pacing (%) – 46.3±31.2 – His-bundle pacing (%) 81.7±9.2 – – pre post pre post pre vs. post LVEDD (mm) 66.9±4.9 59.9±4.7 64.8±8.0 64.7±8.1 <0.01 n.s. EF (%) 29.6±3.8 43.6±5.9 28.1±6.1 28.8±7.3 <0.01 n.s. NYHA class 2.7±0.6 1.4±0.6 2.5±0.6 2.0±0.2 <0.05 n.s. B-blocker dose (metoprolol equivalent dose) 104.6±41.6 214.3±82.6 78.3±56.6 103.1±49.2 <0.001 <0.05
During 12-months of follow-up the mean values of NYHA functional class, EF and LV dimensions did not change in group B but significantly improved in group A. The physiological His-bundle based pacing enabled optimal beta-blocker dosing. The studied groups had no tachyarrhythmia at baseline so the presumable atrial fibrillation-related harm depends on the rhythm irregularity.

Conclusions
His-bundle-based pacing in CHF-chronic AF patients contributes to significant echocardiographic and clinical improvement. Standard single-chamber ICD implantation in CHF-chronic AF patients yields only SCD prevention without influence on remodeling process. The CHF-patients with narrow QRS and chronic AF benefit from substantially higher beta-blockade which can be instituted in His-bundle pacing group.
P1254Stroke severity and subsequent mortality are worse with atrial fibrillation than in patients without atrial fibrillation
Authors: Vinding N E , Kristensen S L , Roerth R , Butt J H , Oestergaard L , Olesen J B , Torp-Pedersen C , Gislason G , Koeber L , Fosboel E L 
Published: October 2019

Abstract

Background
Data on stroke severity and prognosis in patients with AF are lacking and contemporary knowledge thereon could help identify preventive strategies.

Purpose
To investigate stroke severity among patients with and without AF, and secondly determine in-hospital and 1-year mortality in the two groups.

Methods
Using the nationwide Danish Stroke Registry we identified patients with first-time stroke (1 January 2005–31 December 2016). Patients with prior or new AF were matched 1:1 by sex, age, and calendar-year with patients with no history of AF. Stroke severity on admission was determined by the Scandinavian Stroke Scale (SSS) (0–29 points indicates very severe to severe stroke, 30–58 points indicates moderate to mild stroke) based on eye movements, paralysis and level of consciousness. The Kaplan-Meier estimator was used to calculate cumulative risk of death in AF patients versus non-AF patients. Risk of 1-year mortality was evaluated in an adjusted multivariable Cox-proportional hazard model.

Results
We identified 90,042 patients with first-time stroke; 16,186 (18.0%) had prior or new AF, and were included in the study, and matched with patients without AF. The median age was 80 years (p25-p75: 72–86 years) and 52.2% were females. AF patients had a higher comorbidity burden and more severe strokes compared with non-AF patients (median SSS 44 (p25-p75: 25–54) vs. 49 (p25-p75: 36–56), P value <0.0001) and higher proportion with very severe to severe stroke (SSS 0–29) (29.7% versus 19.1%, P value <0.0001). In-hospital mortality was higher among AF-patients versus non-AF patients (11.3% vs 7.8%, P value <0.0001). Crude 1-year cumulative risk of death was higher among AF-patients versus non-AF patients (32.3%,95% CI: 31.6%-33.1% vs. 22.9%, 95% CI: 22.2%-23.6%, P value <0.0001) (Figure 1), and this difference remained significant after adjustment (hazard ratio 1.34, 95% CI 1.28–1.40, P value <0.0001).

Conclusion
In a nationwide contemporary stroke registry cohort, AF was associated with adverse stroke severity compared with stroke patients without AF. In-hospital mortality and 1-year mortality was higher among AF patients compared with non-AF patients.

Acknowledgement/Funding
This study was supported by an internal grant from Department of Cardiology, Copenhagen University Hospital, Rigshospitalet, Denmark