bluuebunny/crossref_metadata_2025_split huggingface dataset:
3256Long-term safety of stereotactic body radiotherapy for ablation of ventricular tachycardia: a multicentric study
Authors: Cvek J , Knybel L , Neuwirth R , Jiravsky O , Sramko M , Peichel P , Januska J , Resova K , Kautzner J 
Published: October 2019

Abstract

Background
Contemporary stereotactic body radiotherapy (SBRT) enables to accurately concentrate high radiation doses to small volumes of myocardial tissue. There is a rising interest in using SBRT to modify arrhythmogenic substrate in patients with previously failed radiofrequency catheter ablation. However, data on the safety of SBRT for the treatment of VT are lacking.

Purpose
This study evaluated the long-term safety of SBRT for the treatment of VT.

Methods
SBRT was performed in patients with structural heart disease and failed catheter ablation for VT. The critical part of the VT substrate was identified by electroanatomic mapping (EAM) using a combination of voltage mapping, pace mapping, and activation mapping; and it was marked on a contrast-enhanced computer tomography study as a target for radioablation. SBRT was performed using a radiosurgery system with real-time motion tracking using the tip of the electrode of an indwelling defibrillator as a fiducial marker. A total radiation dose of 25 Gy was delivered to the ablation target in a single session during free breathing. Radiation-induced toxicity was evaluated according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.

Results
Between 2014 and 2018, 18 patients from two electrophysiology centres underwent SBRT for recurrent, drug-resistant VT after previously failed catheter ablation (17 male, 1 female; mean age 63±9 years; 14 ischemic cardiopathy, 3 dilated cardiopathy, 1 fibroma). The mean volume of the ablation target was 34±17 ml, and the mean duration of the therapy was 78±14 minutes. No patient exhibited acute (up to 3 months) elevation of troponin, pericardial effusion, or a decrease in left ventricular ejection fraction from baseline. Four patients developed acute mild nausea, which waned after antiemetic drugs. Two patients gradually developed significant progression of mitral regurgitation after SBRT. One of the patients was treated medically (grade 3 toxicity), but the other had to undergo mitral valve replacement (grade 4 toxicity). No other cardiac or pulmonary radiation related toxicity was observed during a median follow-up of 23 months. Three patients died at 54, 43, and 18 month after SBRT. None of the deaths was related to VT recurrence or complication of SBRT.
CARTO, Radiation dose and Survival

Conclusions
This is the largest series of patients who underwent EAM-guided SBRT for VT as a bailout therapy after previously failed radiofrequency catheter ablation. Our preliminary data indicate the feasibility and safety of the procedure. To further investigate long-term safety and efficacy of SBRT for VT, we initiated a prospective multicentric study (NCT03819504).

Acknowledgement/Funding
Supported by RVO-FNOs/2014
3269Impact of type 2 diabetes on incidence and phenotype of heart failure in patients with atrial fibrillation
Authors: Polovina M , Milinkovic I , Krljanac G , Veljic I , Petrovic-Djordjevic I , Djikic D , Simic J , Pavlovic A , Kovacevic V , Asanin M , Seferovic P M 
Published: October 2019

Abstract

Background
Type 2 diabetes (T2DM) portends adverse prognosis in patients with atrial fibrillation (AF). Whether T2DM independently increases the risk of incident heart failure (HF) in AF is uncertain. Also, HF phenotype developing in patients with vs. those without T2DM has not been characterised.

Purpose
In AF patients without a history of prior HF, we aimed to assess: 1) the impact of T2DM on the risk of new-onset HF; and 2) the association between T2DM and HF phenotype developing during the prospective follow-up.

Methods
We included diabetic and non-diabetic AF patients, without a history of HF. Baseline T2DM status was inferred from medical history, haemoglobin A1c levels and oral glucose tolerance test. Study outcome was the first hospital admission or emergency department treatment for new-onset HF during the prospective follow-up. The phenotype of new-onset HF was determined by echocardiographic exam performed following clinical stabilisation (at hospital discharge, or within a month after HF diagnosis). HF phenotype was defined as HFrEF (left ventricular ejection fraction [LVEF] <40%), HFmrEF (LVEF 40–49%) or HFpEF (LVEF≥50%). Cox regression analyses adjusted for age, sex, baseline LVEF, comorbidities, smoking status, alcohol intake, AF type (paroxysmal vs. non-paroxysmal) and T2DM treatment was used to analyse the association between T2DM and incident HF.

Results
Among 1,288 AF patients without prior HF (mean age: 62.1±12.7 years; 61% male), T2DM was present in 16.5%. Diabetic patients had higher mean baseline LVEF compared with nondiabetic patients (50.0±6.2% vs. 57.6±9.0%; P<0.001). During the median 5.5-year follow-up, new-onset HF occurred in 12.4% of patients (incidence rate, 2.9; 95% confidence interval [CI], 2.5–3.3 per 100 patient-years). Compared with non-diabetic patients, those with T2DM had a hazard ratio of 2.1 (95% CI, 1.6–2.8; P<0.001) for new-onset HF, independent of baseline LVEF or other factors. In addition, diabetic patients had a significantly greater decline in covariate-adjusted mean LVEF (−10.4%; 95% CI, −9.8% to −10.8%) at follow-up, compared with nondiabetic patients (−4.0%; 95% CI, −3.8% to −4.2%), P<0.001. The distribution of HF phenotypes at follow-up is presented in Figure. Among patients with T2DM, HFrEF (56.9%) was the most common phenotype of HF, whereas in patients without T2DM, HF mostly took the phenotype of HFpEF (75.0%).

Conclusions
T2DM is associated with an independent risk of new-onset HF in patients with AF and confers a greater decline in LVEF compared to individuals without T2DM. HFrEF was the most prevalent presenting phenotype of HF in AF patients with T2DM.
3284Quantification of macrophage presence and identification of thin-cap fibroatheroma by optical coherence tomography image: histopathological validation study
Authors: Fujii K , Kawakami R , Imanaka T , Shibutani H , Kawai K , Hirota S , Shiojima I 
Published: October 2019

Abstract

Background
Intracoronary optical coherence tomography (OCT) is thought to be capable of identifying a vulnerable, rupture-prone plaque based on the presence of a thin-cap fibroatheroma (TCFA). Moreover, recent studies have reported that OCT may be able to identify macrophage infiltration of the fibrous cap, a key characteristic of vulnerable plaque.

Purpose
This study evaluated the accuracy of OCT image for characterizing TCFA and identifying macrophage infiltration in comparison with histopathology.

Methods
A total of 924 focal plaques in 206 coronary arteries from 78 autopsy hearts were examined to compare OCT and histological images. By histology, 16 plaques (1.7%) were classified as TCFAsthat contained a large necrotic core covered by a thin (<65μm) fibrous-cap. Correlating OCT-histological sections were identified and OCT-derived tissue property indexes named normalized standard deviation (NSD) and signal attenuation ratio were applied on the fibrous-cap to identify inflamed fibrous-cap defined as a macrophage percentage >10% by histology.

Results
With histology as standard, the sensitivity, specificity, and negative-predictive-value of TCFAs were extremely high (more than 90%). However, the positive-predictive-value of TCFAs was only 32%, which indicated a high proportion of false-positives. Most false-positive diagnoses of OCT for TCFAs contained large amounts of foam cell accumulations on luminal surface without necrotic core. Twelve of 16 fibrous-caps were considered as inflamed and the remaining 4 were non-inflamed on histology. However, no significant difference in NSD and signal attenuation ratio were identified between them. There was moderate correlation of the fibrous-cap thickness between OCT and histology (r2 = 0.41 and p<0.01).

Conclusions
OCT is a promising intracoronary imaging modality for differentiating tissue characteristics (fibrous, calcified, or lipid-rich plaque) and identifying TCFA. However, it is still challenging to precisely identify inflammation, fibrous-cap thickness, and necrotic core in the native coronary artery. Therefore, careful interpretation is required to assess coronary vulnerable plaque by OCT.

Acknowledgement/Funding
None
3300MiR-126-3P and MiR-223-3p in Prediction of Thrombotic Risk in Patients with Acute Myocardial Infarction and Primary Angioplasty, The Prague-18 Genetic Sub-study
Authors: Hromadka M , Motovska Z , Karpisek M , Hlinomaz O , Miklik R , Tousek F , Jarkovsky J , Rokyta R , Krepelkova I , Izakova J , Widimsky P 
Published: October 2019

Abstract

Background
Balancing the intensity and duration of antiplatelet therapy according to thrombotic risk is a fundamental need in order to optimize therapy effectiveness and safety. Incorporation of new predictors in thrombotic risk stratification is therefore of a crucial importance for antiplatelet therapy net clinical benefit.

Purpose
The present analysis aimed to evaluate the relation of miR-126-3p and miR-223-3p, new markers of platelet activation, in order to facilitate prediction of recurrent thrombotic events after acute myocardial infarction (AMI).

Method
The analysis included 598 patients (age median 62 years, men 77.8%) randomized in the Prague-18 study (ticagrelor vs. prasugrel in AIM treated with primary PCI). During the study follow up, 40.6% of patients switched to clopidogrel. Determination of miR was evaluated 24 hours after admission; miR-126-3p and miR-223-3p were normalized by miR-423-3p and miR-150-5p. Quantitative determination of selected miRNAs was performed with a novel microRNA immunoassay method.
Selected miRNAs were compared with key efficacy endpoints (cardiovascular death, nonfatal MI and stroke), stent thrombosis and all hemorrhagic events, and analysed using univariate and multivariate logistic regressions.

Results
Increased values of miR-223-3p were significantly related to the occurrence of combined ischemic endpoint within 30 days [OR (95% CI) 15.739 (2.066; 119.932) p=0.008] and within one year [3.175 (1.40; 7.186) p=0.006]. Decreased ratio of miR-126-3P/miR-223-3p was significantly related to the occurrence of combined ischemic endpoint within 30 days [0.137 (0.031; 0.609) p=0.009] and one year [0.372 (0.169; 0.819) p=0.014]. MiRNAs were identified as independent predictors even after adjustment for confounding clinical predictors (Study arm, Switch to Clopidogrel, Age, Men, BMI, Smoking, History of Hyperlipidemia, Hypertension, DM, MI, PCI, CABG, Chronic heart failure, Chronic renal failure, Peripheral arterial disease, LBBB, RBBB, TIMI <3 after PCI, Number of diseased vessels >1, Stem disease, Suboptimal of failure of PCI, Time to hospital). Adjusted ORs (95% CI) are 11.828 (1.472; 98.011), p=0.022 and 2.394 (1.021; 5.610), p=0.045 for increased value of miR-223-3p and the occurrence of combined ischemic endpoint within 30 days and one year respectively; 0.151 (0.030; 0.757), p=0.022 and 0.407 (0.179; 0.925), p=0.032 for decreased ratio of miR-126–3P/miR-223-3p and the occurrence of combined ischemic endpoint within 30 days and one year respectively. No association between miRNA and bleeding complications was identified.

Conclusion
The miR-223-3p and miR-126-3p to miR-223-3p ratio are strong independent predictors of thrombotic ischemic events and can be used to stratify patients post AMI.
3306Endothelial cell senescence accelerates atherosclerosis by enhancing monocyte recruitment via hyper-reactivity to inflammatory stimuli
Authors: Honda S , Ikeda K , Hoshino A , Urata R , Yagi S , Emoto N , Matoba S 
Published: October 2019

Abstract

Background
Ageing is a significant risk factor for atherosclerotic diseases. Vascular senescence has been considered to play an important role in the progression of atherosclerosis; however, it remains unclear whether endothelial cell (EC) senescence is causally involved in the pathogenesis of atherosclerosis.

Purpose
The purpose of this study is to elucidate a causative role of senescent EC in the progression of atherosclerosis.

Methods
Telomeric repeat-binding factor 2 (TRF2) plays a central role in telomere maintenance and protection against end-to-end fusion of chromosome. We previously reported that overexpression of TRF2-dominant negative mutant (TRF2DN) induced premature senescence in EC. We recently generated EC-specific progeroid mice by overexpressing TRF2DN specifically in EC (TRF2DN-Tg), and then generated ApoE-KO/TRF2DN-Tg mice to analyze a role of EC senescence in atherosclerosis. These mice were fed with a high cholesterol-diet, and atherosclerosis was assessed by en face analysis of whole aorta and histological analysis of aortic sinus. In vitro studies to analyze the underlying mechanisms were performed using replicative senescent HUVECs.

Results
En face analysis of aorta revealed that atherosclerotic lesions were significantly increased in ApoE-KO/TRF2DN-Tg mice comparing with that in ApoE-KO mice at as early as 2 weeks after high-cholesterol diet. Histological analysis of aortic sinus also exhibited accelerated atherosclerosis in ApoE-KO/TRF2DN-Tg mice in association with increased macrophage infiltration. Mechanistically, we found that the induction of adhesion molecules such as VCAM-1, ICAM-1, and E-selectin in response to low-grade inflammatory stimuli was substantially augmented in senescent ECs comparing with that in young ECs. As a result, monocyte adhesion was significantly enhanced in senescent ECs. Of note, eNOS inhibition did not affect the hyper-reactivity of senescent EC to inflammation, while antagonizing NF-kB abolished it. Nuclear translocation of NF-kB in response to inflammation was not different between young and senescent ECs, suggesting that NF-kB transcriptional activity might be enhanced in senescent ECs.

Conclusion
We revealed a causative role of EC senescence in the progression of atherosclerosis in vivo using unique EC-specific progeroid mice. Our findings revealed that EC senescence is a bona fide risk for atherosclerosis, and thus senescent ECs are attracting pharmacotherapeutic targets for the prevention and/or treatment of atherosclerotic disease in elderly population.
3310Platelet complement C3 deposition predicts platelet hyperactivity in patients with type II diabetes
Authors: Berger M , Maxeiner S , Lysaja K M , Baldia P , Wessel L , Marx N , Schuett K M 
Published: October 2019

Abstract

Introduction
Atherothrombotic disease is associated with significant morbidity and mortality. Diabetes greatly increases the prothrombotic risk of individuals by factors that remain ill defined. Recently, increased plasma levels of complement C3 were associated with prothrombotic alterations in coagulation in patients with diabetes. The aim of this project was to evaluate the role of complement C3 on platelets in patients with type 2 diabetes.

Methods
Patients with type 2 diabetes (N=20) and controls (N=22) were included in the present study and assessed for platelet complement C3 deposition and expression of complement regulating proteins (e.g. CD35, CD55, CD59 and Factor H).

Results
Complement C3 was present on the surface of unstimulated platelets and significantly increased upon platelet activation (C3: 194±10 vs. C3-activated: 778±51 p=0.0001). Expression of complement C3 correlated significantly with platelet expression of CD35 and CD55, that are known to impair C3 breakdown, suggesting a key function in regulation of platelet complement deposition of these proteins (CD35 R2=0.374, p=0.001; CD55 R2 = 0.121 p=0.026). Interestingly, in patients with type 2 diabetes complement C3 deposition predicted platelet hyperactivity measured by P-selectin expression in an univariate analysis while this was not the case in control patients (Diabetes: std. β: 0.527; p=0.013 Controls: std.β 0.087 p=0.740). Using a multivariate approach complement C3 deposition remained a predictor for platelet hyperactivity after correction for dual antiplatelet therapy (DAPT), Aspirin treatment, BMI, age and basal platelet activity in patients with type II diabetes (Diabetes: std. β 0.490 p=0.049 Control: std. β −0.152 p=0.612). Since there was no quantitative difference in complement C3 deposition between the patient groups we hypothesised that a difference in complement activation might explain the differential effects of C3 deposition in these patient groups (Control: 186±54 vs. Diabetes: 202±76 p=0.422). Indeed, presence of the complement C3 metabolite iC3b, which is liberated by complement C3 activation, correlated significantly with HbA1c (R20.174; p=0.015) suggesting an increased complement activation in patients with diabetes. To test whether complement C3 activity influences platelet activity, we preincubated platelets with the complement activator cobra venom factor (CVF) or complement inhibitor CP40 (C3 inhibitor) and Eculizumab (C5 Inhibitor). While additive complement activation showed no effect on platelet activity (p=0.87), complement inhibition by either CP40 and Eculizumab led to a significant reduction in platelet activity (CP40% Inhibition: 15.81% ± 2.42 p=0.0006 Eculizumab % Inhibition: 31,71% ± 7.89, p=0.007).

Conclusion
Our data suggests that complement C3 deposition in patients with type 2 diabetes predicts platelet hyperactivity and these effects might be due to increased complement activation.
3328Relationship between streptococcal infective endocarditis and pre-neoplastic colorectal lesions
Authors: Vilardell P , Moral S , Bosch D , Morales M , Frigola J M , Albert X , Robles R , Kassem H , Aboal J , Brugada R 
Published: October 2019

Abstract

Background
Colorectal cancer is associated with infective endocarditis (IE), due to specific gut pathogens like streptococcus Gallolyticus that use the tumor presence as a point of blood entry. However, the association between streptococcal IE and pre-cancerous lesions such as dysplastic adenomas is unknown.

Objectives
To determine the association with pre-neoplastic colorectal lesions and streptococcal IE.

Methods
Two hundred eighty consecutive patients with IE were included retrospectively in a protocol of clinical, microbiological and imaging follow-up, between January 2008 and December 2018. Pre-cancerous lesions were divided as high and low-grade dysplasia based on World Health Organization criteria. Colorectal cancer was defined as the presence of malignant cell beyond the muscularis mucosa.

Results
Fifty patients (18%) presented neoplastic or pre-neoplastic lesions, and 26 of them (52%) were colorectal: 10 (38%) colorectal cancer and 16 (62%) precancerous lesions (12% high degree (n=2); 88% low degree (n=14)). Both, colorectal cancer (20% vs 5%; p=0.03) and pre-neoplastic lesions (44% vs 3%; p<0.05) were associated with higher incidence of streptococcus Gallolyticus IE (Figure 1). Additionally, 42% (n=11) of colorectal lesions were diagnosed in the IE event. No significant differences were found about cardiac surgery and in-hospital mortality in these patients.
Figure 1. Relationship between S. Gallolyticus IE and colorectal lesions. (a) Statistical significance between colorectal cancer and S. Gallolyticus IE. (b) Statistical significance between pre-neoplastic colorectal lesions and S. Gallolyticus IE.

Conclusions
Pre-cancerous colorectal lesions are also associated with streptococcus Gallolyticus IE, even low-grade lesions. Hence, it is necessary to rule out occult neoplastic and also pre-neoplastic colorectal lesions with colonoscopy in these patients.
4077Sex-specific aging effects on iliofemoral and carotid atherosclerotic plaque composition in vascular surgery patients
Authors: De Bakker M , Van Koeverden I D , Timmerman N , De Kleijn D P V , De Borst G J , Pasterkamp G , Boersma H , Den Ruijter H M 
Published: October 2019

Abstract

Introduction
Knowledge on factors that influence atherosclerotic plaque composition may allow improved risk stratification and treatment selection in iliofemoral and carotid atherosclerotic disease, since outcomes of different treatment strategies are influenced by the type of underlying lesions. The sex- and age-related differences in iliofemoral atherosclerotic plaque composition is largely unknown. Unravelling the intertwined relation between sex, age and plaque composition might provide important implications for the treatment of peripheral artery disease.

Purpose
We aimed to elucidate the associations between sex, age and plaque composition in a histopathological analysis of plaque specimens of patients undergoing iliofemoral endarterectomy. Given the systemic nature of atherosclerosis, analyses are replicated in atherosclerotic plaque specimens obtained from patients undergoing carotid surgery.

Methods
Peripheral atherosclerotic plaques of 790 patients who underwent iliofemoral endarterectomy were harvested between 2002 and 2014. A cohort of patients (n=2006) who underwent carotid endarterectomy was used to replicate analyses on sex-specific aging effects in plaques from a different vascular bed. The atherosclerotic plaques were semi-quantitatively analyzed for the presence of lipid cores, plaque calcifications, plaque hemorrhages and collagen, macrophage and smooth muscle cell content, and quantitatively for microvessel density. Patients were stratified by age tertiles and by sex.

Results
Men had a higher prevalence of lipid cores (25.7% versus 20.5%, odds ratio [OR] 1.62 and 95% confidence interval [CI] 1.06–2.45, P=0.025) and plaque hemorrhage (54.3% versus 42.9%, OR 1.62 and 95% CI 1.16–2.54, P=0.004) when compared to women. Women showed an increase in plaque calcifications, plaque hemorrhage and a decrease in macrophages with increasing age (figure panel B, D, E), whereas men only showed a decrease in collagen content (figure panel C). These sex-specific aging effects were replicated in plaques obtained from the carotid arteries.
s

Conclusion
Atherosclerotic iliofemoral plaques derived from men display more rupture-prone characteristics compared to women. However, advanced age was more often associated with an increase in the presence of vulnerable plaque characteristics in women as compared to men in both the iliofemoral and carotid atherosclerotic plaque.