bluuebunny/crossref_metadata_2025_split huggingface dataset:
P4691Chronic blockade of toll-like receptor 9 ameliorated pulmonary arterial hypertension by reducing perivascular inflammation in rats
Authors: Ishikawa T , Abe K , Ishikawa M , Yoshida K , Watanabe T , Tsutsui H 
Published: October 2019

Abstract

Background/Introduction
Perivascular inflammation plays an important role in the pathogenesis of pulmonary arterial hypertension (PAH). Recent studies have demonstrated that damaged mitochondrial DNA induces sterile inflammation by activating toll-like receptor (TLR)9 in spontaneous hypertensive rats. However, it remains unclear whether TLR9 is involved in perivascular inflammation and subsequent development of PAH.

Purpose
The purpose of the present study is to investigate whether chronic inhibition of TLR9 can ameliorate monocrotaline (MCT)-induced PAH in rats.

Methods
Male Sprague-Dawley rats were injected with MCT (60 mg/kg). First, we conducted immunohistochemistory to examine which cell types express TLR9 in lungs of normal rats and MCT-exposed rats. Second, we extracted cell-free DNA from plasma of rats and amplified genes of COX2 by real-time PCR to detect circulating cell-free mitochondrial DNA, a ligand of TLR9. Third, the administration of a selective TLR9 inhibitor (E6446, 10mg/kg/day, drinking water) or non-selective TLR9 inhibitor (chloroquine: 50mg/kg/day, ip) started three days before MCT injection and sacrificed on day 21. We assessed hemodynamic data and histopathological analysis (EVG stain for medial wall thickness (MWT) in pulmonary arteries (outer diameter: 50 ∼ 100 μm) and CD68 for macrophage accumulation around pulmonary arteries (outer diameter: <50 μm)), and measured the levels of interleukin-6 (IL-6) in lungs by real time PCR. Finally, we investigated survival rate in the reversal protocol, where we started the administration of E6446 on day 14.

Results
TLR9 was expressed dominantly in pulmonary endothelial cells and macrophages in the lungs of both normal rats and MCT-exposed rats. Compared with normal rats, MCT-exposed rats showed increased gene expression of COX2 (0.048±0.001 vs. 0.052±0.001 expressed by 1/Ct) in plasma on day 14. MCT-exposed rats also had increased right ventricular systolic pressure (RVSP: 21±1 vs. 60±2 mmHg), total pulmonary vascular resistance index (TPRI: 0.07±0.01 vs. 0.43±0.02 mmHg/min/mL/kg), MWT (0.07±0.01 vs. 0.26±0,02) and accumulation of macrophages (1.6±0.3 vs. 20.0±1.7 cells/HPF) on day 21. In the prevention protocol, either E6446 or chloroquine significantly prevented the elevations of RVSP (49±4 or 48±3 mmHg) and TPRI (0.29±0.04 or 0.27±0.03 mmHg/min/mL/kg) with reducing MWT (0.18±0.01 or 0.18±0.01) and macrophage accumulation (9.7±1.3 or 9.8±2.5 cell/HPF) on day 21. In addition, these drugs significantly reduced the levels of IL-6 mRNA compared with MCT group (4.4±1.0 or 4.8±1.4 vs. 11.9±1.0). In the reversal protocol, the treatment of E6446 had significantly increased the survival rate (50 vs. 10%).

Conclusions
TLR9 largely contributes to the development of PAH by reducing perivascular inflammation. Inhibition of TLR9 could be a novel therapeutic target for PAH.
P4706Sex-related differences in clinical outcomes after percutaneous transluminal angioplasty in patients with peripheral artery disease
Authors: Januszek R , Pawlik A , Ruzsa Z , Nyerges A , Wojtasik-Bakalarz J , Rakowski T , Kleczynski P , Dudek D , Bartus S 
Published: October 2019

Abstract

Aim
There are inconsistent data on the sex-related differences in clinical outcomes after percutaneous transluminal angioplasty (PTA) in patients with peripheral artery disease (PAD). We aimed to investigate sex-related differences in clinical outcomes after PTA.

Methods
A total of 939 consecutive patients undergoing PTA were enrolled in two large volume centers. Patients were stratified by gender. Baseline characteristics, procedural and long-term clinical outcomes were compared between women and men.

Results
Women represented 37.4% of the study population. Women, compared to men, had more often hypertension (92% vs 86%, p=0.001) and diabetes (54% vs 46%, p=0.02). However, men presented more often with chronic obstructive pulmonary disease (14.8% vs 6.8%, p=0.0003), coronary artery disease (45.4% vs 32.7%, p=0.0001), smoking (60.4% vs 45%, p=0.007) and previous PTA (25% vs 17%, p=0.005). There were no differences in 120-month all-cause mortality between groups (women vs. men: 29% vs. 21%, p=0.6). Men were at higher risk of re-PTA at 5-year follow-up (40% vs. 49%; p=0.03). Moreover, male sex was an independent predictor of re-PTA (age-adjusted odds ratio (OR) (95% CI): 1.276 (1.015–1.614), p=0.03). In multivariable Cox regression analysis, a superficial femoral artery chronic total occlusion (SFA-CTO) (hazard ratio [HR]) (95% confidence interval [CI]): 1.68 (1.12–2.5), body mass index (BMI) (hazard ratio (HR)) (95% CI): 0.93 (0.87–0.99), baseline creatinine level hazard ratio (HR)) (95% CI): 0.95 (0.88–0.99) were identified as independent factors of re-PTA in women.
Figure 1. Months to re-PTA for grouping variable male.

Conclusion
Male sex was identified as an independent predictor of re-PTA. SFA-CTO, BMI and baseline creatinine level were associated with re-PTA in women.
P4707Incidence and outcome of endovascular therapy in subclavian occlusive disease involving the vertebral artery origin
Authors: Schneider V S , Dirschinger R , Wustrow I , Cassese S , Fusaro M , Kastrati A , Laugwitz K L , Ibrahim T , Bradaric C 
Published: October 2019

Abstract

Background
Endovascular revascularization represents the treatment option of choice in symptomatic steno-occlusive disease of the subclavian artery (SA). While the majority of lesions are localized in the proximal segment of the subclavian artery, studies in regards to the medial segment involving the vertebral artery (VA) origin are scarce.

Purpose
The aim of this study was to analyze the technical approaches and outcome of endovascular therapy of subclavian artery disease with a special focus on medial lesions involving the VA origin.

Methods
We retrospectively analyzed all patients who underwent percutaneous revascularization of the subclavian or innominate artery with a special focus on medial lesions involving the VA origin.

Results
In total 196 patients with subclavian or innominate artery intervention were analyzed. The majority of lesions (83%) were located in the proximal, whereas 28 patients (14%) presented with lesions in the medial segment of the SA, and only 3% involved the distal segment. Overall procedural success was high for both stenosis (96%) and occlusion (89%) and did not differ according to the lesion location. Revascularization techniques in the medial segment included stenting of the SA only (13 patients), additional VA balloon-dilatation (6 Patients), and bifurcational stenting of the SA and VA using T-stenting technique (9 patients). Overall periprocedural complication rate was low (6%) and comparable between different SA segments (6% in proximal segment vs. 7% in medial segment vs. 0% in distal segment; p=0.81). Outcome assessed after a median of 12 months (interquartile range 4–30) showed no significant differences in terms of Kaplan-Meier estimated freedom from restenosis between proximal and medial lesions despite the technically demanding approach in the medial segment (90% vs. 95%; p=0.67).
Long-term patency

Conclusion
Endovascular revascularization of medial subclavian artery lesions involving the vertebral artery origin shows comparable safety and efficacy in terms of long-term patency rates compared to lesions located within the proximal subclavian artery. However, more complex endovascular techniques with bifurcational ballooning or stenting is required in a considerable number of patients with medial subclavian artery disease.
P4724Elevated mitral valve pressure gradient is predictive for long-term outcome after percutaneous edge-to-edge mitral valve repair (PMVR) in patients with degenerative MR, but not in functional MR
Authors: Patzelt J , Zhang W , Sauter R , Mezger M , Nording H , Becker A S , Rudolph V , Saad M , Eitel I , Schlensak C , Gawaz M , Boekstegers P , Schreieck J , Seizer P , Langer H F 
Published: October 2019

Abstract

Background
To analyze the effects of residual mitral regurgitation (MR) and mean mitral valve pressure gradient (MVPG) after percutaneous edge-to-edge mitral valve repair (PMVR) using the MitraClip-system on long term outcome.

Methods and results
Two hundred fifty-five patients who underwent PMVR were analyzed. Kaplan-Meier and Cox regression analyses were performed to evaluate the impact of residual MR and MVPG on clinical outcome. A combined clinical endpoint (all-cause mortality, MV surgery, redo procedure, implantation of a left ventricular assist device) was used.
After PMVR, mean MVPG increased from 1.6±1.0 mmHg to 3.1±1.5 mmHg (p<0.001). Reduction of MR severity to ≤2+ postintervention was achieved in 98.4% of all patients. In the overall patient cohort, residual MR was predictive for the combined endpoint while elevated MVPG >4.4 mmHg was not according to Kaplan-Meier and Cox regression analyses. We then analyzed the cohort with degenerative and that with functional MR separately to account for these different entities.In the cohort with degenerative MR, elevated MVPG was associated with increased occurrence of the primary endpoint, whereas this was not observed in the cohort with functional MR.

Conclusions
MVPG >4.4 mmHg after MitraClip-implantation was predictive for clinical outcome in the patient cohort with degenerative MR. In the patient cohort with functional MR, MVPG >4.4 mmHg was not associated with increased clinical events.

Acknowledgement/Funding
This study was supported by grants from the German Research Foundation (KFO 274), the Volkswagen Foundation (Lichtenberg Program) and the German Heart
P4734Electron microscopy reveals evidence of perinuclear clustering of mitochondria in cardiac biopsy proven allograft rejection
Authors: Rosello-Lleti E , Gil-Cayuela C , Tarazon E , Garcia-Manzanares M , Lago F , Gonzalez-Juanatey J R , Martinez-Dolz L , Portoles M 
Published: October 2019

Abstract

Background
Despite improved efficacy of immunosuppression therapy, allograft rejection continues to be a significant risk, especially early after transplantation. Endomyocardial biopsy (EMB) is the standard tool with a recognized role in the surveillance of posttransplant cardiac rejection and is based on optical microscopy analysis. However, this method presents technical limitations.

Purpose
In this work we focus on the analysis of new ultrastructural findings in cardiac biopsy specimens.

Methods
This study include heart transplanted patients from a single center who were referred for EMB as a scheduled routine screening. Participants were divided into 2 groups: patients transplanted without allograft rejection (n=5), and patients with biopsy-proven allograft rejection (n=5). Rejection episodes were assessed according to the International Society for Heart and Lung Transplantation (ISHLT) consensus report.

Results
We detected by electronic microscopy a significative increase in the number of mitochondria (p<0.0001) and dense bodies in the rejection group (p<0.05). But the most significative finding was the presence of local accumulations of mitochondria close to the nuclear envelope, pressing and shaping the morphology of this membrane in all rejection samples. We found these perinuclear clustering of mitochondria in a 68±27% of the total cardiac nucleus observed from rejection samples. We not observed this phenomenon in non-rejection samples, thus reflecting an excellent sensitivity and specificity.
Perinuclear clustering of mitochondria

Conclusion
We observed by electron microscopy a specific phenomenon, perinuclear clustering of mitochondria, in endomyocardial biopsies from patients with cardiac rejection that affects to the architecture of the nuclear membrane. This ultrastructural approach might complement and improve the diagnosis of rejection.

Acknowledgement/Funding
National Institute of Health [PI16/01627, PI17/01925, PI17/01232], “Consorcio Centro de Investigaciόn Biomédica en Red, M.P.”, and FEDER
P4741Oral anticoagulants and their effect on kidneys function, is warfarin safe?
Authors: Novikova T , Berstein L , Kiselyova M , Plotnikova M , Saiganov S 
Published: October 2019

Abstract

Introduction
Patients with atrial fibrillation (AF) and an intermediate or higher risk of stroke and systemic embolization should be treated with oral anticoagulants (OAC). For patients who do not have mitral valve stenosis or a mechanical valve prosthesis, non-vitamin-K dependent oral anticoagulants (NOAC) are preferred over vitamin K antagonists (VKA). All four NOACs are partly eliminated by the kidneys. At the present time it is uncertain which of the two types of anticoagulants – VKA or NOAC – has a lesser deleterious effect on a kidney function.

Purpose
To estimate the influence of the prolonged treatment with OAC on a kidney function.

Methods
The retrospective analysis of 776 inpatients with AF admitted from January 1, 2014 to June 30, 2018.

Results
While in a hospital, 93.6% of AF patients received OAC, of which 50.0% was VKA and 43.6% - NOAC; 1.8% were given antiplatelet therapy (APT) and 4.6% of patients did not receive any antithrombotic therapy (ATT). eGFR was assessed as >90 ml/min in 6.7% of patients, 89 to 60 ml/min – in 45.1% of patients, 59–45 ml/min – in 30.5% of patients, 44 to 30 ml/min – in 13.3% of patients, 29 to 15 ml/min – in 4.1% of patients, and <15 ml/min – in 0.3% of patients. For the analysis of the effect of long-term ATT on the kidney function, 70 patients were selected. Among them, 25 received VKA, 25 received NOAC, 20 patients were on APT (acetylsalicylic acid – ASA). The difference between baseline characteristics of groups was statistically insignificant. After 3.5 years eGFR decreased significantly in VKA group (from 63.69±14.69 ml/min to 48.08±11.2 ml/min, p=0.002); in the NOAC group mean eGFR value was also lower than initial (62.38±16.01 ml/min vs 63,75±21.17 ml/min), but the difference was statistically insignificant (p=0.86). In ASA group eGFR declined from 62,41±17.23 ml/min to 58.25±10.48 ml/min, however, as in the NOAC group, the difference was statistically insignificant (p=0.054). After 3.5 years, significant difference was present between the eGFR values in VKA group and NOAC group (p=0.01), and between the eGFR values in VKA and ASA groups (p=0.02). Decrease of eGFR ≥20% is detected in 31.8% of patients in VKA group, 17.7% of patients in ASA group, and 9.1% of patients in NOAC group.

Conclusion
In real clinical practice, long-term VKA use leads to more significant reduction in the glomerular filtration rate compared to NOAC use. Although the glomerular filtration rate in the ASA patients decreased to a lesser extent than in those on VKA, ASA should not be used for the stroke and systemic embolism prevention in patients with AF due to its low efficacy.
P4761Impact of focal ablation versus isolation of the coronary sinus in patients undergoing repeat radiofrequency catheter ablation of persistent atrial fibrillation
Authors: Della Rocca D G , Di Biase L , Mohanty S , Trivedi C , Natale V N , Chen Q , Al-Ahmad A , Bassiouny M , Gasperetti A , Horton R P , Gianni C , Casella M , Dello Russo A , Tondo C , Natale A 
Published: October 2019

Abstract

Introduction
Non-pulmonary vein (PV) triggers originating from the coronary sinus (CS) are a common finding in atrial fibrillation (AF) patients. To date, no studies have investigated the clinical impact of focal ablation versus isolation of the CS in patients presenting triggers from this area.

Purpose
This study analyzed the effectiveness of two different approaches for CS ablation (total isolation vs focal ablation) in persistent AF patients undergoing repeat AF ablation.

Methods
Consecutive persistent AF patients undergoing repeat ablation were enrolled in this prospective analysis. All patients had triggers from the CS documented during high-dose isoproterenol. Pulmonary vein antrum isolation (PVAI) extended to the posterior wall (PW) plus superior vena cava (SVC) isolation was performed in all patients at first procedure. At repeat procedure, PV, PW, and SVC were re-isolated, if needed. Focal ablation or isolation of the CS was performed based on operator's choice either at first and/or repeat procedure, along with ablation of other non-PV triggers. Patients with triggers from left atrial appendage were excluded from the study.

Results
Overall, 628 consecutive patients (73.4% male, age 66.9±9.0 years) were enrolled. On the basis of the CS ablation strategy, patients were categorized into two groups: Group I received CS isolation (n=389) and Group II received CS focal ablation (n=239). Major clinical characteristics were not different between groups. PV reconnection was documented in 55 (14.1%) patients of Group I and 33 (13.8%) of Group II. The incidence of procedure-related complications was similar between the two groups (10 [2.6%] in Group I vs 6 [2.5%] in Group II; p=0.9). After a follow-up of 18±8 months, 276 (71%) patients in Group I and 115 (48%) in Group II remained arrhythmia-free (p<0.001, figure.1). After adjusting for age, gender and clinically relevant variables, CS isolation was associated with a significantly higher arrhythmia-free survival rate (HR: 0.47; 95% CI: 0.37–0.61, p-value<0.001).

Conclusions
In patients with documented triggers from the CS undergoing repeat ablation of persistent AF, isolation rather than focal ablation of the CS significantly increased freedom from atrial tachyarrhythmias in the long term.
P4764Relationship of the duration of pulmonary vein isolation-refractory non-paroxysmal atrial fibrillation to the middle- to long-term outcome of the ExTRa Mapping-guided ablation
Authors: Okuyama Y , Ashihara T , Ozawa T , Fujii Y , Kato K , Sugimoto Y , Nakagawa Y 
Published: October 2019

Abstract

Introduction
It is reported that for patients with non-paroxysmal (persistent or long-standing persistent) atrial fibrillation (Non-PAF), extended ablation to atrial walls in addition to pulmonary vein isolation (PVI) did not improve the long-term outcome. On the other hand, modulation of Non-PAF drivers (or perpetuators) has been proposed as one of the alternative effective ablation strategies for Non-PAF.

Purpose
To clarify whether the rotor ablation under online real-time high-density phase mapping system is effective for PVI-refractory Non-PAF ablation.

Methods
Under such circumstances, our academic group had recently developed the online real-time high-density phase mapping system (ExTRa Mapping™) by industrial alliance. The phase map moving images were based on 41 intra-atrial bipolar signals recorded by a 20-pole spiral-shaped catheter (2.5 cm in diameter) and on in silicorapid prediction of spatio-temporal atrial excitations (artificial intelligence system). Then we applied the ExTRa Mapping to clinical practice in order to directly visualize rotors in patients with Non-PAF, and investigated the middle- to long-term outcome of the ExTRa Mapping-guided rotor ablation (ExTRa-ABL).

Results
Thirty-eight patients (63±8 y/o, 30 males) with Non-PAF demonstrating refractoriness to PVI were enrolled in this study. Ablation for cavo-tricuspid isthmus and/or superior vena cava isolation was additionally performed at physicians' discretion. After these procedures, the ExTRa-ABL was performed in order to modify Non-PAF substrates, causing rotor control. The modification of the rotors was evaluated by re-mapping with the use of the ExTRa Mapping at the end of each ablation session. Patients were followed at 1, 3, 6 months and every year after the procedure. All of them were followed for 21±8 months. During the follow-up period, Non-PAF was recurred in only 8 of 38 (21%). Furthermore, we found if PVI-refractory Non-PAF duration was shorter than 6 years, the non-recurrence rate remained ≥80% (see Figure), which was markedly better outcome comparing with previous reports with regard to Non-PAF ablation.
Figure 1

Conclusion
Comparing with conventional Non-PAF ablation strategies, our novel approach with the use of the online real-time high-density phase mapping system might improve medium- to long-term outcome of PVI-refractory Non-PAF treatment.
P4770Antithrombotic challenge in the clinical dilemma of high-risk patients with atrial fibrillation: one-year result from ChiOTEAF Registry
Authors: Guo Y T , Wang Y , Chen Y , Lip G Y H 
Published: October 2019

Abstract

Background
The antithrombotic treatment is the main goal of management on atrial fibrillation (AF). However, the optimal thrombophylaxis still remains the problem in the “high-risk” population, such as the elderly, with renal/liver dysfunction, malignancy, stent implantation, etc.

Objectives
The present study aims to explore the optimal antithrombotic strategy in a “high-risk” population with multiple comorbidities.

Methods
The ChiOTEAF (Ethic approval number of Central Medical Ethic Committee of General PLA Hospital: S2014–065–01) is a prospectively, multi-center (44 research centers), real-world registry across China. The protocol was seen in BMJ Open (Guo Y, et al. 2018). A Cox proportional hazard model analysis was performed for the outcome of antithrombotic therapy among this high-risk population.

Results
6148 patients with AF (mean age 74 years old, female 39.4%), were enrolled into ChiOTEAF study between Oct 2014 to Dec 2018. The use of non-vitamin K antagonist oral anticoagulants (NOACs), warfarin, and antiplatelet were 1444 (23.5%), 1300 (21.1%), and 2521 (41.0%), respectively, in this high-risk AF population. During one-year follow-up, there were 186 (3.0%) all-cause death.
In this AF cohort, the patients with chronic kidney disease (CKD)/liver disease were 878 (14.3%), with malignancy were 555 (9.0%), with prior thromboembolism (TE) were 1538 (25%), with prior haemorrhage were 348 (5.7%), and current anemia were 859 (14.0%), respectively. Stent implantation (coronary artery, aortic or peripheral artery) were 671 (10.9%). CHA2DS2-VASc and HAD-BLED scores (mean±standard deviation) were 3.8±1.7, and 2.0±1.1, respectively.
Among the above “clinical dilemma”, the antiplatelet use was common in patients with CKD/Liver disease and stent implantation (43.5%, 56.9%, respectively, p<0.05), the oral anticoagulants (OACs) combined with antiplatelet was most seen in patients with stent implantation (15.4%, p<0.05), OACs alone were highest in patients with prior TE (38.1%, p<0.05), while patients with malignancy and prior bleeding far less received any antithrombotic drugs (41.8%, 31.3%, respectively, p<0.05) (Figure 1).
However, after adjusting baseline characteristics, OACs reduced the risk for all-cause death (hazard ratio, HR, 95% confidential interval, CI) for the patients with CKD/liver disease (HR, 95% CI, 0.28, 0.11–0.69, p=0.006), and for patients with prior TE (HR, 95% CI, 0.43, 0.21–0.91, p=0.028), respectively.

Conclusion
Although suboptimal anticoagulants were common in the “high-risk” AF patients, OACs demonstrated the benefit for AF patients with CKD/liver disease, etc., while more evidences would be needed to optimise the antithrombotic strategy in different complex clinical settings.

Acknowledgement/Funding
The study was supported by Beijing Natural Science Foundation (Z1411ehz745.11462114050) and National Natural Science Foundation of China (H2501)