bluuebunny/crossref_metadata_2025 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

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

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

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

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

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

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

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

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

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)
P4773Oral anticoagulants in patients with atrial fibrillation having an intermediate risk of ischemic stroke but a high risk of bleeding
Authors: Chao T F , Chen S A
Published: October 2019

Background

The use of oral anticoagulants (OACs) for patients with atrial fibrillation (AF) for stroke prevention should be balanced between the reduction on stroke risk and the increase in bleeding. Our aim was to investigate net clinical benefits of OACs among AF patients with a CHA2DS2-VASc score of 1 (males) or 2 (females) who had a HAS-BLED score ≥3.

Method

A total of 404,949 newly diagnosed AF patients were identified from the Taiwan National Health Insurance Research Database. The stroke risk was assessed using the CHA2DS2-VASc score and patients were classified as low (score 0 for males, 1 for females), intermediate (1 for males and 2 for females) and high risk (≥2 for males and ≥3 for females). A high risk of bleeding was defined as a HAS-BLED score ≥3.

Results

The CHA2DS2-VASc and HAS-BLED scores were significantly correlated (r=0.70). Around 72.7% of patients with a high-risk of stroke had a HAS-BLED score ≥3 (Figure A). Among patients with a CHA2DS2-VASc score of 1 (males) or 2 (females) who had a HAS-BLED score ≥3, the use of OACs was associated with a lower risk of adverse events (ischemic stroke, intra-cranial hemorrhage or mortality) with an adjusted hazard ratio of 0.781 (p=0.037) (Figure B).

Conclusion

Even among patients with an intermediate risk of ischemic stroke (CHA2DS2-VASc score 1 for males, 2 for females) having a high risk for bleeding (HAS-BLED score ≥3), use of OACs was associated with a better clinical outcome and should still be considered.
P4791Performance of the HAS-BLED, ATRIA, and PRECISE-DAPT Bleeding Risk Scores in Atrial Fibrillation Patients Using Antiplatelet Agents or Oral Anticoagulants
Authors: Choi S Y , Kim M H , Lee K M , Jang C H , Choi J Y
Published: October 2019

Background

Various bleeding risk scores have been proposed to assess the risk of bleeding in atrial fibrillation (AF) patients undergoing anticoagulation. PRECISE DAPT score has been developed to assess the out-of hospital bleeding risk in patients receiving dual antiplatelet therapy (DAPT). Our objective was to compare the predictive performance between the HAS-BLED (Hypertension, Abnormal Renal/Liver Function, Stroke, Bleeding History or Predisposition, Labile International Normalized Ratio, Elderly, Drugs/Alcohol), ATRIA (Anticoagulation and Risk Factors in Atrial Fibrillation), and PRECISE-DAPT (Predicting Bleeding Complication in Patients Undergoing Stent Implantation and Subsequent Dual Antiplatelet therapy) score in AF patients using antiplatelet agents or anticoagulants

Methods

We recruited 1,114 consecutive AF patients (51% male; median age, 71 years) receiving antiplatelet agents or oral anticoagulants from January 2014 through December 2018. Major bleeding was defined as according to the Bleeding Academic Research Consortium (BARC) criteria (type 3 or 5: hemodynamic instability, need for transfusion, drop in hemoglobin ≥3 g, and intracranial, intraocular or fatal bleeding). The performance of risk scores were assessed by C-statistic.

Results

Bleeding events occurred in 135 patients (12.1%) during 30 days, and 72 patients (6.5%) from 30 days till 1-year follow-up. Based on the C-statistic, PRECISE-DAPT score (AUC: 0.72, 95% CI: 0.69–0.75) had a good performance, significantly better than HAS-BLED (AUC: 0.64, 95% CI: 0.61–0.67) (p=0.008) or ATRIA scores (AUC: 0.57, 95% CI: 0.54–0.60) (p<0.001) for 30-days bleeding prediction. Also, PRECISE-DAPT score had a good C-statistic (AUC: 0.72, 95% CI: 0.69–0.75) for 1-year bleeding events compared with HAS-BLED (AUC: 0.64, 95% CI: 0.60–0.67) (p=0.02) or ATRIA (AUC: 0.61, 95% CI: 0.58–0.65) (p=0.01).

ROC curve for bleeding

Conclusions

The PRECISE-DAPT score has been used for assessing bleeding events during DAPT. Also, the PRECISE-DAPT score predicted bleedings better than HAS-BLED or ATRIA scores in AF patients. So, the PRECISE-DAPT score may be considered as bleeding risk score during DAPT or oral anticoagulation in clinical practice.
P4793Comparing the effectiveness and safety of non-vitamin K antagonist oral anticoagulants and warfarin in the elderly Asian patients with atrial fibrillation
Authors: Chao T F , Liao J N , Lip G Y H , Chen S A
Published: October 2019

Background

Stroke prevention in elderly patients with atrial fibrillation (AF) can be challenging. Comparisons of non-vitamin K antagonist oral anticoagulants (NOACs) and warfarin in the elderly, at different age strata (age 65–74, 75–89, ≥90) in the daily practice have not been well described, particularly in Asians. We aimed to assess the clinical outcomes of NOACs compared warfarin for stroke prevention in elderly patients with AF.

Methods

A total of 64,169 AF patients aged ≥65 years receiving NOACs or warfarin prescription were identified from the Taiwan National Health Insurance Research Database. The risks of adverse events were compared between NOACs and warfarin in all patients age ≥65 and specifically, with different age strata; that is 65–74 years, 75–89 years and >90 years.

Results

Overall NOACs were associated with a significantly lower risk of ischemic stroke (adjusted hazard ratio [aHR] 0.869, 95% confidence interval [CI] 0.812–0.931), ICH (aHR 0.524, 95% CI 0.456–0.601), major bleeding (aHR 0,824, 95% CI 0.776–0.875), mortality (aHR 0.511, 95% CI 0.491–0.532) and composite adverse events (aHR 0.646, 95% CI 0.625–0.667) compared to warfarin. There was heterogeneity in treatment effect for NOACs versus warfarin in different age strata, but the results still favored NOACs even among the very elderly (>90 years). The absolute risk difference and reductions in ICH and composite adverse events with NOAC use were even greater among the elderly compared to warfarin (Figure).

Conclusions

Compared to warfarin, NOACs were associated with a significantly lower risk of adverse events, with heterogeneity in treatment effects among different age strata. Overall, the clear safety signal in favor of NOACs over warfarin was evident irrespective of age strata, being most marked in the most elderly.
4934Biventricular global and regional strain measured by cardiovascular magnetic resonance based tissue tracking
Authors: Qu Y , Buckert D , Ma G S , Rasche V
Published: October 2019

Background

CMR based tissue tracking (CMR-TT), considered as a novel modality, provides additional insight into left and right ventricular (LV/RV) mechanical function and deformation. The vendor-specific reference values of global and regional strains for volunteers without history of cardiovascular disease are necessary as an important step in clinical routine to help detect early abnormality.

Purpose

To determine the reference value of LV/RV multi-dimensional global and segmental strains and diagnostic specificity of global longitudinal peak strain (GLS). Biventricular global and segmental radial, circumferential and longitudinal systolic peak strains (GRS, GCS, GLS and SRS, SCS, SLS) of 150 healthy adults in three age subgroups (G20–40, G41–60 and G61–80) were derived by post-hoc imaging software in standard steady-state free precession cine images acquired at 1.5T. LV strains were calculated with three-dimensional (3D) CMR-TT in the modified AHA 16-segment model via a short-axis stack and long axis 2-, 3-, 4-chamber cine images, and RV strains were generated with 2D CMR-TT via 4-chamber cine images.

Results

The reference values of LV global peak strains resulted as 44.4±13.0% for GRS, −17.0±2.7% for GCS, and −15.4±2.3% for GLS, respectively. RV-GLS was measured as −24.9±5.1%. Global and segmental strains might differ between males and females. Females showed significant age-associated difference of LV global peak strains (P<0.05) as the opposite of males (Figure 1). Females also presented higher magnitude of LV global peak strains than males in the eldest group G61–80 (P<0.05). Unlike LV, no age-associated difference of RV-GLS was detected in both gender groups. However, females showed less negative RV-GLS than males in G20–40 and more negative RV-GLS than males older than 40 years old (P<0.05). The local discrepancy of biventricular SRS, SCS and SLS was observed. It seemed that LV mid-cavity played a more essential role on LV shortening (more negative SCS and SLS) than wall thickening (smaller SRS) compared with base and apex. RV basal and mid SLS, derived from segment 1–4, was more negative than apical SLS derived from segment 5–6. The specificity of LV- and RV-GLS cut-off value (mean value+1.96*standard deviation) generated from the vendor-, age- and gender-specific reference value in evaluating heart contractile function reached 97.3% and 94.7%, respectively.

Conclusions

Considering the vendor-, gender- and age-associated difference of biventricular global strains, specific reference values need to be established to facilitate the wide application of strain in clinical routine. Meanwhile, segmental strains are also fundamental for detecting local abnormality of myocardial deformation.
4941Machine learning based automated diagnosis of ischemic vs non-ischemic dilated cardiomyopathy using 3D myocardial deformation analysis
Authors: Lei L , Satriano A , Magyar-Ng M , Mikami Y , Kalmady S V , Hoehn B , Dykstra S , Heydari B , Flewitt J , Merchant N , Howarth A G , Lydell C P , Greiner R , Fine N M , White J A
Published: October 2019

Background

Late Gadolinium Enhancement (LGE) imaging is a reference standard technique for the differentiation of ischemic cardiomyopathy (ICM) from non-ischemic dilated cardiomyopathy (NIDCM) in patients with heart failure and reduced ejection fraction (HFrEF). 3D myocardial deformation analysis (3D-MDA) offers highly reproducible phenotypic assessments of regional architecture and function that may provide value for artificial-intelligence-assisted cardiomyopathy diagnosis without need for LGE imaging.

Purpose

In this study, we trained and validated a machine-learning-based model to enable automated diagnosis of ischemic versus non-ischemic dilated cardiomyopathy exclusively using regional patterns of deformation among patients otherwise matched by age, sex and global contractile dysfunction.

Methods

100 ICM and 100 NIDCM patients matched for age, sex, and LVEF underwent standard cine SSFP and LGE imaging. Patient diagnoses were established using a combination of clinical and LGE-based criteria. 3D-MDA was performed using validated software (GIUSEPPE) to compute regional 3D strain measures at each cardiac phase in both conventional and principal strain directions. Principal Component Analysis (PCA) was performed on the composite 3D-MDA dataset. The first 20 components were chosen, accounting for approximately 65% of the population variance. Subsequently, a support-vector-machine-based algorithm was used with 10-fold cross-validation to discriminate ICM from NIDCM.

Results

Patients were 63±10 years (ICM: 63±10 years, NIDCM: 63±10 years, p=0.955), 74% male (ICM: 74%, NIDCM: 74%, p=1.000), and had a mean LVEF of 27±8% (ICM: 27±7%, NIDCM: 28±7%, p=0.688). Global time to peak strain was significantly shorter in ICM patients relative to NIDCM patients across all surfaces and in all directions (p<0.05). The highest single-variable Area Under the Curve (AUC) achieved for the classification of ICM versus NIDCM from global data was for minimum principal strain (ICM: 43.7±7.8, NIDCM: 48.3±7.5, p<0.001, AUC: 0.682) (Figure 1). However, a multi-feature machine-learning-based model exposed to all available regional 3D deformation data achieved an AUC of 0.903 (sensitivity 87.7%, specificity 75.5%).

Conclusions

Machine learning-based analyses of3D regionaldeformation patterns allows for robust discrimination of ICM versus NIDCM. Further expansion of the presented findings is planned on a wider, multi-centre cohort.

Acknowledgement/Funding

Dr. White was supported by an award from Heart and Stroke Foundation of Alberta. This study was funded in part by Calgary Health Trust.
4969Enhanced gap junction coupling organised and terminated acute ventricular fibrillation in ex-vivo perfused hearts
Authors: Handa B S , Li X , Roney C , Pitcher D , Chowdhury R A , Peter N S , Ng F S
Published: October 2019

Background

The underlying mechanism of ventricular fibrillation (VF) remains unclear. There are both experimental and clinical data to support the existence of rotational drivers (RDs), though other opposing studies suggest that VF is the result of disorganized myocardial activation. Abnormal electrical coupling between cardiomyocytes through gap junctions (GJ) has been considered an important factor in the genesis and maintenance of VF and pre-treatment with GJ couplers, rotigaptide (RTG), has been shown to reduce VF inducibility.

Purpose

We hypothesized that the degree of GJ coupling determines the underlying mechanism of VF, and that changes in GJ coupling can shift or modify the predominant mechanism of fibrillation along the spectrum between disorganised activity and organised drivers. We proposed that increased organisation of VF is critical to its termination.

Methods

Thirty Sprague-Dawley rat hearts were explanted, perfused ex-vivo and acute VF was induced with burst pacing and 30μM pinacidil. Optical mapping of transmembrane potential was performed at baseline and the effects of GJ coupling on VF dynamics were studied in an acute VF model by perfusing with increasing concentrations of a GJ uncoupler; carbenoxolone (0–50μM, CBX, n=10) or a GJ coupling-enhancer; RTG (0–80nM, n=10). A chronic diffuse fibrosis model (n=10) was generated with 4 weeks of in-vivo angiotensin infusion (500nm/kg/min). Fibrillation dynamics were quantified using phase analysis, phase singularity (PS) tracking and our novel method of global fibrillation organisation quantification, frequency dominance index (FDI), which is a power ratio of highest amplitude dominant frequency in the frequency spectrum.

Results

RTG increased average rotations per RD (Baseline: 2.86±0.10 vs 80nM: 5.66±0.43, p<0.001) whilst CBX caused a reduction (Baseline: 3.77±0.39 vs 50μM: 0.26±0.26, p<0.001). Maximum rotations for a RD increased with RTG (5.4±0.45 vs 48.20±12.32, p<0.001) and decreased with CBX (8.0±1.3 vs 0.3±0.3, p<0.001). Proportion of time PSs were detected in VF increased with RTG (0.44±0.06 vs 0.93±0.02, p<0.001) and decreased with CBX (0.61±0.9 vs 0.03±0.02, p<0.001). RTG reduced meander of longest duration RD (20.6±1.68 vs 11.51±0.77 pixels, p<0.001) for PS >5 rotations. FDI increased with RTG (0.53±0.04 vs 0.78±0.3, p<0.001) and decreased with CBX (0.60±0.05 vs 0.17±0.03, p<0.001). In the diffuse fibrosis group, in comparison to baseline RTG 80nM increased FDI (0.35 vs 0.65, p<0.001) and terminated VF in 40% of hearts.

Conclusion

The degree of GJ coupling is a key determinant of the underlying mechanism of VF. RTG organised fibrillation and stabilised RDs in a concentration-dependent manner whilst CBX disorganised VF. Enhancing GJ coupling with RTG in diseased hearts with fibrosis can terminate VF and may be a potential therapeutic target in acute VF.

Acknowledgement/Funding

BHF Programme Grant PG/16/17/32069
5034Is stroke an issue after transcatheter mitral valve repair? A systematic review and meta-analysis
Authors: Barros Da Silva P , Sousa J P , Oliveiros B , Donato H , Goncalves L , Teixeira R
Published: October 2019

Background

Transcatheter mitral valve repair (TMVR) is a minimally invasive therapeutic procedure used as an alternative to surgery for mitral valve regurgitation in high risk patients. This technique creates a double orifice area, which might be comparable to a mitral prosthesis or mitral stenosis. So far, no strict antithrombotic therapy has been recommended and different post-procedure protocols are being currently applied.

Objectives

To assess stroke rate after TMVR, comparing it with surgical mitral valve repair (SMVR) and optimal medical treatment (OMT).

Methods

We systematically searched PubMed, Embase and Cochrane databases, in December 2018, for both interventional or observational studies comparing TMVR with SMVR and/or OMT in the treatment of severe mitral regurgitation. Only studies including data on post-procedure stroke incidence were selected. Two authors independently screened articles for inclusion, risk of bias and data extraction. Random-effects meta-analysis for TMVR, SMVR and OMT were performed. Due to the low number of pooled events, a cumulative meta-analysis was subsequently implemented. The meta-analysis was registered on the Prospero database.

Results

15 studies were selected for qualitative analysis and, among these, 10 were included in the quantitative analyses (7 of TMVR vs. SMVR and 3 of TMVR vs. OMT), providing a total of 1881 patients. TMVR patients were older and had higher surgical risk scores than SMVR patients. Groups were homogeneous regarding previous atrial fibrillation rate (pooled OR 1.45 [0.82–2.55]), whereas post-procedure de novo atrial fibrillation was more frequent in SMVR when compared with TMVR (pooled OR 0.20 [0.06–0.7]). Although the pooled stroke rate was numerically lower in the TMVR group, there was no statistically difference in the stroke incidence between TMVR and SMVR (pooled OR 0.49 [0.17, 1.42], p=0.19, I2= 0%) – Panel A. On the other hand, cumulative meta-analysis was able to show a significantly lower stroke rate in TMVR, when compared to SMVR (OR 0.4 [0.40, 0.67], p<0.05). As for TMVR vs. OMT, no difference in stroke rate was identified (pooled OR 1.09 [0.60, 1.97], p=0.79, I2=0%) – Panel B.

Forest Plots – Stroke incidence

Conclusions

Post-procedure TMVR stroke rate was similar to that of patients managed with OMT only. For the same outcome, results favored TMVR when compared with SMVR, which might be related to its lower incidence of post-procedure de novo atrial fibrillation. These findings may prove insightful to future recommendations regarding the conundrum of the best antithrombotic strategy, particularly for patients with atrial fibrillation.
5036Increased 1-year mortality among patients discharged following hospitalization for pericarditis - a nationwide cohort study
Authors: Sigvardt F L , Hansen M L , Kristensen S L , Gustafsson F , Ghanizada M , Gislason G H , Madelair C
Published: October 2019

Background

Pericarditis accounts for 5% of all chest pain referrals to the emergency department and is generally considered a benign condition. However, recent studies suggested that pericarditis can be an early predictor of malignant disease, but data on mortality and other morbidity after incident pericarditis is lacking.

Purpose

To assess mortality risk and hospitalization patterns in patients with incident pericarditis.

Methods

In nationwide Danish registries we identified patients discharged from hospital with a first-time diagnosis of pericarditis from 1996 to 2016. Patients with prior myocarditis, heart failure, myocardial infarction and recent thoracic surgery were excluded.

The patients were risk set matched with 8 controls each from the general population on sex and year of birth. We assessed 1-year mortality risk using Kaplan Meier and logistic regression adjusted for baseline comorbidities; cerebrovascular disease, chronic obstructive lung disease, cardiac dysrhythmias, ischaemic heart disease and malignancy. We identified subsequent hospital admissions due to new onset cardiovascular-, respiratory- or malignant disease. Differences in frequencies between the pericarditis group and controls were calculated with Chi squared test.

Results

We identified 8,077 patients with pericarditis, median age 45 years (IQR: 32–59) and 75.6% were men. The absolute 1-year mortality was 2.9% in patients with pericarditis compared to 0.8% in the control group (p<0.001) (Figure 1).

The adjusted odds ratio (OR) of 1-year mortality was 2.79 (95%-CI: 2.14–3.65, p<0.001). Within the first year after incident pericarditis, hospital admission due to recurrent pericarditis was observed in 10.6% of the patients. Further, we observed significantly higher frequencies of other hospital admissions compared to the matched controls; cardiovascular disease: 4.6% vs, 1.2%, p>0.001, respiratory disease: 3.4% vs. 0.7%, p>0.001) and malignant disease: 1.4% vs. 0.5%, p>0.001).

Figure 1

Conclusion

In a nationwide cohort of patients discharged from hospital with incident pericarditis, we observed more than a triple 1-year mortality compared to age- and sex matched controls. Further, we observed a higher frequency of both cardiovascular and non-cardiovascular hospital admissions, highlighting the need for more focus on underlying morbidity in patients presenting with pericarditis.
5130Association between degree of LDL-cholesterol decrease after a myocardial infarction and mortality - a nationwide cohort study
Authors: Schubert J , Lindahl B , Melhus H , Renlund H , Leosdottir M , Allahyari A , Ueda P , Jernberg T , Hagstrom E
Published: October 2019

Background

In clinical trials, patients with myocardial infarction (MI) and elevated LDL-cholesterol (LDL-C) benefit the most from lipid lowering therapy, and more intensive LDL-C lowering therapy is associated with better prognosis.

Purpose

To investigate the association between degree of LDL-C lowering and prognosis in MI patients from a large real-world setting.

Methods

Patients admitted with an MI between 2006 and 2016 and registered in the Swedish MI-registry (SWEDEHEART) were followed until 2018. The difference in LDL-C between the MI hospitalization and a 6–10 week follow-up was measured. In multivariable Cox regression analysis adjusting for clinical risk factors (eg. age, diabetes, prior cardiovascular disease), the association between LDL-C change, mortality and recurrent MI was assessed using restricted cubic splines. Further, the patients were stratified according to quartile decrease in LDL-C from MI hospitalization to the follow-up.

Results

A total of 44,148 patients (median age: 64) had an LDL-C measured during the MI hospitalization and at follow-up. Of these, 9,905 (22.4%) had ongoing statin treatment prior to admission. The median LDL-C at the MI hospitalization was 2.96 (interquartile range 2.23, 3.74) mmol/L and the median decrease in LDL-C was 1.17 (0.37, 1.86) mmol/L. During a median follow-up of 3.9 years, 3,342 patients died and 3,210 had an MI. Patients with the highest quartile of LDL-C decrease (1.86 mmol/L) from index event to follow-up, had a lower risk of mortality, hazard ratio (HR) 0.59 (95% confidence interval [CI] 0.44–0.80) compared to those with the lowest quartile of LDL-C decrease (0.37 mmol/L) (figure). For MI, the corresponding HR was 0.83 (95% CI 0.68–1.02). Ongoing statin-use prior to admission did not alter the effect of LDL-C decrease and outcome in the analysis.

Conclusions

In this large nationwide cohort of MI patients, a gradually lower risk of death was observed in patients with larger decrease in LDL-C from index event to follow-up, regardless of statin use prior to admission. The same trend was observed for recurrent MI, although not reaching statistical significance. This confirms previous findings that efforts should be made to lower LDL-C after MI.