bluuebunny/crossref_metadata_2025 huggingface dataset:
P4622Prediction of in-hospital bleeding for AMI patients undergoing PCI using machine learning method
Authors: Zhao X Y , Yang J G , Chen T G , Wang J M , Li X , Xie G T , Gao X J , Xu H Y , Dou K F , Tang Y D , Qiao S B , Yuan J Q , Yang Y J
Published: October 2019

Background

Prediction of in-hospital bleeding is critical for clinical decision making for acute myocardial infarction (AMI) patients undergoing percutaneous coronary intervention (PCI). Machine learning methods can automatically select the combination of the important features and learn their underlying relationship with the outcome.

Objective

We aim to evaluate the predictive value of machine learning methods to predict in-hospital bleeding for AMI patients.

Methods

We used data from the multicenter China Acute Myocardial Infarction (CAMI) registry. We randomly partitioned the cohort into derivation set (75%) and validation set (25%). Using data from the derivation set, we applied a state-of-art machine learning algorithm, XGBoost, to automatically select features from 106 candidate variables and train a risk prediction model to predict in-hospital bleeding (BARC 3, 5 definition).

Results

16736 AMI patients who underwent PCI were consecutively included in the analysis, while 70 (0.42%) patients had in-hospital bleeding followed the BARC 3,5 definition of bleeding. Fifty-nine features were automatically selected from the candidate features and were used to construct the prediction model. The area under the curve (AUC) of the XGBoost model was 0.816 (95% CI: 0.745–0.887) on the validation set, while AUC of the CRUSADE risk score was 0.723 (95% CI: 0.619–0.828).

Relative contribution of the 12 most important features Feature Relative Importance Direct bilirubin 0.078 Heart rate 0.077 CKMB 0.076 Creatinine 0.064 GPT 0.052 Age 0.048 SBP 0.036 TG 0.035 Glucose 0.035 HCT 0.031 Total bilirubin 0.030 Neutrophil 0.030

ROC of the XGBoost model and CRUSADE

Conclusion

The XGBoost model derived from the CAMI cohort accurately predicts in-hospital bleeding among Chinese AMI patients undergoing PCI.

Acknowledgement/Funding

the CAMS innovation Fund for Medical Sciences (CIFMS) (2016-12M-1-009); the Twelfth Five-year Planning Project of China (2011BAI11B02)
P4662Advanced glycation end products accumulate in aortic valve tissue during calcification development in the absence of diabetes mellitus. A spectroscopic study
Authors: Anousakis-Vlachochristou N , Toutouzas K , Kyriakidou M , Varela E , Kapelouzou A , Lali D , Anastassopoulou I , Anagnostopoulos C , Cokkinos D , Tousoulis D
Published: October 2019

Background

Advanced glycation end products (AGPs) promote human aortic smooth muscle cell calcification in vitro. Moreover, reduction of AGPs levels and inhibition of RAGE signaling decrease vascular calcification in vivo in animal studies. The role of AGPs in aortic valve calcification has not been investigated.

Purpose

We sought to investigate the role of AGPs in aortic valve calcification, in the absence of diabetes mellitus (DM).

Methods

We used human and animal cohorts. Firstly, we obtained aortic valves from patients without DM that underwent aortic valve replacement due to aortic valve stenosis. We studied the valves with Fourier-Transformed Infrared spectroscopy (FT-IR, Nicolet 6700 spectrometer, with Attenuated Total Reflection-ATR accessory, each spectrum consisted of 120 co-added spectra) in order to evaluate chemical changes. In the animal cohort, New Zealand male rabbits where randomized in calcification diet (normal chow+cholesterol 0,5%+3500 IU ergocalciferol/kg daily) and control group and sacrificed at 2, 4, 6, 8 10 and 12 weeks. The valves were longitudinally assessed with FT-IR.

Results

A total of 200 human aortic valves were studied (age 64–78). All patients demonstrated characteristic vibrations at the area about 1165 cm-1, where the C-O-C bonds absorb, attributed to AGPs. Thirty six rabbit valves were used, 3 per group. Glucose levels were within normal range and did not differ between groups. The FT-IR spectra of the rabbit aortic valves showed increasing intensity of the C-O-C band at 1165 cm-1 in experimental group in comparison to control group. The band at 1744 cm-1 is attributed to aldehyde formation due to oxidative stress and inflammation. Shifts and shape changes were detected at the bands of amide I and II at 1650 cm-1 and 1550 cm-1, respectively, concerning protein misfolding, fiber formation and sclerosis. The bands in the region 1299–900 cm-1 correspond to phosphate groups of phospholipidsand the formed calcium phosphate salts and non-biological hydroxyapatite Ca3(PO4)2 formation. All vibrations increased significantly longitudinally during experimental diet period.

Representative FT-IR spectra of valves

Conclusions

Advanced glycation end products are detected in human calcified aortic valves irrespectively of DM. Moreover, AGPs correlate with presence and gradual development of aortic valve calcification in experimental rabbit model, along with acidosis, oxidation and protein secondary misfolding. Accumulation of AGPs in valve tissue is implicated in mechanisms of disease development.
P4674Implementation of the new chronic thromboembolic pulmonary hypertension treatment algorithm: an ongoing effort from a portuguese referral centre
Authors: Alegria S , Loureiro M J , Ferreira F , Cale R , Cabral M , Pereira H
Published: October 2019

Background

To date, the first-line treatment for chronic thromboembolic pulmonary hypertension (CTEPH) is pulmonary endarterectomy (PEA), although a significant number of patients will have inoperable disease or residual pulmonary hypertension (PH). Balloon pulmonary angioplasty (BPA) has provided a new therapeutic option for these patients. In addition, medical therapy (MT) also plays an important role.

Purpose

Characterization of a population of patients with CTEPH or chronic thromboembolic disease (CTED) and comparison of the different treatment strategies according to the updated treatment algorithm.

Methods

Retrospective analysis of patients with CTEPH/CTED followed in a referral centre for the treatment of PH submitted to different treatment strategies: PEA plus MT and BPA in patients with residual PH (group 1), MT plus BPA (group 2), and MT only (group 3). Cox regression was used to identify predictors of all-cause mortality.

Results

58 patients were included (median age 63.5 years, 74% female); 17% had CTED, and the remaining had CTEPH 50% (n=29) were submitted to PEA (group 1), of which 58% had residual PH (21% underwent BPA, n=3). Among the remaining patients, 31% (n=9) underwent MT plus BPA (group 2), and 69% (n=20) were treated with MT only (group 3). Overall, 55% were under pulmonary vasodilator therapy, including 38% with riociguat. Most of the patients (67%) were in functional class III or IV, the distance in the 6MWT was 328±147 meters, the median NT-proBNP was 538pg/ml, 40% had RV systolic dysfunction, the mean mPAP was 42±13 mmHg, and the mean PVR was 11±6 WU. Comparing the different treatment strategies, during follow-up (median 945 days) the following differences were found (comparison between group 1 vs group 2 vs group 3): improvement in functional class (class III-IV: 0% vs 0% vs 58%); distance in 6MWT (438±83 vs 390±79 vs 281±105 meters); evolution of NT-proBNP (−984±1736 vs −198±205 vs +1177±2342); normalization of RV dimensions (89% vs 50% vs 20%); resolution of pericardial effusion (100% vs 100% vs 0%); normalization of mPAP (73% vs 71% vs 0%); PVR (median 3.4 vs 2.7 vs 10.6 WU); all-cause mortality (7% vs 0% vs 35%) (p<0.02 in all).

In the overall population, the most relevant predictors of all-cause mortality were the absence of functional class improvement, baseline and follow-up NT-proBNP, baseline and follow-up SPAP by echocardiogram, and maintenance of treatment with prostanoids (p<0.05 in all).

Conclusion

Our results confirm that, in patients with CTEPH/CTED, PEA is associated with functional, and hemodynamic improvement and increased survival, although BPA is an alternative in patients with inoperable disease or residual PH, with similar results on short-term follow-up. Patients who are not submitted to surgical or percutaneous intervention have a poor prognosis, both in terms of morbidity and mortality.
P4677Balloon pulmonary angioplasty improves pulmonary arterial compliance in patients with inoperable chronic thromboembolic pulmonary hypertension
Authors: Umemoto S , Abe K , Horimoto K , Hosokawa K , Tsutsui H
Published: October 2019

Background

Right ventricular (RV) pressure overload is directly related to the increase in mortality in pulmonary hypertension. Pulmonary arterial compliance (CPA; stroke volume/pulmonary pulse pressure) was reported to be an independent determinant of RV systolic afterload in patients with pulmonary arterial hypertension (PAH). Recently, balloon pulmonary angioplasty (BPA) has been reported to reduce mean pulmonary artery pressure (mPAP) and pulmonary vascular resistance (RPA) in patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH). However, the effects of BPA on CPA remain unclear.

Purpose

The aim of this study was to investigate the impact of BPA on CPA in patients with inoperable CTEPH.

Methods

We retrospectively analyzed 78 patients (388 BPA sessions) with inoperable CTEPH who underwent BPA in our hospital from September 2012 to June 2018. Total number of BPA sessions was 5.0±1.8 (range 1–10). The pressure values were obtained from right heart catheterization at baseline (n=78), just after the final BPA (n=78) and follow-up (n=19) periods. The intervals from baseline to the final BPA and the final BPA to follow-up were 593±498 days and 397±276 days, respectively.

Results

Mean age was 60.5±12.6 years old, and 64 (82%) were female. All patients were symptomatic (WHO functional class II/III/IV 16/55/7). Patients who had pulmonary vasodilators decreased from 70 (90%) at baseline to 23 (28%) at the final BPA and 2 (15%) at follow-up. BPA reduced mPAP and RPA significantly from baseline to the final BPA and follow-up periods. BPA also improved CPA with significant reduction of pulse pressure despite no significant changes in stroke volume between baseline and follow-up (Table). CPA between the final BPA and follow-up was equivalent (p=0.95).

Conclusions

BPA improved CPA just after the final BPA in inoperable CTEPH patients. In addition, CPA was preserved during the follow-up after the final BPA sessions. These data suggest that BPA consistently unloads RV systolic afterload in those patients.
P4679Changes in systemic inflammation and endothelial dysfunction after balloon pulmonary angioplasty
Authors: Magon W , Stepniewski J , Jonas K , Waligora M , Podolec P , Kopec G
Published: October 2019

Introduction

Pulmonary endarterectomy leads to a decrease in systemic inflammation and improvement in endothelial function in patients with chronic thromboembolic pulmonary hypertension (CTEPH). Balloon pulmonary angioplasty (BPA) improves pulmonary hemodynamics in patients with inoperable CTEPH.

Aim

To assess changes in systemic inflammation and endothelial dysfunction after a single BPA session and after completion of the treatment.

Methods

We enrolled consecutive, inoperable CTEPH patients who underwent BPA. Interleukin 6, 10 (IL-6, IL-10), and C-reactive protein (hsCRP) constituted markers of systemic inflammation. Endothelin-1 (ET-1) served as a marker of endothelial dysfunction. Serum concentration of selected markers was assessed in every patient before, 24 hours after the first BPA session and 6 months after completion of the BPA treatment. Age- and sex-matched healthy subjects served as a control group.

Results

We recruited 20 patients with inoperable CTEPH (6 males [30%]), aged 67 [61–74] years in New York Heart Association class III (n=19 [95%]) and II (n=1 [5%]). BPA treatment was completed with a median of 5 [2–8] BPA sessions per patient. Before starting the treatment CTEPH patients, as compared to controls (n=10), had raised serum level of IL-6 (3.82 [2.75 - 6.03] vs. 2.64 [0.88 - 4.75] pg/ml; p=0.04), hsCRP (2.47 [0.93 - 4.27] vs. 1.23 [0.48–3.21] ng/ml; p=0.02) and ET-1 (2.68 [2.24 - 3.64] vs. 1.47 [1.4 - 1.82] pg/ml; p=0.004). There was no difference in IL-10 level.

24 hours after a BPA session we observed an increased level of IL-6, IL-10 and hsCRP. (Tab.) 6 months after completion of the BPA treatment there was a reduced level of IL-6, hsCRP and ET-1 (Tab.)

Table 1. Changes (Δ) in serum concentration of analyzed markers 24 hours after a single BPA session and at 6-months assessment after completion of the BPA treatment (n=20) Initial Δ at 24 hours after single BPA p Δ at 6-months follow-up p ET-1 [pg/ml] 2.68 [2.24; 3.64] −0.2 [−0.5; 0.23] 0.21 −0.47 [−0.96; 0.05] 0.004 IL-6 [pg/ml] 3.82 [2.75; 6.03] 3.67 [1.41; 7.16] 0.008 −0.82 [−3.11; 0.54] 0.04 IL-10 [pg/ml] 0.53 [0.44; 0.58] 0.32 [0.21; 0.87] 0.006 −0.11 [−0.33; 0.14] 0.94 hsCRP [ng/ml] 2.47 [0.93; 4.27] 5.4 [3.96; 10.59] 0.008 −0.36 [−0.94; 0.16] 0.02 ET-1, endothelin 1; hsCRP, C-reactive protein; IL-6, interleukin 6; IL-10, interleukin 10.

Conclusions

Patients with inoperable CTEPH, as compared to healthy controls, exhibit an increased systemic inflammation and endothelial dysfunction, which both improve after completion of the BPA treatment. At short-term follow-up after single BPA session there is an increase in systemic inflammatory response.
P4680Prognostic value of stroke volume index in patients with pulmonary arterial hypertension at intermediate risk
Authors: Dardi F , Gotti E , Palazzini M , Rinaldi A , Zuffa E , Pasca F , De Lorenzis A , Guarino D , Magnani I , Rotunno M , Manes A , Galie' N
Published: October 2019

Background

Current pulmonary hypertension (PH) guidelines stratify the risk of patients with pulmonary arterial hypertension (PAH) using a multiparametric approach. Low, intermediate and high-risk are defined by estimated 1-year mortality of <5%, 5–10% and >10%, respectively. This risk assessment has been recently validated in 3 cohorts of PAH patients and a simplified risk table for patients with idiopathic/heritable (I/H) PAH and PAH associated with connective tissue disease (CTD) and congenital heart disease (CHD) has been recently proposed and validated. However, with this method most of the patients are classified in the intermediate risk category and additional strategies are required to further stratify this group of PAH patients.

Purpose

To evaluate the prognostic value of SVI measured with right heart catheterization (RHC) in patients at intermediate-risk.

Methods

All treatment naïve patients with I/H-PAH, CTD-PAH and CHD-PAH referred to a single centre were included from 2003 to 2017. All patients were assessed at baseline and at the 1st follow-up at 3–4 months after starting PAH-specific therapy (1st F-UP) with RHC, brain natriuretic peptide (BNP) plasma levels, 6-min walking distance (6MWD) and WHO functional class. We applied a simplified risk assessment strategy using the following criteria: WHO functional class, 6MWD, right atrial pressure or BNP plasma levels and cardiac index (CI) or mixed venous oxygen saturation (SvO2). The last 2 criteria were based on which parameter was available; if both were available the worst was chosen. Risk strata were defined as: Low risk= at least 3 low risk and no high-risk criteria; High risk= at least 2 high risk criteria including CI or SvO2; Intermediate risk= definitions of low or high risk not fulfilled. The prognostic value of SVI was assessed using Cox regression analysis. Intermediate risk patients were further stratified in intermediate-low and intermediate-high risk taking into account the value of SVI that best discriminate prognosis (according to ROC curve analysis). Kaplan Meier curves and Log-rank test were used for survival analysis.

Results

Seven hundreds and twenty-five patients were enrolled. SVI is able to stratify the prognosis of PAH patients at 1st F-UP [HR 0.979 (0.964–0.994), p-value= 0.008] but not at baseline [HR 0.986 (0.970–1.002), p-value= 0.085]. The best predictive cut-off value is 38 ml/m2 (AUC= 0.66, sensitivity= 73%, specificity= 59%). Survival curves are shown in the Figure.

Figure 1

Conclusions

SVI assessed at 1st F-UP is predictive of prognosis and the cut off value of 38 ml/m2 is able to further stratify the survival of intermediate risk PAH patients.

Acknowledgement/Funding

None
P4685Validation of noninvasive pulmonary artery pressure/flow relationship: echocardiography vs right heart catheterization
Authors: Caravita S , Yerly P , Baratto C , Dewachter C , Rimouche A , Faini A , Branzi G , Perego G B , Bondue A , Parati G , Vachiery J L
Published: October 2019

Background

Invasive pressure-flow (P/Q) relationship of the pulmonary circulation can detect the presence of pulmonary hypertension (PH) during exercise and provide information on patients' symptoms and assess disease severity. Doppler-echocardiography was reported to provide accurate but imprecise noninvasive estimates of both resting and exercise pulmonary haemodynamics. However, data on the direct comparison of invasive vs noninvasive approaches to build pressure-flow relationship are scarce.

Purpose

To compare echocardiographic estimates with invasive measurements of P/Q relationship of the pulmonary circulation during exercise.

Methods

Patients undergoing a clinically indicated right heart catheterization and echocardiography were studied at rest and during exercise. The ratio between mean pulmonary artery pressure and cardiac output at peak exercise (TPR), as well as P/Q slope throughout exercise were calculated. Both TPR and P/Q slope are abnormal when ≥3 mmHg/L/min. Echocardiographic estimates were compared with invasive measurements.

Results

Sixty patients were included (mean age 65±14 years, 73% female). PH was present at rest in 38 cases (63%), of precapillary origin in 23 (61%). Heart failure with preserved ejection fraction was diagnosed in 23 patients, of which 17 had no PH at rest. TPR at peak exercise and P/Q slope were abnormal (≥3 mmHg/L/min) in the majority of patients (56 and 45 subjects, respectively).

Echocardiographic estimates of P/Q slope and TPR correlated significantly although weakly with invasive measurements (R2=0.38 and 0.56, respectively, p<0.001). Bias of echocardiography for P/Q slope and TPR was 1.1±4.2 and 0.4±2.9 mmHg/L/min, respectively (figure). Sensitivity of echocardiography to detect an abnormal TPR or P/Q slope (i.e. ≥3 mmHg/L/min) was 100 and 98%, respectively, faced by low specificity (0 and 33%, respectively).

Figure 1

Conclusions

Doppler-echocardiography can provide rather accurate and sensitive but imprecise estimates of pressure-flow relationships of the pulmonary circulation during exercise. This intrinsic imprecision may limit its use in clinical practice.
P4693Contemporary survival of adults with a systemic right ventricle
Authors: Segura De La Cal T , Ladoceur M , Li W , Rafiq I , Kempny A , Pires A , Gatzoulis M A , Dimopoulos K
Published: October 2019

Background

In complete transposition of the great arteries (TGA) with previous atrial switch operation and congenitally corrected transposition of the great arteries (ccTGA), the morphological right ventricle and its tricuspid valve support the systemic circulation. This results in late complications, including systemic right ventricle (sRV) failure, systemic atrioventricular valve regurgitation, and rhythm disturbances, affecting long-term outcome. We aimed to describe contemporary survival and determine predictive factors of death in an adult cohort with a sRV.

Methods and results

All adult patients (>16 years of age) with a sRV under active follow-up between January 2000 and December 2018 in our tertiary center were included. Demographic and clinical details were obtained from records. Baseline clinical status, transthoracic echocardiography, cardiopulmonary exercise testing and BNP were taken at the earliest available assessment during the study period.

Two hundred thirty-six patients, 141 with TGA/ 95 ccTGA, were included (mean age at baseline 31±12 years, 45% female sex). Over a median follow-up of 10.2 years IQR [5.6–14.9], 27 patients died, and 2 patients underwent heart transplantation. Cause of death was heart failure in 13 patients, sudden cardiac death in 2, and unspecified in 12. Survival at 5, 10 and 15 years of follow-up was 97.5%, 90.0% and 81.0%, respectively (Figure 1A).

On univariate Cox regression analysis, history of atrial arrhythmia, heart failure, and pulmonary arterial hypertension, baseline NYHA functional class ≥2, BNP≥120ng/L, peak VO2 and moderate/severe sRV function were predictive of death/heart transplantation. In contrast, previous permanent pacing, moderate or severe pulmonary stenosis, and use of beta-blockers were not associated with an increased risk of death. On multivariate analysis, NYHA ≥2 (HR=5.3 95% CI [1.1–25.6], p=0.03) and peak VO2 (HR=0.95 95% CI [0.91–0.99], p=0.01) were the strongest independent predictors of death. Patients with NYHA class≥2 and/or a pVO2<60% of predicted had a 3.6-fold higher risk of death compared to the remainder, even after adjustment for cardiac treatment at baseline (p=0.03, Figure 1B)

Figure 1. (A) Long term survival with 95% confidence intervals. (B) Survival according to the presence of symptoms (NYHA functional class ≥2) and/or a peak VO2 <60% predicted.

Conclusions

Mortality remains considerable in a contemporary cohort of adults with a sRV. Heart failure appears to be the leading cause of death, whereas only a few patients benefit from transplantation. Symptomatic patients with moderate or severe reduction in peak VO2 are at increased risk of adverse outcome in this setting and merit a more proactive approach and management.

Acknowledgement/Funding

Fundaciόn Alfonso Martín Escudero
P4704The efficacy of intravascular ultrasound for patients with peripheral artery diseases presenting aorto-iliac artery disease
Authors: Tsujimura T , Iida O , Takahara M , Yamauchi Y , Shintani Y , Sugano T , Yamamoto Y , Kawasaki D , Yokoi H , Miyamoto A , Mano T
Published: October 2019

Background

The use of intravascular ultrasound (IVUS) promotes better clinical outcomes for intervention in complex lesions. However, the data demonstrating whether use of IVUS improves primary patency following stenting for aorto-iliac lesions in patients with peripheral artery disease (PAD) are limited.

Purpose

The purpose of the current study was to investigate the impact of IVUS use on primary patency 12 months after stent implantation for aorto-iliac lesions.

Methods

We analyzed a clinical database of the OMOTENASHI registry (Observational prospective Multicenter registry study on Outcomes of peripheral arTErial disease patieNts treated by AngioplaSty tHerapy in aortoIliac artery), registering symptomatic PAD patients (Rutherford category 2, 3, or 4) undergoing endovascular therapy for aorto-iliac lesions between January 2014 and April 2016 in Japan. The current study analyzed 803 patients who underwent self-expandable stent implantation at 61 centers with the institutional volume known. The primary endpoint was 12-month restenosis, defined as ≥50% stenosis on computed tomography or angiography, or a peak systolic velocity ratio ≥2.5 on duplex ultrasound. When treatment strategies, endovascular procedures and clinical outcomes were compared between the patients treated with IVUS use and those treated without IVUS use, the propensity score matching was performed to minimize the inter-group difference in baseline characteristics.

Results

A total of 545 patients (67.9%) underwent IVUS-supported stent implantation. Patients treated with IVUS use had a lower prevalence of regular dialysis, whereas they had a higher prevalence of TASC II class D and chronic total occlusion. In patients treated with IVUS use, carbon dioxide contrast agent were more often used, and 0.035-inch guidewire was less frequently selected. Implanted stents in these patients were longer and smaller in diameter. The propensity score matching extracted 138 pairs, with no remarkable intergroup difference in baseline characteristics. Procedure time ≤1 hour was less frequent in patients treated with IVUS use; their radiation time was longer. Endovascular strategies, as well as postoperative medication were not significantly different between patients with and without IVUS use. The 12-month restenosis risk was not significantly different between patients with and without IVUS use (10.2% [6.9 to 14.9%] versus 10.3% [5.4 to 18.6%], P=0.99).

Conclusion

IVUS use in aorto-iliac stenting for patients with PAD was not associated with primary patency at 12 months.

Acknowledgement/Funding

None
P4710Impact of therapeutic angiogenesis using autologous bone marrow-derived mononuclear cells implantation in critical limb ischemia with collagen disease
Authors: Shoji K , Yanishi K , Wakana N , Nakanishi N , Zen K , Nakamura T , Shirayama T , Matoba S
Published: October 2019

Background

Many patients with collagen disease (CD), particularly systemic sclerosis (SSc) and collagen disease-associated vasculitis (CDV), develop critical limb ischemia (CLI) which leads to limb amputation. In SSc vasculopathy, intimal hyperplasia, abnormal vascular contraction, and intravascular micro thrombus due to autoimmune abnormalities are main causes of inadequate blood supply that lead to the development of CLI. Moreover, in CDV, presence of inflammation cells infiltrates and destruction of the vascular wall also lead to vascular stenosis or obstruction. However, conventional therapies including revascularization via surgical bypass showed poor outcomes in CLI patients with CD. Therefore, establishment of new methods to improve peripheral circulation for limb salvage are required.

Purpose

After discovering that circulating endothelial progenitor cells (EPCs) mobilized from the bone marrow participate in postnatal neovascularization, autologous bone marrow-derived mononuclear cells (BM-MNCs) has been performed as a new treatment for many no-option CLI patients caused by arteriosclerosis obliterans, thromboangiitis obliterans or CD. In this study, we would like to assess the long-term clinical outcomes after autologous BM-MNCs implantation in CLI patients with SSc and CDV.

Methods

This study was a retrospective, multicenter, observational, and non-controlled study. We assessed no-option CLI patients with CD who were performed the autologous BM-MNCs implantation in 10 institutes. Overall survival (OS), major-amputation-free (MAF) and amputation-free survival (AFS) rates were primary endpoints of this study. In addition, we assessed improvements of ischemic pain as visual analogue scale (VAS) scores. Safety endpoints were defined as cardiovascular events and all-cause adverse events within 6 months after implantation.

Results

A total of 69 patients (39 with SSc–related diseases (SSc group) and 30 with CDV (CDV group)), were included in this study. The median follow-up duration was 36.5 months. The 10-year OS rate was 59.1% in the SSc group and 82.4% in the CDV group, respectively. The 10-year MAF rates were 97.4% and 82.6%, respectively. The 10-year AFS rates were 57.6% and 67.8%, respectively (Figure 1). The number of major or minor amputations in the SSc group trended to be less than that in the CDV group. In addition, significant improvement in VAS scores were observed in both groups (Figure 2). No patients died, no cardiovascular events, and no severe adverse events associated with BM-MNCs implantation were noted within 6 months after this therapy in both groups.

Figure 1

Conclusions

The BM-MNCs implantation may be feasible in no-option CLI patients with CD. Improvement of ischemic symptoms by BM-MNCs implantation was significant in both groups and, in the SSc group, limb salvage rate tended to be higher than the CDV group.
P4714Individual patient data meta-analysis comparing general anesthesia and deep sedation on safety and length of intensive care unit stay in patients undergoing percutaneous mitral valve repair
Authors: Jobs A , De Waha-Thiele S , Ledwoch J , Sievert H , Rassaf T , Luedike P , Kelm M , Hellhammer K , Horn P , Westenfeld R , Patzelt J , Langer H F , Desch S , Eitel I , Thiele H
Published: October 2019

Background

Percutaneous edge-to-edge mitral valve repair (PMVR) has emerged as a treatment option for patients with severe mitral regurgitation not considered suitable candidates for surgery. The procedure can be performed in general anesthesia (GA) or deep sedation (DS) without mechanical ventilation. However, debate remains about the optimal approach.

Purpose

To compare the impact of the anesthetic method on efficacy, safety, and length of intensive care stay.

Methods

We identified studies comparing GA versus DS in patients undergoing PMVR by searching PubMed and CENTRAL. We included studies for which investigators agreed to provide individual patient data. Analyzed outcomes were a composite safety endpoint comprising all-cause death, stroke, pneumonia, and major to life-threating bleeding as well as length of intensive care unit stay. We performed an one-stage and two-stage meta-analysis on each outcome after multiple imputation of missing data. For two-stage meta-analysis, between-study heterogeneity was estimated according to Paule-Mandel and confidence intervals were derived using the method proposed by Hartung and Knapp.

Results

We included five observational studies (n=647 patients). Procedural success was achieved in 618 of 647 (95.5%) patients. The composite safety endpoint occurred in 92 of 647 (14.2%) patients with no difference between patients treated with GA or DS. In this regard, risk ratio was 0.78 (95% confidence interval, 0.53 to 1.14; P=0.20) following the one-stage approach and 0.73 (95% confidence interval, 0.30 to 1.80; P=0.39) following the two-stage approach. Length of intensive care stay was longer after GA as compared to DS (adjusted mixed linear regression model, 1.94 days, 95% confidence interval, 1.29 to 2.59 days, P<0.001; random effects model pooling study-specific estimates from adjusted linear models 1.40 days, 95% confidence interval, 0.54 to 2.22 days, P=0.0104).

Conclusion

Both, DS and GA offer good procedural success rates and a similar safety profile. However, length of intensive care stay is shorter after DS.
P4748HASBLED score, frailty index or comorbidity index for bleeding risk assessment in patients with atrial fibrillation?
Authors: Fauchier L , Bisson A , Bodin A , Clementy N , Pierre B , Angoulvant D , Babuty D , Hanon O , Lip G
Published: October 2019

Background

Charlson comorbidity index (CCI) is a tool to measure comorbid disease status and a strong estimator of mortality. The quantifiable frailty phenotype has also been validated as predictive of mortality and disability. Claims data can be used to classify individuals as frail and non-frail using the Claims-based Frailty Index (CFI). We evaluated whether these tools may help to predict the risk of bleeding in patients with atrial fibrillation (AF).

Methods

All patients with AF seen in an academic institution were identified and followed up for mortality, stroke and bleeding events. HAS-BLED, HEMORR2HAGES, ATRIA and ORBIT scores, CCI and CFI were calculated for each patient. Hazard ratios were calculated and predictive abilities of the scores were compared using the c-statistic in the whole population and then separately in elderly patients (>75 yo).

Results

Among 8962 patients with AF, 274 major bleeding events were recorded during a follow-up of 874±1054 days. Bleeding occurred more commonly in patients with higher bleeding risk scores, CCI and CFI. The 4 bleeding risk scores significantly had lower c-statistics than CCI and CFI for predicting major bleeding (table). Results were similar whether patients were treated with OAC or no OAC. In elderly patients, the c-statistics were all lower and were not significantly different for the 4 scores, CCI and CFI scores (0.594, 0,572, 0.595, 0.594, 0.616 and 0.591 for HAS-BLED, HEMORR2HAGES, ATRIA, ORBIT, CCI and CFI, respectively).

Predictive values for major bleeding ROC Area 95% Conf. Interval P value vs CCI/CFI HASBLED 0.588 0.555–0.621 0.002/0.003 HEMORR2HAGES 0.564 0.531–0.598 <0.0001/<0.0001 ATRIA 0.559 0.522–0.595 <0.0001/<0.0001 ORBIT 0.577 0.542–0.612 0.0002/0.0003 Charlson, CCI 0.652 0.619–0.684 –/0.58 Frailty index, CFI 0.648 0.615–0.681 0.58/–

Conclusion

Comorbidities and frailty, respectively assessed with CCI and CFI, demonstrated statistically better performances in predicting major bleeding than the 4 established bleeding risk scores in AF, although all c-indexes were broadly similar. The 4 bleeding risk scores, CCI and CFI showed lower performance in predicting bleeding within elderly patients in whom they all performed equally to predict bleeding events. Given their simplicity and similar performances, the user-friendly bleeding risk scores remain attractive tools for the estimation of bleeding risk in elderly patients with AF.
P4756Stroke and bleeding in low, intermediate and high risk patients with atrial fibrillation treated with edoxaban: Results of the ETNA-AF Europe registry
Authors: De Groot J R , De Caterina R , Kelly P , Monteiro P , Deharo J C , De Asmundis C , Lopez De Sa E , Weiss T W , Waltenberger J , Steffel J , Levy P , Bakhai A , Kirchhof P
Published: October 2019

Background

Edoxaban, a direct FXa inhibitor, has been proven non-inferior in efficacy and safer compared to warfarin in the ENGAGE AF-TIMI 48 trial. In routine care, the safety of edoxaban has not been formally established. ETNA-AF-Europe is a multinational, multi-centre, post-authorisation, observational study (NCT02944019) conducted in 825 sites in 10 European countries. Here 13,980 edoxaban-treated patients with AF were enrolled between November 2016 and February 2018, and will be followed-up for 4 years.

Methods

7,672 patients (73.4±9.26 years, 57.5% male) enrolled in the ETNA-AF Europe registry completed the one-year follow-up and were stratified into low-, intermediate- and high-risk for stroke and bleeding using the CHA2DS2-VASc and HASBLED score, respectively. We here analysed the occurrence of stroke, bleeding, intracranial haemorrhage and mortality in such categories.

Results

The mean CHA2DS2-VASc score at baseline was 3.1±1.38 and the mean HAS-BLED score was 2.5±1.1. Not surprisingly, patients at higher risk were older, had a lower body weight, more comorbidities, and a lower creatinine clearance. A higher proportion of patients at high risk received the reduced 30 mg edoxaban dose. Overall, the yearly event rates of stroke, intracranial haemorrhage, major bleeding and death were low. However, these rates increased consistently in patients with higher stroke and bleeding risks. Residual stroke risk on anticoagulation was comparable to the risk of major bleeding (Table 1).

Outcomes by stroke and bleeding risk CHA2DS2-VASc: mean 3.1±1.38 HAS-BLED: mean 2.5±1.1 All patients Low risk (0, 1 if female) Intermediate risk (1, 2 if female) High risk (≥2, 3 if female) Low risk (0, 1) Intermediate risk (2, 3) High risk (≥4) Patients, N 233 1,133 6,304 1,224 4,932 1,516 7,672 First occurrence of outcomes, n (%/year)   All-cause mortality 2 (0.92%) 12 (1.11%) 242 (4.09%) 14 (1.21%) 161 (3.47%) 82 (5.78%) 257 (3.56%)   Intracranial haemorrhage 0 (0.00%) 1 (0.09%) 19 (0.32%) 2 (0.17%) 10 (0.22%) 8 (0.56%) 20 (0.28%)   Major bleeding 0 (0.00%) 6 (0.56%) 62 (1.05%) 2 (0.17%) 43 (0.93%) 23 (1.63%) 68 (0.95%)   Stroke/SEE 0 (0.00%) 4 (0.37%) 59 (1.00%) 3 (0.26%) 41 (0.89%) 19 (1.34%) 63 (0.88%) SEE, systemic embolic event.

Conclusions

In this unselected cohort of patients with AF anticoagulated with edoxaban, high CHA2DS2-VASc and HAS-BLED scores were associated with higher risks of stroke, bleeding and death. Indirectly compared with the expected rates in non-anticoagulated patients, our data underpin the value of anticoagulants such as edoxaban in patients at high risk of stroke and bleeding.

Acknowledgement/Funding

The ETNA-AF Registry was funded by Daiichi Sankyo Europe GmbH, Munich, Germany.
P4766Edoxaban Treatment in routiNe clinical prActice for patients with atrial fibrillation (AF) in Europe (ETNA-AF-Europe): 1-year follow-up according to body mass index
Authors: Weiss T , De Caterina R , Kelly P , Monteiro P , Deharo J C , De Asmundis C , Lopez-De-Sa E , Waltenberger J , Steffel J , De Groot J R , Levy P , Bakhai A , Kirchhof P
Published: October 2019

Background

Non-vitamin K antagonist (VKA) oral anticoagulants (NOACs) have substantially improved anticoagulation therapy for prevention of stroke and systemic embolism in patients with atrial fibrillation (AF), and available routine care data have so far broadly confirmed the safety of different NOACs in routine practice. However, such data for edoxaban are scarce, especially in extremely low and high body weight (BW). These extreme BWs may affect the bioavailability, distribution, and half-life of NOACs and, consequently, outcomes of treatment.

Methods

We analysed outcomes in normal-weight (BMI 18.5–25) vs overweight (BMI 25–30) and obese (BMI >30) patients enrolled into the ETNA-AF-Europe observational study (NCT02944019) collecting information on patients treated with edoxaban in 825 sites in 10 European countries. This snapshot analysis set includes data of 7,672 patients (56.3% of all enrolled patients) which have completed their 1-year follow-up visit (mean follow-up: 343.5 days).

Results

Median patient age was 74 years for all patients, 76 years for patients with a BMI 18.5–25 (group 1), 75 years for patients with BMI 25–30 (group 2), and 72 for patients with a BMI >30 (group 3). CrCl was 64 mL/min for patients with a BMI 18.5–25, 68 mL/min for patients with BMI 25–30, and 72 mL/min for patients with a BMI >30. The CHA2DS2-VASc (mean 3.1±1.38) and HAS-BLED (mean 2.5±1.10) score did not differ significantly between groups. As expected, diabetes and hypertension were significantly less prevalent in leaner patients and - accordingly - inversely correlated to age.

There was no correlation between body weight and life-threatening bleeding (group 1: 0.28%; group 2: 0.40%; group 3: 0.14%). Also, stroke rates (group 1: 0.74%; group 2: 0.81%; group 3: 0.76%) did not differ between groups.

Conclusion

BMI, within the range here assessed, does not affect 1-year outcomes in European AF patients treated with edoxaban.

Acknowledgement/Funding

Daiichi Sankyo Europe GmbH, Munich, Germany
P4767VTE-BLEED score predicts major bleeding in patients with atrial fibrillation
Authors: Klok F A , Chu K G , Valerio L , Van Der Wall S J , Barco S , Konstantinides S , Huisman M V
Published: October 2019

Background

Bleeding risk scores in atrial fibrillation (AF) are used to identify risk factors for bleeding but not to determine anticoagulant therapy since high bleeding risk strongly correlates to high risk of stroke. VTE-BLEED is a simple bleeding risk score (Klok FA Eur Respir J 2016) that predicts major bleeding (MB) in patients with venous thromboembolism, but has never been evaluated in AF.

Aims

To evaluate VTE-BLEED in AF and whether dabigatran dose reduction in VTE-BLEED high-risk patients would result in a lower incidence of MB and the composite endpoint of MB plus stroke/systemic embolism.

Methods

Assessment of VTE-BLEED in 18040 patients of the RE-LY trial (Connolly SJ NEJM 2009) that compared dabigatran (both 150mg BID and 110mg BID) to warfarin. The score was calibrated to fit the AF population. Hazard ratios (HR) were obtained for the VTE-BLEED high-risk patients randomized to dabigatran. The risk ratios for MB and the composite outcome of MB plus stroke/systemic embolism between dabigatran 150mg and 110mg were calculated for the VTE-BLEED high-risk group.

Results

The adapted VTE-BLEED score classified 4060 patients (22.5%) as high-risk. A high score indeed predicted MB in patients treated with dabigatran 150mg BID or 110mg BID, for HRs of 2.48 (95% CI 1.96–3.13) and 2.61 (95% CI 2.04–3.33), respectively. In VTE-BLEED high-risk patients, the risk ratio between the two dabigatran doses was 0.53 (95% CI 0.35–0.78) for MB and 0.55 (95% CI 0.38–0.79) for the composite outcome, both in favor of dabigatran 110mg BID (Figure 1). Compared to the current European label of dabigatran, application of VTE-BLEED to determine dabigatran dosing would result in a different dose for 21% of patients.

Figure 1

Conclusions

VTE-BLEED was validated for AF. Our data suggest that dabigatran dose reduction in VTE-BLEED bleed high-risk patients -in addition to targeting individual modifiable risk factors for bleeding- may lower the risk of MB and improve patient outcome. This finding could have important clinical implications but should be confirmed in future studies.
P4781Comparative effcomparative effectiveness and safety of factor-xa inhibitors vs phenprocoumon in patients with non-valvular atrial fibrillation and malignant diseases, insights from the RELOADED study
Authors: Bonnemeier H , Kreutz R , Enders D , Schmedt N , Haeckl D , Vaitsiakhovich T , Kloss S
Published: October 2019

Background

Data on safety and effectiveness of Factor-Xa inhibitors and phenprocoumon in patients with non-valvular atrial fibrillation (NVAF) and malignant diseases is scarce. Among others, our study aimed to investigate the safety and effectiveness in new users of Factor-Xa inhibitors vs. phenprocoumon, the vitamin-K antagonist (VKA) of choice in Germany.

Methods

We conducted a new user cohort study (one year washout period) in patients with NVAF and malignant diseases. German claims data between January 1st, 2013 and June 30th, 2017 were utilized and a multiple Cox-regression was performed to calculate confounder-adjusted hazard ratios (HRs) for the risk of ischemic stroke (IS)/systemic embolism (SE), intracranial haemorrhage (ICH) as well as renal function worsening, defined by end stage renal disease (ESRD) or dialysis and acute kidney injury (AKI) in Factor-Xa inhibitors and phenprocoumon initiators. Diagnoses of malignant diseases were assessed over the one-year baseline period.

Results

The population comprised 3,779 phenprocoumon initiators, 3,386 rivaroxaban initiators, 2,697 apixaban initiators and 434 edoxaban initiators. In the confounder-adjusted analysis, no difference related to the risk of IS/SE was found for rivaroxaban and edoxaban vs. phenprocoumon, where apixaban showed a numerically increased risk for stroke (figure 1). Point estimates related to the risk of ICH showed the expected beneficial effects for both, rivaroxaban and apixaban. A strong beneficial effect was observed for rivaroxaban when assessing the risk of renal function worsening. Hazard ratios related to the risk of ESRD/dialysis and AKI were 0.27 (0.10; 0.69) and 0.64 (0.38; 1.06), respectively. For apixaban, only the ESRD/dialysis showed a reduction in risk when compared to phenprocoumon, HR 0.42 (0.19; 0.94).

Conclusion

This retrospective database study conducted in Germany adds evidence on the effectiveness and safety profile of Factor-Xa inhibitors over VKA in patients with NVAF and malignant diseases, a critical subgroup of patients where anticoagulation is challenging. However, apixaban showed a numerically increased risk for IS/SE compared to phenprocoumon. Both, rivaroxaban and apixaban showed a risk reduction for renal function worsening within the study period of 63% and 48%, respectively compared to phenprocoumon. Only rivaroxaban showed a risk reduction of 36% for AKI.

Acknowledgement/Funding

The study was funded by Bayer AG
P4798Stereotactic radiotherapy for atrial fibrillation in three cancer patients
Authors: Shoji M , Inaba K , Itami J , Iwasa T , Yoshida M , Matsuyama T , Kumagai K , Hirao K , Qian P , Gardner E , Zei P
Published: October 2019

Background

Although catheter ablation is an effective therapy for atrial fibrillation (AF), risks remain and improved efficacy is desired. Stereotactic radiotherapy is a well-established therapy used to noninvasively treat malignancies with precision.

Objective

We sought to evaluate stereotactic arrhythmia radioablation (STAR) as a therapeutic option for treating AF.

Methods

Three cancer patients with drug refractory AF were enrolled. Planning software using 3-D CT of the left atrium was used to design a desired ablation volume encompassing antral circumferential pulmonary vein isolation, a roof line, and a floor line to create a “BOX” lesion set. Target dose to the treatment volume was 25 Gy, with exposure to the esophagus excluded. After planning, patients were treated in the radioablation suite.

Results

STAR was able to deliver the intended radiation dose to target without complication in 3 patients. No acute complications were seen for up to 6 months. One patient with paroxysmal AF died of deterioration of cancer. The autopsy revealed evidence of fibroblasts and fibrogenesis at the regions of atrial tissues targeted with radioablation. Two patients with longstanding persistent AF remained in AF at 6 months. In one patient, atrial electrograms were recorded at the atrial posterior wall from the esophagus before STAR, and it was absent at 3 months after STAR, indicating electrical isolation.

BOX isolation created by STAR

Conclusions

Although STAR may be safe, further evaluation is warranted regarding effectiveness. For longstanding persistent AF, AF may be difficult to terminate only with a BOX lesion set without electrical cardioversion.
4878Different relationships between blood pressures and clinical events in SPRINT and ACCORD-BP trial
Authors: Shin D.-H , Ahn C M , Kim J S , Kim B K , Ko Y G , Park S H , Choi D H , Hong M K , Jang Y S , Roe M T
Published: October 2019

Introduction

SPRINT showed that intensive control of systolic blood pressure (SBP) <120mmHg was beneficial when compared to the standard treatment (SBP <140mmHg). In contrast, ACCORD-BP trial failed to prove the benefit of intensive SBP lowering in diabetic patients. J-curve phenomenon might be the key to help understanding the different results of two trials.

Methods

SPRINT and ACCORD-BP databases were obtained via BioLINCC. Since BP changes along with the time, timing at which BP became stable after treatment were chosen at 9 months for SPRINT and 1 year for ACCORD BP. The final analytic datasets consisted of 8,787 and 4,306 event-free patients at the time of stable BP, respectively. Clinical events were defined at the primary composite endpoint for each trial. The effects of BP on clinical events were modeled using natural cubic splines in Cox regression models. Degrees of freedom of splines curves were chosen using Akaike Information Criterion.

Results

Analyzing SPRINT database, the spline-based hazard ratio (HR) curve showed a J-curve, which means lowering DBP below 77mmHg could be harmful, while SBP had a linear relationship (HR 1.13 per 10mmHg increase, 95% confidence interval [CI] 1.06∼1.20, p<0.0001; Figure). In ACCORD-BP trial, no J-curve phenomenon was observed. The effect of SBP was linear and almost the same to the result of SPRINT with HR 1.13 (95% CI 1.06∼1.20, p=0.0003). The relationship between DBP and clinical events was non-significant with a negative trend, which means the lower, the worse (HR 0.91, 95% CI 0.82∼1.01 p=0.071).

Conclusions

Despite the different results regarding the benefit of intensive BP control, the effects of SBP on clinical events were quite similar in SPRINT and ACCORD-BP trial. Instead,differences existed in the relationships between DBP and clinical events. Understanding the meaning of different patterns of relationships including J-curve might be the key to determine the optimal BP control.