bluuebunny/crossref_metadata_2025_split huggingface dataset:
P4604Insights into left ventricular remodelling and clinical outcomes after Wharton's jelly multipotent stem cells transcoronary administration in a pilot cohort of CIRCULATE-AMI Trial (NCT03404063)
Authors: Kwiecien E , Drabik L , Mazurek A , Urbanczyk M , Szot W , Kostkiewicz M , Banys R P , Brzyszczyk-Marzec M , Czyz L , Kozynacka A , Plazak W , Olszowska M , Majka M , Podolec P , Musialek P 
Published: October 2019

Abstract

Introduction
CIRCULATE-Acute Myocardial Infarction Trial (NCT03404063) is a double-blind controlled trial (RCT) that is randomizing consecutive patients with their first, large AMI (LVEF ≤45% and/or cMRI -infarct size ≥10% of LV) successfully treated by infarct-related artery (IRA) primary percutaneous coronary intervention reperfusion (TIMI ≥2) to transcoronary administration of Wharton Jelly Multipotent Stem Cells (WJMSCs) vs. placebo (2:1), preceded by evaluation of safety, WJMSCs myocardial uptake, and echocardiographic, cMRI and SPECT left ventricular remodelling and hemodynamic changes in pilot study cohort (PSC).

Purpose
To evaluate LV remodelling and hemodynamic features following WJMSCs transplantation in CIRCULATE-AMI PSC.

Methods
Ten consecutive patients (age 32–65 years) were administered 30 000 000 WJMSCs via the infarct-related artery at ≈5–7 days after AMI using transradial approach and a coronary-non-occlusive catheter dedicated to cell delivery. Within 3 years of follow up SPECT was performed at baseline and 1 year, echo and cMRI were performed at baseline, 1 year and 3 years.

Results
3-year observation (cMRI) shows a significant decrease of median left ventricular mass (LVM) between WJMSCs administration and 1 year 140 g (IQR 128–150) vs. 97 g (95–128), that is sustained at 3 years 93 g (80–119), p<0,001. There were no significant changes of left ventriular end-diastolic volume (LVEDV) in all diagnostic methods: SPECT baseline vs. 1 year (157.1±27.1 ml vs. 174±24 ml); cMRI baseline vs. 1 year vs. 3 years (171.6±17.7 ml vs. 198.2±23.4 ml vs. 181.9±17.6 ml) and Echo (137±13.3 ml vs. 135±2.9 ml vs. 148±21.8 ml), p value >0,05 for all. Furthermore, there was a significant increase in stroke volume measured by SPECT baseline vs. 1 year (53.3±7.6 ml vs. 68.2±5.2ml); cMRI baseline vs. 1 year vs. 3 years (72.7±5.2 ml vs. 96.9±8.1 ml vs. 93.2±7.8 ml) and Echo (64.3±2.9 ml vs. 68.8±4.1 ml vs. 81.9±7.1 ml), p<0,05 for all. By 3 years there was one non-index territory AMI. There were no other adverse events in the study cohort.
cMRI Left Ventricular Mass evolution

Conclusions
Long-term follow up in CIRCULATE-AMI PSC suggests that transcoronary administration of WJMSCs in a recent large AMI in humans might be associated with an inhibition of LV adverse remodelling and a significant hemodynamic improvement. Our currently running randomized double-blind controlled trial will verify LV remodelling evolution in WJMSCs-treated patients.

Acknowledgement/Funding
K/ZDS/00564 Jagiellonian University Medical College; STRATEGMED 265761 “CIRCULATE” National Centre for Research and Development/Poland
P4613Long-term impact of postnatal nutritional programming on cardiac sensitivity to ischemia-reperfusion injury in vivo and on cardio-protective pathways in mice
Authors: Rigal E , Greco C , Porcherot I , Meloux A , Rochette L , Vergely C 
Published: October 2019

Abstract

Introduction
Nutritional disturbances during the postnatal period may be responsible for a predisposition, or “programming”, to increased cardio-metabolic risk and to a progressive alteration of left ventricular contractility in adulthood. This nutritional perinatal programming may also lead to an alteration of cellular pathways involved in cardiac protection, such as the specific RISK and SAFE pathways, highlighted during pre- and post-ischemic conditioning or those of sirtuins (SIRT), histone deacetylases involved in the regulation of essential biological process.

Purpose
Our aim was to evaluate in mice the impact of postnatal overfeeding (PNOF) on cardiac sensitivity to ischemia-reperfusion (I-R) injury in vivo and on the myocardial expression of genes involved in heart protection against ischemia.

Methods
PNOF was induced by the reduction of litter size of C57/BL6 mice immediately after birth: normally-fed group (NF) was composed of 9 male pups/mother and overfed group (OF) of 3 pups/mother. In vivo ischemia-reperfusion injury was induced by the ligation of the anterior interventricular artery for 45 minutes followed by 24 h of reperfusion in hearts from 6-months aged mice. The gene expressions of proteins of interest composing the cardioprotective pathways (RISK pathway: Akt, ERK; SAFE pathway: JAK/STAT3; Sirtuins: SIRT1) were measured by RT-qPCR in mice aged 4 and 6 months.

Results
PNOF induced in OF group an early and permanent increase in body weight (+23%, p<0.01, n=11) and a significant increase of infarct size (+32%, p<0.05, n=11) at 6 months. Hearts OF mice aged 4 months showed a decreased expression of cardioprotective pathways, represented by a reduction in the gene expression of ERK1, Akt, PI3K, STAT3 and SIRT1. At 6 months, the expression of cardioprotective pathways was also reduced in OF group, with the diminution of the gene expression of STAT3, Akt and Erk1.

Conclusion
Nutritional programming through short-term PNOF induced a long-lasting decrease in the expression of signaling pathways involved in cardiac cellular protection, which could explain why 6-months old mice show increased susceptibility to myocardial I-R injury in vivo. The mechanism of these alterations needs further exploration, but could involve alterations in cardiomyocyte's balance between apoptotic and regenerative pathways, and epigenetic modifications.

Acknowledgement/Funding
French Fundation
P4617Early electrocardiographic changes as markers of coronary microvascular obstruction in acute myocardial infarction with ST segment elevation
Authors: Garcia Talavera C S , Camblor Blasco A , Rivero Monteagudo A L , Arroyo Rivera M B , Cortes Garcia M , Franco Pelaez J A , Navarro Del Amo F , Tunon Fernandez J 
Published: October 2019

Abstract

Background
Coronary microvascular obstruction (CMVO), occurs frequently even after a quickly epicardial revascularization of the infarct-related artery (IRA), and has been associated with an increased risk of adverse cardiovascular events and poor prognosis in patients with ST-segment myocardial infarction (STEMI). After primary coronary intervention (PCI), incomplete ST-segment elevation (STE) resolution in the ECG has been related to CMVO and worse clinical outcome. However, there is lack of information regarding other ECG changes. The aim of this study is to describe the initial ECG changes in STEMI and evaluate their association with CMVO.

Methods
From January 2007 to December 2017, all patients with the diagnosis of STEMI that underwent urgent coronary angiography were retrospectively included. Clinical, echocardiographic, and electrocardiographic data were taken from medical records. A univariate and multivariate analysis was performed to evaluate the relationship between initial ECG changes (before PCI) and CMVO defined as final TIMI <3 in the IRA.

Results
1022 patients were included; the mean age was 67.8 years (±14), 73.7% were male and 14.4% had previous coronary artery disease. The most frequent IRA was the anterior descending artery in 43.2% of the cases and CMVO was found in 18.3% of the patients. The mean value of STE sum (defined as the sum of STE in V1-V6, I and aVL in anterior STEMI and the sum of II, III, aVF, V5 and V6 in non-anterior STEMI), maximum STE in one lead and number of leads with STE was 11.36mm (± 8.2), 3.65mm (± 2.3) and 4.14mm (± 1.4), respectively. After a univariate analysis, STE sum, maximum STE in one lead and number of leads with STE were associated with CMVO, while only STE sum remained significantly associated with the presence of CMVO after a multivariate analysis (Table). The resolution of STE in the first 2 hours after PCI was a protector factor for CMVO.
Univariate and Multivariate Analysis Univariate Multivariate Variables OR 95% CI p OR IC 95% p Sum of STE 1.03 1.01–1.04 0.013 1.03 1.01–1.05 0.005 Number of leads with STE 1.13 1.02–1.26 0.021 1.04 0.87–1.23 0.67 Maximum STE 1.09 1.02–1.16 0.016 1.04 0.92–1.17 0.49 Resolution of STE 0.35 0.25–0.49 <0.001 0.36 0.25–1.18 <0.001 STE, ST-segment elevation.

Conclusion
Initial ECG changes such as STE sum, number of leads with STE and maximum STE in one lead can be used as early predictors of CMVO and poor prognosis. STE resolution in the first 2 hour was associated with a lower incidence of CMVO as reported in previous studies.

Acknowledgement/Funding
None
P4619Comparison of the CRUSADE, ACUITY-HORIZONS, and ACTION bleeding risk scores for predicting in-hospital bleeding in acute myocardial infarction patients undergoing primary PCI
Authors: Mehmedbegovic Z , Milasinovic D , Jelic D , Zobenica V , Matic D , Dedovic V , Radomirovic M , Pavlovic A , Veljic I , Zaharijev S , Asanin M , Vukcevic V , Stankovic G 
Published: October 2019

Abstract

Background
Considering clinical importance of bleeding complications in patients with acute myocardial infarction (AMI), bleeding risk stratification is a key part of the management of these patients. CRUSADE, ACTION and ACUITY-HORIZONS bleeding risk scores are available for predicting in-hospital major bleeding events in patients with acute myocardial infarction.

Purpose
We aimed to evaluate performance of the three above mentioned risk scores for predicting in-hospital bleeding events defined according to The Bleeding Academic Research Consortium (BARC) criteria.

Methods
From a prospective electronic registry of a high-volume catheterization laboratory in a period from January 2009 to December 2017, a total of 6505 consecutive patients with acute myocardial infarction who underwent pPCI were included in analysis. Calibration and discrimination of the three risk models were evaluated by the Hosmer-Lemeshow (H-L) goodness-of-fit test and C-statistic, respectively.

Results
Overall there were 372 (5.7%) bleeding events out of which 117 (1.8%) fulfilled stage BARC 3 or higher bleeding criteria. All three scores showed good model calibration as assessed by the H-Ls test and very good discriminative power for BARC 3 of higher bleeding events detection as assessed by C-statistics (Table 1 & Figure 1):
Bleeding events stage BARC 3 or higher were statistically highly related with higher in-hospital mortality (13.7% vs. 3.5%; p<0.000).
Table 1 Risk score H-L H-L p AUC 95% CI p CRUSADE 11.46 0.177 0.761 0.750–0.771 vs. ACUITY = ns vs. ACTION <0.000 ACUITY-HORIZONS 10.47 0.236 0735 0.724–0.745 vs. ACTION = ns ACTION 5.74 0.677 0.701 0.698–0.712
Figure 1

Conclusions
All three evaluated scores showed very good discriminative capacity for predicting BARC 3 or higher bleeding events in patients undergoing pPCI for AMI.
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

Abstract

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

Abstract

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

Abstract

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

Abstract

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.