bluuebunny/crossref_metadata_2025_split huggingface dataset:
Circulating CD4+T/methylation signatures of network-oriented SOCS3, ITGAL, NFIC, NCOR2, PGK1 genes associate with hemodynamics in pulmonary arterial hypertension patients
Authors: Benincasa G , Maron B A , Affinito O , D'Alto M , Franzese M , Argiento P , Schiano C , Romeo E , Bontempo P , Golino P , Berrino L , Loscalzo J , Napoli C 
Published: October 2021

Abstract

Background
CD4+ T cells are associated with pulmonary arterial hypertension (PAH) pathogenesis but mechanistic insights are limited.

Purpose
To identify differential CD4+ T methylation signatures in healthy controls vs PAH and evaluate a putative association with the cardiopulmonary hemodynamic profile of affected patients.

Methods
We used RRBS platform to profile CD4+ T DNA methylome in the CLEOPAHTRA clinical trial.

Results
Differentially methylated CpG sites (N=631) annotated to N=408 genes (DMGs). Most of them (65%) were hypermethylated and localized in distal intergenic (36%) and promoter regions (31%). Promoter-related network analysis established the PAH subnetwork highlighting 5 hub DMGs (SOCS3, GNAS, ITGAL, NCOR2, NFIC) and 5 non-hub DMGs (NR4A2, GRM2, PGK1, STMN1, LIMS2) as potential candidate genes (Figure 1). The Infinium Human MethylationEPIC BeadChip on CD4+ T cells from an independent study population confirmed the global RRBS-methylation trends. Both in idiopathic and Associated-PAH, each of these 10 network-oriented DMGs was strongly correlated with at least one hemodynamic parameter such as right atrial pressure (RAP), cardiac index (CI), mean pulmonary arterial pressure (mPAP), pulmonary vascular resistance (PVR), and pulmonary capillary wedge pressure (PCWP) (Figure 2). In addition, mRNA levels of the ITGAL, NFIC, NCOR2, PGK1 genes and the IL-6-STAT3-SOCS3 signaling axis were significantly upregulated in PBMCs from patients with PAH vs controls suggesting putative drug targets. Furthermore, both SOCS3 methylation and mRNA levels were positively correlated with cardiac index (CI) in idiopathic PAH whereas both PGK1 methylation and mRNA levels were positively correlated with RAP and inversely with CI in Associated PAH suggesting putative non-invasive biomarkers.

Conclusions
This hypothesis-generating study shows for the first time that circulating CD4+ T methylation signatures, inclusive of SOCS3, ITGAL, NFIC, NCOR2, and PGK1 genes may yield insight into pro-inflammatory mechanisms that exacerbate vascular remodeling in PAH and suggest non-invasive biomarkers to optimize patient phenotyping and, possibly, prognostication in PAH.

Funding Acknowledgement
Type of funding sources: Public grant(s) – National budget only. Main funding source(s): PRIN2017F8ZB89 from Italian Ministry of University and Research (MIUR) (PI Prof Napoli) and Ricerca Corrente (RC) 2019 from Italian Ministry of Health (PI Prof. Napoli). Figure 1Figure 2
Impact of COVID-19 pandemic on surgical care of patients with acute aortic conditions
Authors: Yuan X , Rosendahl U , Asimakopoulos G , Quarto C , Rosser B , Gaer J , Petrou M , Bhudia S , Bahrami T , Nienaber C ,   Aortic Centre, Royal Brompton and Harefield Hospital NHS Trust
Published: October 2021

Abstract

Background
The outbreak of COVID-19 pandemic catastrophically interrupted medical care systems causing substantial decrease in the admission of patients and consecutively a sharp decline in the number of surgeries and interventions. In several European countries, the nationwide lockdown severely restricted movement which may have contributed to this phenomenon on top of anxiety of patients to contract COVID-19 when admitted to hospital.

Purpose
The aim of this analysis was to evaluate the impact of the COVID-19 pandemic onto acute and elective thoracic aortic surgeries and interventions and to compare the data with the same period in 2019 in a single aortic centre.

Methods
Information on admission and surgery/intervention was extracted from hospital electronic record system. Patients who were admitted for treatment of aortic conditions between January 1st to June 30th both in 2019 and 2020 were identified and selected for this analysis. The time from referral to admission and surgery/intervention was noted for service delay analysis. Aortopathies were classified as type A aortic dissection, type B aortic dissection, aortic aneurysm and others. In a daily central hub meeting, urgency was defined as emergent (operation required before the next working day), urgent (operation needed within 48 hours), and elective. Patients' condition and comorbidities were represented by ACEF II score.

Results
Total case volume of 81 in 2019 reference period was reduced to 70 in 2020 (−14%). Elective cases significantly declined from 59 (72.8%) in 2019 to 30 (42.8%) in 2020 (−49%). Urgent and emergent cases were performed more frequently in 2020 with 40 cases versus 22 in 2019 (+45%).
The ACEF II score showed no difference for patients in both periods (2.1±1.9 vs. 2.5±2.1, p=0.221), however, a trend to higher ACEF II score in 2020 consistent with a higher proportion of urgent and emergent cases.
The overall in-hospital delay (from admission to surgery) was not significant affected with 1 (IQR 1–2) versus 1 (IQR 0–2); p=0.991. However, with the official declaration of a pandemic and introduction of restrictions, no in-hospital delay was documented.
In-hospital mortality was observed lower in 2019 as compared in 2020 (6.1% vs 11.4%, P=0.251).

Conclusion
The first wave of COVID-19 pandemic disrupted the aortic service, however, acute care for urgent thoracic aortic conditions and subsequent procedures even increased compared to 2019 as a result of both centralised allocation system and decline of elective cases. Acute aortic syndromes were managed despite COVID-19 according to current guidelines.

Funding Acknowledgement
Type of funding sources: None. Impact of COVID on aortic case load
Prospective application of a risks-adjusted antithrombotic protocol in elderly patients treated with the last generation of everolimus-eluting stents. The SIERRA-75 (EPIC-05) registry
Authors: De La Torre Hernandez J M , Lopez Palop R , Jimenez Mazuecos J M , Carrillo Saez P , Gutierrez Barrios A , Pinar E , Cid B , Fernandez L , Garcia Camarero T , Urbano C , Oteo J F , Jimenez Diaz V A , Gomez Menchero A , Galindo Fernandez E , Perez De Prado A ,   SIERRA-75 (EPIC-05)
Published: October 2021

Abstract

Background
Elderly patients show a higher incidence of ischemic and bleeding events after PCI.

Purpose
We sought to investigate clinical outcomes in elderly patients revascularized with last generation everolimus-eluting stent (EES) treated with antithrombotic strategies guided by bleeding and ischemic risks.

Methods
Prospective multicenter registry including patients over 75 years revascularized with EES and subsequent antithrombotic therapy guided according to a protocol based on clinical presentation, PCI complexity and the PRECISE DAPT score. The primary safety endpoint was a composite of cardiac death, myocardial infarction and definitive/probable stent thrombosis and the primary efficacy endpoint was TLR. An historical matched group of patients treated with current drug eluting stents other than EES was used as control.

Results
Finally, 1,064 patients were included, 80.8±4.2 years, 36.6% women, 72% ACS and 53.6% complex PCI. Primary safety endpoint was met in 6.2% and primary efficacy endpoint in 1.5%. Bleeding BARC 2–5 was reported in 7.8% and definite or probable stent thrombosis in 1.3%. The multivariable adjusted model showed no significant association of the prescribed short/long therapies with any endpoint. No stent thrombosis were reported in the subgroup with shorter DAPT duration. As compared to control group, bleeding BARC 2–5 was significantly lower in SIERRA-75 group (7.4% vs 10.2%, p=0.04) as well as the composite of MACE and bleeding (14.3% vs 18.5%, p=0.02).

Conclusions
In elderly population the use of last generation EES along with a predefined risks-adjusted antithrombotic regimen seems to be associated with an improved prognosis in terms of ischemic and bleeding outcomes.

Funding Acknowledgement
Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Abbott Laboratories
Clinical outcomes following use of sirolimus coated balloon in side-branches during provisional stent technique in true bifurcations
Authors: Athulorala S , Loku Waduge B H , Kalkat H , Saif A , Fawzy A M , Bhatia G , Kumar N , Freestone B H , Ment J , Lee K , Pitt M , Pulikal G , Basavarajaiah S 
Published: October 2021

Abstract

Introduction
Provisional stenting is the preferred strategy even in true bifurcations, however, to minimise the need for repeat revascularization of side-branches, the use of drug coated balloons has been suggested. Most of the data available in the literature are on Paclitaxel coated balloons, a drug which is almost obsolete in stents due to its cytotoxic properties. There is limited data on Limus coated balloons (SCB), a drug which is the default for all the currently available drug eluting stents. In this study, we explore the clinical outcomes following use of SCB in side-branches during provisional stent technique in true bifurcations.

Methods and results
We evaluated all de novo lesions treated with DCB for true bifurcations between March 2018 and October 2020 at our centre. The results are reported as cardiac death, target vessel myocardial infarction (TVMI), target lesion revascularisation (TLR) and MACE (combination of cardiac death, target vessel MI and TLR).
During the study period 110 patients with de novo lesions were treated with SCB for bifurcation lesions. Of them; 66 were in true bifurcations. The mean age of patients were 66.3±10.7 years, 75% (n=50) were male, 40 (61%) were in the setting of acute coronary syndrome, 52% (n=34) had diabetes and 32% (n=21) had CKD. Pre-dilatation was performed in all cases and none of them needed bailout stenting. Small vessels (&lt;3.0 mm) accounted for 72% (n=48) of cases. Non-compliant balloons and scoring balloons to prepare the lesion was used in 51% (n=34) and 13% (n=9) of cases respectively. The mean diameter and length of SCBs were 2.6±0.4 mm and 23.2±7.3 mm respectively.
During a median follow-up of 729 days (2-years); there were no cardiac deaths, TVMI occurred in one case (2%), TLR in 3% (n=2) and the overall MACE rate was 3% (n=2). There were no documented cases of acute vessel closure

Conclusion
The results from long term follow-up with this relatively new technology of DCB in treatment of side-branch in true bifurcation is encouraging. We have demonstrated low rates of hard endpoints, TLR and MACE rates despite complex group of patients (61% ACS, 52% diabetics and 32% CKD). These results are encouraging, but going forward, we need more data from larger patient trials. In the meanwhile our data should instil confidence to adopt this technology in clinical practice.

Funding Acknowledgement
Type of funding sources: None.
Does the use of scoring balloon prior to drug coated balloons improve clinical outcomes in de Novo coronary lesions?
Authors: Fawzy A M , Loku Waduge B H , Kalkat H , Saif A M , Athulorala S , Bhatia G , Kumar N , Freestone B H , Ment J , Lee K , Pitt M , Pulikal G , Basavarajaiah S 
Published: October 2021

Abstract

Aims
The use of scoring balloon prior to drug coated balloon has been proven to be effective in restenotic lesions. However, their effect in de novo lesions has not been tested. Logic tells that the use of scoring balloons should enhance the drug uptake into the vessel wall. In this study, we evaluated this concept of scoring balloon prior to DCB in de novo lesions and compared to those who were treated with a conventional approach (semi-compliant and/or non-compliant balloons).

Methods and results
We evaluated all de novo lesions treated with DCB between March 2018 and October 2020 at our centre. The results are reported as cardiac death, target vessel myocardial infarction (TVMI), target lesion revascularisation (TLR) and MACE (combination of cardiac death, target vessel MI and TLR).
During the study period 348 patients with de novo lesions were treated with DCB. Of those, 49 were predilated with scoring balloon prior to use of DCB and the remaining 299 were predilated with non-scoring balloons (semi-compliant and/or non-compliant). The majority of the baseline characteristics had no statistically significant differences (table 1), with the exception of the mean diameter of the lesions were larger in the scoring balloon group than non-scoring balloon group: 2.7±0.5 vs. 2.49±0.4; p=0.003 and mean length of lesions were longer in the non-scoring balloon group: 26±8.8 vs. 23±7.7; p=0.02. During the median follow-up of 660 days, clinical outcomes between the scoring and non-scoring balloons were; cardiac death: 0 vs. 8 (3%); p=0.5, TVMI: 2 (4%) vs. 8 (3%); p=0.9, TLR: 3 (6%) vs. 25 (8.4%); p=0.8, MACE: 4 (8%) vs. 34 (11%) p=0.7

Conclusion
There were no differences in the clinical outcomes between the two groups indicating that use of scoring balloon prior to DCB may not offer additional benefit, although this needs to be confirmed in a larger patient group.

Funding Acknowledgement
Type of funding sources: None.
Sex differences in transradial access site characteristics and crossover in STEMI
Authors: Zafirovska Taleska B , Petkoska D , Jovkovski A , Vasilev I , Taravari H , Kitanoski D , Kedev S 
Published: October 2021

Abstract

Objective
To assess the differences according to sex in radial artery access site characteristics and crossover and it's influence on the success of ST segment elevation myocardial infarction (STEMI) procedures with primary chosen transradial access site in a large series of patients.

Background
Transradial angiography (TRA) is now the default access site for PPCI, but technically is a more challenging approach mostly due to anatomic challenges connected to the radial artery.

Methods
All 5092 consecutive STEMI patients from our center, in the period from March 2011 until December 2017 were examined. Patient were divided in two groups according to sex. Preprocedural radial artery angiography was performed in all patients. Clinical and procedure characteristics, type of radial anatomy variants, transfer to other access sites, transfer direction and procedure time were analyzed. Access site bleeding complications and in-hospital mortality were also recorded. Primary end-point of the study was the occurrence of TRA failure and need to crossover to another access site to finish the procedure.

Results
From the STEMI population in this period the female group had 1326 PPCI treated patients and the male group 3766 patients. The female group of patients was older 65±11 than the male group 59±11 (p&lt;0,0001). BMI was 27 vs. 30 in the male group (p=0.0003). Most common risk factors in both groups were hypertension, smoking and diabetes, with the latter being more frequent in the female group p&lt;0,0001. Radial artery anomalies were more frequent in the female group 8,8% vs 6,5% (p&lt;0,0001), with complex RA loop and tortuous RA having double percentage than in their male counterparts. Primary chosen TRA access site failure occurred in 4.6% (61) vs. 3.5% (97) of STEMI patients (p&lt;0.0001). Most common access site crossover site was right ulnar access in both groups with 57 and 61% accordingly. Access site bleeding complications, were more common in the female group with 4.4% vs. 3.2%, also this difference persisted in EASY score hematoma 3 to 5. Clinical radial artery spasm was significantly more frequent in female patients 5,7% vs. 2.2% (p&lt;0.0001). In-hospital mortality rate was similar in the two group of patients.

Conclusion
Female sex is a significant risk factor for TRA failure in STEMI usually connected to smaller size of RA and the more common finding of radial artery anomalies and spasm.

Funding Acknowledgement
Type of funding sources: None.
The timing and mechanism of high-grade AV block post-TAVI: knowing your enemy
Authors: Gomes D , Felix Oliveira A , Campante Teles R , Gama F , Carmo P , Brito J , De Araujo Goncalves P , Cavaco D , Sousa Almeida M 
Published: October 2021

Abstract

Background
Complete atrioventricular block (AVB) requiring permanent pacemaker implantation (PPMI) is still a major limitation of transcatheter aortic valve implantation (TAVI) procedures. Although right-bundle branch block (RBBB), membranous septum (MS) length and self-expandable prothesis are recognizable risk factors, their predictability to PPMI is far from satisfactory. While some patients develop persistent intra-procedure high-grade AVB (H-AVB), others present much later with severe bradycardia.

Purpose
This study aims to describe and compare the characteristics of patients who develop AVB during or after TAVI.

Methods
Single centre prospective registry of 506 consecutive patients submitted to TAVI with no previous pacemaker between 2017 and 2020. Post-procedure PPMI (up to 30 days after discharge) was studied and divided into two groups according to the development of persistent intra-procedure H-AVB (Group A) or post procedure H-AVB (Group B). Baseline ECG, computed tomography and TAVI-related characteristics were analyzed.

Results
A total of 88 patients (17,3%), aging 83±6 years, 36.4% male, underwent post-TAVI PPMI (6 after discharge). Previous conduction disturbances were present in 50 (56.8%) patients and 25 (28.4%) had RBBB. 83% were submitted to self-expandable TAVI. Forty-two patients (47.7%) had persistent intra-procedure H-AVB (Group A) whereas 52.3% had post-procedure H-AVB (Group B). In patients with persistent intra procedure H-AVB previous RBBB was significantly more frequent (45.2%, n=19) when compared to patients with post-procedure H-AVB (13%, n=6; p=0.001). Contrarily, AF and previous left-bundle branch block (LBBB) were more likely in Group B. No difference in valvular calcification, MS length, prosthesis type or implantation technique was noted (picture 1). In the group with post-procedure H-AVB, 21.7% had transient AVB during TAVI and all developed de novo LBBB or first-degree AVB post-TAVI. Among these, 33 patients (71.7%) developed delayed H-AVB (&gt;48h post-procedure) while the remaining presented earlier.

Conclusions
In patients with PPMI post-TAVI, those with persistent intra-procedure H-AVB had higher rates of previous RBBB, while those with post-procedure H-AVB frequently had a normal baseline ECG. Anatomical and procedural characteristics did not differ between groups. Further studies are needed to confirm these results.

Funding Acknowledgement
Type of funding sources: None.
Pacemaker implantation rate after TAVI with the latest generation balloon-expandable valve SAPIEN 3 Ultra
Authors: De Torres-Alba F , Kaleschke G , Vormbrock J , Deschka H , Baumgartner H 
Published: October 2021

Abstract

Introduction
The latest generation balloon-expandable transcatheter heart valve SAPIEN 3 Ultra (S3-Ultra) was recently released and has shown promising initial results. So far, the pacemaker (PM) implantation rate after transcatheter aortic valve implantation (TAVI) with the S3-Ultra system compared to the SAPIEN 3 (S3) system has not been widely investigated.

Aims
To compare the PM implantation rate after TAVI with the latest generation S3-Ultra system with the S3 system in an unselected cohort of patients at risk.

Methods
We analyzed the development of conduction abnormalities after TAVI in 1780 consecutive patients treated with S3 and S3-Ultra between January 2014 and February 2021. After excluding valve-in-valve procedures (n=31) and patients with previously implanted PM (n=203) 1546 patients were finally analyzed. All patients at risk (i. e. those without previous PM) were monitored with ECG for at least 7 days after TAVI.

Results
Of 1546 patients, 1382 were treated with S3 (20 mm, 14; 23 mm, 524; 26 mm, 558; 29 mm, 286) and 164 with S3-Ultra (20 mm, 0; 23 mm, 77; 26 mm, 87). There were no significant differences in baseline demographic, ECG and procedural characteristics. There was no significant difference in the rate of new developed conduction abnormalities or PM implantation rate between S3 and S3-Ultra in the overall cohort (37.8% S3 vs 33,7% S3-Ultra, p=0.451 for all new conduction abnormalities, 13.8% S3 vs 14.6% S3-Ultra, p=0.756 for PM implantation). This comparable PM implantation rate between the two systems was consistent when analyzing only the 23 and 26 mm valve sizes of the S3 system (12.1% S3 vs. 14.6% S3-Ultra, p=0.361) and when excluding the first period of S3 implantation at our institution (2014) before a modification of the implantation technique that lead to a drop in the rate of PM implantations (S3 2015–2020 12.9% vs S3-Ultra 14.6%, p=0.534).

Conclusions
In our cohort, the PM implantation rate after TAVI with the S3-Ultra system was comparable to that of its predecessor.

Funding Acknowledgement
Type of funding sources: None.
Leukocyte telomerase concentration is inversely associated with central wave reflection in patients with hypertension
Authors: Pavlova O S , Denisevich T L , Belskaya M I , Shafranovskaya E V , Ogurtsova S E , Mrochek A G 
Published: October 2021

Abstract

Introduction
Telomere length and telomerase are biomarkers of aging and cardiovascular diseases. Arterial stiffness is associated with vascular age and higher risk of cardiovascular diseases. Decreased reparative cell's potential may cause vascular ageing and predispose to the progression of hypertension.

Objective
To determine association leukocyte telomerase concentration (TC) and relative telomere length (RTL) with arterial stiffness in hypertensive patients.

Material and methods
The study included 120 people (70 patients with uncomplicated arterial hypertension (AH) and 50 normotensive individuals). Mean age of hypertensives was 54.8±9.3 and of normotensives was 50.2±9.73 years. Dietary habits, smoking, level of physical activity, body mass index, waist circumference, presence of obesity, blood pressure (BP) level, family history of cardiovascular deseases, depressive episodes and psychological stress according the international questionnaires, glucose; cholesterol, angiotensin II, renin and aldosteron in blood were assessed in the participants. Aortic BP, aortic pulse pressure, augmentation index (AIx), AIx adjusted for heart rate 75 beats per minute (Aix@HR75), pulse wave velocity (PWV) were determined by the applanation tonometry. RTL of peripheral blood leukocytes was performed by real-time PCR. The leukocyte TC was measured using the enzyme immunoassay.

Results
There were no differences between patients with AH and normotensives in both leukocyte TC (4.9 (4.0; 8.0) versus 6.2 (4.1; 9.4), p=0.281) and RTL (0.94 (0.86; 1.0) versus 0.96 (0.83; 1.0), p=0.978). In hypertensive and normotensive groups the mean systolic aortic BP were 130.6±17,7 and 109.9±11.7 mmHg (p&lt;0.001), aortic pulse pressure – 41.5±9,7 and 33.6±10,4 mmHg (p&lt;0.001), Aix@HR75 – 16.0 (7.0; 28.0) and 27.0 (13.0; 35.0)% (p=0.004), PWV –7.9±1.4 and 8.1±1,7 m/s (p=0.409) respectively. In patients with AH the mean leukocyte TC was lower with an increased Aix@75 (&gt;25%) in contrast to the group of patients with normal Aix@75 (4.45 (3.9; 7.8) versus 7.97 (4.6; 10.0) ng/ml; p=0.043). Based on the multivariate logistic regression analysis independent factors influencing on the Aix@75 were leukocyte TC &lt;5 ng/ml with the family history of AH (OR=1.9, 95% CI: 1.1–3.4; p=0.036), the degree of AH combined with decreased salt sensitivity (OR=3.1; 95% CI: 1.3–7.5; p=0.010) and age (OR=1.2; 95% CI: 1.1–1.2; p=0.001).

Conclusions
Decrease of the leukocyte telomerase concentration associated with the raise of augmentation index in patient with uncomplicated AH. As a parameter of central wave reflection the augmentation index may considered as an early sign of biological and vascular aging in hypertension.

Funding Acknowledgement
Type of funding sources: Public grant(s) – National budget only. Main funding source(s): The state program of scientific research “Fundamental and applied sciences for medicine”