bluuebunny/crossref_metadata_2025_split huggingface dataset:
P6470Ventriculo-arterial coupling in severe aortic stenosis: does the flow-gradient pattern play a role?
Authors: Vijiiac A E , Neagu C , Cherry A , Onciul S , Zamfir D , Onut R , Stoian M , Iancovici S , Petre I , Dorobantu M 
Published: October 2019

Abstract

Background
Ventriculo-arterial coupling (VAC) assesses the interplay between ventricular contractility and afterload and it is calculated as the ratio between arterial elastance (Ea) and end-systolic left ventricular elastance (EES). Severe aortic stenosis (AS) carries different configurations according to transvalvular flow rates and pressure gradients and each of these entities has its particularities in terms of physiology and clinical outcome. Little has been studied so far regarding the changes of VAC in severe AS.

Purpose
We sought to assess the VAC non-invasively in patients (pts) with severe AS and to characterize it according to the flow-gradient pattern.

Methods
We included 61 consecutive pts with severe AS (78±13 years, 30 men, indexed aortic valve area <0.6 cm2/m2), for whom we performed a comprehensive echocardiography. VAC was determined as the ratio between Ea and EES. Patients were divided in 4 groups, depending on stroke volume index (low-flow [LF] vs. normal-flow [NF]: 35 ml/m2) and mean transaortic pressure gradient (low-gradient [LG] vs. normal gradient [NG]: 40 mm Hg). This resulted in the following flow-gradient patterns: LFLG, LFNG, NFLG, NFNG. Data were compared between groups with one-way analysis of variance and then with a Tukey test.

Results
There were 11 pts (18%) in the LFLG group, 20 pts (32.8%) in the LFNG group, 8 pts (13.2%) in the NFLG group and 22 pts (36%) in the NGNG group. The arterial elastance was highest in the LFLG group: 3.37±1.49 vs. 2.79±0.92 in the LFNG, 2.05±0.57 in the NFLG and 1.54±0.49 in the NFNG group (p<0.001). The ventricular elastance was also highest in the LFLG group (4.03±2.46) vs. 3.16±1.33 in the LFNG, 2.21±1.22 in the NFLG and 2.29±0.78 in the NFNG group (p=0.007). VAC was most impaired in the NFLG group (1.35±1.08), followed by LFNG group (1.00±0.47), LFLG group (0.93±0.27) and NFNG group (0.70±0.14) (p=0.01). Valvulo-arterial impedance (ZVA) was highest in the LFNG group: 7.78±2.15, followed by 7.38±2.17 in the LFLG group, 4.93±1.17 in the NFLG group and 4.33±1.23 in the NFNG group (p<0.001). VAC and ZVA showed no significant correlation (p=0.27), with VAC being significantly more impaired in patients with abnormal ZVA (>4.5 mm Hg/ml/m2): 0.99±0.60 vs. 0.73±0.20 (p=0.02).

Conclusion
The ventriculo-vascular interaction in severe AS varies noticeably according to the flow-gradient pattern. Low-gradient states, particularly NFLG, have the most impaired VAC. This study supports the idea that these 4 configurations are different clinical entities and it highlights the importance of integrating the flow-gradient pattern for a comprehensive evaluation of AS severity.

Acknowledgement/Funding
This work was supported by CREDO Project - ID: 49182, financed through the SOP IEC -A2-0.2.2.1-2013-1 cofinanced by the ERDF
P6472Novel cardiac imaging prognostic markers of clinical outcome in patients with bicuspid aortic valve and chronic aortic regurgitation
Authors: Kockova R , Linkova H , Hlubocka Z , Praveckova A , Polednova A , Sukupova L , Benes J , Blaha M , Honsova E , Penicka M 
Published: October 2019

Abstract

Background
Patients with chronic aortic regurgitation (AR) can have a substantial myocardial damage despite being asymptomatic. Early surgical strategy might be beneficial. Bicuspid aortic valve (BAV) is a congenital heart disease present in almost 30% of these patients.

Purpose
Identify novel imaging predictors of early disease progression.

Methods
Prospective three-centre study of patients with chronic AR of at least moderate to severe (3+) grade and BAV morphology. Patients without currently recognised indication for surgical treatment were enrolled. Baseline examination included echocardiography (ECHO) with 3-dimensional (3D) vena contracta area and magnetic resonance (MR) with regurgitant fraction measured from flow sequence. All imaging studies were analysed in CoreLab. The primary endpoint was defined as a combination of cardiovascular death, surgical treatment or hospitalization for heart failure.

Results
A total of 83 patients with BAV and at least 3+ AR were enrolled during 2015–2018. Median follow-up was 759±455 days, primary composite endpoint occurred in 13 patients who met criteria for surgical treatment, no patient died or was hospitalized for heart failure. Baseline parameters were compared between two groups: patients with and without endpoint. Clinical and laboratory data did not differ between the two groups. Left ventricular (LV) ejection fraction was normal in all patients. LV diameters and volumes were significantly larger in patients with primary endpoint. This was most pronounced in MR measured indexed volumes in end-diastole and end-systole, P=0.003 and P=0.003. Non-invasive markers of diffuse myocardial fibrosis (native T1 relaxation time and global longitudinal strain, P=0.614 and P=0.137 respectively) were not different. Novel markers of AR severity were significantly increased in surgically treated patients: 3D vena contracta 0.26±0.10 cm2 versus 0.38±0.11 cm2 (P<0.001), MR regurgitant fraction 33.9±15.4 versus 50.2±12.2% (P=0.001). Both 3D vena contracta with cutoff value ≥0.4 cm2 (sensitivity=85%, specificity=84%, area under the curve=0.85) and MR regurgitant fraction with cutoff value ≥34% (sensitivity=94%, specificity=58%, area under the curve=0.76) showed high accuracy to identify patients who require early surgical intervention. Adding 3D vena contracta and MR regurgitant fraction to indexed LV end-systolic volumetric parameters significantly increases the predictive value for early disease progression with p=0.001 and p=0.006 (Likelihood-ratio test).
3D vena contracta predictive value

Conclusions
Novel imaging parameters of AR severity such as 3D vena contracta and MR derived regurgitant fraction predict early disease progression in patients with BAV and at least 3+ chronic AR. These values significantly increase the predictive value of traditional parameters based on LV size measures.
P6476Surgery does not appear to improve survival in patients with endocarditis and substance use disorder
Authors: Abdollah H , Brogly S B , Payne D , Lajkosz K , Coverdale N S , Gomes T , Hamilton A 
Published: October 2019

Abstract

Background
Cohort studies of surgery compared with medical treatment (MT) on endocarditis mortality are conflicting. We conducted a population-based study to estimate associations between treatment and mortality.

Methods
1,381 patients with substance use disorder (SUD) and 5,053 without (NSUD) hospitalized for endocarditis were included. Treatment was modeled as a time-dependent variable: patients who underwent surgery after admission were classified as MT until surgery occurred and surgically treated thereafter. Patients without surgery were classified as MT. Adjusted hazard ratios (aHR) between treatment and death (in-hospital, 30 days, one, two, five years) by SUD status were estimated.

Results
Among SUD patients, there was a trend towards reduction in in-hospital death with surgery vs. MT (aHR 0.61 [95% CI: 0.35–1.04]), but no difference at 30 days (aHR 0.79 [95% CI: 0.42–1.48]). Mortality was higher in SUD patients who underwent surgery compared with MT at one (aHR 1.30 [95% CI: 0.95–1.76]), two (aHR 1.27 [95% CI: 0.97–1.65]), and five years (aHR 1.37 [95% CI: 1.09–1.72]). In NSUD patients, in-hospital mortality (aHR 0.93 [95% CI 0.76–1.16]) did not differ, but 30 day mortality (aHR 1.36 [95% CI 1.04–1.77]) was higher with surgery versus MT, and lower at one (aHR 0.87 [95% CI: 0.73–1.03]), two (aHR 0.75 [95% CI: 0.64–0.88]), and five years (aHR 0.70 [95% CI: 0.61–0.81]).
Kaplan-Meier Survival Curves of Patients

Interpretation
Surgery compared with MT conferred no long-term survival benefit in SUD patients. In NSUD patients, surgery was associated with an initial increased risk of early death followed by a lower risk after one year.

Acknowledgement/Funding
Grant from Department of Surgery, Queen's University
P6477Preoperative renal injury and multi-elevated biomarkers are associated with adverse outcomes in patients with severe aortic stenosis undergoing surgical valve replacement
Authors: Spampinato R , Bochen R , Stoeger G , Sieg F , Noack T , Etz C , Borger M A 
Published: October 2019

Abstract

Background
The presence of early stages of renal injury (AKI) and biomarkers has been associated with adverse outcomes in cardiac surgery.

Purpose
We aimed to determine whether preoperative AKI is associated with long-term all-cause mortality in patients with severe aortic stenosis (AS) undergoing surgical aortic valve replacement (SAVR) and if the combination of AKI with multi-elevated biomarkers (Amino-terminal pro-B-type natriuretic peptide, BNP; high-sensitivity cardiac troponin T, hsTNT; and C reactive protein, CRP) has a better prognostic utility.

Method
From a prospective registry of patients with AS referred for SAVR, 560 participants (68±8.8 years; 329 men) were retrospectively included when echocardiograms, serum creatinine and biomarkers were available within 30-days before surgery. Kaplan-Meier (KM) curves for all-cause mortality were created for groups of patients based on the presence of AKI, defined as a stage I or more according to the Acute Kidney Injury Network classification. To further describe the utility of multi-elevated biomarkers, 4 groups were created and the KM-curves and c-statistics evaluated. Mean follow-up was 737±410 days and 30 (5.4%) patients died.

Results
Patients with preoperative AKI (n=68) were significantly older (70±7.6 vs. 67±8.9 years, p=0.02), more likely to have hypertension, diabetes, a worse functional class (NYHA III-IV: 59% vs. 36%, p<0.001), worse glomerular filtration rate (60±20 vs. 81±26, p<0.001), an elevation of multiple biomarkers (hsTNT, BNP, and CRP), and a higher logistic-EuroScore (3.8±2.8 vs. 3.0±2.2, p=0.04). But there were no differences in the incidence of coronary artery disease, LVEF (57±10 vs. 59±11%), aortic valve area index, or in surgical characteristics. Those patients with AKI exhibited higher 3-year all-cause mortality (11.7% vs. 5.7%, p=0.04). Interestingly, the combination of AKI with 3 elevated biomarkers was associated with a more than fourfold increase in 3-year all-cause mortality (47.5% vs. 4.3%, p<0.0001), and the c-statistics (AUC 0.599 vs 0.710, p<0.001) suggested a better prediction for long-term death.
Figure 1

Conclusions
This study demonstrates an adverse association of preoperative AKI with survival following SAVR, which was accentuated when combined with multi-elevated biomarkers, suggesting the need for less invasive strategies and/or closer postoperative follow–up in such patients.
P6478Resting and exercise pulmonary artery systolic pressure to rule out later development of pulmonary arterial hypertension in systemic sclerosis
Authors: Gargani L , Codullo V , Argiento P , Moreo A , Pieri F , Mori F , Epis O , Moggi-Pignone A , Montecucco C , Valentini G , Matucci-Cerinic M , Sicari R , Ghio S , Bossone E , D'Alto M 
Published: October 2019

Abstract

Background
Patients with systemic sclerosis (SSc) are at risk of developing pulmonary arterial hypertension (PAH), which is often diagnosed late when the benefits of vasoactive therapies are limited. The concept of exercise pulmonary hypertension as a possible transitional phase anticipating resting PAH has been assessed in several pathologies, but has not been endorsed by the latest European Guidelines, because not supported by sufficient data.

Purpose
To evaluate whether PASP values at rest and at peak exercise, estimated at echocardiography, could be predictors of further development of PAH.

Methods
Four hundred and twenty-nine SSc patients without a previous diagnosis of PAH, enrolled at 4 referral Centres, underwent standard exercise Doppler echocardiography with PASP estimation at rest and at peak stress. Patients were then followed-up to assess the development of PAH, as diagnosed by a complete diagnostic work-up including right heart catheterization. PAH was defined by pre-capillary pulmonary hypertension (mean pulmonary artery pressure ≥25 mmHg with pulmonary arterial wedge pressure ≤15 mmHg), without significant interstitial lung disease and/or left heart disease.

Results
During the median follow-up of 75 months (IQR 29–114), 16 patients developed PAH. A combined cut-off of ≥24 mmHg as resting PASP and ≥40 as peak PASP was identified as the best predictor of further development of PAH (see Figure). Both resting PASP and peak PASP were predictors of PAH at univariate analysis (resting PASP OR 1.13, 95% C.I. 1.07–1.19, p<0.0001; peak PASP OR 1.13, 95% C.I. 1.07–1.18, p<0.0001). At multivariate analysis, only peak PASP was independently associated to PAH development (OR 1.13, 95% C.I. 1.04–1.18, p<0.001). Only one patient among those with resting PASP <24 mmHg and peak PASP <40 mmHg (34.7% of the total population) developed PAH during the follow-up (after 10 years from normal exercise Doppler echocardiography).
Kaplan-Meier curves

Conclusions
Exercise increase in PASP is an independent predictor of later development of PAH in SSc. An increase in exercise PASP is frequent and is not necessarily associated with a later development of PAH, whereas the very high negative predictive value of a normal PASP both at rest and at peak exercise can be used in the clinical practice to confidently rule out about one third of patients.

Acknowledgement/Funding
Italian Ministry of Health (Ricerca Finalizzata 2011-2012)
P6486Flow state, gradients and anatomopathological valvular calcification: influence in aortic stenosis surgical outcomes
Authors: Museli J T , Zambruno L , Coria N , Giunta G , Salmo J F , Vigliano C , Guevara E 
Published: October 2019

Abstract

Introduction
Aortic stenosis (AS) patients are heterogeneous. The relationship between stenosis severity, transvalvular flow state and gradients is conflictive and non-linear.

Objective
To evaluate the relationship between transvalvular flow state and gradients with the anatomopathological aortic valve characteristics and perioperative morbimortality among patients (pt) submitted to aortic valve replacement (AVR).

Methods
We analyzed 516 pt with symptomatic severe AS (effective valve area <1 cm2) with preserved left ventricular ejection fraction (>50%) submitted to AVR. Perioperative mortality and a combined endpoint (death, low cardiac output syndrome and acute renal injury) were analyzed dividing the population by transvalvular flow (35 ml/m2) and mean gradient (40 mmHg), both measured by echocardiography. A morphologic evaluation of 383 operatively excised native cardiac valves was performed. Valvular thickening and calcification were categorized in mild, moderate and severe.

Results
Male subjects represented 52.9% (283 pt). Mean age were 69±11.5 years. Pt showed a mean ejection fraction of 61±4.8%, the peak gradient was 86.2±24 mmHg, and mean gradient was 53±18 mmHg.
Cardiac low output syndrome (normal flow (NF) – 14%, low flow (LF) – 23%; p<0,02), IABP (NF 1,8%, LF 6%, p<0,02) and perioperative mortality (NF 2,7%, LF 7%, p<0,02) were more frequent in low flow pt (185 – 35%).
Bicuspid valves represented 24.5% of the whole population. Bicuspid patients were younger 64±9 vs 73±12 years (p<0.05) and had more moderate–severe calcification (MSC) 93.4% vs 75.6% (p<0.05).
No difference was found in moderate -severe thickening (MSTh) and MSC when analyzing the population by flow (35 ml/m2). On the contrary, low gradient pt (<40mmHg) had lower MSC and MSTh. (Table)
Finally, 4 groups were considered: normal flow–high gradient NFHG (52.2%), normal flow–low gradient NFLG (12%), low flow–high gradient LFHG (25.5%) and low flow–low gradient LFLG (10.1%). A trend toward more perioperative events was seen in the LF-LG group despite less calcified and thickened valves. (Figure)
Table 1 Normal Flow Low Flow P value Normal gradient Low gradient P value M-S thickening 143 (58.1%) 80 (58.3%) NS 186 (62.4%) 37 (43.5%) 0.0018 M-S calcification 195 (79.2%) 119 (86.8%) NS 263 (88.2%) 51 (60%) <0.05 Bicuspid valve 62 (25%) 32 (23%) NS 62 (25.2%) 32 (23.3%) NS M-S: Moderate-Severe.
Figure 1

Conclusions
In our population of severe symptomatic AS with preserved ejection fraction submitted to AVR, low gradient pts had less calcified and thickened valves. LFLG pts presented a trend towards more perioperative events despite having less valvular calcification.
P6495Role of vascular smooth muscles cells in naked mole rats during ageing (Heterocephalus glaber)
Authors: Mgrditchian-Griffo T , Faulkes C G F , Thornton S T , Shanahan C S , Hayward R H , Li Z L , Cruickshank K C , Regnault V R , Lacolley P L 
Published: October 2019

Abstract
Vascular stiffening and a prothrombotic state consistently increase with age. We have shown previously that Vascular Smooth Muscle Cells (VSMCs) have a major role in both vascular stiffening and thrombin generation in the vascular wall in a context of hypertension (Arterioscler Thromb Vasc Biol 2015). Naked mole rats (NMRs) are the longest-lived rodent species, have a maximum lifespan exceeding 30 years, living approximately ten times longer than a similarly sized mouse, and do not develop arterial stiffening with age (AJP, 2014).
The objective was to analyze arterial composition as well as phenotypic VSMC changes from primary cultures in NMRs at 2- and 10-year old.
We used Thoracic aortas of young (2-year-old) and adult (10-year-old) NMRs for the study of arterial wall as well as for the preparation of VSMCs' primary cultures.
Our results showed no difference in elastin/collagen ratio and no intimal thickening in NMRs at 10-years-old compared to 2-years-old (n=4 in each group). Primary cultures showed positive alpha-actin staining without VSMC morphological changes up to 6 passages using standard conditions (20% fetal bovine serum). Smoothelin and myosin-heavy chain are similar at both ages. VSMCs density was identical in 2- and 10-years-old NMRs, whereas cell hypertrophy was observed in older animals.
Focal adhesions assessed by vinculin staining were unchanged between the two groups. There was no increase in plasma thrombin generation and at the surface of VSMCs up to 10 years of age associated with no increase in fibrinogen and factor VIII, both known to increase normally with age in humans.
Our findings showed an absence of canonical signs of normal vascular ageing in NMRs that are normally present in rodent and humans. The retaining of a VSMC phenotype and focal adhesion distribution support previous data observed in ageing. These results reinforce the current concept of VSMCs as emergent cells in the process of ageing.
P6500Genetics links abdominal and thoracic aorta aneurysm
Authors: Ijpma A S , Heijsman D , Roos-Hesselink J W , Verhagen H J M , Ter Raa S , Majoor-Krakauer D 
Published: October 2019

Abstract

Introduction
Familial disease, with a genetic cause, occurs in at least 20–30% of the families of patients with an aortic aneurysm. In these families there is an increased risk for relatives. Therefor family screening is recommended around the age of 50–60 years for first degree relatives of patients with an abdominal aneurysm (AAA) and relatives of patients with thoracic aorta aneurysms (TAA). However current guidelines do not specify the extend of aorta screening for relatives of patients with AAA and patients with TAA. Current practice is that first degree relatives of AAA patients are offered abdominal echo screening for AAA and relatives of TAA patients cardiologic echo for TAAA. Although co- occurrence of AAA with TAAA in rare genetic disease is well known, for other familial aneurysm disease, the frequency of the co-occurrence of AAA and TAAA has not been established.

Purpose
To improve family screening for familial aneurysm, and identify the role of underlying genetic defects.

Methods
To determine the genetics of AAA, whole exome sequencing and CT family screening of the complete aorta was performed in 391 families with familial aneurysm. These families are nested in a patient cohort ascertained form unselected consecutively diagnosed AAA patients visiting the Vascular Surgery Clinic at the our MC.

Results
In 391 families, 360 relatives had a dilated aorta. The spectrum of aortic features in the relatives included 210 (58%) relatives with AAA, 102 (28%) relatives with TAA. Co-occurrence of AAA and TAA was noted in 41 (11%) relatives. In addition 66 (18%) and 79 (22%) had a dilation in the arteria iliaca communis sinistra resp. dextra. In 18 families pathogenic mutations in 11 aneurysm genes were detected.

Conclusion
To reduce underdiagnoses of relatives of AAA patients, CT screening of the total aorta and the iliac arteries is the method of choice, and should replace echo screening of specific parts of the aorta in relatives. Updating the guidelines for family screening for aortic aneurysms is needed to improve early detection and treatment of family members with aorta dilatations.

Acknowledgement/Funding
Stichting Lijf en Leven
P6502Association between diabetes mellitus and abdominal aortic aneurysm: a mendelian randomization study
Authors: Chen Q.-C , Yao C , Wang S.-M 
Published: October 2019

Abstract

Background
It is generally acknowledged that those with diabetes mellitus (DM) have at least a 10-fold risk for cardiovascular disease (CVD). However, patients with DM have been shown with a lower incidence of abdominal aortic aneurysm (AAA) in epidemiological data. Related research has illustrated that the aortic may be protected in the hyperglycemic microenvironment while the causality of this relationship is still uncertain.

Purpose
Here, we undertake a two sample Mendelian randomization (MR) study to evaluate whether DM genetically influences the risk of AAA.

Methods
We analyzed the genetic summary data from the DIAGRAM (Diabetes Genetics Replication And Meta-analysis) consortium and MRC-IEU (Integrative Epidemiology Unit) consortium. Base on the result from GIAGRAM consortium (26488 DM cases and 83964 controls), 25 single nucleotide polymorphisms (SNPs) associated with DM as the instrumental variables in MR study. Then, for each of the 25 SNPs associated with DM, we retrieved their summary data from MRC-IEU Consortium (263 cases and 462747controls). Inverse-variance weighting (IVW) was conducted to obtain the associations of DM with AAA and several sensitivity analyses were also performed to assess the potential violation of MR assumptions.

Results
DM was not significantly associated with risk of AAA (odds ratio [OR], 1.ehz746.1092; 95% confidence interval [CI], 0.9998–1.0002; P, 0.9622). Weighted median (OR, 1.0002; 95% CI, 0.9999–1.0005; P, 0.1992) and MR Egger analysis (OR, 1.0003; 95% CI, 0.9995–1.0012; P, 0.4071) suggested similar effect estimates of DM on AAA. With the large P value for the intercept, the result of MR-Egger regression method indicated no evidence for the presence of horizontal pleiotropy (Egger regression intercept, 3.9e-05, P, 0.384). In a leave-one-out analysis, no single SNP was observed with strong driving effect of DM on AAA.

Conclusions
Through 25 genetically identified SNPs in this two sample MR study, DM is not associated the risk of AAA this large study using two-sample MR, which did not support the result from previous epidemiological data. In conclusions, this large MR study provides evidence to suggest that DM may not be causally associated with AAA.