bluuebunny/crossref_metadata_2025_split huggingface dataset:
P3450Aortic stiffness is significantly associated with left ventricular mass in females but not in males: insights from the CORINTHIA study
Authors: Papaioannou T , Oikonomou E , Lazaros G , Christoforatou E , Vogiatzi G , Tsalamandris S , Chasikidis C , Kalambogias A , Mystakidi V.-X , Galiatsatos N , Santouri M , Latsios G , Deftereos S , Tousoulis D 
Published: October 2019

Abstract

Introduction
Arterial stiffening may contribute to the increase of left ventricular mass (LVM) and the development of left ventricular hypertrophy (LVH). Although male gender has been also found to be an independent determinant of LVH, it is unknown if the adverse effect of increased aortic stiffening on LVM differs between males and females.

Aim
To evaluate the association of aortic stiffness as assessed by carotid-to-femoral pulse wave velocity (cf-PWV) with LVM and LVH in a general population and compare these associations between males and females.

Methods
Demographic, laboratory and clinical data of 1686 subjects (693 males and 993 females) from the cross-sectional, observational study “Corinthia” were analyzed. All subjects underwent applanation tonometry and pulse wave analysis for the measurement of cf-PWV and echocardiography examination for the computation of LVM which was adjusted by body surface area providing the LVM index (LVMI). Multivariate linear regression analysis was performed for the determination of independent factors related with LVMI. Receiver operator curve analysis (ROC) was used to compare the ability of cf-PWV to predict LVH, in males and females separately.

Results
In the female population, significant and independent determinants of LVMI were: age (beta=0.243, p<0.001), urea (beta=0.119, p=0.001), hypertension (beta=0.089, p=0.028) and cf-PWV (beta=0.096, p=0.021). In contrast, in the male population, LVMI was independently related with age (beta=0.242, p<0.001), systolic blood pressure (beta=0.095, p=0.027), LDL (beta=-0.087, p=0.047) and creatinine (beta=0.092, p=0.031). ROC analysis showed that cf-PWV is a stronger predictor of LVH in females than in males (figure).

Conclusion
Increased aortic stiffness measured by cf-PWV is significantly related with increased LVMI regardless from age and other risk factors only in females. Moreover cf-PWV was a stronger predictor of left-ventricular hypertrophy in females than males. These findings should be further explored in prospective studies.
P3454Myocardial reverse remodeling occurs to a comparable extent in male and female aortic-banded rats following pressure unloading
Authors: Ruppert M , Korkmaz-Icoz S , Loganathan S , Olah A , Sayour A A , Barta B A , Merkely B , Karck M , Szabo G , Radovits T 
Published: October 2019

Abstract

Background
Sex differences have been intensely investigated during the development of pressure overload (PO; e.g. aortic stenosis, arterial hypertension)-induced left ventricular (LV) myocardial hypertrophy (LVH). However, it is less clear whether sex-related differences also affect the regression of pathological LVH after pressure unloading.

Purpose
Therefore, we investigated the potential influential effect of sex on myocardial reverse remodeling in a relevant rat model of banding and debanding of the abdominal aorta.

Methods
PO of the left ventricle was induced in male (M) and female (F) rats by abdominal aortic banding (AB) for 6 or 12 weeks. Sham operated animals served as controls. Pressure unloading was evoked by removing the aortic constriction at week 6 (debanded). Serial echocardiography was performed to detect temporal alterations in LV morphology and geometry. Furthermore, distinct aspects of LV systolic and diastolic function were assessed by pressure-volume analysis. Structural changes, such as cardiomyocyte hypertrophy and interstitial fibrosis were measured on histological sections. Fetal gene expression (a molecular marker of pathological LVH) was analyzed by quantitative real-time PCR.

Results
In both male and female AB rats, PO induced the development of marked LVH as confirmed by increased LV mass, heart weight-to-tibial length ratio (HW/TL [g/cm]: 0.47±0.01 AB-M vs. 0.36±0.01 Sham-M, p<0.05; 0.36±0.02 AB-F vs. 0.26±0.01 Sham-F, p<0.05) and cardiomyocyte diameter. Similarly, reactivation of fetal gene expression (indicated by increased atrial natriuretic peptide [ANP]) and enhanced interstitial collagen accumulation was also observed in male and female AB groups as well. The extent of myocardial hypertrophy was greater among female AB animals, while fibrosis was more severe in male AB rats. In both genders, LVH was associated with prolonged ventricular relaxation (active relaxation time constant, Tau [ms]: 19.6±0.8 AB-M vs. 13.1±0.4 Sham-M, p<0.05; 15.2±1.3 AB-F vs. 12.2±0.3 Sham-F, p<0.05). However, systolic function was impaired only in males (ejection fraction, [%]: 44.4±2.3 AB-M vs. 57.5±2.1 Sham-M, p<0.05; 49.7±2.2 AB-F vs. 53.4±1.7 Sham-F, n.s.). Contrary to the sex-dependent differences during the development of LVH, removing the aortic constriction resulted in a comparable degree of reverse remodeling on the morphological (decreased LV mass, HW/TL), histological (decreased CD and interstitial fibrosis), molecular (reduced ANP expression) and functional (recovered ejection fraction and Tau) levels in both male and female rats.

Conclusion
Pressure unloading at a relatively early time point leads to myocardial reverse remodeling to a comparable degree in male and female rats.

Acknowledgement/Funding
NVKP-16-1-2016-0017; ÚNKP-18-3-I-SE-9
P3459Research Network in Africa (RNA): gender differences in cardiovascular risk factors and complications in 12 African countries
Authors: Diop I B , Antignac M , Nhavoto C , Sidy Ali A , Balde D , Empana J P , Dzudie A , Thiam S , Cavagna P , Adoubi A , Perier M C , Takombe J L , Ikama M S , Houenassi M D , Jouven X 
Published: October 2019

Abstract

Background
Cardiovascular diseases are rapidly growing epidemic in Sub-Saharan Africa. Unlike other regions of the world, death rates due to hypertension are greater for women than men in Africa. Scarce data were available on factors associated with gender in cardiovascular risk factors and complications in Sub-Saharan Africa.

Purpose
To assess gender differences in cardiovascular risk factors pattern in patients with hypertension in 12 Sub-Saharan countries.

Methods
We conducted a cross-sectional survey in urban clinics of twelve countries in Africa. Data were collected on demographics, treatment and standardized BP measures were made among the hypertensive patients attending the clinics. BP control was defined as BP<140/90 mmHg and hypertension grades were defined according to European Society of Cardiology guidelines. The separate association between women factors and BP control was investigated using Generalized Linear Mixed-Effects Models adjusted on age; A random effect on the country was added (generalized estimated equation models) to account for inter-country variability.

Results
The EIGHT study enrolled 2198 patients with hypertension in 12 sub-Saharan countries between January 2014 and November 2015. The proportion of women (60,2%) was higher than men and varied significantly according to countries (p<0.001), ranged from 33.7% (Guinea) to 71.9% (Gabon). Mean age was 57.7±12.0 years for women and 59.2±11.4 years for men (p<0.001).
Compared to men, women had a higher rate of family cardiovascular background (79% vs 70%, for women and men respectively) (p<0.0001), cardiovascular risk factors (74.3% vs 68.1) (p=0.008), such as obesity (25.8% vs 12.1%) (p<0.0001), sedentary behavior (42.1% vs 35.0%) (p=0,006). BP control didn't differ according to gender, the repartition of grades of hypertension was similar between women and men and proportion of uncontrolled BP was 77.2% in women and 77.8% in men (p=0.4), with same proportion of women and men receiving antihypertensive treatment (96 vs 97.5%) (NS).
However, African women had less cardiovascular complications than men (39% vs 52.4%) (p<0.0001) (OR: 0.50 [CI 95% 0.41–0.61]).

Conclusions
Our study highlighted gender differences in cardiovascular risk factors pattern in Sub-Saharan hypertensive patients. Tailoring medical (public health) programs to improve cardiovascular disease prevention that take into women characteristics may enhance their effectiveness.
P3461Sex-specific pattern of left ventricular hypertrophy and diastolic function in patients with type 2 diabetes mellitus
Authors: Wu M Z , Chen Y , Yu Y J , Tse H F , Yiu K H 
Published: October 2019

Abstract

Background
Few prospective studies have evaluated sex-specific pattern, natural progression of left ventricular (LV) remodeling and diastolic dysfunction in patients with type 2 diabetes (T2DM).

Purpose
The aim of this study was to study the sex-specific prevalence, longitudinal changes of LV remodeling and diastolic dysfunction in patients with T2DM. Further the prognostic value of diastolic function in women and men was also evaluated.

Methods
A total of 386 patients with T2DM (mean age 61±11 years; women, 48.2%) was recruited. Detailed echocardiography was performed and LV geometry, systolic and diastolic function were measured at baseline and follow-up. A major adverse cardiovascular event (MACE) was defined as cardiovascular death, heart failure hospitalization or myocardial infarction. Multivariable cox-regression adjusted for age, hypertension, LVEF and HbA1c was used to assess the association between sex-specific diastolic function and the development of a MACE.

Results
Despite a similar age, prevalence of hypertension and body mass index, women had a higher prevalence of LV hypertrophy and diastolic dysfunction at baseline and follow-up compared with men. A total of 26 patients developed a MACE (4 cardiovascular death, 14 hospitalization for heart failure, 8 myocardial infarction) during follow-up. Women with diastolic dysfunction had a higher incidence of MACE than those with normal diastolic function but this association was neutral in men. Multivariable Cox-regression analysis indicated that diastolic dysfunction was associated with MACE in women (hazard ratio 6.35, 95% confidence interval 1.18–34.19, P<0.05) but not men (hazard ratio 1.85, 95% confidence interval 0.58–5.92, P=0.30).

Conclusions
LV hypertrophy and diastolic dysfunction, both at baseline and follow-up, were more common in women than men. Pre-clinical diastolic dysfunction was independently associated with MACE only in women with T2DM but was neutral in men.
P3463Cardiometabolic risk factors in women with a history of hypertensive disorders of pregnancy
Authors: Chulkov V , Tarasova O , Vereina N , Chulkov V L , Sinitsin S 
Published: October 2019

Abstract

Introduction
A history of hypertensive disorders of pregnancy (HDP) has the unique potential to identify women at higher risk of future maternal cardiovascular disease (CVD), for whom targeted risk-reduction interventions may be particularly helpful.

Purpose
The aim of the study was to assess the factors and biomarkers of cardiometabolic risk in women with a history of hypertensive disorders of pregnancy.

Methods
Cross-sectional study of risk factors and biomarkers of cardiometabolic risk among young women with a history of HDP in comparison with normotensive patients during pregnancy. 117 women were studied: gr. 1 – 33 with a history of HDP, 40 [40–43] years; gr. 2 – 44 without a history of HDP, 39 [32–43] years. The control group consisted of 40 patients, 25 [23–28] years. The time interval after delivery was on average 5 to 19 years. We measured serum glucose, insulin, HOMA-IR, lipids, leptin, adiponectin. Left ventricular mass index (LVMI) was estimated by TTE. Data are presented as M±SD and Me (Q25–Q75).

Results
Women with HDP more often had hypertension (n=27; 82%), obesity (n=20; 39%) and smoking (n=9; 27%), p1–2,3 <0.05. A higher plasma levels of glucose mmol/L (5.5±0.7 vs 5.2±0.6 and 5.1±0.5), leptin ng/ml (42 [30–50] vs 24 [13–32] and 19 [10–29]) and lower plasma levels of adiponectin were observed in gr.1 vs gr. 2 and controls. Mean value of LVMI (g/m2) was statistically higher in women with HDP vs. without HDP and controls (119.9±23.7 vs 85.9±15.2 and 77.6±11.3), p1–2,3 <0.05.

Conclusion
It is shown that in women with a history of HDP subsequent changes in carbohydrate and lipid metabolism in combination with arterial hypertension and abdominal obesity, which constitute a cluster of the metabolic syndrome, are revealed after careful examination. These changes are also accompanied by insulin resistance, hyperinsulinemia, adipokine imbalance and more pronounced target organ damage.
P3466Cardiac output in end-stage liver disease increases with the severity of liver dysfunction
Authors: Koshy A N , Cailes B , Gow P , Testro A , Sajeev J K , Han H , Ko J , Weinberg L , Lim H , Teh A , Farouque O 
Published: October 2019

Abstract

Background
End-stage liver disease is associated with significant systemic and haemodynamic alterations that affect cardiac function. Cirrhotic cardiomyopathy remains an ill-defined entity among cardiologists. Understanding the complex interplay between liver dysfunction and cardiac function can lead to a better understanding of the compensatory mechanisms of the heart in liver failure.

Purpose
To investigate whether severity of liver disease affects baseline cardiac output in a large contemporary cohort of patients undergoing liver transplant work-up.

Methods
Consecutive patients that underwent pre-liver transplant (LT) workup between 2010–2017 were included. All patients underwent a resting echocardiogram. Cardiac output (CO) was prospectively recorded at baseline by pulsed-wave Doppler examination of the left ventricular outflow tract from the apical window and systemic vascular resistance (SVR) was calculated as 80 x (mean arterial pressure (MAP)/CO). Severity of liver disease was characterized by the model of end-stage liver disease (MELD) and Child-Pugh scores.

Results
560 patients were included (mean age 57.5±7.7, 74.8% male). Mean MELD score was 19±7 and Child-Pugh Score was 9±3. There was an inverse linear relationship between the severity of liver disease by the MELD score and baseline SVR (rho 0.40, P<0.001). As SVR reduced, there was also a significant rise in baseline CO with a strong inverse correlation between the two variables (rho 0.86, p<0.001). There was a significant linear correlation between the severity of liver disease and baseline CO with both the scores (MELD Score rho 0.42, p<0.001; Child Pugh rho 0.44, p<0.001) (Figure).
Baseline CO in LT Patients by Severity

Conclusions
Baseline CO increased with the severity of liver dysfunction due to a reduced afterload. A higher resting CO may lead to patients encroaching on their cardiac reserve at rest. This provides a pathophysiological insight suggesting a limited role for beta-blockers, particularly in patients with advanced liver cirrhosis.
P3467Tricuspid annular isovolumic acceleration is more useful for the assessment of right ventricular systolic function in patients after repair of tetralogy of Fallot with pulmonary regurgitation
Authors: Toyono M , Yamada S , Aoki-Okazaki M , Takahashi T 
Published: October 2019

Abstract

Introduction
The detrimental impact of pulmonary regurgitation (PR) on right ventricular (RV) function of patients after repair of tetralogy of Fallot (TOF) is recognized. Although tricuspid annular isovolumic acceleration (IVA) is useful for the evaluation of RV function, it requires complicated measurement. Tricuspid annular plane systolic excursion (TAPSE) is measured easily and has also been validated as a marker of RV systolic function.

Hypothesis
We assessed the hypothesis that IVA has advantage to the stratification of the detrimental impact of PR on RV systolic function after TOF repair compared with TAPSE.

Methods
We prospectively examined patients after TOF repair. Patients <1 year after the repair, those with the history of sustained arrhythmia and those who required concomitant tricuspid and/or pulmonary valve surgery were excluded from the study. IVA was measured by dividing the myocardial velocity during isovolumic contraction by the time interval from the onset of the myocardial velocity during the isovolumic contraction to the time at the peak velocity of this wave. TAPSE was measured using M-mode echocardiography with the M-line passing through the lateral annulus of tricuspid valve in the apical 4-chamber plane. PR jets were evaluated in the parasternal short-axis plane. PR degree was assessed by the number of correspondence to the following conditions; 1) diastolic flow reversal in the main pulmonary artery, 2) diastolic flow reversal in the branch pulmonary arteries, 3) pressure half-time of PR signal <100 msec and 4) the ratio of the duration of the PR signal to the total duration of diastole <0.77. PR degree was graded from 0 to 4.

Results
Twenty-two patients were enrolled to the study. Age, female, period after the TOF repair and body height of the patients were 11±6 years, 55%, 9±5 years and 137±28 cm, respectively. In all the patients, IVA and TAPSE were 160±27 cm/sec2 and 12±2 mm, respectively. PR degrees were graded as 2, 3 and 4 in 4, 14 and 4 patients, respectively. By the Kruskal-Wallis test, only IVA showed a significant difference among the 3 PR degrees.

Conclusion
In conclusion, IVA can be a useful index for the stratification of RV function in patients after TOF repair with various degrees of PR.
P3479Sequential stimulation and inhibition of lysophosphatidic acid receptor 4 are critical for cardiac differentiation and repair
Authors: Cho H J , Lee J W , Lee C S , Ryu Y R , Kim H S , Yang H M 
Published: October 2019

Abstract

Background
The clinical application of cell therapy to repair the damaged heart needs to understand the precise differentiation process of stem cells and the characteristics of cardiac progenitor cells.

Purpose
We examined the cardiac-specific markers that expressed on the cell surface and determined their functional significance during cardiac differentiation.

Methods and results
We screened cell-surface expressing proteins on cardiac progenitor cells at differentiation day 3 compared to undifferentiated pluripotent stem cells (PSCs). Among candidates, we identified lysophosphatidic acid receptor 4 (LPAR4) that is a G protein-coupled receptor. During in vitro differentiation of mouse PSCs toward cardiac cells, LPAR4 expression peaked for 3–5 days and then and declined immediately. Also in vivo, LPAR4 was specifically expressed in the early stage of heart development in embryos and disappeared completely in adults, suggesting that stimulatory signal of LPAR4 at an early stage should be shut off for further progression of differentiation. We next have identified the LPAR4 downstream signaling molecule, p38MAPK, by comparing PSCs and LPAR4 knockdown PSCs. In both mouse and human PSCs, ODP (LPAR4 specific agonist) followed by p38MAPK blocker (SB203580) treatment significantly increased cardiac differentiation efficiency. Furthermore, we investigated whether LPAR4 is the maker for adult cardiac progenitor cells. We found that LPAR4-positive cells were rarely present in normal adult mouse hearts, but LPAR4-positive cells were increased when the heart was damaged. LPAR4-positive cells from adult hearts differentiated into cardiomyocytes. After myocardial infarction (MI), the sequential stimulation and inhibition of LPAR4 with ODP and p38MAPK blocker resulted in the reduction of infarct size and improvement of left ventricular dysfunction.

Conclusion
We demonstrated that LPAR4 is a cardiac progenitor-specific marker and its functional significance during cardiac differentiation and regeneration. Our findings provide a new insight in cell-free cardiac repair by the modulation of progenitor-specific downstream signaling.

Acknowledgement/Funding
Grants from “Strategic Center of Cell and Bio Therapy” (grant number: HI17C2085) and “Korea Research-Driven Hospital” (HI14C1277)
P3488Mechanistic insight on the cardioprotective effect of levosimendan against doxorubicin induced cardiomyopathy: Pivotal role of PKA signaling
Authors: Efentakis P , Varela A , Sanoudou D , Davos C , Klinakis A , Papapetropoulos A , Cokkinos D V , Iliodromitis E K , Wenzel P , Andreadou I 
Published: October 2019

Abstract

Background
Levosimendan (LEVO) an inodilator indicated for the treatment of heart failure exerts multifaceted cardioprotective effects. Case-studies indicate protection against doxorubicin (DXR)-induced cardiotoxicity, but this effect remains elusive. We have previously shown that LEVO exerts cardioprotection against DXR-induced cardiomyopathy in a rat in vivo model, in a PKA/PKG-dependent manner.

Purpose
We sought to elucidate the mechanism of LEVO's induced cardioprotection and clarify the contribution of PKG and PKA pathways converging onto phospholamban (PLN).

Methods
As previously observed, LEVO at a dose of 24μg/kg protects against DXR cardiotoxicity, with protein kinase B (Akt)/ endothelial nitric oxide synthase (eNOS) and protein kinase A and G (PKA/PKG) pathways emerging as the main contributors to cardioprotection. Moreover, phospholamban seems to be the end-target of the signaling cascade. To verify the contribution of phospholamban, phospholamban deficient mice (PLN−/−) were assigned to PLN−/−/DXR (18mg/kg) and PLN−/−/DXR+LEVO (acute) (LEVO bolus, 24 μg/kg) groups for 14 days. Echocardiographic analysis was conducted in all groups and protocols. Furthermore, in order to solidify the mechanism of LEVO-mediated cardioprotection, primary adult ventricular murine cardiomyocytes (AVMCs) were isolated and treated with doxorubicin or/and LEVO as well with L-NAME, DT-2 and H-89 (eNOS, PKG and PKA inhibitors, respectively) and cardiomyocyte-toxicity was assessed.

Results
In the transgenic PLN−/− mice, LEVO did not exert cardioprotection, whilst the co-administration of doxorubicin and levosimendan led to an impaired Left ventricular function [FS (%): PLN−/−/Control: 39.01±0.42 vs PLN−/−/DXR: 38.12±0.51 in (NS); PLN−/−/DXR+LEVO: 35.38±0.86 (**p<0.01 vs PLN−/−/Control, *p<0.05 vs PLN−/−/DXR]. The latter data suggest that phospholamban is crucial for LEVO's cardioprotective effect. Finally, by investigating the contribution of different molecular pathways -shown to be induced by LEVO in vivo- on the AVMCs, we found that only PKA inhibition by H-89, abrogated LEVO-mediated cytoprotection, indicating that the effect is cAMP-PKA dependent.

Conclusions
Single-dose LEVO prevented DXR cardiotoxicity through a cAMP-PKA-phospholamban pathway, highlighting the role of inotropy in DXR cardiotoxicity. These preclinical data can stand as promising grounds for further clinical investigations.