bluuebunny/crossref_metadata_2025_split huggingface dataset:
P1518Impact of psychological risk factors on cardiovascular prognosis in patients after coronary artery bypass grafting: data from a 5-year-follow-up study
Authors: Raykh O I , Sumin A N , Korok E V 
Published: October 2019

Abstract

Psychosocial stress is acknowledged as one of risk of development of cardiovascular pathology. The interrelation between existence personality type D and prevalence of atherosclerosis is recently established. However, predictive value of type D personality in different cultures and the countries are not fully understood.

Purpose
Study aim was to investigate the association of type D personality with the development of cardiovascular complication in patients in five years after coronary artery bypass grafting (CABG).

Materials and methods
Evaluation of psychological status and combined risk of nonfatal (strokes, nonfatal myocardial infarctions, repeat procedures of revascularization and hospitalization due to relapse or progression of angina pectoris) and fatal (general and cardiovascular mortality) cases before and in five years after CABG. Patients with chronic ischemic heart disease (n=602, 112 (18.5%) females and 490 (81.5%) males, mean age=57.7±7.3 years.) who had had CABG were included in the study. Who were formed in two groups: patients with the presence of type D (n=134) and patients without type D (n=468). The study of the psychological status was carried out using questionnaire DS-14. Analysis of long-term results were assessed using the Kaplan–Meier method.

Results
During the 5 years frequency of fatal cases in both groups amounted 8.3% and 8.1% (p=0.145), in turn nonfatal end-points in group with type D amounted 31.8%, and 15.9% in group without type D (p=0.044). Presence of type D personality at initial examination increased 3.21 times combined risk of nonfatal and fatal cases (OR 3.21, 95% CI 2.02–6.14, p=0.002). In long term period there were no differences in survival between groups type D and without type D (95.5% vs. 96.8%), There were differences in groups type D and without type D in nonfatal events (strokes, nonfatal myocardial infarctions, secondary endpoint: repeat procedures of revascularization and hospitalization due to relapse or progression of angina pectoris) (respectively, 97.1% vs 88.0%, (p=0.34).

Conclusion
Type D patients had a greater risk for nonfatal cardiac events compared with non Type D patients. Accumulated proofs indicate that in detection of patients at risk of development of stress induced cardiac complications after CABG it is reasonable to use approach which involves consideration of personality type.
P1522Validating a new device for precise assessment of pulse wave velocity in arteries of various structures in patients in different age groups
Authors: Olszewski R , Sondej T , Sieczkowski K , Obiala K , Jannasz I , Targowski T , Dobrowolski A P 
Published: October 2019

Abstract

Background
Arterial stiffness (AS) is a process that develops with age and obesity, but is also an independent predictive factor for the development of hypertension, and cardiovascular complications. Measuring the pulse wave velocity (PWV) is the most common method of assessing arterial stiffness. Two methods of PWV evaluation dominate in the world (carotid-femoral and brachial-ankle). However, recent studies have indicated that the age-related increase in PWV was not even uniform in different arteries and the AS gradient is a better predictor of mortality than the classic PWV one. So we need the devices for a more accurate assessment of AS in different areas. Our group constructed a precise, multi-site system (M3S) for the simultaneous, real-time, synchronous measurement of PWV. M3S has a maximum of eight photopletysmographic (PPG) detectors – Fig. 1A.

Aim
The purpose of the study is to validate the PWV measurement by M3S device against a gold standard (SphygmoCor XCEL) for patients in different age groups.

Methods
Measurements collected from 62 subjects (36 young [19–24], 26 older [62–89]) using the M3S were compared with simultaneously recorded SphygmoCor XCEL measurements. With the 59 paired PWV values, we investigated the agreement between the M3S prototype and the SphygmoCor XCEL device using Pearson correlation analysis and Bland-Altman plot. We also performed analysis on the determinants and reproducibility of PWV measured with both devices.

Results
The correlation coefficient for PWV measured with the two devices was 0.87 (p<0.001) – Fig. 1B. Compared with the SphygmoCor XCEL device, the M3S prototype slightly underestimated PWV by r=−0.47 m/s (±1.96 standard deviations SD: +2.2 m/s, r=−3.2 m/s). The coefficient of variation (CV) between the difference and the average of the M3S and SphygmoCor XCEL measurements was 19% (p=0.10) – Fig. 1C.
Figure 1. A. Block diagram of M3S measurement system with configuration for PWV validation. B. Relationship between PWV for SphygmoCor XCEL (carotid-femoral) and M3S (forehead-toes (right, left mean). C. Bland-Altman plot for the analysis of the difference between the SphygmoCor XCEL and M3S devices.

Conclusion
This technique used by the M3S could provided a multi-site measurement of PWV. It can be potentially extended for measurement and non-invasive characterization of global arterial stiffness with the possibility of calculating the different AS gradients.
P1544Circulating secretoneurin concentrations provide incremental prognostic information to established risk indices in patients with moderate to severe aortic stenosis
Authors: Brynildsen J , Myhre P L , Lyngbakken M N , Klaeboe L G , Stridsberg M , Christensen G , Edvardsen T , Omland T , Rosjo H 
Published: October 2019

Abstract

Background
Secretoneurin (SN) concentrations provide important prognostic information in patients with myocardial dysfunction. Whether preoperative SN concentrations improve risk assessment in patients with moderate to severe aortic stenosis (AS) is unknown.

Methods
We included 57 patients with moderate to severe AS referred for presurgical evaluation and recorded all-cause mortality during follow-up. All patients were examined with comprehensive echocardiography, electrocardiogram (ECG), and high-sensitivity cardiac troponin T (hs-TnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) measurements.

Results
Median (quartile 1–3) SN concentration in the AS patients was 141 (121–163) pmol/L. Lower estimated creatinine clearance and use of diuretics, but not standard ECG or echocardiographic indices and cardiac biomarkers, were associated with increasing SN concentrations. In total, 15 patients (26%) died during 3.5 years median follow-up. SN concentrations were higher in non-survivors than survivors: 156 (133–209) vs. 140 (116–155) pmol/L, p=0.007. The optimal cut-off concentration for SN in discriminating long-term mortality was 147 pmol/L (sensitivity 67% [95% CI 38–88%], specificity 74% [58–86%]) and patients with SN concentrations above the optimal cut-off had worse prognosis than patients below the cut-off (Figure; p=0.005 with the log-rank test). Higher SN concentrations were associated with increased risk of mortality after adjustment for clinical risk factors, echocardiographic and ECG variables, hs-TnT and NT-proBNP concentrations, and whether patients were subjected to aortic valvular surgery (n=34): hazard ratio per lnSN 15.13 (95% CI 1.05–219.00); p=0.046. Receiver operating characteristics area under the curve for SN to predict mortality was 0.74 (95% CI 0.60–0.88) compared to 0.73 (0.59–0.87) for hs-TnT and 0.67 (0.51–0.82) for NT-proBNP.

Conclusions
SN concentrations seem to reflect additional pathophysiology to established risk indices and improve risk assessment in patients with moderate to severe AS.
P1549Serum soluble Klotho is associated with extent of coronary artery calcification in patients with stable angina pectoris undergoing percutaneous coronary intervention
Authors: Koga S , Ikeda S , Akashi R , Yamagata Y , Yonekura T , Kawano H , Maemura K 
Published: October 2019

Abstract

Background
Klotho, which was originally identified as an aging suppressor, is a key regulator of bone and mineral metabolism. Transmembrane and soluble forms of Klotho protein have been identified. The transmembrane form serves as an obligate co-receptor for fibroblast growth factor 23 (FGF23). However, the physiological importance of soluble form of Klotho has not been determined.

Purpose
The present study aimed to test the hypothesis that circulating soluble Klotho levels can predict the presence or extent of coronary artery calcification (CAC) in patients with coronary artery disease.

Methods
We analyzed CAC of culprit lesions in patients with 75 stable angina pectoris who were not on dialysis and were scheduled for percutaneous coronary intervention (PCI) following intravascular ultrasound (IVUS). Arc and length of each calcium within the culprit lesion was measured by IVUS. The main outcome measure was the calcium index; a volumetric IVUS-derived measure which was calculated as total calcium length/lesion length × maximal calcium arc/360°. Low calcium index was defined as calcium index <0.042 of the first quartile value. Serum Klotho and FGF23 were measured before PCI. Patients were divided into two groups according to median serum Klotho value: low-Klotho (n=37, ≤460 pg/mL) and high-Klotho group (n=38, >460 pg/mL).

Results
Compared with patients with low-Klotho, those with high-Klotho had higher estimated glomerular filtration rate (eGFR) (69±20 vs. 55±16 mL/min/1.73 m2, p<0.001), lower FGF23 levels (51±24 vs. 67±41 pg/mL, p=0.010). Patients with high-Klotho had significantly lower calcium index than those with low-Klotho (0.17±0.21 vs. 0.24±0.23, p=0.043). Serum Klotho levels correlated significantly and inversely with calcium index (r=−0.31, p=0.006). The correlation between Klotho and calcium index was pronounced at analysis in patients with eGFR <60 mL/min/1.73 m2 (r=−0.52, p<0.001). Logistic regression analysis showed that high-Klotho is a sole significant independent factor associated with low calcium index (odds ratio 7.17, p=0.004). Presence of high-Klotho had high sensitivity and negative predictive value for identifying low calcium index (83% and 92%, respectively).

Conclusions
Serum Klotho values were independently and inversely associated with the degree of CAC assessed by IVUS. These findings have important clinical implications for serum Klotho as a biomarker that reflects the extent of CAC.
P1551A genetic risk score predicts recurrent events after myocardial infarction in young adults
Authors: Rincon L M , Sanmartin M , Alonso G L , Rodriguez J A , Muriel A , Casas E , Navarro M , Carbonell A , Lazaro C , Fernandez S , Jimenez Mena M , Fernandez Golfin C , Esteban A , Garcia Bermejo M L , Zamorano J L 
Published: October 2019

Abstract

Background
To evaluate whether a genetic risk score (GRS) improves the prediction of recurrent events in young non-diabetic patients presenting with an acute myocardial infarction and identifies a more aggressive form of atherosclerosis in this population.

Methods and results
We performed a prospective study including 81 consecutive non-diabetic patients aged below 55 y.o. presenting with an acute myocardial infarction (48±6 y.o., 89% male). A comprehensive study including serum biomarkers, genetic testing and cardiac CT was performed. We studied the association of a GRS composed of 11 genetic variants with a primary composite end-point (all-cause mortality, recurrent acute coronary syndrome, and cardiac re-hospitalisation). After a median follow-up of 4.1 (3.5 - 4.4) years 24 recurrent events were documented. A significantly higher prevalence of 9 out of 11 risk alleles was noted compared with general population. The GRS was significantly associated with recurrent events, especially when baseline LDL-cholesterol levels were elevated. Compared with the low-risk GRS category, the multivariate-adjusted hazard ratio for recurrent events for the intermediate-risk GRS category was 10.2 (95% CI 1.1–100.3, p=0.04) and for the high-risk GRS was 20.7 (2.4–181.0, p=0.006) when LDL-C ≥2.8 mmol/L. Inclusion of the GRS improved the C statistic (ΔC statistic =0.086), the continuous Net Reclassification Index (30%) and the Integrated Discrimination Improvement (0.05) compared with a multivariate clinical risk model. Cardiac CT detected coronary calcified atherosclerosis and numerous plaques but it had a limited value for prediction of recurrences. No association was observed between extracellular matrix metabolism biomarkers and GRS or recurrent events in this population.
Cox regression analysis between GRS terciles and LDL-C Univariate analysis Multivariate analysis* HR (95% CI) p-value HR (95% CI) p-value* Low GRS 1 1 Intermediate GRS 2.0 (0.7–5.8) 0.21 LDL-C≤110 mg/dL (≤2.8 mmol/L) 1.0 (0.3–4.0) >110 mg/dL (>2.8 mmol/L) 10.2 (1.1–100.3) 0.04 High GRS 3.0 (1.0–9.2) 0.05 LDL-C≤110 mg/dL (≤2.8 mmol/L) 0.3 (0.1–1.9) >110 mg/dL (>2.8 mmol/L) 20.7 (2.4–181.0) 0.006 *Multivariate model adjusted for GRACE risk score and LDL-C and interaction. There was a strong interaction between GRS terciles and LDL-C (p<0.01).
Recurrent events based on genetic risk

Conclusions
A multilocus genetic risk score identified non-diabetic young patients at increased risk for recurrent events after a myocardial infarction. The significance of LDL-cholesterol in relation to genetic predisposition for recurrences merits further evaluation.

Acknowledgement/Funding
Instituto de Salud Carlos III (PI12/0564, PI14/01152 and PI15/00667), the CIBERCV and the Spanish Society of Cardiology (2015/CC)
P1604Validating previously reported Brugada syndrome-associated common variants identified in caucasian population in the Han Chinese BrS cohort in Taiwan: SADS-BrS registry
Authors: Juang J.-M , Chen C Y , Liu Y B , Lin L Y , Ho L T , Huang H C , Lai L P , Hwang J J , Wu C K , Lin T T , Yu C C , Lu T P , Chattopadhyay A , Yu Q Y , Lin J L 
Published: October 2019

Abstract

Background
Brugada syndrome (BrS) is a sudden arrhythmic death. The prevalence of BrS is higher in the Southeast Asian populations than that in Caucasian patients. A previous genome-wide association study (GWAS) has reported 13 SNPs significantly associated with BrS. However, no study was performed to validate whether these SNPs are enriched in BrS patients in Han Chinese (HC).

Purpose
Evaluating the common variants previously reported in Caucasian BrS patients could be generalized to HC BrS patients in Taiwan

Methods
We genotyped 200 unrelated BrS patients using Affymetrix TWB Array (N=653,291 SNPs, a customized array for HC in Taiwan). The controls are obtained from the Taiwan Biobank (N ≈ 16,000) using the same array. An imputation workflow was shown in Figure 1. To confirm the accuracy of the imputed genotype of each variant, Sanger sequencing was performed in 10% of randomly selected cases.

Results
Among the 3 most important common variants (rs11708996 in SCN5A, rs10428132 in SCN10A and rs9388451 in HEY2/NCOA7) reported in the previous GWAS mainly conducted in Caucasian BrS patients, 2 of them (rs10428132 and rs9388451) were successfully replicated in the HC population in Taiwan (P<0.01). We also found that the differences of minor allele frequency (dMAF: the MAF of cases minus the MAF of controls) of the two variants were relatively smaller between the BrS cases and healthy controls in HC population compared with that in Caucasian populations (dMAF, rs9388451: 0.15 (Caucasian) vs −0.07 (HC); rs10428132: 0.28 (Caucasian) vs 0.11 (HC)). For the remaining 10 common variants reaching genome-wide significance (P=5×10–8) in Caucasian BrS patients, 9 of them were also significantly enriched in the HC BrS patients after the Bonferroni correction (P<0.05/12=0.0042). We next analyzed the variants identified in the previous GWAS on ECG traits (PR interval, QRS duration, QTc interval, and heart rate) in the Caucasian population. Among the reported 75 variants associated with ECG traits, 5 common variants (rs6798015 (PR), rs1760876 (QRS), rs6795970 (PR/QRS), rs2074238 (QTc) and rs314370 (heart rate)) were significant after Bonferroni correction (P<0.05/75=0.00066).
Figure 1

Conclusions
The preliminary results indicated that 85% of common variants of SCN10A and HEY2/NCOA7 previously reported in Caucasian BrS patients are replicated in BrS patients in the HC population but not the common variant of SCN5A (rs11708996). Furthermore, the common variants of SCN10A and HEY2/NCOA7 related to cardiac depolarization or repolarization may also contribute to the development of BrS.

Acknowledgement/Funding
NTUH 106-S3469, NTUH106-S3458 and NTUH 106-018
P1612The ablation of VEGFR-1 signaling promotes angiotensin II induced cardiac dysfunction and sudden death
Authors: Tirronen A , Downes N L , Huusko J , Laakkonen J , Yla-Herttuala S 
Published: October 2019

Abstract

Introduction
Concentric left ventricular hypertrophy (LVH) and diastolic dysfunction develops as an adaptive response to pressure overload. Eventually this may lead to decompensated hypertrophy characterised by interstitial fibrosis, contractile dysfunction as well as changes in metabolism and electrophysiology, consequentially triggering heart failure. The molecular mechanisms involved in cardiac remodelling are not fully understood but maladaptive angiogenesis could promote the transition from adaptive LVH to decompensated heart failure. Angiogenesis is mediated by vascular endothelial growth factors but their role in LVH has remained unresolved.

Purpose
In this study, we wanted to investigate whether vascular endothelial growth factor receptor 1 (VEGFR-1) signaling has a role in the progression of LVH and development of heart failure.

Methods
We used wild type littermate controls and domain specific knock out mouse lacking the intracellular VEGFR-1 tyrosine kinase domain (VEGFR-1 TK−/−) and induced pathological hypertrophy with subcutaneous angiotensin II infusion. We examined the cardiac function with echocardiography and acquired surface ECG signal during the development of LVH. Mice were followed up for 14 days before sacrification and sample collection. Cross-sectional cardiac samples were stained with Masson's trichrome to assess the level of fibrosis and immunostained for lectin to determine capillary area. Additionally, we performed a CD31 whole mount staining to visualise capillary 3D network. To analyse changes in gene expression levels, we performed RT qPCR measurements.

Results
VEGFR-1 TK deficiency led to increased mortality (33.3%) and lack of adaptive LVH. Whereas wild type mice responded to angiotensin II infusion with a significant increase in ejection fraction (55.5% to 69.9%) within the first 6 days, VEGFR-1 TK−/− mice displayed a 5.2% decrease and without adaptive thickening of the LV anterior wall. The most striking difference was seen in LV volume, where wild type mice displayed a 63.3% reduction but in VEGFR-1 TK−/− mice it remained unaltered after angiotensin II infusion. Histological analyses showed that VEGFR-1 TK−/− mice displayed significant cardiomyocyte hypertrophy combined with ventricular dilatation but without changes in fibrosis or angiogenesis. ECG analysis revealed that VEGFR-1 TK−/− mice exhibited widening of the QRS complex, similar to human LVH, and this was accompanied by increased ANP/BNP levels.

Conclusions
In this study, we show that the ablation of VEGFR-1 TK signaling has an unexpected role in pressure overload inducing mortality. VEGFR-1 TK−/− mice displayed dilated LVH and a protracted response to angiotensin II infusion, suggesting that VEGFR-1 signaling is required for the adaptive response and concentric hypertrophy of the myocardium.
P1613Brown adipose tissue dysfunction has a critical role for the development of heart failure in murine pressure overload model
Authors: Yoshida Y , Shimizu I , Walsh K , Minamino T 
Published: October 2019

Abstract
Prognosis of severe heart failure is unacceptably high, and it is our urgent task to find therapies for this critical condition. It has been reported that low body temperature predicts poor clinical outcomes in patients with heart failure, however, underlying mechanisms and pathological implications are largely unknown. Brown adipose tissue (BAT) was initially characterized as a heat generating organ, and studies suggest that BAT has crucial roles for the maintenance of systemic metabolic health. Here we show that BAT dysfunction develops in a murine thoracic aortic constriction (TAC) model, and has a causal role for promoting pathologies in failing heart. TAC operation led to a significant reduction both in intraperitoneal and subcutaneous temperature. TUNEL-positive cells significantly increased in BAT during left ventricular (LV)-pressure overload, and in-vitro studies with differentiated brown adipocytes suggested that the chronic activation of adrenergic signaling promotes apoptosis in these cells. Gain of BAT function model, generated with BAT implantation into peritoneal cavity, improved thermogenesis and ameliorated cardiac dysfunction in TAC. In contrast, genetic model of BAT dysfunction promoted cardiac dysfunction. Metabolomic analyses showed that BAT dysfunction led to an increase of oxidized choline that promoted metabolic dysfunction in the failing heart. Electron microscope study showed that oxidized choline induced mitochondrial dysfunction in vitro as well as in vivo settings. Extracellular flux analyzerindicated that oxidized choline suppresses oxidative phosphorylation in mitochondria. We found that dilated cardiomyopathy patients have lower body temperature, and confirmed by metabolomic study that both choline and oxidized choline are increased in circulation. Maintenance of BAT homeostasis and suppression of oxidized choline would become a novel therapeutic target for heart failure.