bluuebunny/crossref_metadata_2025 huggingface dataset:
5198HbA1C correlates subclinical atherosclerosis in non-diabetes
Authors: Wang W.-T , Hsu P.-F , Wang Y.-J , Ding Y.-Z , Liou T.-L , Wang Y.-W , Huang S.-S , Lu T.-M , Huang P.-H , Chen J.-W , Leu H.-B , Chan W.-L , Lin S.-J
Published: October 2019

Objective

We investigated the association of lipid parameters and coronary atherosclerosis related to normal blood sugar (BS) and impaired fasting glucose (IFG), and factors contributing to coronary atherosclerosis.

Methods

We analyzed 1209 non-diabetic subjects who underwent coronary computed tomography angiography (CCTA). Atherosclerotic plaque pattern severity and patterns were evaluated based on serum glucose values. The association between low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), and high-density lipoprotein cholesterol (HDL-C) and plaque patterns in non-diabetic subjects were also analyzed.

Results

Non-diabetic subjects (age: 58.6±9.7 years; 861 male) were enrolled. Higher glucose levels were correlated with a higher prevalence of mixed plaque, significant (>50% stenosis) high-risk plaque, and calcified plaque in non-diabetic patients. Although serum LDL-C levels were mostly controlled by statin use, atherosclerotic plaques progressed, with increasing A1c values. Multivariate logistic regression analysis showed that age, male gender and A1C were independently associated with the presence of significant mixed plaques after considering BMI, blood pressure, renal function, lipid parameters, uric acid, and smoking habit.

Conclusions

Although decreasing HDL-C and increasing TG correlated with the presence and severity of coronary atherosclerosis, increasing A1c is independently associated with the presence of high-risk plaque in non-diabetes even if LDL-C is controlled by statin therapy.
5877Comorbidity assessment for mortality risk stratification in elderly patients with acute coronary syndrome
Authors: Soler Costa M , Nunez J , Ruiz V , Bonanad C , Formiga F , Valero E , Martinez Selles M , Marin F , Ruescas A , Garcia Blas S , Minana G , Abu-Assi E , Bueno H , Ariza-Sole A , Sanchis J
Published: October 2019

Background

The Charlson's is the most used comorbidity index. It comprises 19 comorbidities, some of which are infrequent in elderly patients with acute coronary syndrome (ACS), while some others are manifestations of cardiac disease rather than comorbidities.

Purpose

Our goal was to simplify comorbidity assessment in elderly non-ST-segment elevation ACS patients.

Methods

The study group consisted of 1 training (n=920, 76±7 years) and 1 testing (n=532; 84±4 years) cohorts. The end-point was all-cause mortality at 1-year follow-up. Comorbidities were assessed selecting those medical disorders other than cardiac disease that were independently associated with mortality by multivariable analysis.

Results

A total of 130 (14%) patients died in the training cohort. Six comorbidities were predictive: renal failure, anemia, diabetes, peripheral artery disease, cerebrovascular disease and chronic lung disease. The increase in the number of comorbidities yielded a gradient of risk on top of well-known clinical predictors: ≥3 comorbidities (27% mortality, HR=1.90, 95% CI 1.20–3.03, p=0.006); 2 comorbidities (16% mortality, HR=1.29, 95% CI 0.81–2.04, p=0.30); and 0–1 comorbidities (7.6% mortality, reference category). The discrimination accuracy (C-statistic= 0.80) and calibration (Hosmer-Lemeshow test, p=0.20) of the predictive model using the 6 comorbidities was comparable to the predictive model using the Charlson index (C-statistic=0.80; Hosmer-Lemeshow test, p=0.70). Similar results were reproduced in the testing cohort (≥3 comorbidities: 24% mortality, HR=2.37, 95% CI 1.25–4.49, p=0.008; 2 comorbidities: 14% mortality, HR=1.59, 95% CI 0.82–3.07, p=0.20; 0–1 comorbidities: 7.5% reference category).

Kaplan-Meyer curves for mortality

Conclusion

A simplified comorbidity assessment comprising 6 comorbidities provides useful risk stratification in elderly patients with ACS

Acknowledgement/Funding

This work was supported by grants from Spain's Ministry of Economy and Competitiveness through the Carlos III Health Institute
5893Adipose tissue secreted ceramides and related sphingolipids - potential modulators of vascular redox signalling in cardiovascular disease
Authors: Akawi N , Checa A , Kotanidis C , Akoumianakis I , Daskalakis E , Herdamn L , Wheelock C , Antoniades C
Published: October 2019

Background

Adipose tissue (AT) plays a vital role in the modulation of vascular biology via known adipokines and other yet unidentified secreted molecules. Recent technological advances of omics-based approaches have enabled the identification of more metabolites that drive the currently recognised cross talk between the AT and the vasculature.

Purpose

The main aim of this study is to explore the role of AT secreted ceramides on the regulation of vascular superoxide (O2·−) generation in cardiac patients.

Methods

Untargeted metabolic profiling for the secretome of paired thoracic and subcutaneous ATs from 48 patients undergoing cardiac surgery (the Oxford cohort for heart, vessels and fat) along with the subsequent sphingolipids-targeted quantification were performed using liquid-chromatography/mass-spectrometry. Immortalized human aortic endothelial cells (teloHAEC) were treated exogenously with C6-ceramide (CerC6) for 20min and O2·− production was measured using lucigenin-enhanced chemiluminescence.

Results

Metabolomics differential (A) and enrichment analysis (not shown) highlighted the significant differences in sphingolipids secretion levels between the two fat depots. Higher amount of ceramides were produced and secreted from the thoracic depot with C16-ceramide (CerC16) representing the most abundant differentially secreted ceramide (B). Compared to the lowest tertile, the middle and highest tertiles of ceramides in thoracic AT were significantly associated with higher O2·− generation in patients' vessels namely saphenous veins (SV) and internal mammary arteries (IMA) (C). Exogenous treatment of teloHAEC with ceramide increased O2·− generation and eNOS uncoupling evidenced by more negative O2·− after addition of L-NAME, an inhibitor of eNOS (D).

Results Overview

Conclusions

In this study, we demonstrate for the first time that sphingolipids, in particular ceramides, secreted from AT of cardiac patients may modulate their vascular redox state via dysregulating vascular eNOS signalling leading to endothelial dysfunction –a hallmark of cardiovascular disease.

Acknowledgement/Funding

the NovoNordisk Foundation (NNF15CC0018486)
6112Usefulness of the trans-stent fractional flow reserve gradient for predicting clinical outcomes
Authors: Lim H , Yang H M , Yoon M H , Seo K W , Choi B J , Choi S Y , Seo J Y , Jin U , Tahk S J
Published: October 2019

Aims

The clinical meaning of a trans-stent pressure gradient after DES implantation has not been estimated adequately. We evaluated the usefulness of a fractional flow reserve (FFR) gradient across the stent (ΔFFRstent) for long-term clinical outcomes after percutaneous coronary intervention (PCI) with a drug-eluting stent (DES).

Methods and results

FFR pull-back and intravascular ultrasound (IVUS) were performed after successful PCI in 135 left anterior descending artery lesions. ΔFFRstent was defined as the FFR gradient across the stent. The ΔFFRstent/length was defined as the ΔFFRstent value divided by the total stent length multiplied by 10 [= (ΔFFRstent ÷ stent length) x 10]. Major adverse cardiac events (MACEs) were the composite of all-cause death, target vessel related myocardial infarction, and target lesion revascularisation. Despite successful PCI without significant complications on IVUS, ΔFFRstent >0 was observed in 98.5% of cases. ΔFFRstent ≥0.04 and ΔFFRstent/length ≥0.009 predicted suboptimal stenting defined as final minimal stent area <5.5 mm2. During 2183±898 days, the MACE-free survival rate was significantly lower in patients with ΔFFRstent ≥0.04 and ΔFFRstent/length ≥0.009 compared to those with lower values (69.6 vs. 93.4%, log-rank p=0.031; 72.1 vs. 97.7%, log-rank p=0.003, respectively). ΔFFRstent/length ≥0.009 (hazard ratio 10.1, p=0.032) was an independent predictor of MACE.

Trans-stent FFR and MACE

Conclusion

A trans-stent FFR gradient was frequently observed in DES-treated patients despite successful PCI results. ΔFFRstent and ΔFFRstent/length are useful indicators for optimising a DES and are related to long-term outcomes.
6123A novel ECG parameter predicts lack of eligibility for Subcutaneous Implantable Cardioverter Defibrillator (S-ICD) in patients with Brugada Syndrome
Authors: Mazzanti A , Marelli S , Chargeishvili T , Trancuccio A , Marino M , Bulian F , Monteforte N , Bloise R , Napolitano C , Priori S G
Published: October 2019

Background

A conclusive estimate of the eligibility rate for the use of subcutaneous implantable cardioverter defibrillators (S-ICD) in patients with Brugada Syndrome (BrS) is lacking.

Objective

We aimed to: 1) evaluate the eligibility for S-ICD in patients with BrS using a novel automated tool; 2) investigate predictors of ineligibility for S-ICD, based on baseline 12-lead electrocardiogram.

Methods

Automated screening for S-ICD was performed in 118 consecutive BrS patients using the programmer provided by the S-ICD producer. The system automatically assessed the acceptability of each of the three sense vectors used by the S-ICD for the detection of cardiac rhythm. Eligibility was defined when at least one vector was acceptable both in supine and standing position.

Results

The clinical characteristics of 118 BrS patients were as follow: age 43±11 years; 89% males; 2% with aborted cardiac arrest; 14% with a history of syncope; 81% with spontaneous type 1 ECG pattern; 21% with a familial history of sudden cardiac death; 24% with an SCN5A mutation. No patients had an indication for pacing. Only 8/118 (7%) patients were ineligible for S-ICD. Of note, 5/8 (63%) patients who failed the screening exhibited a slurred S wave of ≥80 ms duration in the peripheral lead aVF on the 12-lead baseline electrocardiogram, vs. 4/110 (4%) of those who passed the screening (sensitivity of S wave in aVF for screening failure 63%, specificity 97%; p<0.001). Remarkably, the presence of a slurred S wave of ≥80 ms duration in lead aVF remained significantly associated to the failure of eligibility for S-ICD (odds ratio 50, p<0.001) in a multivariable analysis that included the previous history of symptoms, the presence of a spontaneous type 1 ECG pattern, the gender and the presence of SCN5A mutations.

ECG predictor of S-ICD screening

Conclusion

Up to 93% of BrS patients are eligible for S-ICD when the automated screening tool is used. The presence of a slurred S wave in lead aVF on the 12-lead electrocardiogram is a powerful predictor of screening failure.
6127Maternal, fetal and obstetric outcome in patients with thoracic aortic disease: an ancillary analysis of the ROPAC registry
Authors: Campens L , Baris L , De Backer J , Roos-Hesselink J
Published: October 2019

Background

Cardiovascular disease is the leading cause of death during pregnancy with thoracic aortic dissection being one of the main causes. Thoracic aortic disease (TAD) is most commonly related to hereditary disorders and congenital heart malformations such as bicuspid aortic valve (BAV). Pregnancy is considered as a trigger for aortic complications in women with underlying aortic disease. With this analysis, we aim to study the maternal and fetal outcome of pregnancy in women with TAD.

Methods

The Registry Of Pregnancy And Cardiac disease (ROPAC) is a large, prospective and global registry and enrolled 4418 women from January 2011 onwards with known cardiac disease (mainly congenital and valvular disease) before pregnancy.

Results

TAD was present in 217 woman prior to pregnancy. Almost half of them were Marfan patients (MFS), 20% had a BAV, 7.4% Turner syndrome and 23% of patients had no underlying genetic defect or associated congenital heart defect. 35.5% of patients had aortic dilatation of which 6% had an aortic diameter above 45mm.

Half of patients had previous pregnancies with no significant difference in parity between woman with and without aortic dilatation. Four patients of which 3 MFS patients had an acute aortic dissection (three type A and one type B aortic dissection) but no lethal (maternal of fetal) events occurred. Two patients presented with ventricular arrhythmia of whom one MFS patient. Caesarian section was not performed significantly more frequent in patients with aortic dilatation. Birth weight was lower in the group of woman with aortic dilatation, related to the use of beta-blocking agents. However, intra-uterine growth retardation and prematurity did not occur more frequently.

Conclusion

This ancillary analysis of the ROPAC data provides the first large prospective data on pregnancy risk of patients with a wide range of TAD.

MFS patients are highly represented in the registry and are a vulnerable group to develop severe complications during pregnancy or peripartum with occurrence of aortic dissection in 3% of patients and ventricular arrhythmia in one. Serial follow-up by a specialized multidisciplinary team throughout pregnancy and postpartum period and patient tailored management of delivery is advised.
P4995Neuregulin-1 compensates for endothelial NO synthase deficiency in the heart and kidney
Authors: Shakeri H , De Moudt S , Leloup A J , Jacobs G , De Meyer G R Y , De Keulenaer G W , Fransen P , Guns P.-J.F , Segers V F
Published: October 2019

Background

Decreased eNOS activity is the hallmark of endothelial dysfunction and is associated with cardiovascular and renal disorders. Besides NO, endothelial cells produce numerous other small molecules, peptides, and proteins, which modulate the function of adjacent cells. For instance, neuregulin-1 (NRG-1) is an endothelium-derived growth factor, which plays crucial roles in cardiovascular development, has cardioprotective properties, and induces growth and differentiation of cell types in different organs, including the kidney.

Purpose

Although the cardioprotective effects of endothelium-derived NO and NRG-1 are well established, their interaction is not clear. Therefore, we studied the interaction between the NO/eNOS and NRG-1/ErbB signalling pathways in a transgenic eNOS knock-out mouse model (eNOS−/−) treated with subpressor doses of angiotensin II (AngII).

Methods

eNOS−/− mice and their wild type (WT) littermates (n=64, 15 weeks old) were randomized for implantation of osmotic minipumps with AngII (400 ng/kg.min) for 28 days or sham surgery. Mice were randomized to receive either daily NRG-1 injections (20 μg/kg, intraperitoneal) or vehicle for 4 weeks (n=8/group). Hypertrophy and fibrosis were measured in left ventricle (LV) and kidneys using echography and immunohistochemical staining.

Results

Although blood pressure was higher in eNOS−/− mice compared to their WT littermates, it was unaffected by a subpressor dose of AngII. Masson's trichrome staining showed that AngII significantly increased LV (interstitial and perivascular) and renal fibrosis in eNOS−/− mice, but not in WT controls (see figure for LV data). NRG-1 reversed this AngII-induced LV and renal fibrosis caused by eNOS deficiency. There was also significant hypertrophy of LV and kidneys in eNOS−/− mice treated with AngII, which was again normalized by NRG-1 treatment. Moreover, NRG-1 significantly attenuated albuminuria induced by eNOS deficiency under AngII treatment.

Conclusions

This study demonstrates that the anti-fibrotic and anti-hypertrophic effects of NRG-1 are independent from the NO/eNOS pathway in both heart and kidney. Strikingly, NRG-1 is able to compensate for some of the negative effects of eNOS deficiency, at least in conditions of AngII stimulation.

Acknowledgement/Funding

supported by university of Antwerp
P4999Cardiomyocyte ErbB4 receptors are essential for developmental cardiac hypertrophy and cardiac function in adult hearts
Authors: Reichelt M , Wang Z , Thorn C , Paravicini T , Thomas W G
Published: October 2019

Background/Introduction

Activation of ErbB4 by neuregulin 1 (NRG1) promotes cardiomyocyte hypertrophy and proliferation in both adult and neonatal mice, while treatment of patients with NRG1 following myocardial infarction reduces scar size and improves function. In mice, deletion of ErbB4 from cardiomyocytes mid-gestation results in development of dilated cardiomyopathy and reduced survival, pointing to a critical role for ErbB4 in the heart.

Purpose

We sought to evaluate the role of ErbB4 in the adult heart.

Methods and results

We deleted ErbB4 in αMHC-MerCreMer (cCre Tg+/)/ErbB4 homozygote floxed (ErbB4 fl/fl) mice at ∼2 months of age with 10 injections of Tamoxifen (20 mg/kg/day). Contractile function was reduced in vivo (echocardiography, 16%) and ex vivo (isolated-perfused, 33%) 3 months after gene deletion, while survival in mice up to 8 months after tamoxifen treatment was mot modified by cardiomyocyte ErbB4 deletion. We next evaluated the role of ErbB4 in response to physiological and pathological hypertrophic stressors. ErbB4 deletion did not modify cardiac enlargement in response to Angiotensin II (1000ng/kg/min, 14 days) or exercise (twice daily swimming, 20 min/session increasing 10 min/day to 90 min followed by 7 days at 90 min/session). Taken together, this indicated that ErbB4 is not essential for survival and adaptation in the adult heart, pointing instead towards a critical window for ErbB4 in neonatal heart development. To test this hypothesis, ErbB4ff and ErbB4ww neonates were injected at P1 with AAV9-cTNT-eGFP-iCre (2.16x1011viral particles, temporal vein) and culled at P6. We confirmed the presence of iCre mRNA, and suppression of ErbB4 in ErbB4 ff/ff mice, coincident with increased NRG1a, and reduced body and ventricular weights. By day 28, a number of hearts showed evidence of dilated cardiomyopathy.

Conclusion

Thus, ErbB4 is critical to cardiac hypertrophy and growth in neonatal mice, and maintains adult heart function.

Acknowledgement/Funding

National Health and Medical Research Council
P5000Wnt/b-catenin signalling drives angiotensin II induced cardiac fibrosis via WISP-1
Authors: Connolly G M , Li Z , Young M , Brown B A , Johnson J L , Williams H , George S J
Published: October 2019

Background

Myocardial infarction (MI) and hypertension lead to myocardial injury, which induces negative remodelling and cardiac fibrosis. Cardiac fibrosis, which involves inflammatory cell infiltration and myofibroblast activation, causes worldwide mortality and morbidity. In response to MI or hypertension induced by prolonged angiotensin II (AngII) exposure, activated myofibroblasts produce extracellular matrix proteins. However, if unchecked, excessive collagen deposition occurs leading to myocardial stiffening, heart failure and arrhythmias.

Purpose

The underlying mechanisms leading to pathological collagen deposition are not fully elucidated. There is debate regarding the involvement of the Wnt signalling pathway and its product Wnt Inducible Signalling pathway protein-1 (WISP-1) in cardiac fibrosis. Therefore, this project aimed to investigate the interaction of AngII and the Wnt/β-catenin signalling pathway in cardiac fibrosis.

Methods

The effect of AngII (100nM) on collagen levels in human cardiac fibroblasts was investigated in vitro (data expressed as fold change from control ± SEM). In vivo experiments (n=6–8) determined the involvement of the Wnt/b-catenin pathway, specifically WISP-1, in response to AngII infusion (500ng/kg/min) for 4 weeks (Apolipoprotein E−/−/WISP-1+/+ vs. ApolipoproteinE−/−/WISP-1−/− mice on a high-fat diet, data expressed as mean positive pixel % ± SEM).

Results

AngII significantly increased collagen type 1 protein levels produced by human cardiac fibroblasts (2.94±0.75 vs 1±0, p<0.05). Inhibition of Wnt/b-catenin signalling with 25nM iCRT14 significantly suppressed AngII-induced collagen levels (0.46±0.07 vs. 1±0, p<0.05). As expected, AngII infusion significantly induced hypertension in all mice. Immunohistochemistry demonstrated type 1 collagen was markedly higher in AngII mice than control mice (1.07±0.27 vs. 0.29±0.06, p<0.05). However, in the absence of WISP-1, AngII did not enhance collagen type 1 levels. Further immunohistochemical analysis of murine hearts demonstrated that AngII infusion caused significant alterations in the Wnt/β-catenin signalling markers AXIN-2 (35±3.9 vs. 10.7±2.6 p<0.05) and PPAR-d (92±1.4 vs. 17.3±4.3 p<0.05). This effect was reduced by WISP-1 deletion. Furthermore, AngII-infusion disrupted N-cadherin junctions (0.55±0.08 vs. 0.29±0.02 p<0.05) suggesting modulation of cell-to-cell contacts and enhanced β-catenin signalling.

Conclusion

This study indicates that AngII enhances cardiac fibrosis via modulation of the Wnt signalling pathway, in part via WISP-1. Further delineation of this interaction may lead to the use of Wnt/β-catenin or WISP-1 inhibitors to suppress myocardial injury induced cardiac fibrosis in post-MI or hypertensive patients.

Acknowledgement/Funding

Elizabeth Blackwell Institute, British Heart Foundation
P5241Balancing limited resources, infra-structure deficits & cultural differences in sustaining the growth of LATIN telemedicine program
Authors: Mehta S , Botelho R , Fernandez F , Feres F , Abizaid A , Cade J , Perin M , Prudente M , Cavalcanti R , Dusilek C , Nola F , Pisana L , Safie R , Aboushi H , Lopez C
Published: October 2019

Background

In resource-constrained nations, population-based AMI coverage is daunting. Telemedicine can transform with efficient, cost-effective and scalable programs. We present our data with screening >780,000 patients with innovative hub and spoke strategies.

Purpose

Scientifically pristine protocols, rigorous training, unflinching quality assurance, technology upgrades and education of broad stakeholders are essential attributes for creating population-based AMI programs.

Methods

Latin America Telemedicine Infarct Network (LATIN) required methodical groundwork during a 12-month pilot prior to its formal launch and sustenance for 5 years. It involved scrupulous site selection, technology, and telemedicine optimization and system-wide process metrics. Spokes are the LATIN nucleus and require constant (3-T) training: Triage, Telemedicine, and Transportation. Plus, a mandatory deconstruct of their role in LATIN, of urgent transfer and desist non-critical care. Telemedicine requires constant upgrading of platform, tele-equipment and cloud computing. Ambulance availability is a constant challenge as is the battle with payers. Data entry has required meticulous training and oversight. Strict QA processes have monitored critical metrics: Spokes (Door In Door Out, DIDO and Transport Times); Hubs (Door to Balloon Times, D2B); Telemedicine Platform (Time to Telemedicine Diagnosis, TTD).

Results

Linear growth is observed in the number of sites and telemedicine screenings with simultaneous and sustained improvements in D2B and TTD. 784,395 patients were screened at 350 LATIN centers (Brazil 143, Colombia 118, Mexico 82, Argentina 7). With expanded reach, 8,440 (1.08%) patients were diagnosed and 3,924 (46.5%) urgently reperfused, including 3,048 (77.7%) with PCI. Time to Telemedicine Diagnosis (TTD) was 3 min, tele-accuracy 98.9%, D2B 51 min and in-hospital morality 5.2%. Major reasons for non-treatment were insurance, lack of ICU beds and delayed presentation.

Conclusions

As other regions of the world develop large, population-based AMI management initiatives, LATIN can provide important lessons in the sustainability of these processes.
P5268Prognostic implications of cardiac magnetic resonance in patient with mid range ejection fraction: can we predict worse outcomes?
Authors: Lorente Ros A , Pascual Izco M , Flores M , Hinojar Baydes R , Alonso Salinas G L , Fernandez Mendez M A , Plaza Martin M , Garcia De Vicente A , Del Prado Diaz S , Abellas Sequeiros M , Garcia Martin A , Gonzalez Gomez A , Zamorano Gomez J L , Fernandez-Golfin Loban C
Published: October 2019

Purpose

According to current ESC guidelines, mid-range ejection fraction (mrEF) might represent a separate subgroup of patients with distinct underlying characteristics, prognosis and treatment response. Cardiac magnetic resonance (CMR) is the gold standard for measuring volumes, mass and ejection fraction of the heart. We aimed to find long-term prognostic value of various CMR parameters in patients mrEF.

Methods

137 patients with mrEF underwent CMR (1.5T) between 2012 and 2018 and were consecutively included. Volumes, mass and ejection fraction were assessed using short axis SSFP images and the Simpson method (using commercially available software). Myocardial fibrosis was determined by late gadolinium enhancement (LGE). Clinical parameters after a median of 762 (230–1315 days) were recorded. Patients with other significant cardiac affection rather than mrEF were excluded (pre-capillary pulmonary hypertension and significant valve disease). The primary endpoint was defined as a combined outcome of all-cause death or heart failure decompensation requiring in-hospital admission.

Results

Mean age was 63.0±12.4 years. 76.6% were males. Mean left ventricle ejection fraction (LVEF) was 45±2.69%. Main aetiologies were ischemic (46%), idiopathic (32.12%), myocarditis (9.5%), tachycardiomyopathy (6.57%) enolic (2.2%) stress cardiomyopathy (0.7%) and others (2.9%).

A combined model for predicting outcomes in patients with mrEF using CMR parameters was obtained. This model was able to predict 32.7% (coefficient of determination, R-squared) of the adverse events (p<0.01). Significant CMR parameters and results are shown on table 1.

Combined model for predicting outcomes in patients with mrEF using CMR parameters Variable p value iRVEDV (indexed right ventricular end-diastolic volume) <0.01 RVEF (right ventricle ejection fraction 0.03 iRVESV (indexed right ventricular end-systolic volume) <0.01 Presence of late enhancement (yes/no) 0.09 iLA (indexed left atrial) Volume <0.01 iLV (indexed left ventricle) mass <0.01 Variables and their significance are shown individually.

Conclusions

In patients with mid-range ejection fraction, RV volumes and ejection fraction, as well as LV mass and LA volume, were significant predictors of worse outcomes in a combined model. If supported by further studies, these findings may help the clinician select the patients with higher risk of complications and in need of a closer follow-up.
P5272Right versus Left Ventricular Remodelling after Surgical myectomy for HOCM
Authors: Abdelkhalek M , El Sawy A , Doss R , Samaan A , Donia M , Morais P , Aguib Y , Bogaert J , Elguindy A , Romeih S , Aguib H , Yacoub M
Published: October 2019

Background

Surgical myectomy for (HOCM) results in complex structural and functional changes. “Remodelling” in different cardiac chambers. To date, changes in the Right versus the left Ventricle have not been studied.

Methods

Fourty five patients (mean age = 32±16, 68% males) who underwent extended septal myectomy for LVOTO and Fourty “normal” controls (mean age = 32±12 years, 52% males) were studied by cardiac magnetic resonance imaging (CMR). The patients were studied pre-operatively and 6–18 months post-operatively (median = 9 months). The images were analysed by both commercial and in-house software.

Results

After myectomy. Follow up CMR showed changes in RV mass (21±5 to 23±7) g/m2, volume (60±15 to 66±12) ml/m2 and shape using 3 different methods. RV deformation parameters showed significant changes with circumferential strain (−8±2 to −14±4), filling (38±16 to 62±19) ml/s/m2 and ejection rate (−44±17 to −75±22). Changes in RV were substantially higher than those observed in the LV (Figure. 1, Table. 1). All patients reported significant symptomatic improvement with 31 (78%) patients in NYHA class I and 9 (22%) in class II at follow up. Significant reduction in peak gradient across the LVOT by 75%.

Table 1. Summary of reported parameters related to RV Shape for pre and post operation HOCM patients and Normal Healthy Volunteers LV RV Pre Post Normal P-value Pre Post Normal P-value EDV ml/m2 75±18 81±14 73±10 0.005 60±15 66±12 71±12 0.002 ESV ml/m2 20±9 24±8 26±6 0.008 16±7 19±9 26±7 0.02 SV ml/m2 56±13 57±10 51±13 0.38 44±11 48±10 49±14 0.009 EF 74±7 70±7 65±5 0.001 74±8 72±7 64±6 0.228 Mass g/m2 74±33 62±29 27±8 0.0456 21±5 23±7 18±5 0.2100 PFR ml/m2 173±48 141±48 141±40 <0.0001 38±16 62±19 55±24 <0.0001 PER ml/m2 −179±35 −172±42 −144±42 0.29 −44±17 −75±22 −57±22 <0.0001 Peak Strain −20±3 −20±3 −20±3 0.49 −8±2 −14±4 −12±3 <0.0001

Conclusion

LV septal myectomy is followed by structural and functional remodelling which is more extensive in the right than the left ventricle. The clinical significance of these findings needs further study.
P5281Synthetic extracellular volume quantification by cardiac magnetic resonance imaging - a reliable tool in clinical practice?
Authors: Unbehaun C , Nunn S , Vietheer J , Wolter J S , Zipse L , Kriechbaum S , Weferling M , Fischer-Rasokat U , Keller T , Liebetrau C , Hamm C W , Rolf A
Published: October 2019

Background

Extracellular volume (ECV) quantification by CMR imaging allows the measurement of changes in the extracellular space indicating diffuse edema and fibrosis, especially in early stages of myocardial disease. Usually venous hematocrit (Hct) is needed in order to calculate standard ECV. Recent findings suggest the alternative use of the blood pool T1-relaxation time (T1blood) instead of the venous Hct to generate “synthetic Hct ” and furthermore “synthetic ECV”, allowing a more routine and user-friendly application without the need of a current blood sample.

Purpose

Purpose of this study is to re-evaluate whether the connection between venous Hct and T1blood can be used to generate a synthetic ECV in a large number of volunteers and patients with various myocardial diseases from a tertiary care centre.

Methods

945 volunteers and patients were divided into a derivation (n=490) and a validation group (n=455). Standard ECV was calculated using T1-relaxtion times acquisitioned in the septal myocardium and blood pool, each on pre- and post-contrast Images using a modified look-locker sequence at a 3 Tesla MR-scanner. In addition venous Hct was measured in a blood sample drawn prior to the scan. Synthetic Hct was derived through linear regression analysis between venous Hct and 1/T1blood and was then compared to venous Hct. Also we derived standard ECV and synthetic ECV and examined these using Lin's rho and Bland-Altman comparison.

Results

In the derivation group venous Hct and 1/T1blood showed a linear relationship (R2=0,22; p=ehz746.02521). This was used to calculate synthetic Hct and synthetic ECV. Synthetic ECV correlated well with standard ECV (Lin's rho= 0,903; p<0,0001). Mean difference 0,004, limits of agreement −0,038 and 0,047. See table 1 for patient characteristics and figure 1 for Bland-Altman plot on standard and synthetic ECV.

Table 1. Patient characteristics Sex female (%) 312 (33%) Age, yrs 60±15 EDVi, ml/m2 86±31 ESVi, ml/m2 43±30 LVEF, % 54±16 Hematocrit, % 43±5

Figure 1

Conclusion

Despite only weak correlation of synthetic and venous Hct we found excellent correlation in synthetic and standard ECV. Therefore we could confirm the value of synthetic ECV in a large cohort of volunteers and patients, providing a feasible and non-invasive marker for extracellular myocardial alterations in everyday clinical practice.
P5300Study of b2-adrenergic receptor (ADRB2) gene polymorphism in patients with coronary artery disease and obesity
Authors: Zaletova T , Bogdanov A , Derbeneva S , Nesterova V , Shevtchenko I
Published: October 2019

Introduction

B2-adrenoreceptors participate in mobilizing fat from fat cells to enable energy production in response to hormones (adrenaline, noradrenaline); they stimulate glycogenolysis in the liver and glucose release into the circulation to replenish energy needs; and enhance glycogen breakdown in skeletal muscles. Glu27 allele is associated with an increased risk of obesity when the diet is rich in carbohydrates. In the 27Glu variant the production of adrenoreceptors is increased, thus increasing sensitivity to beta-agonists; hyperinsulinemia and hypertriglyceridemia can be also observed. In 27Gln variant, on the contrary, beta-agonists production and sensitivity to them are reduced, and increased production and insulin resistance are likely to affect patients with normal body weight.

Objective

To search for molecular and genetic predictors of metabolic disorders (a combination of protein hypercatabolism (high protein oxidation rate (POR) and decreased oxidation of carbohydrates (low carbohydrate oxidation rate (COR), identified with respiratory indirect calorimetry in the previous studies.

Methods

The study involved 182 patients with multivessel coronary artery disease and clinical features of coronary artery disease (CAD), requiring surgical myocardial revascularization, and a body mass index of 35.0–50.0 kg/m2. The average age was 59.6±3.5 years old. Frequencies of allele and genotype polymorphism in ADRB2 (27Glu) were analyzed.

Multiplicative mode of inheritance “MD−” “MD+” χ2 P OR value 95% Cl ADRB2(27Glu)   Allele C 0.60 0.885 3.56 0.03 0.21 0.05–1.10   AlleleG 0.40 0.115 4.11 0.91–18.76   Genotype C/C 0.40 0.77 3.44 0.03 0.22 0.03–1.22   Genotype C/G 0.50 0.23 3.13 0.56–19.95   GenotypeG/G 0.10 0.00 4.27 0.16–116.34 MD: metabolic disorders (↑POR+↓COR).

Results

Our results showed that metabolic changes in obesity may be associated with ADRB2 gene mutation, namely when 27Glu variant is present. Thus, the odds ratio for developing metabolic disorders with G allele was 3.44 times higher (p=0.02, CI (95%) = 1.24 - 19.46), and in patients with genotype G/G - 4.27 times higher (p=0.03, CI (95%) = 15.6 - 199.5).

Acknowledgement/Funding

Research No. 0529-2019-0061 Diagnostics, prevention and dietaterapy of patients with alimentary-dependent diseases
P5312Sleep duration and carotid atheromatic burden. Insights from the Corinthia study
Authors: Oikonomou E , Tsalamandris S , Vogiatzi G , Lazaros G , Christoforatou E , Chasikidis C , Mistakidi C V , Galiatsatos N , Asimakopoulou M , Papamikroulis G A , Zacharia E , Anastasiou M , Mavrantzas T , Papakonstantinou M , Tousoulis D
Published: October 2019

Background

Sleep is an essential physiological process and disturbance of sleeping pattern may be associated with cardiovascular risk profile and atheromatosis. Short but also long sleep duration (LSD) may be adversely affect cardiovascular parameters.

Purpose

To study how sleep duration is associated with cardiovascular risk profile and carotid atherosclerotic burden.

Methods

Corinthia study is a cross sectional epidemiological study based on 2043 inhabitants (age 40–99 years) of Corinthia region in Greece. Ultrasonography was used to measure intima media thickness (IMT) in the left and right common carotid artery, carotid bulb and internal carotid artery. The mean IMT (meanIMT) were determined as representative values of carotid atherosclerosis burden. Thickness of IMT>1.5 mm or protrusion >50% compared to adjacent segments was considered as atherosclerotic plaque. Based on questionnaires of Corinthia study, total sleeping time per day was recorded. A sleep duration of 7 to 8 h was consider normal (NSD), sleep duration <6 h was consider very short (VSSD), 6–7 h sleep duration was considered short (SSD) and participants with >8 h sleep duration was categorized as LSD.

Results

Concerning gender more men than women were categorized in the NSD (26% vs. 21%, p<0.001). Subjects in the NSD were also younger compared to subjects categorized in other sleeping patterns (VSSD: 66±12 y vs. SSD: 63±12 y vs. NSD: 62±12 y vs. LSD: 66±12 y, p<0.001), have less prevalence of diabetes mellitus (p<0.05). There was no difference according to sleeping pattern in body mass index, prevalence of hypertension, cardiovascular disease, hyperlipidemia and on current smoking habits according to sleeping patterns. Interestingly, meanIMT (VSSD: 1.08±0.51 mm vs. SSD: 0.97±0.42 mm vs. NSD: 0.97±0.41 mm vs. LSD: 1.14±1.64 mm, p=0.04) and carotid atherosclerotic plaque (VSSD: 35% vs. SSD: 25% vs. NSD: 20% vs. LSD: 30%, p=0.006) was decreased in NSD subjects. Importantly, even after adjustment for the confounders logistic regression analysis revealed that subjects in the NSD group have 50% less odds of carotid atheromatic plaque than subjects in the VSSD (Odds ratio: 0.5, 95% CI 0.28–0.90, p=0.02) (Figure).

Conclusion

A balanced sleeping pattern with 8h of sleep daily can act as an additive cardioprotective factor in the modern western type societies. Short especially less than 6 hours and long (>8 hours) sleeping duration may act as a cardiovascular risk factor.
P5321The association of Lp(a) levels and cardiovascular disease in adult patients with familial hypercholesterolemia: analysis from the HELLAS-FH registry
Authors: Liberopoulos E , Rizos C , Skoumas I , Tziomalos K , Rallidis L , Kotsis V , Athyros V , Skalides E , Kolovou G , Garoufi A , Koutagiar I , Papagianni M , Kiouri E , Antza C , Elisaf M
Published: October 2019

Introduction

Familial hypercholesterolemia (FH) as well as elevated Lp(a) levels are both associated with increased cardiovascular disease (CVD) risk. There are limited data on the association of Lp(a) levels with CVD in FH Patients.

Purpose

To evaluate the association between Lp(a) levels and CVD in adult FH patients included in the HELLAS-FH registry in Greece.

Methods

Adult patients with FH and measured Lp(a) levels were included in this analysis. Demographics, CVD prevalence and lipid profile were evaluated.

Results

A total of 337 patients were evaluated (46% male, 48.3±15.4 years old). The median [IQR] of Lp(a) at baseline was 22.6 (9.7–56.2) mg/dL. Patients were categorized into 4 different groups according to the Lp(a) levels quartiles. There was no gender or age difference between the 4 groups. Moreover, all groups had similar smoking status, hypertension, body mass index and type 2 diabetes prevalence. There was no significant difference between groups regarding baseline and on treatment lipid profile. We observed a significant positive association between Lp(a) quartile and coronary artery disease (CAD) prevalence (p=0.004). Patients in the highest vs lowest quartile had greater CAD prevalence (21.7% vs 7%, p=0.006). No association was observed between Lp(a) quartile and the prevalence of cerebrovascular disease or peripheral artery disease.

Conclusions

Elevated Lp(a) levels have a positive correlation with CAD in patients with FH.
P5331Aspirin use for prevention of cardiovascular events in patients with high lipoprotein(a): a population-based study
Authors: Karrthik A , Gad M , Bazarbashi N , Ahuja K , Sammour Y , Kaur M , Ahmed H , Kapadia S
Published: October 2019

Background

High lipoprotein(a) [Lp(a)] levels have been shown to increase Myocardial Infarction (MI) and all-cause mortality. However, studies evaluating the optimal preventive measures for that subset of cardiac patients are scarce. This study aims to study the outcomes of aspirin use versus no aspirin for the prevention of all-cause mortality and myocardial infarction in patients with high Lp(a) levels.

Purpose

We sought to determine the effect of Aspirin in reducing the rate of MI and all-cause mortality among patients with high lipoprotein(a) [Lp(a) ≥50mg/dL]

Methods

Patients who attended the preventive cardiology clinic from 2005 to 2016 and included in the Preventive Cardiology Database were included in the current single-center, retrospective, observational cohort study that was conducted according to the guidelines of the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology Statement) checklist. The primary outcome was the incidence of myocardial infarction and the secondary outcome was all-cause mortality. Patients were excluded in cases of I) Lp(a)a <50mg/dL, II) history of malignancy, or III) being on anticoagulation/ dual antiplatelet therapy. The median duration of follow-up was 92 months from time of Lp(a) measurement to the last follow-up. Continuous variables were expressed as means ± standard deviation or median (IQR), and categorical variables were expressed as percentages (%). All statistical tests were two-sided. A propensity score-matched analysis was performed with 1:1 nearest match for Age, Gender, Race, Smoking status, BMI, Diabetes, Peripheral artery disease, Carotid artery disease, coronary artery disease, chronic kidney disease, Heart failure, Hypertension, Dyslipidemia, Stroke, family history of coronary artery disease, Lp (a), LDL, HDL, Triglycerides, glucose and total cholesterol.

Results

1,805 patients fulfilled the inclusion and exclusion criteria out of 7,410 patients initially identified with recorded Lp(a) levels in the Preventive Cardiology Database. Of these, 376 patients were taking aspirin, and 1429 patients were not receiving aspirin. After propensity score matching for different baseline characteristics and comorbidities as mentioned above, 316 patients were matched in each group. Patients who were on Aspirin had a significantly lower rate of MI events compared to patients who were not on aspirin (6.96% vs 12.02%, P=0.03) and a lower rate, however statistically non-significant, of all-cause mortality (2.84% vs 4.11%, P=0.385).

Conclusion

The use of aspirin in patients with elevated Lp(a) levels significantly lowers the rate of myocardial infarction events. Larger randomized clinical trials are warranted to evaluate the use of aspirin for primary and secondary prevention of major adverse cardiovascular events in patients with high Lp(a) levels.
P5336Waist:Hip ratio (WHR): a better predictor of cardiovascular risk (CVR) than BMI in people living with HIV
Authors: Manmathan G P R , Little C , Kotecha T , Ngwu N , Hunter A , Kinloch S , Burns F , Johson M A , Rakhit R D
Published: October 2019

Introduction

Antiretroviral therapy (ART) has dramatically reduced morbidity and mortality among people living with HIV (PLWH), including wasting syndrome. Metabolic and cardiovascular diseases are leading causes of death for PLWH in high-income countries.

Obesity is increasing in the HIV population but a lack of data exists in PLWH, and the association with cardiovascular risk. The aim to determine if central obesity (measured using waist to hip ratio) is a better predictor of CV risk than Body Mass Index (BMI) which is the current standard to define obesity in PLWH.

Methods

Single centre, prospective study performed in a large metropolitan HIV unit. 129 PLWH had weight, height, waist and hip circumference, and blood pressure (BP) recorded. Data on sex, age, ethnicity, past medical history including CV risk factors and kidney disease, smoking status and postcode was used to calculate waist to hip ratio (W/H), BMI and Q-Risk2.

Results

The study population included 30 (23%) women and 98 (77%) men; 76 (59%) Caucasian, 38 (30%) black African/Caribbean and 14 (11%) were other ethnicity. In total, 43 (34%) were overweight and 31 (24%) obese using BMI measurement, this changed to 25 (20%) and 39 (30%) when using WHR.

Q-Risk2 demonstrated that 82 PLWH (64%) had mild risk, 25 (20%) moderate, and 21 (16%) were high cardiovascular risk (excluding HIV as a risk factor).

There was significant correlation between WHR and Q-Risk2 (r=0.44, p<0.01,graph A) but not between BMI and Q-Risk2 (r=0.13, p=0.15, graph B). ROC analysis demonstrates that WHR is able to predict Q-Risk2 (AUC 0.74, 95% CI 0.66–0.82, p<0.01) with a cut-off of 0.98 having 67% sensitivity and 81% for predicting Q-Risk2 >20 (high risk). WHR performed significantly better than BMI (AUC 0.58, 95% CI 0.49–0.67, p=0.24) at predicting Q-Risk2 (p=0.02 for difference, graph C).

W/H ratio and BMI against Q-Risk 2

Conclusion

Temporal change in waist circumference can indicate change in abdominal fat, with increased abdominal fat being associated with increased CV risk. WHR is superior to BMI at predicting high risk (Q-Risk >20%). It should be included as part of routine clinical assessment and lifestyle intervention implemented to reduce CV risk in PLWH.
P5339Association between high-sensitive troponin I and subclinical coronary atherosclerosis in well-controlled HIV-infected adults
Authors: Vassara M , Siwamogsatham S , Buddhari W , Tumkosit M , Ketloy C , Apornpong T , Boonyaratavej S , Avihingsanon A , Chattranukulchai P
Published: October 2019

Background and objectives

Patients with human immunodeficiency virus (HIV) infection live longer and the prevalence of coronary heart disease is increasing among them. High-sensitive troponin I (hs-TnI) is associated with coronary artery calcification as determined by non-contrast cardiac computed tomography (CT) in general population without established cardiovascular disease (CVD). Nevertheless, the relationship in well-controlled HIV-infected patients has not been validated.

Design and methods

A cross-sectional study among HIV-infected adults aged >50 years free from known CVDs. All subjects underwent non-contrast cardiac CT and blood test for serum hs-TnI was concomitantly performed. Relationship between Agatston score, a parameter used to quantify coronary artery calcification and serum hs-TnI level was analysed using spearman correlation and logistic regression models.

Results

A total of 338 HIV-infected adults (median age 54 years, 62% men) were included. All of them were in antiretroviral therapy with a median 18 years of exposure. The median CD4 cell count was 614 cell/mm3, 98% were virologically suppressed. Hs-TnI was correlated with coronary artery calcification with the correlation coefficient of 0.287 (p<0.0001). Multivariated logistic regression analysis demonstrated that serum hs-TnI concentration was associated with an increased odd of coronary artery calcification (Agatston score>0) (OR 1.64; 95% CI, 1.05–2.56, p=0.029). To detect coronary artery calcification, using the hs-TnI in addition to Thai CV risk score slightly increased the ROCAUC from 0.6827 to 0.692 (p=0.45).

Distribution of CAC score over hs-TnI

Conclusion

Among well-controlled HIV-infected patients without established CVDs, hs-TnI concentration was associated with coronary artery calcification. This could be a potential biomarker for an early risk stratification of subclinical coronary atherosclerosis in this population. The association with long-term adverse cardiovascular outcome needs to be validated in the future study.
P5348Aspirin versus clopidogrel treatment for refractory migraine with patent foramen oval
Authors: Toomsoo T
Published: October 2019

Background

The association between migraine with aura (MA+) and persistent foramen ovale (PFO), as well as other right-to-left shunts, is described. Observational studies suggested that when a PFO is closed patients who have MA+ are usually improved. Many observational studies have shown that when PFOs are closed in patients who have had a stroke the patients have a high prevalence of migraine before the procedure and ∼80% report that their migraine symptoms were improved after the closure procedure. Migraine with aura is also improved by medical treatment (aspirin, clopidogrel).

Purpose

To investigate the MA+ reduction effect with the aspirin or clopidogrel in 90 with MA+ with PFO.

Methods

MA+ patients were screened for PFO by transcranial sonography and echocardiography. Participants with documented right to left shunt (RLS) and ≥12 monthly MA+ days received aspirin or clopidogrel therapy for 60 days. Those with ≥50% reduction in monthly MA+ days were deemed responders and completed 10 additional treatment months.

Results

The 90 participants had a mean age of 33.2 years and mean MA+ frequency of 16.4 d/mo. A total of 57/80 were female. A total of 66/80 met criteria for episodic MA+, 14/80 for chronic MA+, 59/80 had a moderate–large RLS. 38 of 80 participants (47%) were responders. MA+ reduction continued through 10 treatment months in all responders. MA+ responder rates were not statistically different in participants with episodic or chronic MA+ or with small/larger RLS shunt magnitude, treatment with aspirin or with clopidogrel. All three (8%) patients had aspirin side effects, without serious adverse events.

Conclusion

Both medications reduced MA +symptoms and participants seemed to have less MA+ and only small amount had side effects with aspirin.

Acknowledgement/Funding

None