bluuebunny/crossref_metadata_2025 huggingface dataset:
P5280The impact of background phase offset errors in cardiovascular magnetic resonance phase contrast imaging: a multi-scanner study
Authors: Minderhoud S C S , Van Der Velde N , Wentzel J J , Attrach M , Wielopolski P A , Budde R P J , Helbing W A , Roos-Hesselink J W , Hirsch A
Published: October 2019

Background

Phase contrast (PC) CMR flow measurements (FM) are widely used for blood flow assessment, but they suffer from phase offset errors (POE). Stationary phantom correction limits these inaccuracies, however, this adds scan time. Stationary tissue (ST) correction is an alternative method that does not require additional scanning. The aim of this study was to evaluate the impact of POE, to assess interscanner variation, and to evaluate the ST correction usage.

Methods

We included 166 patients in which both aorta and main pulmonary artery FM were acquired including static gelatin phantom data. Subjects were scanned on three types of 1.5T scanners from the one vendor. Uncorrected and ST corrected FM were compared with phantom corrected FM, our reference value, and corrected for BSA. A difference of >10% in net flow was defined as clinically relevant. Regurgitation fraction was calculated and POE influences were assessed. Regurgitation severity was graded and POE influence on severity grading was assessed.

Results

Of the 166 cases included, the median age was 27 (5–74) years. Overall, the median difference between no corrected and phantom corrected FM was ≤6%, however, with a wide range of over- and underestimation (−155%–78% change) (figure). ST correction resulted in larger differences compared to no correction (p<0.01). Clinically significant differences were seen in 19% of all FM with no correction and in 30% of with ST correction (p<0.01). Furthermore, there were significant differences between scanners (no correction 10%, p<0.01; ST correction, p<0.01). Regurgitation severity indexing changed in 38 (11%) cases with no correction and in 48 (48%) with ST correction.

Magnitude of flow change with and without offset corrections (n=332) Flow (ml/m2) Δ no correction and phantom correction (%) Δ ST correction and phantom correction (%) Clinically significant difference (>10%) Mean ± SD Median IQR Range Median IQR Range No correction, N (%) ST correction , N (%) MRI 1 (n=126) 50±12 3 0 to 6 −8 to 30 5 −3 to 9 −26 to 28 13 (10%) 34 (27%) MRI 2 (n=102) 48±13 −2 −15 to 6 −155 to 78 5 −3 to 11 −74 to 52 50 (49%) 50 (49%) MRI 3 (n=104) 48±12 −1 −1 to 0 −7 to 14 2 −2 to 5 −39 to 29 1 (1%) 16 (15%) Total (n=332) 49±12 0 −2 to 4 −155 to 78 3 −2 to 8 −74 to 52 64 (19%) 100 (30%)

Conclusion

Background POE have a significant impact on flow quantification and regurgitation severity. Unexpectedly, background correction using ST correction worsens accuracy compared to no correction. POE vary greatly between scanners. Therefore, careful assessment of FM at each scanner is essential to determine if routine phantom scanning is necessary.
P5305Oxidized high-density lipoprotein is associated with progression of coronary artery calcification
Authors: Miki T , Miyoshi T , Kotani K , Kohno K , Asonuma H , Sakuragi S , Koyama Y , Nakamura K , Ito H
Published: October 2019

Introduction

As a residual cardiovascular risk, high-density lipoprotein (HDL) is of great interest in lipid management. Native HDL has an anti-atherogenic role, while oxidized HDL (oxHDL) has atherogenic property because of reduced anti-inflammatory properties compared with native HDL. Meanwhile, recent studies showed that rapid progression of coronary artery calcification (CAC), a marker of subclinical atherosclerosis, was associated with greater incidence of cardiovascular events. However, the role of oxHDL in the pathogenesis of CAC remains unclear.

Purpose

The purpose of this study was to examine the association between the annual change in oxHDL and the progression of CAC (Agatston score) in a substudy of prospective multicenter randomized study.

Methods

In the principal study, patients with a CAC score of 1 to 999 were treated with pitavastatin with/without eicosapentaenoic acid. Measurement of CAC with MDCT and a blood test were performed at baseline and at the 1-year follow-up. The principal study showed 30–40% of annual change in CAC in all patients and no difference in the progression of CAC among treatment groups. In this substudy (n=140), patients were divided into 2 groups: CAC progression (change in Agatston score of >0, n=103) and no CAC progression (n=37). The serum concentration of oxHDL was measured using an antibody against oxidized human apoA-I with ELISA. The difference in oxHDL between patients with hypercholesterolemia and healthy subjects (n=30) was also evaluated.

Results

OxHDL levels were significantly lower in healthy subjects than in patients with hypercholesterolemia (150 [107–176] and 167 [132–246], respectively; median [25th-75th percentile], U/ml) (p=0.006). The baseline log-transformed oxHDL level was correlated with total cholesterol (r=0.21, p=0.01), HDL-cholesterol (r=0.33, p<0.01), and triglycerides (r=−0.21, p=0.01), but not correlated with age, body mass index, hemoglobinA1c, LDL-cholesterol, serum creatinine, or high-sensitivity C-reactive protein. After treatment, the oxHDL level significantly decreased from 167 (132–246) at baseline to 122 (103–149) (median [25th–75th percentile], U/ml) (p<0.001). The annual change in CAC was significantly positively associated with changes in oxHDL (r=0.17, p=0.04), triglycerides (r=0.17, p=0.04), and hsCRP (r=0.22, p=0.01) but not associated with changes in LDL-C or HDL-C. Multiple logistic analysis demonstrated that the decrease in oxHDL per 10 U/ml was independently associated with CAC progression after adjusting for variables including baseline oxHDL, LDL-cholesterol, Agatston score and current smoking (odds ratio, 0.95; 95% confidence interval, 0.90–0.99; p=0.04).

Conclusion

The decrease in oxHDL is associated with the attenuation of CAC progression, suggesting that oxHDL is a potential target for preventing atherosclerosis.
P5334A 15-year follow-up of 315 patients with familial hypercholesterolemia from the North-West region of Russia
Authors: Konstantinov V , Kuznetsova T , Korneva V , Serebrenitskaya M
Published: October 2019

Familial hypercholesterolemia (FH) is one of the most common inherited diseases that lead to premature atherosclerosis and coronary heart disease (CHD).

Aim of the study

to ascertain genetic and environmental factors influencing the time course of FH during a 15-year follow-up in a large FH cohort from the North-West region of Russia.

We screened more than 1ehz746.0302 high risk patients in order to reveal FH in Saint-Petersburg and Petrozavodsk using DLCN criteria. In most patients DNA analysis was also performed.

Definite FH (≥8 according to DLCN) was found in 315 patients (221 - in Saint-Petersburg, 94 - in Petrozavodsk). These patients were followed-up for 15 years and more. CHD was more frequent in male patients, patients older than 60 years of age and was associated with higher levels of total cholesterol, LDL cholesterol, lower levels of HDL cholesterol, arterial hypertension, smoking and higher DLCN scoring. Patients without CHD had lowest LDL/HDL ratio (5.2±0.45) whereas patients with stable and progressive CHD had LDL/HDL ratio - 7.7±0.89 and 10.4±0.78, respectively (p≤0.05). Genetic study revealed only 1 homozygous patient and 1 patient with apoB-100 (FDP) gene mutation. Only 1 case of FH-North Karelia mutation that is typical for Finland was found in Petrozavodsk. Most of revealed mutations in LDL-receptor gene were unique i.e. found only in 1 family. This suggest the absence of a strong founder effect associated with FH in the North-West Region of Russia. Due to high heterogeneity of FH-causing mutations we failed to establish interrelations between type of LDL-receptor gene mutations and severity of atherosclerosis and CHD time course. 14% of FH patients didn't take any hypolipidemic medications at the onset of the follow-up, whereas 61% took statins and 25% statin + ezetimibe. Homozygous patient was treated both with statin, ezetimibe, evolocumab and LDL-apheresis. Nevertheless, 26% of the treated group didn't achieve the target LDL-C levels. It is interesting that 40% of patients who didn't reach LDL-goals were current smokers (compared with 5% of patients who reached LDL-goals). 33 patients (10.5%) died during the follow-up mostly due to cardiovascular complications. Death rates in FH patients were strongly associated with age, male sex, LDL/HDL ratio, smoking and effectiveness of hypolipidemic treatment. FH is strongly associated with high CHD risk; the time course of FH is much more favourable in females, in patients with low LDL/HDL ratio and free of other modifiable risk factors. Type of LDL-receptor gene mutation doesn't influence lipid levels or clinical manifestations of FH.
P5343The presence of anti-apolipoprotein A1 autoantibodies is associated with a pro-atherogenic profile in HIV-infected patients
Authors: Frias M , Pagano S , Fetaud-Lapierre V , Lecour S , Kamau F , Strijdom H , Vuilleumier N
Published: October 2019

Background

With the access to antiretroviral therapy (ART), the mortality related to the human immunodeficiency virus (HIV) has dropped, shifting the clinical challenges towards chronic disease management, including cardiovascular disease (CVD) risk assessment. Factors that potentially contribute to the physiopathology of HIV-related CVD include the HI-virus itself, adverse effects of ART, and processes such as dyslipidemia, inflammation, immune/autoimmune activation and endothelial injury. Among autoantibodies of possible cardiovascular relevance, those directed against apolipoprotein A-1 (anti-apoA-1 IgG) were shown to predict major adverse cardiovascular events and promote atherogenesis.

Purpose

The aim of the study was to evaluate the prevalence of anti-apoA1 IgG in HIV-free and ART experienced and naïve HIV-infected patients as well as the association between anti-apoA1 IgG levels and, indices of viral suppression, clinical parameters (10 year Framingham Risk Score (FRS)) and inflammatory biomarkers, known to underlie atherosclerosis burden in these patients.

Methods

Anti-apoA1 IgG serum levels were assessed by a homemade ELISA assay in 144 participants from a South African cohort divided in three groups: HIV-free (n=50), HIV-infected/ART experienced (n=50) and HIV-infected/ART naïve (n=44). Inflammatory biomarkers were measured.

Results

HIV-infected patients displayed an increased pro-atherogenic biomarker profile compared to HIV-free subjects, but not difference in the FRS was observed between these two groups. Regarding anti-apoA1 IgG, 24% of HIV-free patients tested positive compared to 40% and 70% in HIV-infected/ART experienced and naïve groups, respectively. HIV-infected, anti-apoA1 IgG positive patients showed a significant decrease in CD4+ counts (p=0.003) and a significant increase in viremia (p=0.0130), mean heart rate (p=0.0243), albuminuria (p=0.0155), pro-inflammatory biomarkers (IFNγ, IL-10, TNFα, MIPα; all p<0.05), circulating levels of intercellular adhesion molecule (ICAM-1) (p=0.0217) and vascular cell adhesion molecule (VCAM-1) (p=0.003) compared to anti-apoA1 IgG negative ones. Of note, while this profile was maintained in HIV-infected/ART experienced, these significant differences were lost in HIV-infected/ART naïve patients. No significant difference in FRS was observed between anti-apoA1 IgG positive vs negative individuals in all groups.

Conclusions

HIV-infected patients presented with an increased prevalence of anti-apoA1 IgG compared to HIV-free subjects. In HIV-infected/ART experienced patients, anti-apoA1 IgG levels were associated with low CD4+ counts, levels of adhesion molecules and pro-inflammatory responses, features associated with increased cardiovascular events. ART highlighted pro-atherogenic differences between HIV-infected anti-apoA1 IgG negative and positive patients.
P5368The prevalence and management of familial hypercholesterolemia in patients with acute coronary syndrome in Poland: results of the TERCET registry
Authors: Dyrbus K , Gasior M , Desperak P , Nowak J , Osadnik T , Banach M
Published: October 2019

Background

Prevalence of familial hypercholesterolemia (FH) is high among patients with coronary artery disease (CAD). However, data on FH among patients with acute coronary syndrome (ACS) are still scarce.

Purpose

Therefore, we aimed to assess the prevalence, lipid-lowering therapy and short- and long-term outcomes in patients with FH among patients with ACS.

Methods

We finally included 19,582 consecutive patients from the Hyperlipidaemia Therapy in the tERtiary Cardiological cEnTer (TERCET) Registry for years 2006–2018. Among them, there were 7,319 patients admitted with ACS: 3,085 due to ST-segment elevation acute coronary syndrome (STEMI), 2,256 due to NSTEMI, and 1,978 due to unstable angina (UA). Stable CAD [sCAD] group n=12,462 that was treated as a reference one. Based on the personal and familial history of premature cardiovascular disease and low-density lipoprotein cholesterol (LDL-C) concentration, the Dutch Lipid Clinic Network (DLCN) algorithm was used for FH diagnosis.

Results

At the time of hospitalization, the overall occurrence of probable/definite FH and possible FH were 1.2% and 13.5% respectively. In patients with ACS, 1.6% had probable/definite FH and 17.0% possible FH. The highest occurrence of FH was observed in STEMI subgroup, where 20.6% of the patients had ≥3 points according to the DLCN criteria. There were significant differences in hypolipemic treatment between the FH subpopulations. In patients with definite/probable FH 92.3% and 91.5% were administered statins at discharge, respectively (including 52.9% prescribed intensive statin therapy). Patients with definite and probable FH had higher 30-day mortality than patients without FH (8.2% and 3.8% vs 2.0%, respectively; p=0.0052). However, no significant differences were observed between the FH groups in the 12-, 36- and 60-month follow-up (Figure). Propensity-score matching analysis showed that definite/probable FH patients had significantly higher all-cause mortality at the 36- and 60-month follow-up in comparison to non-FH subjects (11.4% vs 4.8% and 19.2% vs 7.2%, respectively; p≤0.021 for both).

Outcomes depending on DCLN FH diagnosis.

Conclusions

The prevalence of FH according to the DLCN criteria in the Polish very high-risk population is even 14.7% and is significantly higher in patients with ACS than in patients with sCAD. Among patients included in the Registry, the occurrence of FH rises to 20.6% in the STEMI subgroup, and to 17.2% in the NSTEMI subgroup. Propensity-score matching analysis confirmed that FH itself is a cause of increased all-cause mortality in the long-term follow-up.

Acknowledgement/Funding

None
P5387CRISPR/dCas9 Activated Expression of Cardiomyocyte Differentiation Factors in CDCs in Myocardial Infarctions
Authors: Sano T , Ishigami S , Bandaru S , Ito T , Sano S
Published: October 2019

Background

Existing therapies against myocardial infarction (MI) involve disease management by preventing additional damage to the heart muscle. However, new treatment strategies are in greater demand, which deems to focus on restoring cardiac function by replacing the damaged cells after MI, rather than merely manage the disease. Cardiosphere-derived cells (CDCs) have emerged as a potential source of cardiac regenerative therapy. In spite of being a promising option, the poor differentiation potential of CDCs to develop into a functional population of cardiomyocytes has always been a significant setback.

Purpose

The purpose of the present study centers to overcome the aforementioned setback by enhancing the efficiency of rat CDCs to develop into a large population of cardiomyocytes by intrinsic activation of cardio-specific differentiation factors (TNNT2, GATA4, Mef2c) by Crispr/dcas9 assisted transcriptional enhancement system.

Methods

In the foremost step, an exhaustive screening was performed to identify the specific sequences in endogenous regulatory regions (enhancers and promoters) responsible for transcriptional activation of the TNNT2 gene. Once, potential regulatory regions at proximal and distal end of TNNT2 were identified, crRNAs were designed complementing these regions for recruiting Crispr/dcas9 system fused with transcriptional activator like VP64 (CRISPR-dCas9-VP64). Two distinct plasmids were constructed with crRNA (RFP fused) inserts and CRISPR-dCas9-VP64 (GFP fused) followed by transfection in CDCs those isolated from the heart of a neonatal rat. Post transfection, CDCs were then analyzed for the quantitative expression of cardiomyocyte differentiation factors as well as for fibroblast differentiation factors in comparison with un-transfected CDCs.

Results

We identified a panel of specific crRNA targeting the enhancers and promoters which demonstrated significantly higher expression of differentiation factors like troponin, GATA4, and Mef2c. Further, the fluorescent visualization with GFP and RFP was prominent in the CDCs confirming that these panel of crRNA enhanced the expression of differentiation factors compared to the un-transfected counterparts. Interestingly, the same panel crRNA, in contrast, demonstrated diminished expression of fibroblast differentiation factors like Col1A1, clearly emphasizing that the CRISPR dCas9 system recruitment at regulatory regions forms an efficient molecular targeting system for enhancing the differentiation potential of CDCs into cardiomyocytes.

Conclusion

We have identified endogenous regulatory regions responsible for an intrinsic activation of cardio-specific differentiation factors assisted by Crispr/dcas9 gene transcriptional system. We anticipate the method developed herein can enhance and cardiomyogenic efficiency of CDCs to differentiate into a large population of cardiomyocytes to treat Ischemic heart diseases.
P5399microRNA-486 mediates exercise-induced cardiac growth and prevents cardiac ischemia-reperfusion injury
Authors: Bei Y , Lu D , Meng X , Zhu Y , Liang X , Xiao J
Published: October 2019

Background

Molecules mediating exercise-induced physiological cardiac growth may be beneficial to prevent cardiac injury and remodeling. MicroRNA-486 (miR-486) is a muscle-enriched microRNA which was found to be increased in exercised heart. However, the role of miR-486 in exercise-induced cardiac growth is largely unknown.

Purpose

We aimed to study the function of miR-486 in exercise-induced cardiac growth, and to investigate its potential role in protection against cardiac ischemia/reperfusion (I/R) injury.

Methods

Male C57BL/6 adult mice were subjected to 3-week swimming exercise to induce physiological cardiac growth. Knockdown of miR-486 was performed by intramyocardial injection of miR-486 sponge to evaluate the role of miR-486 in exercise-induced cardiac growth. Moreover, intramyocardial injection of miR-486 overexpression lentivirus was performed to investigate whether miR-486 could reduce infarct size in mice suffered from acute I/R injury (30 min ligation and 24 hr reperfusion of left anterior descending coronary artery). Meanwhile, the functional role of miR-486 was evaluated in neonatal rat cardiomyocytes (NRCMs) treated with oxygen glucose deprivation/reperfusion (OGDR) using Tunel staining. Finally, function-rescue assays were performed to identify target genes of miR-486.

Results

Exercise significantly upregulated miR-486 in the heart, which was reduced by intramyocardial injection of miR-486 sponge. Exercise induced-cardiac growth was abolished in mice with intramyocardial injection of miR-486 sponge, as evidenced by reduced heart weight/body weight ratio and heart weight/tibia length ratio compared to control exercised-mice, suggesting a potential role of miR-486 in mediating exercise-induced cardiac growth. Meanwhile, we found that intramyocardial injection of miR-486 overexpression lentivirus was able to reduce the infarct size as determined by TTC staining. Moreover, in OGDR-induced apoptosis of NRCMs, miR-486 mimics was able to reduce cardiomyocyte apoptosis, while miR-486 inhibitor performed the opposite. Finally, PTEN and FoxO1 were identified as target genes of miR-486 in the control of cardiomyocyte apoptosis.

Conclusions

miR-486 mediates exercise-induced cardiac growth and protects against cardiac I/R injury. Increasing miR-486 might serve as a potential target to reduce myocardial apoptosis upon I/R injury.

Acknowledgement/Funding

This work was supported by the grants from National Natural Science Foundation of China 81722008, 91639101 and 81570362 to JJ Xiao, 81770401 to Y Bei
P5412Prevalence of RV failure assessed by echocardiography in acute dyspnoea cohort
Authors: Cerlinskaite K , Bugaite J , Gabartaite D , Verikas D , Krivickiene A , Motiejunaite J , Zaliaduonyte-Peksiene D , Zakarkaite D , Mebazaa A , Kavoliuniene A , Celutkiene J
Published: October 2019

Introduction

Recently more attention has been placed on right ventricle (RV) parameters in acute settings. The present study investigates echocardiographic RV parameters in patients with acute heart failure (AHF) or non-AHF acute dyspnoea.

Purpose

To determine the patterns of RV injury in different profiles of acute dyspnoea.

Methods

Prospective multicentre observational study included 1455 acutely dyspnoeic patients from 2015 to 2017. RV focused echocardiography was performed during the first 48 hours in 452 (31%) patients. They were compared in three patient profiles based on cause of dyspnoea and history of chronic HF (CHF): 1) AHF; 2) Non-AHF with CHF (Non-AHF+CHF); 3) other non-AHF patients (Non-AHF+other).

Results

Significant differences in RV morphology and function were observed in the study groups (Table 1). RV global function assessed by tricuspid annular plane systolic excursion (TAPSE) and RV longitudinal shortening was mostly affected in AHF patients. This was accompanied by more enlarged RV and increased right atrial pressure (RAP), assessed by the inferior vena cava diameter and respiratory collapse. Less severely impaired RV function and increased RAP were also observed in non-AHF+CHF patients indicating RV involvement in the chronic disease. Normal RV parameters dominated in Non-AHF+other group, however pulmonary artery systolic pressure >40 mmHg was observed in all profiles, suggesting similar severity of pulmonary hypertension in cardiac or pulmonary causes of acute dyspnoea.

Table 1. RV parameters in acute dyspnoea profiles Parameter AHF (n=291) Non-AHF + CHF (n=73) Non-AHF + other (n=88) p value LVEF, % 38 [25–55] 50 [40–55] 55 [50–55] <0.001 RV basal diameter, cm 4.5 [3.9–5.2] 4 [3.5–4.5] 4 [3.5–4.55] <0.001 TAPSE, cm 1.5 [1.2–1.8] 1.8 [1.6–2] 2 [1.5–2.4] <0.001 RV free wall strain, -% −15.3 [−19; −11.24] −19.3 [−24.5; −15.78] −23 [−24.5; −19.69] <0.001 Entire RV strain, -% −12.03 [−15.17; −9.11] −16.4 [−19.31; −10.5] −18 [−18.75; −16.9] <0.001 PASP >40, % 66% 51% 50% 0.039 IVC diameter, cm 2.4 [2–2.8] 2 [1.7–2.4] 1.8 [1.4–2.3] <0.001 IVC collapse, % 34.9 [19.7–50.2] 44.1 [28.7–59.3] 52.6 [35–72.7] <0.001 LVEF, left ventricular ejection fraction; RV, right ventricle; TAPSE, tricuspid annular plane systolic excursion; PASP, pulmonary artery systolic pressure; IVC, inferior vena cava; AHF, acute heart failure; CHF, chronic heart failure.

Conclusions

Our data confirm more pronounced acute failure of right ventricle in acute heart failure patients than in chronic heart failure patients admitted due to other causes of dyspnoea. Pulmonary hypertension is present in a majority of the acute dyspnoea patients.

Acknowledgement/Funding

The work was supported by the Research Council of Lithuania, grant Nr. MIP-049/2015 and approved by Lithuanian Bioethics Committee, Nr. L-15-01.
P5414Factors influencing mortality in a long-term follow-up after heart transplantation; role of immunomonitoring
Authors: Alyaydin E , Welp H , Pogoda C , Pistulli R , Reinecke H , Tuleta I
Published: October 2019

Background

Despite relevant improvements in the last years, increased mortality limits the success of heart transplantation therapy. Although many factors influencing mortality have been identified, the most studies analyzed relatively short follow-up time following heart transplantation.

Purpose

Therefore, the aim of our present study was to evaluate risk factors for enhanced mortality with emphasis on quantitative changes in immunological blood cells late after heart transplantation.

Methods

174 patients with a mean time after heart transplantation of 13.1±6.5 years were retrospectively analyzed using data collected during follow-up visits in our center. Clinical examinations, results of laboratory tests, including immunomonitoring of CD4+, CD8+, CD19+ cells and natural killer cells, ultrasound vessel visualization and coronary angiography were evaluated with respect to the all-cause mortality.

Results

In patients who were still alive at the time of data analysis (group 1, n=134), glomerular filtration rate, erythrocyte count, hemoglobin and mean corpuscular hemoglobin concentration were significantly increased compared to the group encompassing patients who died before this time point (group 2, n=40) (p<0.05 for all). In contrast, c- reactive protein (CRP), leukocyte count, triglycerides and N-terminal pro-brain natriuretic peptide were significantly decreased in group 1 versus group 2 (p<0.05 for all). In the first group the patients were relevantly less frequently on dialysis, presented lower NYHA classes, later onset of cardiac allograft vasculopathy and received hearts from donors with lower body mass (p<0.05 for all). Additionally, patients from the first group were characterized by significantly higher CD4 and lower CD8 percentages as well as a tendency towards higher CD19 cell count. In a multivariate cox regression analysis CD4 percentage (hazard ratio (HR): 0.454, confidence interval (CI): 0.236–0.871; p=0.018), onset of cardiac allograft vasculopathy (HR: 0.422, CI: 0.190–0.941; p=0.035) and CRP (HR: 0.325, CI: 0.170–0.621; p=0.018) were independent risk factors for increased mortality.

Conclusions

Increased inflammation, anemia, renal and heart insufficiency, early onset of cardiac allograft vasculopathy, worse functional status and donor associated factors such as higher body mass correlated significantly with enhanced mortality among patients after heart transplantation. In contrast to the early phase following heart transplantation, where the suppression of CD4+ cell number contributes to the decrease in the frequency of acute rejections, aggressive reduction of CD4+ cells by high doses of immunosuppressive agents late after cardiac transplantation may augment risk of mortality. It may be explained due to the creation of a subclinical chronic immunosuppressive condition and potentiation of side effects of immunosuppressive drugs.
P5415Sleep disordered breathing in patients before and after heart transplantation: association with biomarkers and clinical parameters
Authors: Medvedeva E , Korostovtseva L S , Simonenko M A , Sazonova Y V , Sviryaev Y V
Published: October 2019

Background

Sleep-disordered breathing (SDB) is highly frequent in patients with severe heart failure (HF). SDB, and predominantly central sleep apnea (CSA), may improve after recovery of cardiac function, but available data are limited and inconclusive, especially in patients who have undergone heart transplantation. The assessment of the severity of sleep apnea is mainly based on the apnea-hypopnea index (AHI), but this event-based parameter alone may not sufficiently reflect the complex pathophysiological mechanisms underlying SDB potentially contributing to adverse outcomes in patients with heart failure.

Purpose

To assess SDB in patients with severe HF before and after heart transplantation, their relationship with biomarkers and clinical parameters.

Methods

We included 117 patients (mean age 52.4±4.7 years) with HF NYHA class II-IV in the prospective cohort study, follow-up period was 5 years. The left ventricular ejection fraction (LVEF) was 28.05±9.57%. All patients underwent a comprehensive clinical examination, echocardiography, polysomnography (PSG, Embla N7000, Natus, USA). The plasma level of NT-proBNP, was analyzed by immunoassay (ELISA). The SPSS statistical software (version 23.0) was used.

Results

PSG showed the following types of SDB in the studied cohort: obstructive sleep apnoea (OSA) was diagnosed in 48 patients (41%), central - in 20 (17%), mixed - in 26 (22%). Among them mild SDB was diagnosed in 29 cases, moderate in 32 and severe in 33 patients. SDB was not found in 23 patients. The following correlations were identified: NT-proBNP and obstructive apnea index (OAI) (r=−0.44, p=0.007), NT-proBNP and sleep efficiency (r=−0.71, p=0.006), AHI and body mass index (BMI) (r=0.32, p=0.01), OAI and BMI index (r=0.34, p<0.001), desaturation index and BMI (r=0.43, p<0.001), average saturation oxygen and BMI (r=−0,6, p<0,001). Twenty-three patients underwent heart transplantation. According PSG-data 1 year after transplantation we observed decrease of central apnea index (CAI) (p=0,04). On the other hand, OAI increased (p=0,01) independently of the significant change in BMI (p=0,08).

Conclusion

We found very high rate of SDB (80%) in patients with severe HF, the predominant type was OSA. AHI, OAI and indicators of oxygen saturation correlate with BMI and biomarkers before heart transplantation. After 1 year after transplantation CAI decreased, assessment of the dynamics of obstructive sleep apnea requires further study.
P5428QRS narrowing more than 15 ms after CRT implantation is strongly associated with the long-term survival
Authors: Hameli E , Theuns D A M J , Lenzen M J , Yap S C , Szili-Torok T , Caliskan K
Published: October 2019

Background

Cardiac resynchronization therapy (CRT) is used in selected heart failure patients with electrical cardiac dyssynchrony with a prolonged QRS duration and a left ventricle ejection fraction (LVEF) ≤35%. QRS duration post CRT implantation can probably predict responders and survivors. The aim of our study is to investigate the effect of QRS change on long-term survival post CRT implantation.

Methods

We performed a retrospective cohort study in patients receiving a CRT device in our tertiary referral center between January 2009 and January 2018. Clinical and electrocardiographic (ECG) data were collected at baseline, one week after CRT implantation, six months, and yearly during follow-up. The primary endpoint was death, left ventricle assisting device implantation, or heart transplantation. At the end, the cohort was dichotomized to the cut-off value of ≥15ms according current literature.

Results

The study population consisted of 219 patients of whom 145 (66%) patients were survivors and 74 (34%) non-survivors. Non-survivors were significantly older (63 vs. 68 years, p=0.001), male gender (67% vs. 82%, p=0.015), had more often diabetes mellitus (20% vs. 39%, p=0.002), chronic obstructive pulmonary disease (12% vs. 28%, p=0.003), an ischemic etiology of heart failure (42% vs. 61%, p=0.009) with previous myocardial infarction (29% vs 53%, p=0.001), previous revascularization (32% vs. 49%, p=0.019), atrial fibrillation (21% vs. 39%, p=0.004), worser NYHA class (p=0.008), and amiodarone use (10% vs. 22%, p=0.024). Blood urea nitrogen (BUN) (8.1 mmol/L vs. 10.4 mmol/L, p<0.001) and creatinine levels (96 μmol/L vs. 114 μmol/L, p=0.001) were also higher in the non-survivors group. Median QRS duration (168 ms IQR [154 to 182]) at baseline was comparable between survivors and non-survivors (170 ms vs. 166 ms, p=0.17). However, median QRS change one week after CRT implantation was significantly better in the survivors (−19 ms IQR [−30 to −2] vs. −6 ms IQR [−24 to +12], p=0.004). The QRS change at the last FU (median 5.1 years IQR [2.9 to 7.8] was consistently higher in the survivor group (−16 ms IQR [−29 to 0] vs. +1 ms IQR [−27 to +20], p=0.004). Dichotomized to ΔQRS narrowing of ≥15 ms after CRT implantation showed significantly better long-term survival (figure).

Kaplan-Meier curve

Conclusion

QRS narrowing cut-off of ≥15 ms post CRT implantation is strongly associated with the long term survival in chronic heart failure patients with reduced LVEF.
P5437The BNP reporter mouse by knock-in technology is useful for the analysis of mechanism in reactivation of BNP in adult heart
Authors: Okamoto R , Hashizume R , Ito R , Suzuki N , Kiyonari H , Ito M
Published: October 2019

Background

It has been thought BNP is induced by undetermined stretch-activated receptors, however, which receptor is associated remains unknown. The stretch-activated receptors include mechanically gated channels, which can be activated by a mechanical stimulus alone, and mechanically modulated channels, which require nonmechanical stimuli such as agonists. It has been recently shown that 1.1kb segment of mouse NPPB promoter dose not reproduce the pattern of reactivation of BNP in adult heart, although it could monitor the expression of BNP in neonatal cardiomyocytes.

Purpose

Our aim is to develop a true BNP reporter mouse and examine whether this mouse is useful or not for the investigation of BNP reactivation mechanism in adult heart and for the measurement of serum-induced BNP expression in patients with heart failure.

Methods

We generated the BNP reporter mice by knocking luciferase cDNA in the initiation site of NPPB. In vivo imaging of luciferase was performed in the BNP reporter mice after the intraperitoneal injection of luciferin. The luciferase activity was examined in neonatal cardiomyocyte, isolated adult cardiomyocytes, adult cardiac dissected tissue with or without 120–150% stretch or angiotensin II stimulation. Left anterior descending (LAD) coronary artery was ligated to study myocardial infarction. Cardiac dissected tissue segments from the BNP reporter mouse were incubated for 8 hours with 20% serum from patients with or without heart failure and the luciferase activity was measured after homogenization.

Results

The in vivo imaging system showed the activity of BNP was high in 1 day-old neonates and the reactivation of BNP in the adult heart after LAD ligation could be monitored by the luciferase activity (figure). The treatment of Ang II could increase the activity of pBNP more than ten folds in heart tissue from adult mice. On the other hand, the 120–150% stretch did not show any effect on the activity of pBNP in this system. We could not observe any activation of pBNP in cultured neonatal or adult cardiomyocytes demonstrated by immunostain with antibodies against luciferase after 120–150% stretch. Interestingly, the luciferase activity was extensively higher in cultured heart tissue segments from the BNP reporter mice after the treatment of serum from patients with heart failure than without heart failure.

In vivo imaging of BNP reporter mice

Conclusion

These results indicate the BNP reporter mouse by knock-in technology is useful for the analysis of mechanism in reactivation of BNP in adult heart and the elevation of BNP in patients of heart failure partly due to the serum-derived induction of BNP from heart.
P5443NOD2 knock down worsens diastolic dysfunction in murine angiotensin II-induced heart failure
Authors: Mueller I , Lin J , Pappritz K , Tschoepe C , Van Linthout S
Published: October 2019

Background

Heart failure with preserved ejection fraction (HFpEF) is associated with cardiac inflammatory responses, indicating a potential role of the immune system in the pathology of diastolic dysfunction. The cytoplasmatic pattern recognition receptor, nucleotide binding oligomerization domain 2 (NOD2) belongs to the innate immune system and induces among others the NLRP3 inflammasome, known to be involved in myocarditis and coronary heart disease.

Purpose

The aim of this study was to explore the role of NOD2 in Angiotensin II (AngII)-induced diastolic heart failure.

Methods

In NOD2−/− knock down and C57Bl6/j-wild type (WT) mice, diastolic dysfunction was induced by subcutaneous administration of 1.4mg/kg*day–1 AngII. Twenty-one days after first AngII administration, left ventricular (LV) function was evaluated by pressure tip catheter. Cardiac fibrosis, inflammation, and the expression of NOD2 and the NLRP3 component Apoptosis-associated speck like protein containing a caspase recruitment domain (ASC) were determined via immunohistochemistry, real-time PCR or Western Blot.

Results

LV NOD2 mRNA expression was 2.3-fold (p<0.0005) and 1.9-fold (p<0.0005) lower in NOD2−/− control and NOD2−/− AngII mice compared to their respective WT littermates. In parallel, LV protein expression of the downstream NLRP3 component Apoptosis-associated speck like protein containing a caspase recruitment domain (ASC) was 1.5-fold (p<0.05) lower in NOD2−/− AngII mice versus WT AngII mice, whereas LV protein IL-1β levels were unchanged. LV diastolic dysfunction was more pronounced in NOD2−/− AngII mice versus WT AngII mice, as displayed by a 19% (p<0.05) increased LV relaxation time and 24% (p<0.057) impaired dP/dtmin, with no changes in the ejection fraction (EF: NOD2−/− AngII 72.5%±5.4 versus WT AngII 65.6±3.5). In parallel, LV presence of CD68-positive cells was 1.8-fold (p<0.05) higher in NOD2−/− AngII compared to WT AngII mice. Concomitantly, NOD2−/− AngII mice displayed 1.3-fold (p<0.05) and 1.7-fold (p<0.05) higher LV mRNA expression of the chemokine macrophage inflammatory protein (MIP)-2 and monocyte chemotactant protein (MCP)-1 compared to WT AngII mice, respectively. Furthermore, cardiac interstitial fibrosis in NOD2−/− mice with AngII-induced diastolic dysperformance was more pronounced versus the WT AngII group, as indicated by a 2.0-fold (p<0.0005), 2.0-fold, and 1.6-fold (p<0.05) higher LV ColI/ColIII ratio, and TGF-β and TIMP-1 mRNA expression, respectively.

Conclusion

NOD2−/− deteriorates LV diastolic dysfunction and worsens pathophysiological key mechanisms in mice with AngII-induced diastolic heart failure.
P5456The role of ST2 as an early marker of endothelial dysfunction in hypertensive patients
Authors: Farcas A D , Stoia M A , Mocan M , Chiorescu R M , Mocan-Hognogi D L , Goidescu C M , Anton F P
Published: October 2019

Background

The association between endotelial dysfunction and progression of diastolic dysfunction suggests that endotelial and myocardial impairment might have similar pathogenic pathways. Moreover, in hypertensive diabetics the endotelial function is worse in those with impaired diastolic performance compared to normal diastolic performance. ST2 provides additional data to echocardiography in early detection of diastolic performance alteration in hypertension (HT) and is a prominent predictive marker of worse clinical outcome in hypertensive patients. There is scarce data on ST2 role in detection of early vascular involvement in hypertensive patients.

Purpose

The aim of the study is to evaluate whether ST2 levels correlate with impaired endotelial function in hypertensive patients.

Methods

Our prospective study included 84 hypertensive patients (mean age 52.9±14.4 yrs, 54.3% males and 45.7% females), after they signed an informed consent. All patients underwent clinical and laboratory (including ST2) evaluation. To investigate endothelial function, we performed ultrasound measurement of the brachial artery diameter both at rest and during reactive hyperemia in the muscle distal to the brachial artery (BA) which causes endothelium-dependent vasodilatation. The study methodology was approved by the Ethical Committee and statistical data processing was performed with SPSS.

Results

Patients were assigned to group A – those without left ventricular hypertrophy (LVH) and group B – those with LVH. There were no significant differences regarding gender, age and HT stage between groups A and B. Patients in group A had lower ST2 levels [18.83 (13.98 - 42.05) vs 55.63 (48.6 - 100.21) vs, p<0.001] and fewer risk factors (1.4 vs 2.6, p<0.01) compared to group B. We found significant differences regarding diastolic performance parameters between the groups. The relative increase in diameter (% FMD; DD = D 100) was significantly higher in group A than group B (6.67±0.43% vs 3.10±0.33%, p<0.01). ST2 levels were greater in group B and correlated with the degree of endotelial dysfunction evaluated by flow-mediated dilatation (FMD) (r=0.411, p<0.01). Multiple regression analysis showed that ST2 had a significant negative correlation with the relative increase in arterial diameter while multivariate Cox regression analysis showed ST2 was an independent predictor of endothelial dysfunction severity in hypertensive patients (hazard ratio: 4.012, 95% confidence interval: 1.207–31.24, P=0.031).

Conclusions

ST2 levels correlate with cardiovascular risk and are a significant predictive marker of endothelial dysfunction in hypertensive patients regardless of diastolic dysfunction.
P5475Essential thrombocytosis is associated with worse hospital outcomes in patients presented with acute myocardial infarction: a propensity score analysis of the National Inpatient Sample
Authors: Wu L , Liu B , Zheng Y
Published: October 2019

Background/Introduction

Essential thrombocytosis (ET) is a rare disease characterized by vasomotor symptom, thrombotic event, and hemorrhage. Due to its rare occurrence, limited data are available to examine the impact of ET on acute myocardial infarction (AMI).

Purpose

To evaluate the impact of ET on hospital outcomes of AMI.

Methods

We use the 2016 National Inpatient sample database to identify all the admissions with a principal diagnosis of AMI with or without ET. A matched control group was then generated using propensity score from age, sex, race, location, insurance, income, hospital type, hospital location, Charlsoncat Comorbidity Score. Prevalence, baseline characteristic of AMI patient with or without ET was described and compared. Univariable logistic regression was used to measure mortality and the rate of catheterization.

Results

ET was found in 0.28% (1,814) in total AMI admissions (641,854). Age (69.52 vs 69.70), female percentage (48.04% vs 48.03%) and baseline comorbidities including STEMI (27.49% vs 25.08%), diabetes (33.03% vs 30.51%), heart failure (40.18 vs 45.89%) and chronic kidney disease (22.05% vs 26.28%) was found to be comparable between two groups (p>0.05, table 1). Compared to non ET group, ET is associated with significantly higher hospital mortality (5.74% vs 2.43%, OR 2.44 [1.09–5.48], p=0.03), prolonged length of stay (7.61 vs 4.30 days, p<0.01). Interestingly, ET is also associated with lower utilization of cardiac catheterization (37.46% vs 46.52%, p=0.01).

Essential Thrombocytosis and AMI Parameter AMI with ET Matched control: AMI without ET Odds ratio (95% CI) P value (n=1,814) (n=1,814) Age, years 69.52±0.72 69.70±0.70 p>0.05 Female, % 48.04 48.03 p>0.05 STEMI, % 27.49 25.08 p>0.05 Hypertension, % 81.57 83.08 p>0.05 Diabetes, % 33.03 30.51 p>0.05 Heart failure, % 40.18 45.89 p>0.05 Chronic kidney disease, % 22.05 26.28 p>0.05 Mortality, % 5.74 2.43 2.44 (1.09–5.48) p=0.03 Catheterization, % 37.46 46.52 0.68 (0.51–0.91) P=0.01 Length of stay, days 7.61±0.48 4.30±0.21 P<0.01 Values are reported as mean ± S.E. Categorical variables are represented as frequency.

Conclusion

ET is infrequently observed in patients with AMI. Having ET is associated with higher hospital mortality, longer hospital stay and lower utilization of cardiac catheterization.

Acknowledgement/Funding

None
P5479Educational attainment is an independent predictor of adverse outcomes in patients with coronary artery disease
Authors: Ghazzal B Z , Kelli H M , Mehta A , Tahhan A S , Kim J H , Dong T A , Dhindsa D S , Sandesara P B , Hayek S S , Alkhoder A A , Liu C , Ko Y , Vaccarino V , Sperling L S , Quyyumi A A
Published: October 2019

Background

Educational attainment is an indicator of socioeconomic status and is inversely associated with cardiovascular risk factors and risk for incident coronary artery disease (CAD). Whether the level of educational attainment (EL) in patients with CAD influences outcomes remains understudied.

Purpose

To ascertain the relationship between EL and adverse outcomes in patients with CAD. We hypothesize that EL will be inversely associated with adverse outcomes in this high-risk patient population.

Methods

Subjects undergoing cardiac catheterization for known or suspected CAD were recruited in a cardiovascular biobank and had their highest level of educational attainment assessed using predefined options of elementary/middle school, high school, college, or graduate education. The primary outcome of interest was all-cause mortality and secondary outcomes included a composite of cardiovascular deaths and nonfatal myocardial infarction (MI) events, and nonfatal MI events during follow-up. Cox proportional hazards regression models were used to analyze the association between EL and adverse outcomes after adjustment for demographic characteristics, cardiovascular risk factors, cardiovascular medication use, and estimated zip code-based annual family income.

Results

Among the 6,318 subjects (mean age 64 years, 63% male, 23% black) enrolled, 998 (16%) had received graduate or a higher qualification, 2,689 (43%) had received a college education, 2,403 (38%) had received a high school education, and 228 (3%) had received elementary/middle school education. During a median follow-up of 3 years,there were 1,110 deaths from all causes, 851 cardiovascular deaths/nonfatal MI, and 286 nonfatal MI events. After adjusting for covariates and compared to patients with graduate education or higher, those with lower EL (elementary/middle school, high school, or college education) had a higher risk of all-cause mortality [hazard ratio 1.66, (95% CI 1.08, 2.54), 1.58 (95% CI 1.22, 2.04), and 1.45 (95% CI 1.13, 1.57), respectively]. Similar findings were observed for secondary outcomes. EL dichotomized at graduate education was associated with all-cause mortality (hazard ratio 1.48, 95% CI 1.16, 1.88), but this relationship was significantly modified by sex (p-interaction 0.023) and the association was attenuated among male patients (hazard ratio 1.23, 95% CI 0.94, 1.61) but not female patients (hazard ratio 2.70, 95% CI 1.53, 4.77).

Conclusions

Lower educational attainment is an independent predictor of adverse outcomes in patients with CAD. The causal link between low education level and increased CV risk needs further investigation.

Acknowledgement/Funding

Dr. Quyyumi is supported by NIH grants 5P01HL101398-02, 1P20HL113451-01, 1R56HL126558-01, 1RF1AG051633-01, R01 NS064162-01, R01 HL89650-01, HL095479-0