bluuebunny/crossref_metadata_2025 huggingface dataset:
P5275Cardiovascular magnetic resonance predictors of long term clinical outcome in myocarditis
Authors: Sanguineti F , Garot P , Hovasse T , Unterseeh T , Troussier X , Dinan-Magniez A , Garot J
Published: October 2019

Background

The natural history of acute myocarditis (AM) remains partially unknown and predictors of outcome are still debated. The study objectives were to determine the potential value of cardiovascular magnetic resonance (CMR) parameters for the long-term Major Adverse Cardiac Events (MACE) prediction in patients presenting with suspected AM. In our centre we published in 2015 a first analysis of the CMR myocarditis registry which included patients presenting with suspected AM in routine practice, clinically followed-up for 18 months (median follow up). This first analysis, in disagreement with the published data, did not find CMR predictors of MACE except for the LVEF.

Purpose

As in myocarditis MACE could have a gradual evolution, to confirm our initial results, the aim of this study is to reinvestigate in the same population, the potential value of CMR parameters with a longer follow-UP (median 8.34 years, interquartile range: 7.7 to 9.16 years).

Methods

In a single-centre longitudinal prospective study, 203 routine consecutive patients with clinical suspicion of AM and initial CMR-based diagnosis of AM (typical Late Gadolinium Enhancement, LGE) were clinically followed up. Various CMR parameters were evaluated as potential predictors of outcome. The primary endpoint was defined as the occurrence of at least one of the combined MACE: cardiac death or aborted sudden cardiac death, cardiac transplantation, sustained documented ventricular tachycardia, heart failure, recurrence of acute myocarditis, and the need for hospitalization for cardiac causes.

Results

The vast majority of patients (70,44%; N=143) presented with chest pain, mild to moderate troponin elevation and ST-segment or T wave abnormalities. Various CMR parameters were evaluated on initial CMR performed 3±2 days after acute clinical presentation (LV functional parameters, presence/extent of edema on T2, presence/extent of Early Gadolinium Enhancement (EGA) and extent of late gadolinium enhancement lesions). Out of the 203 patients, 35 (17.2%) experienced at least one major cardiovascular event during follow-up. Among all CMR parameters, initial alteration of LVEF was confirmed a MACE independent predictor by multivariate analysis (HR: 1.03 per 10% decrease, 95% CI: 1.01 to 1.06, p=0.04). Furthermore, at longer FU analysis, absence of EGA predicted adverse clinical outcome (HR: 2.7, 95% CI: 1.12 to 6.27, p=0.02) suggesting a potential protecting role of inflammatory response.

Conclusions

In routine clinical practice, in patients without severe hemodynamic compromise and a CMR-based diagnosis of AM, various CMR parameters such as the presence, extent and myocardial localisation of late gadolinium-enhanced LV myocardial lesions, were not predictive of events at long term follow up. CMR predictor of adverse clinical outcome were an initial alteration of LVEF and the absence of EGA.
P5284Fully automated quantification of biventricular volumes and function in cardiovascular magnetic resonance: applicability to clinical routine settings
Authors: Backhaus S J , Staab W , Steinmetz M , Ritter C O , Lotz J , Hasenfuss G , Kowallick J T , Schuster A
Published: October 2019

Background

Cardiovascular magnetic resonance (CMR) represents the clinical gold standard for the assessment of biventricular morphology and function. Since manual post-processing is time-consuming and prone to observer variability, efforts have been directed towards automated volumetric quantification. In this study, we sought to validate the accuracy of a novel approach providing fully automated quantification of biventricular volumes and function in a “real-world” clinical setting.

Methods

Three-hundred CMR examinations were randomly selected from the local data base. Fully automatic quantification of left ventricular (LV) mass, LV and right ventricular (RV) end-diastolic and systolic volumes (EDV/ESV), stroke volume (SV) and ejection fraction (EF) were performed overnight using commercially available software. Parameters were compared to manual assessments. Sub-group analyses were further performed according to image quality, scanner field strength, the presence of implanted aortic valves and repaired Tetralogy of Fallot (ToF).

Results

Biventricular automatic segmentation was feasible in all 300 cases. Overall agreement between fully automated and manually derived LV parameters was good (LV-EF: intra-class correlation coefficient [ICC] 0.95; bias −2.5% [SD 5.9%]), whilst RV agreement was lower (RV-EF: ICC 0.72; bias 5.8% [SD 9.6%]). Lowest agreement was observed in case of severely altered anatomy, e.g. marked RV dilation but normal LV dimensions in repaired ToF (LV parameters ICC 0.73–0.91; RV parameters ICC 0.41–0.94) and/or reduced image quality (LV parameters ICC 0.86–0.95; RV parameters ICC 0.56–0.91), which was more common on 3.0T than on 1.5T.

Conclusions

Fully automated assessment of biventricular morphology and function is robust and accurate in a clinical routine setting with good image quality and can be performed without any user interaction. However, in case of demanding anatomy (e.g. repaired ToF, severe LV hypertrophy) or reduced image quality, quality check and manual re-contouring is still required.

Acknowledgement/Funding

DZHK - German Centre for Cardiovascular Research
P5289Myocardial deformation after ST-elevation infarction measured by CMR feature tracking strain
Authors: Sjogren H , Pahlm U , Engblom H , Erlinge D , Heiberg E , Arheden H , Carlsson M , Ostenfeld E
Published: October 2019

Background

Left ventricular (LV) functional assessment is of imminent value after ST-elevation infarction (STEMI). LV longitudinal strain (LS) evaluates ventricular function on a myocardial level. Feature Tracking (FT) assesses strain from cine cardiac magnetic resonance (CMR) images. It is unknown how LV FT Regional LS (RLS) and Global LS (GLS) changes between the sub-acute and chronic phase after STEMI compared to controls and how GLS and RLS are related to culprit vessel (LAD, LCX or RCA) and infarction size (IS).

Aims

To assess 1) GLS with FT after 2–6 days (sub-acute) and 6 months (chronic phase) after STEMI compared with controls, 2) if GLS changes between sub-acute and chronic phase, and 3) the relationship between GLS and RLS to IS and infarct location.

Methods and results

Seventy-seven patients underwent CMR 2–6 days and 6 months after STEMI as well as 27 healthy controls. GLS was impaired at the sub-acute (−8.9±2.3%) and chronic phase (−14.3±2.9%) compared to controls (−18.4±2.4%; p<0.001 for both). GLS improved between the sub-acute and chronic phase (p<0.001). GLS correlated to IS (R=0.47 sub-acute; 0.49 chronic, p<0.001). LAD infarctions had lowest GLS and largest IS. RLS was more impaired in the culprit vessel territory compared to remote. RLS in the RCA region was lower for LAD than RCA infarctions. RLS was impaired in all 6 wall-regions in LAD infarctions, while LCX and RCA infarctions had preserved RLS in remote myocardium.

Global Longitudinal Strain (GLS)

Conclusion

GLS is impaired after STEMI and improves, but do not normalize, to the chronic phase. GLS is only moderately correlated to IS, indicating that other factors and co-morbidities are important to determine ventricular function. Even though RLS is most impaired in the affected region, remote regions can be substantially impaired in LAD-infarctions, why it would be difficult to pinpoint the culprit vessel based on RLS.
P5290Impact of extreme obesity on long-term outcomes following percutaneous coronary intervention
Authors: Biswas S , Dinh D , Noaman S , Duffy S J , Lefkovits J , Brennan A , Ajani A , Clark D J , Freeman M , Oqueli E , Hiew C , Reid C M , Stub D , Chan W
Published: October 2019

Background

Obesity is a growing health concern worldwide, particularly in developed countries where there has been an unprecedented rise in the proportion of overweight and obese individuals in the population. Previous studies have reported a protective effect of obesity compared to normal BMI in patients undergoing percutaneous coronary intervention (PCI). However, it is unclear whether this effect extends to the extremely obese over long-term follow-up.

Objective

To determine whether an obesity paradox persists in contemporary PCI practice over long-term follow-up, and in particular to further evaluate the association between extreme obesity and long-term clinical outcomes after PCI.

Method

We prospectively collected data on 25,645 patients undergoing PCI between 1 January 2005 and 30 June 2017 who were enrolled in the statewide multi-centre Melbourne Interventional Group Registry. This registry collects data on all patients undergoing PCI at 6 academic tertiary hospitals. Patients were stratified by World Health Organization-defined BMI categories. Long-term mortality data was obtained by linkage to the National Death Index (NDI), a database that contains records of all deaths occurring in Australia. The primary endpoint was NDI-linked mortality. Median length of follow-up was 4.4 years (IQR 2.0–7.6 years).

Results

Of the study cohort, 24.6% had normal BMI (18.5–24.9 kg/m2), 0.9% were underweight (BMI <18.5 kg/m2) and 3.3% were extremely obese (BMI ≥40 kg/m2). As BMI increased, mean age decreased while the prevalence of diabetes increased (p<0.001). The proportion of females at both extremes of BMI. Procedural characteristics were similar across the groups although there was more radial access and less femoral access used with increasing BMI (p<0.001). In terms of secondary prevention therapy, underweight patients were significantly less likely to receive a beta blocker, ACE inhibitor and statins, compared to the other BMI groups. In-hospital, 30-day and long-term mortality were all highest for underweight patients (37.7%) and lowest for the moderately obese patients (BMI 35–40 kg/m2) (12.2%). After adjustment for age, comorbidities and presentation with cardiogenic shock, a U-shaped association between the different BMI categories and adjusted hazard ratio for long-term mortality was observed (Figure 1).

Figure 1

Conclusion

An obesity paradox is still apparent in contemporary practice with elevated BMI up to 35 kg/m2 associated with reduced long-term mortality after PCI. However, this protective effect appears not to extend to patients with extreme obesity. Factors behind this phenomenon are likely multifactorial and require further mechanistic and epidemiological studies.
P5292Obesity paradox, hyperlipoproteinemia(a), autotaxin concentration and stenotic atherosclerosis of different vascular territories
Authors: Afanasieva O , Tmoyan N , Razova O , Afanasieva M , Ezhov M , Pokrovsky S
Published: October 2019

Background

Controversial data have recently emerged about the role of obesity in the development of cardiovascular diseases, otherwise known as “Obesity paradox”. Autotaxin (ATX) hydrolyzes lysophosphatidylcholine to lysophosphatidic acid, a lipid mediator involved in pathological processes, including obesity.

Purpose

To investigate the association between obesity and stenotic atherosclerosis of different vascular territories.

Methods

The study included 1225 patients with results of instrumental examination of coronary, carotid and lower limbs arteries. Stenotic atherosclerosis (≥50%) in any vascular bed was diagnosed in 889 patients.

Results

The patients were divided into two groups depending on body mass index (BMI) (table). The groups were comparable on age, lipids and frequency of CHD. The obesity negatively associated with lower extremity artery disease (LEAD) (odds ratio (OR) 0.51; 95% CI 0.36–0.72, p<0.01) adjusted for gender, age, smoking, type 2 diabetes, lipids and Lp(a). Multifocal atherosclerosis was also negatively associated with obesity (OR 0.44; 95% CI 0.28–0.71, p<0.01). ATX level was lower in patients with LEAD (median [25; 75%]: 492 [418; 573] ng/ml) vs. patients without LEAD (520 [424; 618] ng/ml, p<0.05). The similar results for ATX concentration were shown for patients with multifocal atherosclerosis vs. without stenotic atherosclerosis: 478 [414; 571] ng/ml vs. 551 [412; 678] ng/ml, p<0.05. The corresponding trend was observed in patients with and without coronary heart disease (CHD) (502 [421; 594] vs. 545 [425; 638] ng/ml, p=0.05). ATX level was associated with BMI (r=0.34, p<0.01) and negatively correlated with LEAD and multifocal atherosclerosis in obesity patients (r=−0.2, p<0.05 in both cases).

Characteristics of study groups Parameters Control, BMI <30 kg/m2, n=846 Obesity, BMI ≥30 kg/m2, n=379 Hypertension 585 (69%) 316 (83%)*** Type 2 diabetes 133 (16%) 115 (30%)*** Lipoprotein(a), mg/dl 23.9 [9.0; 54.7] 18.0 [6.6; 49.2]* Lipoprotein(a) ≥30 mg/dl 372 (44%) 137 (36%)* Autotaxin, ng/ml 513.5±137.3 528.4±140.1 Carotid atherosclerosis 293 (35%) 127 (33%) CHD 539 (64%) 206 (54%)** LEAD 224 (26%) 66 (17%)*** *p<0.05, **p<0.005, ***p<0.0005 compare with control group.

Conclusion

“Obesity paradox” was observed in the patients with LEAD, CHD and multifocal atherosclerosis and it could be associated with lysophosphatidic acid pathway.
P5302Significant correlation of visceral adiposity and adipocytokines with arterial inflammation in genetic dyslipidaemias
Authors: Koutagiar I , Toutouzas K , Antonopoulos A S , Skoumas I , Benetos G , Georgakopoulos A , Oikonomou E K , Kafouris P , Pianou N , Miliou A , Pitsavos C , Tousoulis D , Antoniades C , Anagnostopoulos C D
Published: October 2019

Background

The adipose tissue is now established as a major regulator of cardiovascular status, mediated by the secretion of several bioactive molecules, including adipocytokines. Individuals with genetic dyslipidaemias of either familial combined hyperlipidemia (FCH) or heterozygous familial hypercholesterolemia (heFH) subtype are characterized by accelerated atherosclerosis. Nonetheless, limited data exists on the relationship between adiposity and arterial inflammation, a marker of cardiovascular risk, in this setting.

Purpose

To investigate the relationship between adiposity indices and arterial inflammation evaluated by 18F fluorodeoxyglycose positron emission tomography (PET/CT) in patients with hereditary lipid metabolism disorders.

Methods

Consecutive patients with either FCH or heFH, free of statin therapy, and normolipidaemic individuals underwent PET/CT imaging. Arterial FDG uptake was estimated as the average value of target-to-background ratio (TBR) within aortic and carotid wall. Volumes of subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) were measured from CT images between the proximal (cephalic) end of the L1 and distal (caudal) end of the L3 vertebrae by selecting all voxels with attenuation between −190 and −30 Hounsfield Units (HU). Serum adiponectin and leptin levels were measured with ELISA by available commercial kits. For comparisons with arterial TBR, adiponectin and leptin concentrations above and below the 25th percentile, were stratified as high and low, respectively.

Results

In total, 60 individuals (20 FCH, 20 heFH and 20 controls) were included. A modest but significant correlation between SAT volume and arterial TBR (R=0.386, p=0.004) was detected. This relationship did not remain significant after controlling for VAT volume (p=0.303). A strong correlation between VAT volume and arterial TBR (R=0.621, p=0.001) was observed. This relationship remained significant after controlling for SAT volume (R=0.541, p<0.001). Arterial TBR values were higher in individuals with low plasma adiponectin levels (p=0.010). In addition, patients with higher leptin levels exhibited increased arterial FDG uptake compared to subjects with low serum leptin concentrations (p=0.05)

Conclusions

Abdominal adipose tissue imaging markers and serum adipocytokines correlate with arterial inflammation as assessed by PET/CT in patients with familial dyslipidaemias highlighting the role of abdominal adipose tissue for atherosclerosis progression in this population.
P5303Relationship of the dynamics of serum collagen and epicardial adipose tissue in patients with coronary heart disease and visceral obesity
Authors: Dyleva Y A , Gruzdeva O V , Uchasova E G , Borodkina D A , Belik E V , Kokov A N , Brel N K , Pecherina T B , Kashtalap V V , Karetnikova V N , Barbarash O L
Published: October 2019

Purpose

Study of the effect of epicardial adipose tissue and in serum collagen in patients with myocardial infarction depending on the presence of visceral obesity.

Methods

88 patients with CVD were assessed and divided into two groups based on the presence of visceral obesity (VO). Magnetic resonance imaging (MRI) was used to determine the area of the visceral (VAT) and subcutaneous adipose tissue (SAT) of the abdominal region, the thickness of epicardial adipose tissue, and the percentage of myocardial cardiac fibrosis a year after MI. VO was verified when the area of VAT >130 cm2. We investigated changes in serum collagen: collagen protein type I (COL-1), N-terminal propeptide of procollagen type III (PIIINP) and C-terminal propeptide of procollagen type I (PICP). All study was carried out in compliance with the Helsinki Declaration, and its protocol was approved by the Ethical Committee of Research Institute. Statistical analysis was performed using Statistica 10.0. All patients gave written informed consent to participate in the study.

Results

With VO, the thickness of the left ventricular epicardial tissue (EATLv) was 1.75 times greater, and that of the right ventricle (EATrv), 1.43 times more than in patients without VO. In the group of patients with VO, the presence of a direct correlation was established between the magnitude of the area of VAT and EATLv (r=0.26, p=0.02), EATrv (r=0.26, p=0.01). the results indicate that myocardial damage on the background of an acute MI is characterized by higher concentrations of COL-1 (29065 pg/ml), PICP (638 ng/ml) and PIIINP (31431 pg/ml), in the presence of VO during the hospital period of MI, and exceeded the figures of patients without VO 2.15, 1.07 and 1.19 times, respectively. One year after MI, the COL 1 level in both groups decreased compared with the acute MI period (1.68 times in patients without VO and 2.75 times in patients with VO), it still remained higher in patients with VO in 1,4 times higher. And the level of PICP was not significantly different on the first day of MI and a year after suffering MI in the studied groups. PIIINP decreased only in the group of patients without VO.

The data of the correlation analysis showed that EATLv was in direct connection with the level of serum collagen in patients with VO: EATLv - COL-1 (1 day (r=0.73; p=0.01), 1 year (r=−0, 84; p=0.00); EATLv - PICP (1 day (r=0.63; p=0.01), 1 year (r=0.57; p=0.03) and EATLv - PIIINP (1 day (r=0.61; p=0.03), 1 year (r=0.31; p=0.01).

Conclusions

Thus, the presence of VO in patients with MI is associated with higher concentrations of COL 1, PICP, PIIINP, both in the acute period of MI, and one year after a coronary catastrophe. The thickness of EAT is directly dependent on the degree of VO, and the concentration of COL-1, PICP and PIIINP on the value of EATLv.
P5328Clinical and demographic predictors of attenuated LDL-C response to PCSK9 inhibition with bococizumab: Insights from the SPIRE trials
Authors: Siddiqi H , Everett B M , Rose L M , Ridker P M
Published: October 2019

Background

While there exists significant inter-individual variability in low density lipoprotein cholesterol (LDL-C) response to proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition, predictors of this response remain uncertain. The Studies of PCSK9 Inhibition and the Reduction of Vascular Events (SPIRE) randomized control trials evaluated the efficacy of bococizumab, a humanized murine PCSK9 antibody, in patients at high cardiovascular risk.

Purpose

This study's purpose is to determine predictors of attenuated LDL-C response to bococizumab.

Methods

SPIRE 1 and 2 trial subjects allocated to bococizumab (n=13,675) were included. Subjects with an increase in LDL-C or non-compliance to bococizumab, or development of anti-drug or neutralizing antibodies were excluded. The remaining 8281 subjects were divided into quintiles of percent LDL-C reduction from baseline to 14 weeks. The first quintile (Q1) was considered an attenuated response. Multivariate logistic regression was used to discern significant predictors of attenuated response (Q1) compared to robust response (Q5).

Results

Q1 included 1657 subjects with median 35% LDL-C reduction (range 0.4% - 48%), whereas Q5 included 1658 subjects with median 83% LDL-C reduction (range 78% - 99%). Female sex, diabetes, white race, younger age, higher baseline non-high-density lipoprotein cholesterol (non-HDL-C), lipoprotein (a) [Lp(a)] and high-sensitivity C-reactive protein (hsCRP) were significantly associated with an attenuated response compared to a robust response (each p<0.05, Table).

Multivariate logistic regression for attenuated percent LDL-C response to bococizumab from baseline to 14 week Baseline characteristic Adjusted odds ratio (95% confidence interval) P-value Female 3.30 (2.72, 4.00) <0.0001 Diabetes 1.57 (1.32, 1.86) <0.0001 White race 1.44 (1.07, 1.93) 0.016 BMI (per 1kg/m2) 1.09 (1.07, 1.11) <0.0001 Age (per year) 0.98 (0.98, 0.99) 0.0005 Ln hs-CRP (per 1mg/L) 1.19 (1.11, 1.29) <0.0001 Lp (a) (per 10mg/dL) 1.11 (1.09, 1.14) <0.0001 Non-HDL-C (per 10mg/dL) 1.05 (1.02, 1.07) <0.0001 Odds ratios mutually adjusted for the listed variables.

Conclusions

In the SPIRE 1 and 2 trials, excluding subjects with anti-drug and neutralizing antibodies, significant predictors of an attenuated LDL-C response to PCSK9 inhibition with bococizumab included female sex, diabetes, younger age and white race.

Acknowledgement/Funding

Pfizer
P5349Platelet/lymphocyte ratio as an inflammatory marker and predictor of short-term neurological outcomes in survivors after cardiac arrest
Authors: Rodriguez L , Martinez L A , Rosillo S O , Martin L , Merino C , Marco I , Velez A , Caro-Codon J , Garcia De Veas J M , Iniesta A M , Rial V , Gonzalez O , Armada E , Lopez-Sendon J L , Lopez-De-Sa E
Published: October 2019

Background

Platelet/lymphocyte ratio (PLR), an inflammatory marker associated with poor outcomes in different clinical situations, may play a role in the proinflammatory state triggered during hypoxic-ischemic brain injury secondary to cardiac arrest.

Purpose

To study PLR dynamics and its relationship with neurologic outcomes in survivors after CA treated with target-temperature-management (TTM).

Methods

Observational retrospective study from a prospective database of survivors of in-hospital and out-of-hospital CA admitted to our Acute Cardiac Care Unit between August 2006 to December 2018. All patients received TTM according to our local protocol.

Results

A total of 466 patients were included. Mean age was 62.7±14.4 years and 102 (21.9%) were women. Baseline characteristics are shown in Table 1. 430 (92.2%) of CA were witnessed, 312 (67.0%) had ventricular fibrillation as initial cardiac rhythm. Among them, 236 (51.1%) survived until hospital discharge and 208 (45.1%) presented favorable neurological outcomes (a score 1 or 2 on cerebral performance category (CPC)). The mean value of PLR at admission and during targeted temperature was 100.4±5.2 and 224.5±7.3 respectively (mean difference 123.1±7.1, p<0.0001). This increase in PLR was significantly higher among patients with worse neurological outcomes (CPC 3–5, mean DPLR 138.2±5.5) at 3 months compared with survivors with CPC 1–2 (mean DPLR 108.2±6.3, p=0.0348 for paired comparison between both groups).

Table 1 Hypertension, n (%) 235 (54.9) Diabetes, n (%) 113 (26.4) Dyslipidaemia, n (%) 171 (40.0) Smocking habit, n (%) 208 (48.5) Time to ROSC mean ± SD, min 26.6±18.6 Mean arterial pressure at HA mean±DS, mmHg 81.3±22.1 pH at HA mean ± SD 7.18±0.16 Lactic at HA mean ± SD 6.37±4.42 ROSC: return of spontaneus circulation; HA: hospital admission.

Conclusion

Our findings reflect the impact of inflammation in neurological outcomes after OHCA treated with TTM. Major increases of PLR constitute a novel marker of poor prognosis during early assessment of OHCA patients.
P5356NT-proBNP is a valuable diagnostic tool of heart failure even during post partum period
Authors: Squillace M , Gherbesi E , Schiavone M , Gobbi C , Malanchini G , Denora M , Mallia V , Schillaci M , Ossola M W , Bonanomi C , Lombardi F
Published: October 2019

Background

Post-partum period is characterized by complex haemodynamic changes that may lead to heart failure (HF) in a minority of patients. B-type natriuretic peptides inactive amino terminal fragment (NT-proBNP) is an established biomarker in the management of HF. Patients presenting with dyspnea are considered at high risk of HF if NT-proBNP is above 125 pg/ml. Higher levels of NT-proBNP in the post natal period were reported to be associated with increased risk of cardiovascular events, but there is no defined cut-off value established for prediction of HF in this setting.

Purpose

We conducted this study to identify an adequate cut-off value which would predict haemodynamic overload among post-partum women.

Methods

All women who gave informed consent during an obstetric clinical evaluation at our tertiary centre between 01/01/2018 and 30/09/2018 were included in the study. NT-proBNP was measured within 24 hours from delivery. The primary endpoint of the study was the development of signs and symptoms of heart failure (with the need of intravenous diuretics or a cardiological evaluation) within 15 days after delivery. We therefore analyzed the ability of different cut-off of NT-proBNP values in predicting the primary outcome. Confidence intervals (CI) for sensitivity and specificity were calculated with the Wilson score method.

Results

252 women were included in the study. Eleven of them developed in the study timeframe signs and symptoms of HF (4.3%); all of them were treated with diuretics. Nine patients were evaluated with echocardiography and 3 of them required cardiological counseling. The cut-off value of 600 pg/mL was found to have the best sensitivity (73%, CI 95% 0.43–0.9), specificity (98%, CI 95% 0.95–0.98), positive likelihood ratio (29, CI 95% 12–69) and negative likelihood ratio (0.28, IC 95% 0.10–0.70). The diagnostic odds ratio was 104 (CI 95% 22–494, p<0.001). Mean NT-proBNP was 169±121 pg/mL (cutoff <600 pg/mL) versus 852±245 pg/mL.

Different cut-off evaluated NT-proBNP value (pg/mL) Specificity Sensibility Diagnostic Odds ratio 125 42 81 3.4 (95% CI 0.7–16, p=0.1) 300 85 72 14 (95% CI 4–62, p<0.01) 600 98 73 104 (95% CI 22–494, p<0.01) 700 98 66 65 (95% CI 12–341, p<0.01)

Conclusion

Our study suggests that NT-proBNP higher than 600 pg/mL is a high risk marker for developing HF in the post partum period. This value is slightly higher compared to the one adopted among the general population for diagnosis of HF and may reflect the peculiar haemodynamic changes of this setting.
P5386Transplantation of endothelial progenitor cells in the treatment of coronary artery microembolism in rats
Authors: Xue Y , Zhang P , Miao G , Zhou B
Published: October 2019

Objective

As the impairment of myocardial micro-environments due to coronary micro-embolization (CME) compromises the treatment effect of percutaneous coronary intervention and leads to adverse prognosis, we hypothesized that endothelial progenitor cells (EPCs) transplantation could improve cardiac function in the condition of CME.

Materials and methods

Low- (2×105) and high- (2×106) dose rat bone marrow-derived EPCs were transplanted in a model of CME. To develop a CME model, rats were injected with autologous micro-blood clots into the left ventricle. Echocardiography was examined before and 1, 7, and 28 days after EPC transplantation; serum cTNI, vWF,and cardiac microRNA expression were examined one day after EPCs transplantation. Heart morphology and VEGF, vWF, and bFGF expression were examined one day after EPC transplantation.

Figure 1. Results

Results

After 10 days of culture inductions, BM-EPCs have high purity as confirmed by flow cytometry. Cardiac function reflected by LVEF significantly decreased after CME treatment and rescued by low-dose EPC. Compared to the sham group, cTNI, and vWF serum levels increased significantly after CME treatment and rescued by low-dose EPC and high-dose EPC. Low-dose EPC treatment decreased myocardial necrosis and fibrosis and elevated cardiac expression of VEGF and vWF, while decreasing the cardiac expression of bFGF. Low-dose EPC treatment significantly suppressed cardiac expression of microRNA-19a but significantly enhanced microRNA-21, microRNA-214, and microRNA-486-3p expression. In conclusion, our results indicate that low-dose EPC transplantation may play a pro-angiogenic, anti-fibroblast, anti-fibrosis, and anti-necrosis role and enhance cardiac function in a rat model of CME through a microRNA-related pathway.

Acknowledgement/Funding

Supported by the State Key Laboratory of Low-Dimensional Quantum Physics Open Project Fund (No. KF201608)
P5392Epicardium derived cells promote sympathetic ganglionic outgrowth towards myocardium in vitro
Authors: Ge Y , Smits A M , Van Munsteren J C , Van Herwaarden T , Vegh A M D , Goumans M J T H , Schalij M J , De Ruiter M C , Jongbloed M R M
Published: October 2019

Background

The autonomic nerve system is essential to maintain homeostasis in the body. In the heart, autonomic innervation is important for adjusting the physiology to the continuously changing demands such as stress responses. After cardiac damage, excessive neurite outgrowth, referred to as autonomic hyperinnervation, can occur which is related to ventricular arrhythmias and sudden cardiac death. The cellular basis for this hyperinnervation is as yet unresolved. Here we hypothesize a role for epicardium derived cells (EPDCs) in stimulating sympathetic neurite outgrowth.

Purpose

To investigate the potential role of adult EPDCs in promoting sympathetic ganglionic outgrowth towards adult myocardium.

Method

Fetal murine superior cervical ganglia were dissected and co-cultured with activated adult mesenchymal epicardium-derived cells (EPDCs) or/and adult myocardium in a 3D collagen gel culture system. Four experiment groups were included: Group 1: Vehicle cultures (ganglia cultured without EPDC/myocardium) (n=48); Group 2: ganglia co-cultured with EPDCs (n=38); Group 3: ganglia co-cultured with myocardium (n=95); and group 4: ganglia co-cultured with both EPDCs and myocardium (n=96). The occurrence of neurite outgrowth was assessed in each group. The density of neurites that showed directional sprouting (i.e. sprouting towards myocardium) was assessed as well with a semi-automatic quantification method. Finally, sub-analyses were made by taking gender into account.

Results

Cervical ganglia cultured with EPDCs alone (group 2) showed increased neurite outgrowth compared to vehicle cultures (group 1), however the neurites did not show directional sprouting towards EPDCs. When co-cultured with myocardium (group 3), directional neurite outgrowth towards myocardium was observed. Compared to the ganglia-myocardium co-cultures, directional outgrowth was significantly increased in co-cultures combining myocardium and EPDCs (group 4), and the neurite density was also significantly augmented. Comparison between males and female ganglia demonstrated that more neurite outgrowth occurred in female-derived ganglia than in male-derived ganglia under the same co-culture conditions.

Conclusion

Activated adult EPDCs promote sympathetic ganglionic outgrowth in vitro. Sex differences exist in the response of ganglia to EPDCs, and female-derived ganglia appear more sensitive to EPDC-signalling. Results support a role of EPDCs in cardiac autonomic innervation and open avenues for exploring of their role in ventricular hyperinnervation after cardiac damage.
P5397Mesenchymal stem cells derived from bone marrow promotes cardiomyocytes survival under hypoxia through exosomal miR-210
Authors: Cheng H , Song X Y , Chen L , Xu R D , Qin Q , Fu M Q , Qian J Y , Zou Y Z , Ma J Y , Ge J B
Published: October 2019

Mesenchymal stem cells derived from bone marrow promotes cardiomyocytes survival under hypoxia through exosomal miR-210

Background

A paracrine effect was regarded as the key mechanism involved in the MSC (mesenchymal stem cell)-based treatment for myocardial infarction. In our pilot experiments, hypoxia remarkably promotes MSC to paracrine exosomal miR-210, which could significantly enhance the cardiomyocytes survival in hypoxic incubation, suggesting that exosomal miR-210 played critical roles in the favorable paracrine effect of MSC on cardiomyocytes.

Purpose

The aim of this study was to investigate the important mechanism by which MSCs promote the tolerance of cardiomyocytes to hypoxia by secreting exosomal miR-210.

Methods and results

The exosomes were isolated from MSCs conditioned medium through ultracentrifugation, and we detected that miR-210 was the most abundant in MSC-exosome and increased most prominently in the hypoxia. The extracted exosomes were prepared for conditioned medium and the effect on myocardial protection was examined. The viability of control group was much better than the cardiomyocytes treated with hypoxia, but it was further increased in the presence of MSC-exosome, however, measurement was significantly lower in cardiomyocytes in hypoxia with exosomes derived from MSCs treated with GW4869. Subsequently, the co-localization of miR-210 with exosome-specific surface markers CD81 and CD63 were observed by immunofluorescence technique. Continuous magnetic live cell imaging was used to observe the uptake of exosome by cardiomyocytes, and fluorescence localization was used to observe the localization of miR-210 with Cy3 fluorescence in cardiomyocytes. Then, we demonstrated that MSCs exosomal miR-210 exerts the cardioprotective effect by regulating the AIFM3 (apoptosis-inducing factor mitochondria-associated protein 3), and we directly overexpressed miRNA-210 in cardiomyocytes and the results showed that the regulatory activity of the intake of exosomal miR-210 was consistent with that of the biological exosomal miR-210. Finally, we verified the protective effect on the ischemic myocardium by constructing rat myocardial infarction models. The level of apoptosis was detected at 1 week after myocardial infarction. The left ventricular ejection fraction and ventricular remodeling were measured at 4 weeks. In vivo, we demonstrated that explanted miR-210 from transplanted MSCs significantly reduced myocardial necrosis and apoptosis induced by ischemia and improved cardiac function and myocardial remodeling.

Conclusion

Here, we show that the exosomal miR-210 secreted by MSCs significantly increase the viability of cardiomyocytes and cardiac function. These findings suggest that exosomal miR-210 is a key effector that mediates the protection against hypoxia.

Acknowledgement/Funding

National Natural Science Foundation of China (Grant Nos. 81470467)
P5402Inhibition of microRNA-210 as a novel therapeutic strategy to protect against atherosclerosis development
Authors: Alexandru N , Safciuc F , Tanko G , Constantin A , Nemecz M , Filippi A , Dragan E , Georgescu A
Published: October 2019

Background

MicroRNAs are involved in many processes such as cell proliferation and differentiation, angiogenesis, apoptosis, mitochondrial metabolism and DNA damage repair. Circulating levels of microRNA-210 (miR-210) are associated with the risk for cardiovascular mortality at patients with coronary artery disease.

Purpose

The aim was to investigate the effects and involved mechanisms of a novel treatment, miR-210 inhibitor (antagomiR-210), on the activation of inflammation and immune system, and overproduction of reactive oxygen species in atherosclerosis.

Methods

Golden Syrian hamsters were divided into: (1) simultaneously hypertensive - hyperlipidemic (HH) by combining two feeding conditions for 4 months, that mimic atherosclerosis; (2) HH with subcutaneous injection at months 1,2,3 containing antagomiR-210, or scramble (Scr)-miR negative control, or vehicle (phosphate-buffered saline, PBS) alone; (3) controls (C), age-matched normal healthy animals.

Results

The results showed that atherosclerosis significantly increased miR-210 levels in circulation, liver and thoracic aorta, which were abolished by antagomiR-210 administration. The preventive treatment of atherosclerosis with antagomiR-210 induced the following effects: (i) reduced the cholesterol, triglyceride and hepatic enzyme levels in plasma; (ii) increased the levels of circulating endothelial progenitor cells and reduced circulating microvesicle concentrations; (iii) improved endothelial cell functions; (iv) lowered inflammation by the reduction of TNF-α levels in plasma and infiltrated macrophage number into liver and thoracic aorta; (v) diminished immune system activation by decreasing the PD-1 levels in circulation, PD-L1/PD-L2 expression in liver/thoracic aorta and T cell number infiltrated into liver/thoracic aorta; (vii) reduced oxidative stress by decreasing O2·− generation into liver/thoracic aorta; (viii) lowered the expression of miR-210 target protein, protein tyrosine phosphatase 1B (PTP1B), in plasma/liver/thoracic aorta, and of its downstream molecules (PI3K, AKT1/2/3, eNOS, ERK1/2) in liver and thoracic aorta.

Conclusion

The results revealed the antagomiR-210 ability to modulate the pro-inflammatory, immune-stimulatory and pro-oxidant microenvironment within the atherosclerotic animal model, via direct targeting to PTP-1B and PI3K/AKT/eNOS and MAPK/ERK/ROS as downstream pathways.

In summary, our data provide new insight in molecular basis of an encouraging therapeutic strategy based on miR-210 inhibition for the treatment of atherosclerosis and cardiovascular disease.

Acknowledgement/Funding

CNCS-UEFISCDI, projects no. PN-III-P1-1.2-PCCDI-2017-0527 and no. PN-III-P1-1.2-PCCDI-2017-0797, and by the Romanian Academy
P5413Effect of empagliflozin as add-on therapy on serum uric acid level in patients with type 2 diabetes hospitalized for acute decompensated heart failure: a prospective randomized controlled study
Authors: Tamaki S , Yamada T , Morita T , Furukawa Y , Iwasaki Y , Kawasaki M , Kikuchi A , Kawai T , Seo M , Abe M , Nakamura J , Yamamoto K , Fukunami M
Published: October 2019

Background

Elevated serum uric acid (UA) level has been shown to be associated with reduced survival among patients (pts) with heart failure. Sodium glucose cotransporter 2 (SGLT2) inhibitors have been reported to lower serum uric acid level in pts with type 2 diabetes mellitus (T2D). Empagliflozin, one of the SGLT2 inhibitors, has been shown to reduce the risk of cardiovascular mortality in T2D pts with cardiovascular disease, and involvement of UA lowering effect by empagliflozin in the reduction of cardiovascular mortality has been suggested. However, little is known about the effect of empagliflozin as add-on therapy on serum UA level in T2D pts with acute decompensated heart failure (ADHF).

Purpose

We sought to elucidate the effect of empagliflozin as add-on therapy on serum UA level in T2D pts with ADHF.

Methods

We enrolled 38 consecutive T2D pts admitted for ADHF. On admission, enrolled pts were randomly assigned in a 1:1 ratio to either empagliflozin add-on therapy (EMPA(+)) or conventional glucose-lowering therapy (EMPA(−)). All pts in EMPA(+) group received empagliflozin (10 mg/day) throughout the study period. Left ventricular ejection fraction (LVEF) was measured at baseline using echocardiography. Body weight and vital signs, such as blood pressure and heart rate, were measured, and blood and urine samples were collected at baseline and 1, 2, 3 and 7 days after randomization. Renal handling of UA was evaluated by fractional excretion of UA (FEUA).

Results

Twenty pts were assigned to the EMPA(+) group, and 18 pts were assigned to the EMPA(−) group. There were no significant baseline differences in LVEF, plasma brain natriuretic peptide level, body mass index, or serum creatinine level between the EMPA(+) and EMPA(−) groups. In addition, prevalence rate of hyperuricemia, serum UA level, and FEUA did not significantly differ between the two groups at baseline. However, there was significant difference in the change in serum UA level from baseline at 2, 3 and 7 days after randomization between the two groups (Figure A). As a result, serum UA level was significantly lower in the EMPA(+) group than in the EMPA(−) group at 7 days after randomization (6.2±1.8 mg/dL vs 7.8±1.8 mg/dL, p=0.0127). Moreover, FEUN of the EMPA(+) group was significantly higher at 1, 2 and 7 days after randomization (Figure B), which suggested that serum UA level was lowered in the EMPA(+) group by increased urinary excretion of UA.

Figure 1

Conclusions

This study demonstrated that empagliflozin as add-on therapy can lower serum UA level in T2D pts with ADHF through the effect on the urinary excretion rate of UA.
P5421Prevalence of electromagnetic interference from left ventricular assist devices in patients with implantable cardioverter defibrillator/pacemakers
Authors: Kooij C , Yalcin Y C , Theuns D A M J , Constantinescu A A , Brugts J J , Manintveld O C , Yap S C , Szili-Torok T , Bogers A J J C , Caliskan K
Published: October 2019

Background

Many patients eligible for left ventricular assist device (LVAD) therapy already have an implantable cardioverter defibrillator (ICD) and/or pacemaker (PM). However, electromagnetic interference (EMI) between the LVAD and ICD/PM devices could be cumbersome.

Purpose

The aim of this study was to investigate the prevalence of EMI between different types of ICD/PM in patients implanted with an LVAD.

Methods

Data was obtained through a retrospective electronic patient database analysis of all LVAD patients (including HeartMate II (HMII) and HeartMate 3 (HM3)), from our tertiary referral center, from December 2006 to February 2019. Device switches have also been taken into account due to elective replacement. Electromagnetic interference was defined as ICD/PM telemetry interference (i.e. the inability to interrogate ICD/PM)

Results

In total, 109 patients received an LVAD (mean age 52±12, 83% male), Of these, 86 (79%) patients had an ICD/PM at LVAD implantation. One patient with ICD/PM was excluded from further analysis because of missing follow-up data. Among the 85 patients (45 HM II and 40 HM3), 11 (13%) experienced EMI; 5 (11%) with a HM II and 6 (15%) with a HM3 (p=0.59). The implanted ICD/PM devices were from Medtronic (n=25), Abbott (n=23), Biotronik (n=18), Boston Scientific (n=18), and Microport (n=1). EMI with the HM II was present in St Jude/Abbott devices (type 1 Atlas, 1 Unify, 1 Fortify, and 2 Promote). In HM 3 LVAD patients, EMI was observed in Biotronik devices (1 Lumax, 1 Ilivia, 1 Ilesto, and 2 Iperia) and Medtronic (Claria).

Conclusion

In our cohort of HM II and HM 3 LVAD patients, at least one in seven patients experienced EMI from either the HM II or HM3 LVAD with the ICD/PM. Electromagnetic interference from HM II LVADs was mainly present in patients with St Jude/Abbott ICD/PM devices However, in the HM3 patients, EMI was mainly present in patients with Biotronik devices, which is not yet widely known!
P5446Circulating long non-coding RNA ENSTehz746.04020507296 is a prognostic indicator in patients with dilated cardiomyopathy
Authors: Chen C , Zhang X D , Wang D W
Published: October 2019

Background

Long non-coding RNAs (lncRNAs) participate in the pathogenesis of cardiovascular diseases. However, whether circulating lncRNAs serve as dilated cardiomyopathy (DCM) biomarkers remains unclear.

Methods

Totally, 266 controls and 818 patients were enrolled. Firstly, microarray-based circulating lncRNA profiling was performed in 10 normal controls and 10 patients with DCM. Secondly, the top twenty differentially expressed lncRNAs were validated by quantitative real-time PCR in 64 controls and 64 DCM patients. Moreover, lncRNA-sequencing was performed in three human heart-derived cell types and the correlation between circulating lncRNAs levels and the severity of heart failure was evaluated in validated population. The validated two lncRNAs were assessed in 198 DCM patients and 198 matched controls. Finally, the sensitivity and specificity of circulating lncRNAs expression in DCM diagnosis were evaluated using receiver-operating characteristic curve analysis, while Cox regression and Kaplan-Meier curve analysis were further performed in 552 DCM patients.

Results

Eight candidate lncRNAs biomarkers were obtained after microarray screening and real-time PCR validation. Among them, five were validated in the second cohort. However, only the circulating levels of lncRNA ENSTehz746.04020507296 and ENSTehz746.04020532365 were significantly correlated with the cardiac function, as well as detectable in at least one of the human heart -derived cell types by lncRNA-seq. Importantly, low circulating ENSTehz746.04020507296 level was associated with high event-free survival in patients with DCM.

Conclusions

Circulating lncRNA ENSTehz746.04020507296 was a prognostic biomarker in patients with DCM.
P5451Catestatin and chronic heart failure patients with an acute decompensation event: clinical characteristics and 30-day all-cause mortality
Authors: Borovac J A , Glavas D , Susilovic Grabovac Z , Rusic D , Stanisic L , Bradaric A , Ticinovic Kurir T , Bozic J
Published: October 2019

Background

Catestatin (CST) is a cardiovascular regulator with pleiotropic systemic functions that might affect the course of acutely decompensated heart failure (ADHF).

Purpose

To determine the association of serum CST with the 30-day all-cause mortality and to compare clinical and laboratory parameters between ADHF patients within the lowest vs. highest quartile of CST concentration.

Methods

Eighty-two consecutive ADHF patients, as adjudicated per ESC 2016 HF criteria, were enrolled in the study during 2018–2019.

Results

Mean age of the enrolled cohort was 70.8±9.3 years and 54.9% were women. Seventy percent of patients were in NYHA III functional class and nearly half had a reduced LVEF. Median CST value was 5.6 ng/mL (IQR 3, 12). During the 30-day follow-up, ten patients died (12.2%) due to all causes. CST levels were significantly higher among patients that died compared to survivors (21.9±6.3 vs. 10.2±1.5 ng/mL, p=0.0139, respectively). Patients in the highest CST quartile had higher mortality and disease burden accompanied by more prominent laboratory abnormalities, compared to patients in the lowest CST quartile. Compared groups did not significantly differ in terms of dosages and type of baseline HF pharmacotherapy.

Table 1. Clinical characteristics Variable Lowest CST quartile (<3 ng/mL) Highest CST quartile (>12 ng/mL) p-value Age, years 72.8±8.3 70.0±7.9 0.281 Women, % 45.0 60.0 0.342 LVEF, biplane Simpson, % 39.0 41.0 0.645 30-day all-cause mortality, % 0.0 20.0 0.035 Mean NYHA functional class 2.83±0.38 3.21±0.42 0.007 Mean CKD stage, CKD-EPI 2.37±0.83 3.06±0.99 0.029 Mean arterial pressure, mmHg 99.7±17.8 100.1±19.2 0.953 NT-proBNP, pmol/L 535.3±522.4 1550.0±992.2 0.040 C-reactive protein, mg/L 9.37±7.47 32.90±18.35 0.015 High-sensitivity cardiac Troponin I, ng/L 20.60±18.05 30.02±27.38 0.256 Creatinine, μmol/L 102.9±38.9 150.6±91.2 0.038 Urea, mmol/L 9.6±3.5 14.3±7.1 0.012 Neutrophil-to-lymphocyte ratio 3.6±1.9 5.4±3.1 0.045 Hemoglobin, g/L 137.3±17.4 124.6±18.8 0.038

Figure 1. CST and 30-day mortality

Conclusions

Higher levels of catestatin measured during the hospitalization event among ADHF patients are associated with 30-day all-cause mortality and worse in-hospital profile thus might facilitate short-term prognosis.

Acknowledgement/Funding

None