scholarly journals The relationship between glycosylation of proBNP at threonine 71, BNP, BNP1–32 and obesity in patients with heart failure

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
L.K Lewis ◽  
S.D Raudsepp ◽  
T.G Yandle ◽  
C.J Pemberton ◽  
R.N Doughty ◽  
...  
Keyword(s):  
Heart Failure ◽  
New Zealand ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Funding Source ◽  
Obese Patients ◽  
Ventricular Ejection Fraction ◽  
National Budget ◽  
National Heart Foundation ◽  
Public Grant

Abstract Background Heart failure (HF) is a leading cause of morbidity and mortality worldwide. Measurement of BNP and NTproBNP are used in HF for diagnosis and prognosis but levels of these peptides are inappropriately low in obesity, a condition which is associated with increased HF. Cleavage of proBNP to produce BNP and NT-proBNP requires proBNP to be unglycosylated at threonine 71 (T71). Gycosylation at T71 is affected by obesity, resulting in lower plasma NT-proBNP concentrations in patients with higher BMI. However the relationships between BMI, proBNP glycosylation and BNP (particularly the bioactive cardio-protective peptide BNP1-32) have not previously been described. Methods Validated in-house assays for BNP, BNP1-32, proBNP, proBNP unglycosylated at T71 (NG-T71) and the commercial Roche assay for NT-proBNP were applied to plasma samples obtained from patients with HF (n=321, PEOPLE study: Prospective Evaluation of Outcome in Patients with Left Ventricular Ejection Fraction). Results Median (IQR) concentrations of BNP, BNP1-32, proBNP, NG-T71 and NTproBNP were 10.7 (5–21), 5 (2–9), 27.8 (9–62), 6.2 (3–22) and 217 (104–425) pmol/L respectively. BMI was inversely related to NG-T71, NT-proBNP, BNP and BNP1-32 (r=−0.19, −0.40, −0.36 and −0.34 respectively, all p<0.01) but not proBNP (r=0.11, ns). ProBNP levels in patients with BMI above or below 30 kg/m2 were similar (29.8 (11.2–56.6) and 22.5 (3.9–65) pmol/L, p=0.51), whereas NG-T71, NT-proBNP, BNP and BNP1-32 levels were increased (p<0.001) in patients with BMI <30 (11.6 (3–25.6), 263 (153–486), 13.8 (6.5–25.5) and 6.3 (2.8–10.4)) compared to BMI >30 (3 (1–16), 127 (63–274), 7.8 (3–14) and 3.6 (1.1–7) respectively. The BMI >30 group had increased ProBNP:NT-proBNP, ProBNP:BNP and ProBNP:BNP1-32 ratios (all p<0.001) and proBNP:NG-T71 (p=0.037), whereas ratios of NG-T71 to BNP, BNP1-32 or NT-proBNP were not related to BMI. Patients with diabetes (n=90) also had lower BNP, BNP1-32 (both p<0.01), NG-T71 and NT-proBNP concentrations (both p<0.05), but not proBNP (p=0.46), and a trend towards a higher proBNP:BNP1-32 ratio (p=0.06). Discussion and conclusion The negative association between BMI and plasma NT-proBNP and BNP is not well understood. We recently reported that obese patients with HF have reduced circulating levels of proBNP unglycosylated at T71. In this expanded sample we show that whilst proBNP remains unaffected by BMI, both immunoreactive BNP and more specifically bioactive BNP1–32 levels, and NT-proBNP, are decreased with obesity in conjunction with increased glycosylation at T71. Increased glycosylation at proBNP-T71 reduces the amount of proBNP cleaved to form NT-proBNP and BNP resulting in decreased production and lowered circulating concentrations of these clinically used marker peptides. Our results provide a robust mechanism to explain the reduction in NT-proBNP and BNP levels observed in obese patients and confirm this is associated with reduced bioactive BNP1–32. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): National Heart Foundation of New Zealand, nHealth Research Council of New Zealand

Right ventricular speckle tracking in patients with heart failure – a comparison of right ventricular measures

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
I.J Lundorff ◽  
M Sengeloev ◽  
S Pedersen ◽  
D Modin ◽  
N.E Bruun ◽  
...  
Keyword(s):  
Risk Factors ◽  
Heart Failure ◽  
Right Ventricular ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Funding Source ◽  
Private Company ◽  
Ventricular Ejection Fraction ◽  
Risk Of Mortality ◽  
Patients With Heart Failure

Abstract Background RV dysfunction is associated with increased mortality and morbidity in patients with heart failure. Due to the complex shape and position of the RV, assessing RV function from echocardiographic images remains a challenge. Purpose We have previously found that global longitudinal strain from 2DSTE is superior to left ventricular ejection fraction (LVEF) in identifying HFrEF patients with high risk of mortality. In this study we wanted to examine RV 2DSTE in patients with HFrEF and compare its prognostic value to conventional RV measures. Methods and results Echocardiographic examinations were retrieved from 701 patients with HFrEF. RV estimates were analysed offline, and end point was all-cause mortality. During follow-up (median 39 months) 118 patients (16.8%) died. RV GLS and RV FWS remained associated with mortality after multivariable adjustment, independent of TAPSE (RV GLS: HR 1.07, 95% CI 1.02–1.13, p=0.010, per 1% decrease) (RV FWS: HR 1.05, 95% CI 1.01–1.09, p=0.010, per 1% decrease). This seemed to be caused by significant associations in men as TAPSE remained as the only independent prognosticator in women. All RV estimates provided prognostic information incremental to established risk factors and significantly increased C-statistics (TAPSE: 0.74 to 0.75; RVFAC: 0.74 to 0.75; RVFWS: 0.74 to 0.77; RVGLS: 0.74 to 0.77). Conclusions RV strain from 2DSTE was associated with mortality in patients with HFrEF, independent of TAPSE and established risk factors. Our results indicate that RV strain is particularly valuable in male patients, whereas in women TAPSE remains a stronger prognosticator. RV GLS and the risk of mortality Funding Acknowledgement Type of funding source: Private company. Main funding source(s): PGJ reports receiving lecture fee from Novo Nordisk.

GENECHOC study: genetic markers of arrhythmic risk in heart failure

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
S Anys ◽  
S Rigade ◽  
S Rigade ◽  
E Baron ◽  
E Baron ◽  
...  
Keyword(s):  
Heart Failure ◽  
Genetic Markers ◽  
Left Ventricular ◽  
European Ancestry ◽  
Left Ventricular Ejection ◽  
P Value ◽  
Funding Source ◽  
Ventricular Ejection Fraction ◽  
Cardioverter Defibrillator ◽  
Genome Wide

Abstract Background Ventricular arrhythmic events are responsible for 50% of death in heart failure but no reliable predictive marker is known to discriminate patients at risk of fatal arrhythmia. Interestingly, familial predisposition has been reported suggesting a role of genetic factors. Purpose Identify genetic markers increasing the arrhythmic risk in heart failure population. Method We prospectively included heart failure patients with left ventricular ejection fraction (LVEF) under 35% and a cardioverter defibrillator in primary prevention in 22 French centres between 2009 and 2017. Patients were followed for 72 months and divided into two groups: cases with an arrhythmic event during follow-up and controls. A Genome Wide Association Study (GWAS) was done. Single Nucleotide Polymorphisms (SNPs) genotyping was performed on Affymetrix Axiom Precision Medicine Research Array plates. To complement the directly genotyped SNPs we performed large-scale imputation based on the Haplotype Reference Consortium European ancestry panel leading to a dataset of 7,5 million of SNPs. Results 332 cases and 567 controls were included (86% men, mean age at implantation 52±11 years). 78% of patients had ischaemic cardiopathy, 20% had dilated cardiomyopathy. Mean LVEF was 27±5%. No statistical difference was found between cases and controls on clinical parameters, biological results, electrocardiographic measures. No locus shows genome-wide significant association (p<5.10–8) on the GWAS analysis. However, 16 signals with a p-value between 5.10–8 and 5.10–5 were investigated. eQTL and chromatin conformation point to 35 genes with cardiac expression previously associated with heart failure, cardiomyopathies, cardiogenesis, arrhythmias and inflammation. Variants identified point to regulatory regions of the genome and may then propose a molecular mechanism predisposing patients to arrhythmias. Conclusion No locus raises genome-wide significance, but several signals with a nominal p-value point to relevant genes and pathways. Replication of the GWAS is ongoing on a cohort of 156 new patients with a less severe cardiopathy implanted with a cardioverter defibrillator in secondary prevention. Funding Acknowledgement Type of funding source: Public hospital(s). Main funding source(s): Nantes University Hospital

Residual inflammation is a major determinant of myocardial recovery and cardiovascular outcome in takotsubo patients

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
L Lachmet-Thebaud ◽  
B Marchandot ◽  
K Matsushita ◽  
C Sato ◽  
C Dagrenat ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiac Death ◽  
Left Ventricular ◽  
Cardiovascular Outcome ◽  
Left Ventricular Ejection ◽  
Funding Source ◽  
Ventricular Ejection Fraction ◽  
Cox Regression Analysis ◽  
The Impact

Abstract Background Recent insights have emphasized the importance of myocardial and systemic inflammation in Takotsubo Syndrome (TTS). Objective In a large registry of unselected patients, we sought to evaluate whether residual high inflammatory response (RHIR) could impact cardiovascular outcome after TTS. Methods Patients with TTS were retrospectively included between 2008 and 2018 in three general hospitals. 385 patients with TTS were split into three subgroups, according to tertiles of C-reactive protein (CRP) levels at discharge (CRP<5.2 mg/l, CRP range 5.2 to 19 mg/l, and CRP>19 mg/L). The primary endpoint was the impact of RHIR, defined as CRP>19 mg/L at discharge, on cardiac death or hospitalization for heart failure. Results Follow-up was obtained in 382 patients (99%) after a median of 747 days. RHIR patients were more likely to have a history of cancer or a physical trigger. Left ventricular ejection fraction (LVEF) at admission and at discharge were comparable between groups. By contrast, RHIR was associated with lower LVEF at follow-up (61.7 vs. 60.7 vs. 57.9%; p=0.004) and increased cardiac late mortality (0% vs. 0% vs. 10%; p=0.001). By multivariate Cox regression analysis, RHIR was an independent predictor of cardiac death or hospitalization for heart failure (hazard ratio: 1.97; 95% confidence interval: 1.11 to 3.49; p=0.02). Conclusions RHIR was associated with impaired LVEF recovery and was evidenced as an independent factor of cardiovascular events. All together these findings underline RHIR patients as a high-risk subgroup, to target in future clinical trials with specific therapies to attenuate RHIR. Main results Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): GERCA (Groupe pour l'Enseignement, la prévention et la Recherche Cardiovasculaire en Alsace)

scholarly journals Adipose-targeted overexpression of mitochondrial-targeted catalase does not improve cardio-metabolic parameters in mice with diet-induced obesity

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
A J Croft ◽  
C Kelly ◽  
D Chen ◽  
L Murtha ◽  
S Sugito ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Metabolic Dysfunction ◽  
Metabolic Complications ◽  
Ventricular Ejection Fraction ◽  
Cardiac Tissues ◽  
National Budget ◽  
Diet Induced Obesity ◽  
National Heart Foundation

Abstract Background Obesity is associated with significant cardio-metabolic complications. Adipokines, and cytokines released from adipose tissue (AT) stimulate excessive mitochondrial production of reactive oxygen species (ROS). ROS-mediated oxidative modifications is associated with development of insulin resistance and impaired cardiac function. We hypothesised that adipose-targeted overexpression of mitochondrial-targeted catalase (AT-mCAT) could lead to improvement in diet-induced cardio-metabolic dysfunction. Methods/Results mCAT (floxed) and AdipoQ-Cre mice were crossed to generate mice overexpressing catalase with a mitochondrial-targeting sequence predominantly in AT (AT-mCAT). Wild-type (WT) and AT-mCAT male mice were fed normal chow (NC) or high-fat/high-sucrose (HFHS) diet (36%fat/34%sucrose) for 4 months. At endpoint, echocardiography showed reduced cardiac output in all groups v WT NC (p<0.05); reduced IVSd in AT-mCAT NC and HFHS groups v WT NC (p<0.01); reduced left ventricular ejection fraction in AT-mCAT HFHS v WT NC (p<0.05) and no differences in fractional shortening or E/A ratio between groups. Glucose tolerance tests (2g/kg) showed impairment in WT HFHS and AT-mCAT HFHS v WT NC (p<0.01, p<0.05 respectively). Triglyceride levels were increased in WT HFHS and AT-mCAT HFHS v WT NC (p<0.05). Analysis of hypertrophic signalling in cardiac tissues by ELISA showed p-AKT/total Akt levels were decreased in AT-mCAT hearts regardless of diet (WT NC v AT-mCAT NC p<0.01; WT HFHS v AT-mCAT HFHS p<0.05). Conclusion Our results confirm previous findings that diet-induced obesity is a systemic condition. Targeting adipose tissue with mitochondrial catalase may not be adequate to prevent development of cardio-metabolic dysfunction. More systemic approaches may be required to combat obesity-induced cardio-metabolic impairment. FUNDunding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): National Heart Foundation of Australia

Partial normalisation of cardiac mechanics with active CRT in patients with chronic failure: a novel application of 3.0T CMR

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
A Koshy ◽  
J Gierula ◽  
M Paton ◽  
P Swoboda ◽  
A.G Toms ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiac Output ◽  
Ejection Fraction ◽  
Cardiac Mechanics ◽  
Left Ventricular ◽  
Cardiac Response ◽  
Left Ventricular Ejection ◽  
Funding Source ◽  
Ventricular Ejection Fraction ◽  
Heart Rates

Abstract Introduction Cardiac resynchronisation therapy (CRT) is a routine treatment for chronic heart failure (CHF) with reduced ejection fraction and conduction delay to improve prognosis. Cardiac mechanics in patients with CHF are believed to be altered from controls based on invasive and echocardiographic based data. Technological advancements in cardiac magnetic resonance (CMR) and devices enable investigation of the cardiac response to CRT over a range of heart rates. Methods Patients with a CRT-D device were enrolled from heart failure clinics at Leeds General Infirmary, UK. After a MRI safety assessment, a baseline device check was conducted by a cardiac physiologist. Left ventricular (LV) volumes and systolic BP were measured at baseline and heart rates of 75, 90, 100, 115, 125, and 140 (randomised order) with CRT active and intrinsic conduction. All scans were conducted using a 3.0 T Siemens Prisma MRI scanner. Analysis of the scans used commercially available software. LV contractility was derived as a ratio of the LV end systolic volume and systolic BP. A post scan device interrogation was conducted to assess for scanning safety. Control participants with a 3.0T MR-conditional dual chamber pacemakers completed a similar protocol. Results Scanning was conducted in 17 CRT patients and 13 controls with a pre and post device and lead interrogation. No patient experienced symptoms related to scanning or device failure. The mean LV ejection fraction at baseline in the CRT cohort was 33.7±12.9%. Left ventricular ejection fraction fell across both cohorts as paced heart rate increased with reduced deterioration in control patients and those with CRT active. Peak LV cardiac output was significantly higher during active CRT (p<0.05). LV contractility was relatively static with CRT disabled (r2=0.13, p=0.38) and improved with CRT active (r2=0.91, p=0.01) and in controls (r2=0.74, p=0.01). Peak LV strain occurred at 100bpm during active CRT and in control patients whereas CRT disabled resulted in earlier deterioration. Conclusion We have demonstrated improvements in cardiac output and contractility consequent to active CRT using 3.0T CMR and subsequently validated via strain analysis. CRT appears to partially normalise cardiac mechanics across the range of heart rates studied. Further work is required to explore this phenomenon on a cellular or metabolic level. Funding Acknowledgement Type of funding source: Private grant(s) and/or Sponsorship. Main funding source(s): AK is supported by an unconditional grant provided by Medtronic

Determinants and prognostic implication of improved left ventricular ejection fraction in chronic heart failure patients with reduced ejection fraction

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
K Hu ◽  
L Schregelmann ◽  
D Liu ◽  
B Lengenfelder ◽  
G Ertl ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Ejection Fraction ◽  
Survival Benefit ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Funding Source ◽  
Ventricular Ejection Fraction ◽  
Independent Determinant

Abstract Background Previous studies have demonstrated that left ventricular ejection fraction (LVEF) is not associated with overall survival in patients with chronic heart failure (CHF). This study aimed to examine if improved EF is associated with better survival in these patients. Methods Study subjects were selected from the database in the REDEAL trial, which included all patients with CHF and a LVEF of <50% referred to our hospital between 2009 and 2017. Of these, 902 patients completed at least twice echocardiography examinations (BL and FUP) at a minimal interval of 12 [median 17 (14–25)] months. Results At baseline, there were 522 patients with BL_EF >35% (aged 68±12 years, male 74.5%, median EF 44%) and 381 patients with BL_EF ≤35% (aged 65±13 years, male 74.5%, median EF 29%). Survival was similar between groups (76.6% vs. 73.8%, P=0.322). Over a median echocardiography follow-up of 17 months, FUP_ EF increased by 1.3% (−4.0–8.0%) in the subgroup of BL-EF>35% and increased by 11.0% (2.0–20.0%) in the subgroup of BL_EF≤35%. Survival analysis showed that absolute change in EF was significantly associated with survival in the subgroup of BL_EF≤35% but not in the subgroup of BL_EF>35%. Therefore, further analysis was conducted among patients in the subgroup of BL_EF≤35%. In this subset of BL_EF≤35%, improved EF was defined as a FUP_EF of >40%. 171 (44.9%) patients presented with improved EF, EF remained unchanged or reduced in the rest 210 patients (55.1%, FUP_EF≤40%). Patients with improved EF was associated with better survival over a median clinical follow-up of 19 (11–32) months (80.7% vs. 68.1%, P=0.001). Multivariable Cox regression analysis showed that improved EF remained an independent determinant of overall survival after adjusted for potential clinical covariates including age, sex, diabetes, hyperuricemia, renal dysfunction, coronary artery bypass grafting, sleep-disordered breathing, and prior ICD or CRT_D implantation (HR 0.59, 95% CI 0.38–0.91, P=0.018). In this subgroup of BL_EF≤35%, age and sex-independent determinants of improved EF included without prior myocardial infarction (OR 0.40, 95% CI 0.24–0.67, P<0.001), without ICD or CRT-D implantation (OR 0.32, 95% CI 0.17–0.61, P=0.001), and smaller LV end-diastolic diameter (OR=0.94, 95% CI 0.90–0.99, P=0.012). Conclusions Longitudinal improvement in LVEF is significantly associated with survival benefit in the subgroup of baseline EF≤35% but not in the subgroup of baseline EF>35%. In the subgroup of baseline EF≤35%, improved LVEF remains an independent determinant of survival benefit Determinants of improved LVEF in HF patients with baseline EF≤35% include without myocardial infarction, without ICD implantation, and smaller LV chamber at baseline. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): This work was supported by the German Federal Ministry of Education and Research

Expression of miRNA-21 level in hypertrophic cardiomyopathy patients with chronic heart failure and preserved left ventricular ejection fraction: results of a 6-year follow-up

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
V Davydova ◽  
T.G Bezhanishvili ◽  
M.E Filatova ◽  
S.E Andreeva ◽  
A.A Streltsova ◽  
...  
Keyword(s):  
Heart Failure ◽  
Hypertrophic Cardiomyopathy ◽  
Left Ventricular ◽  
Functional Class ◽  
Expression Level ◽  
Left Ventricular Ejection ◽  
Control Group ◽  
Funding Source ◽  
Ventricular Ejection Fraction ◽  
Saint Petersburg

Abstract Introduction Recently it is found that circulating miRNA-21 is associated with chronic heart failure (CHF) and ischemic heart disease. Its clinical significance in hypertrophic cardiomyopathy (HCM) and CHF with preserved left ventricular ejection fraction (LVEF) (≥50%) has to be investigated. Purpose The aim of this study was to analyze the expression of miRNA-21 in the peripheral blood of HCM patients and CHF with preserved LVEF (≥50%). Materials and methods From 2014 to 2019 years we examined 180 HCM patients. The study population consisted of 60 patients ≥19 years old (51.5 [36.2; 65.7]) with symptomatic HCM and CHF with preserved LVEF (≥50%). The diagnosis of HCM was established according to the guideline of the European society of cardiology on the diagnosis and treatment of HCM, 2014. The control group included 45 healthy donors without cardiovascular diseases and other severe pathologies, matched by age and sex with the studied group. Total RNA was extracted from plasma of patients. MiRNA-21 and reference RNA U6 cDNA was prepared based on StemLoop-technology. Expression was examined using semiquantitative RT-PCR protocol. Calculation of the relative gene expression level of miRNA-21 was done according to the standard procedure 2-ΔCt. IBM SPSS software package and Microsoft Excel 2010 were used for the statistical analysis of the collected data. Results The serum expression level of miRNA-21 in HCM patients (n=60) varied from 0.13 to 477.7 (4.92 [1.77; 13]) and was significantly higher than those in the control group (0.01 - 9.85 (0.84 [0.55; 1.23]), with statistically significant difference (p=0.001). The HCM group was divided according to CHF severity: I-II functional class (NYHA) (n=42) and III-IV functional class (NYHA) (n=18) subgroups. It was found a significant increase of expression microRNA-21 level in both subgroups HCM patients, compared with control group (p=0.001). The expression level of miRNA-21 also differed between HCM patients and CHF III-IV functional class (NYHA) vs those, who had CHF I-II functional class (NYHA) – 1.1–477.7 (13 [3.88; 41]) vs 0.1–119.4 (3.25 [1.41; 6.06]), respectively (p=0.003). In HCM patients and CHF III-IV functional class (NYHA) (n=18) the expression level of miRNA-21 positively correlated with LVEF (r=0.609; p<0.05). Conclusion HCM patients with CHF III-IV functional class (NYHA) and preserved LVEF (≥50%) demonstrated high expression level of miRNA-21. Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): Almazov Federal Medical Research Centre, Saint-Petersburg, Russian Federation, Pavlov University, L'va Tolstogo str. 6-8, Saint Petersburg, Russian Federation

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