bluuebunny/crossref_metadata_2025_split huggingface dataset:
P2563Effects of rivaroxaban on cardiac remodeling after experimental myocardial infarction in mice
Authors: Nakanishi N , Kaikita K , Ishii M , Oimatsu Y , Mitsuse T , Tsujita K 
Published: October 2019

Abstract

Background
Rivaroxaban, a direct activated factor X (FXa) inhibitor, has been established for prevention and treatment of arterial and venous thrombosis. Although FXa plays an important role in thrombosis, FXa also involves in inflammation via the protease-activated receptor (PAR)-1 and PAR-2 pathway. We assessed the hypothesis that rivaroxaban might protect cardiac remodeling after myocardial infarction (MI) in mice.

Methods
MI was induced in wild-type mice by permanent ligation of the left anterior descending coronary artery. At 1 day after MI, mice were randomly assigned to the rivaroxaban and vehicle groups. In the rivaroxaban group, the mice were provided with regular chow diet including rivaroxaban (2400ppm) after the randomization. We evaluated the cardiac function by echocardiography, expression of mRNA and protein in the infarcted and non-infarcted area 7 days after MI. Furthermore, we measured infarct size, infiltration of inflammatory cells by pathological analysis 7 days after MI.

Results
The fractional shortening (%FS) and Interventricular Septal thickness in diastole (IVSTd) was significantly improved 7 days after MI in the rivaroxaban group compared with the vehicle group (%FS, p=0.01; IVSTd, p=0.013). As for pathological analysis, rivaroxaban decreased infarct size (p=0.026) and the number of infiltrated macrophages in the non-infarcted area (p=0.011) compared with vehicle. The mRNA expression in tumor necrosis factor (TNF)-α, transforming growth factor (TGF)-β in the infarcted area and atrial natriuretic peptide (ANP) in the non-infarcted area was significantly lower in the rivaroxaban group compared with the vehicle (TNF-α, p=0.015; TGF-β, p=0.019; ANP, p=0.012). PAR-1 and PAR-2 mRNA expression in the infarcted area significantly decreased 7 days after MI in the rivaroxaban group compared with the vehicle (PAR-1, p=0.005; PAR-2, p=0.037). Furthermore, western blot analysis demonstrated that the phosphorylation of Extracellular Signal-regulated Kinase (ERK) and c-Jun N-terminal Kinase (JNK) in the non-infarcted area significantly decreased 7 days after MI in the rivaroxaban group compared with the vehicle (ERK, p=0.015; JNK, p=0.002).

Conclusions
The present study showed that rivaroxaban protected against cardiac dysfunction, probably due to the suppression of PAR-mediated increase of pro-inflammatory cytokines post-MI. Rivaroxaban might be potentially effective for improving the cardiac remodeling after MI.

Acknowledgement/Funding
This study was supported in part by trust-research grant from Bayer Yakuhin, Ltd.
P2576Sports in children and adolescents with congenital heart defects
Authors: Bauer U M M , Helm P , Siaplaouras J , Niessner C , Sticker E , Flemming M , Apitz C 
Published: October 2019

Abstract

Background
Age-appropriate physical activity is an important basis for healthy physical and mental development for children and adolescents with congenital heart defects (CHD)

Purpose
The main goal of this study was to learn more about the physical activity of young and adolescent CHD-patients to understand patient's needs physical activity and to improve the medical advice regarding physical activity and sports by taking the CHD-severity into account.

Methods
An online-questionnaire was developed. CHD patients registered in the German National Register for Congenital Heart Defects were invited by email/post to join the study. In total, 1,718 patients took part. 1,262 patients have finished the questionnaire and are included in the statistical analysis (average age: 11.6±3.1 years; 588 women). CHD severity: 411 patients with simple CHD, 423 with moderate CHD, 364 with complex CHD and 64 with unclassified CHD. The study participants were asked to answer questions regarding physical activity and (school) sports to evaluate their activity level and their individual needs regarding sports.

Results
We identified 831 (65.9%) patients who reported they were exercising sports for at least three days or more for 60 minutes or longer per week (simple CHD: 68.9%; moderate CHD: 64.5%; complex CHD: 63.5%; other CHD: 68.8%). Over all 47 patients (3.7%) stated that they had no regular school sports and 12 patients (1%) reported to have less than one regular sports lessen per week. Out of the 1,215 patients who reported to have regular school sports (simple CHD: 97.3%; moderate CHD: 98.1%; complex CHD: 94.5%; other CHD: 87.5%), the patients stated about how hard they usually work in a regular sports lesson as follows: “without sweating and without shortness of breath” (188 patients, 15.5%; simple CHD: 15.4%; moderate CHD: 17.1%; complex CHD: 14.8%; other CHD: 7.1%), “a little bit sweaty and a bit short of breath” (825 patients, 67.9%; simple CHD: 68.8%; moderate CHD: 65.3%; complex CHD: 68.9%; other CHD: 75%), “a lot of sweat and a lot of shortness of breath” (202 patients, 16.6%; simple CHD: 15.8%; moderate CHD: 17.6%; complex CHD: 16.3%; other CHD: 17.9%).

Conclusions
Overall, young and adolescent patients with CHD appear to be exercising sports regularly and are well integrated into school sports. Although there are slight differences between the individual degrees of CHD severity. These differences can be interpreted as minor fluctuations.
P2609H2FPEF score as a prognostic value in HFpEF patients
Authors: Sueta D , Nishihara T , Yamamoto E , Tsujita K 
Published: October 2019

Abstract

Background
The H2FPEF score is recognized as a simple method to diagnose heart failure (HF) with preserved left ventricular ejection fraction (HFpEF).

Purpose
We investigated the value of the H2FPEF score in predicting subsequent cardiovascular events in HFpEF patients.

Methods
This study was a retrospective, single-center, observational study. We calculated the H2FPEF scores for 404 consecutive HFpEF patients. Subjects were subdivided into low- (0–3), intermediate- (4–6), and high-score (7–9) groups and followed for 50-months. The primary and secondary endpoints were composite cardiovascular/ cerebrovascular events (cardiovascular death, non-fatal myocardial infarction, unstable angina pectoris, hospitalization for HF decompensation and non-fatal stroke) occurrence and HF-related events (hospitalization for HF decompensation) occurrence at 50-months, respectively.

Results
Kaplan–Meier analyses demonstrated a significantly higher incidence of cardiovascular/cerebrovascular events in proportion to a higher H2FPEF score (log-rank test, P=0.005). The HF-related event rate was higher in proportion to the H2FPEF score (log-rank test, P<0.001). Multivariate Cox hazard analyses identified the H2FPEF score (per 1 point) as an independent predictor of cardiovascular and HF-related events (Table, hazard ratio, 1.179; 95% confidence interval, 1.066–1.305; P=0.001 and hazard ratio, 1.288; 95% confidence interval, 1.134–1.463; P=0.001, respectively). Receiver operating characteristic analysis showed that the H2FPEF significantly predicted cardiovascular events (Figure A, AUC 0.626, 95% CI 0.557–0.693; P<0.001) and HF-related events (Figure B, AUC 0.680, 95% CI 0.600–0.759; P<0.001). The cutoff H2FPEF score was 5.5 for the identification of cardiovascular and HF-related events.

Conclusion
The H2FPEF score is a potentially useful marker for the prediction of cardiovascular and HF-related events in HFpEF patients.
P2617Activity of the adrenomedullin system to personalize post-discharge treatment in acute heart failure
Authors: Kozhuharov N , Wussler D , Sabti Z , Twerenbold R , Walter J , Du Fay De Lavallaz J , Strebel I , Breidthardt T , Mueller C 
Published: October 2019

Abstract

Objectives
Activity of the adrenomedullin system was quantified by using bioactive-adrenomedullin (bio-ADM), the biologically active moiety, and midregional proadrenomedullin (MR-proADM), a prohormone fragment, to 1) identify acute heart failure (AHF) phenotypes with disproportional benefit or harm from specific treatments at hospital discharge, 2) predict mortality, and 3) compare the prognostic utility of both biomarkers.

Methods
This prospective multicentre study using central adjudication of AHF measured bio-ADM in all patients and MR-proADM in a predefined subgroup in a blinded fashion on admission. Both biomarkers were measured at discharge as well. Interaction with specific treatments at hospital discharge and the biomarkers' prognostic utility during 365 days' follow-up were assessed.

Results
Among 1,886 patients with adjudicated AHF, 514 patients (27.3%) died during the 365 days' follow-up. Patients with bio-ADM plasma concentrations above the median were at a much higher risk of death (HR 1.87, 95% CI 1.57–2.24; p<0.001). After adjusting for age, creatinine plasma concentrations, and medical treatment at discharge, those patients derived disproportional benefit if treated with diuretics and/or angiotensin-converting-enzyme inhibitors/angiotensin receptor blocker (interaction p-values <0.05). These findings were confirmed only for the diuretics treatment when quantifying the adrenomedullin system using MR-proADM plasma concentrations (n=764). For predicting mortality, both biomarkers performed well and MR-proADM had a higher predictive accuracy as compared to bio-ADM (p<0.001).
Table 1. Interaction p-values in multivariate models using a cox proportional hazard analysis for predicting all-cause mortality at 365 days including age, bio-ADM or MR-proADM, creatinine at discharge, and medication at discharge Diuretics ACE inhibitors or ARB Beta blockers Aldosterone antagonists lg bio-ADM*, ng/l <0.001 0.011 0.760 0.175 lg bio-ADM†, ng/l <0.001 0.020 0.807 0.396 lg MR-proADM*, nmol/l 0.031 0.095 0.169 0.441 lg MR-proADM†, nmol/l 0.001 0.126 0.741 0.272 *At admission; †at discharge. ACE: Angiotensin-converting-enzyme; ARBs: Angiotensin receptor blocker; bio-ADM: bioactive adrenomedullin; MR-proADM: midregional proadrenomedullin.
Figure 1

Conclusion
Quantifying the activity of the adrenomedullin system helps to personalize post-discharge treatment and risk-prediction in AHF.

Acknowledgement/Funding
Swiss National Science Foundation, Swiss Heart Foundation, University of Base, Sphingotec
P2624Association between renal dysfunction and cardiac sympathetic innervation in patients with heart failure
Authors: Marsico F , Paolillo S , Gargiulo P , Esposito I , Dell'aversana S , Renga F , Esposito L , Perrone Filardi P 
Published: October 2019

Abstract

Introduction
In heart failure (HF) a strict interaction exists between heart and kidney. Previous studies reported a significant impact of sympathetic overdrive, that causes beta-adrenoceptor desensitization, in both renal and heart failure progression. It can be hypothesized that renal failure might be associated with impaired sympathetic activity assessed directly at the myocardial level in patients affected by HF.

Purpose
Aim of the present observational study was to assess the relationship between renal dysfunction and cardiac sympathetic innervation in HF patients with mildly and severely reduced ejection fraction (HFrEF and HFmEF).

Methods
Two-hundred and sixty-three patients (84% males; 66±10.8 years) with mild-to-severe HF (EF 31±6.8%) underwent iodine-123 meta-iodobenzylguanidine (123I-MIBG) myocardial scintigraphy to assess sympathetic innervation, evaluating early and late heart to mediastinum (H/M) ratios and washout rate. All patients also underwent clinical evaluation and venous blood sample collection for the assessment of serum creatinine and consequently the estimation of glomerular filtration rate (eGFR) by EPI formula.

Results
A direct correlation was found between EPI-eGFR and late H/M (r=0,215; p<0.001) (figure 1), with an inverse correlation between NYHA class and late H/M (r=0,152; p=0.013), and a direct correlation between left ventricular EF and late H/M (r=0,348; p<0.001). These results were not confirmed for early H/M, nor washout rate. Dividing the population in reduced eGFR and normal eGFR (cut-off ≤60 ml/min/1,73m2), a statistical significant reduction of late H/M value was found in patients with reduced eGFR (late H/M = 1,49±0,21) compared with patients with preserved eGFR (late H/M = 1,56±0,26) (p=0.020). In a multivariate model, adjusting eGFR for NYHA class and left ventricular EF, reduced eGFR and left ventricular EF remained significant predictors of reduced late H/M (p=0.006 and p<0.001, respectively).
Figure 1. linear regression curve

Conclusions
Patients with impaired renal function and HF show impaired cardiac sympathetic activity compared to HF patients with preserved renal function, and reduced eGFR estimated by EPI formula is a significant predictor of reduced late H/M evaluated by 123I-MIBG. Thus, in future studies, the combination of these two parameters might provide addictive prognostic information in HF patients.
P2630Incidence and prognostic impact of new-onset left bundle branch block in patients with heart failure and reduced ejection fraction
Authors: Kristensen S L , Roerth R , Jhund P S , Beggs S , Kober L , Abraham W T , Desai A , Solomon S , Packer M , Rouleau J , Zile M , Dickstein K , Petrie M C , McMurray J J V 
Published: October 2019

Abstract

Background
Cardiac resynchronization therapy (CRT) improves survival in patients with heart failure, reduced ejection fraction (HFrEF) and left bundle branch block (LBBB). However, little is known about the incidence of LBBB in HFrEF and the risk factors for developing this. We addressed these questions in the PARADIGM-HF and ATMOSPHERE trials.

Methods
We identified 7703 patients with a non-paced rhythm on their baseline ECG, a QRS<130 ms, and at least one follow-up ECG (done at annual visits and end of study). Patients were stratified by baseline QRS duration (≤100 ms - reference; 101–115 ms and 116–129 ms) and followed until development of QRS duration ≥130 ms with a LBBB configuration or latest available ECG. The crude LBBB incidence rate per 100 person-years (py) was identified in the three QRS duration subgroups. Additionally, we examined risk of the primary composite outcome of cardiovascular death or HF hospitalization, and all-cause mortality, in patients with incident LBBB vs. no incident LBBB.

Results
Overall, 313 of 7703 patients (4%) developed LBBB during a mean follow-up of 2.7 years, yielding an incidence rate of 1.5 per 100 py. The rate ranged from 0.9 in those with QRS ≤100 ms to 4.0 per 100 py in patients with QRS 116–129 ms. Other predictors of incident LBBB included male sex, age, lower LVEF, HF duration and absence of AF. The risk of the primary composite endpoint was higher among those who developed incident LBBB vs no incident LBBB; event rates 13.5 vs 10.0 per 100 py, yielding an adjusted HR of 1.43 (1.05–1.96). For all-cause mortality the corresponding rates were 12.6 vs 7.3 per 100 py; HR 1.55 (1.16–2.07) (Table 1).
Table 1. Risk of outcomes according to incident LBBB during follow-up No. events Crude rate per 100py Adjusted* HR (95% CI) HF hospitalization or CV death   No incident LBBB 2145 10.0 (9.6–10.4) 1.00 (ref.)   Incident LBBB 43 13.5 (10.0–18.2) 1.43 (1.05–1.96) All-cause mortality   No incident LBBB 1662 7.3 (6.9–7.6) 1.00 (ref.)   Incident LBBB 48 12.6 (9.5–16.7) 1.55 (1.16–2.07)

Conclusion
Among patients with HFrEF, the annual incidence of new-onset LBBB (and a potential indication for CRT), was around 1.5%, ranging from 1% in those with QRS duration below 100 ms to 4% in those with QRS 116–129 ms. Incident LBBB was associated with a much higher risk of adverse outcomes, highlighting the importance of repeat ECG monitoring in patients with HFrEF.

Acknowledgement/Funding
Novartis
P2634Prognostic value of admission left ventricular outflow tract velocity time integral in hospitalized heart failure patients with preserved ejection fraction: a report from the JASPER registry
Authors: Omote K , Nagai T , Kamiya K , Aikawa T , Tsujinaga S , Kato Y , Komoriyama H , Kobayashi Y , Iwano H , Yamamoto K , Yoshikawa T , Saito Y , Anzai T 
Published: October 2019

Abstract

Background
There are little effective treatment strategies for heart failure with preserved ejection fraction (HFpEF) to achieve a reduction of morbidity and mortality. Thus, accurate prognostication of patients with HFpEF could help improve their outcomes by identifying high-risk patients who might potentially benefit from intensive inpatient and outpatient monitoring and early referral for advanced HFpEF therapy. The left ventricular outflow tract velocity time integral (LVOT-VTI) is a representative non-invasive parameter for evaluating stroke volume, which can be a determinant of adverse outcomes in hospitalized patients with heart failure. However, the prognostic implication of admission LVOT-VTI for hospitalized HFpEF patients is undetermined.

Purpose
The aim of the present study was to investigate whether admission LVOT-VTI could predict poor clinical outcomes in hospitalized patients with HFpEF.

Methods
We examined consecutive 535 hospitalized HFpEF patients (left ventricular ejection fraction ≥50%) due to acute decompensated heart failure from the JASPER (JApanese heart failure Syndrome with Preserved Ejection fRaction) multicenter registry, obtained between November 2012 and March 2015. Patients without accessible LVOT-VTI data on admission were excluded. Finally, 214 patients were examined. The primary outcome of interest was composite of all-cause death and rehospitalization due to heart failure.

Results
Mean age was 78±11 years, 100 were male, and median plasma brain-type natriuretic peptide level was 400 (interquartile range [IQR] 223–711) pg/ml. During a median follow-up period of 688 (IQR 162–810) days, adverse events occurred in 83 patients (39%), including 47 (22%) all-cause death, 51 (24%) rehospitalization due to heart failure. The c-index of LVOT-VTI for predicting the composite of adverse events was 0.59 (95% CI 0.51 to 0.67), and the optimal cut-off value of LVOT-VTI was 15.8 cm. Low LVOT-VTI (≤15.8 cm) was significantly associated with higher adverse events compared to high LVOT-VTI (>15.8 cm) (Figure). Multivariable Cox regression analysis revealed that lower LVOT-VTI was an independent determinant of adverse events (HR 0.94, 95% CI 0.91 to 0.98, P=0.005) even after adjustment for pre-specified confounders including age, sex, systolic blood pressure, serum sodium, albumin, plasma brain-type natriuretic peptide and renal function.
Figure 1

Conclusions
Lower admission LVOT-VTI was an independent determinant of worse clinical outcomes in hospitalized HFpEF patients, indicating that LVOT-VTI on admission could be a useful marker for risk stratification in these patients.
P2641Renal and cardiovascular benefits of treatment with angiotensin receptor blockers in patients with hypertension and chronic kidney disease: A systematic review and meta-analysis
Authors: Burnier M , Ruilope L R , Bader G B , Durg S D , Brunel P B 
Published: October 2019

Abstract

Background
Blood pressure (BP) control is critical in delaying the progression of chronic kidney disease (CKD), which otherwise results in an increased risk of cardiovascular morbidity and mortality. Angiotensin II receptor blockers (ARBs) or angiotensin-converting enzyme inhibitors, are recommended by several guidelines as first-line treatment for patients with hypertension and CKD.

Purpose
We reviewed and analysed the effect of ARB treatment on BP and renal outcomes (estimated glomerular filtration rate (eGFR), serum creatinine (SCr), creatinine clearance (CrCl) or proteinuria) in patients with hypertension and CKD with or without diabetes, including large clinical trials such as RENAAL and IDNT.

Methods
MEDLINE, EMBASE, and BIOSIS databases were searched for literature from the earliest available date to July 2017. Randomised (parallel-group) controlled trials of ≥8 weeks assessed the impact of ARBs on systolic/diastolic BP (SBP/DBP), eGFR, SCr, CrCl or proteinuria were included in the analysis. Meta-analysis (post- versus pre-treatment) and meta-regression were conducted in R-statistical software (v3.4.1) using meta- and metafor-packages. Mean difference (MD, generic inverse variance) with 95% confidence intervals (CIs) was used to pool data for an outcome in a single forest plot. The risk of bias (quality) of included studies was assessed by the six items of the Cochrane instrument.

Results
Of the 165 articles assessed for eligibility, 24 studies were included in the analysis (19 evaluated ARBs as monotherapy, 4 evaluated ARBs in combination with other antihypertensives and 1 evaluated ARBs both as mono- and combination therapy). Treatment with ARBs as monotherapy for ≥8 weeks to <1 year significantly reduced mean office SBP (MD, −12.60 mmHg; 95% CI, −18.53 to −6.67)/DBP (−6.52 mmHg; −11.27 to −1.77) (p<0.01). BP reduction was also significant (p<0.01) with ARB monotherapy for ≥1 year SBP (−14.84 mmHg; −17.82 to −11.85)/DBP (−10.27 mmHg; −12.26 to −8.27). ARBs also significantly reduced SBP/DBP when combined with other antihypertensive treatments for ≥8 weeks to <1 year as well as for ≥1 year (Figure). Moreover, ARBs induced significant reductions (p<0.01) in proteinuria (≥8 weeks to <1 year [MD, −0.6 g/L; 95% CI, −0.93 to −0.26; ≥1 year [−0.9 g/L; −1.22 to −0.59]), but no significant changes in eGFR, CrCl or SCr levels. The beneficial effect of ARBs was maintained overtime with no significant additional impact on SBP change (estimate: 0.025; 95% CI, –0.14 to 0.19) or eGFR (estimate: 0.068; 95% CI, −0.14 to 0.28; p=0.53). The overall risk of bias was judged to be low.
Effect of ARBs on blood pressure changes

Conclusion
Treatment with ARBs effectively and sustainably lowered BP and proteinuria with no significant change in eGFR in patients with hypertension and CKD with or without diabetes.