bluuebunny/crossref_metadata_2025_split huggingface dataset:
P2581Unique molecular profile of exosomes from epicardial fat of patients with atrial fibrillation
Authors: Shaihov - Teper O , Ram E , Levin - Kotler L , Naftali - Shani N , Leor J 
Published: October 2019

Abstract

Background and aim
Exosome, the smallest vesicles that originate from intracellular compartments, contains and delivers specific bioactive proteins, lipids, mRNA, and miRNA to facilitate intercellular signaling. However, the role and mechanism of exosomes in atrial remodeling and fibrillation (AF) has not been determined. While epicardial fat (eFat) and inflammation have been linked to atrial remodeling and fibrillation (AF), the role of eFat exosomes in the pathogenesis of AF remains unknown. Thus, we aimed to determine whether eFat exosomes play a role in the initiation and progression of AF.

Methods and results
We collected eFat specimens from patients with and without chronic or paroxysmal AF undergoing heart surgery. Isolated fat specimens were cut into small pieces and incubated as organ cultures. We isolated exosomes from the medium of the explant by differential ultra-centrifugation and characterized the vesicle size distributions, morphology, specific markers, and molecular cargo. Immunoblotting of CD63, CD81 and TSG101 confirmed the presence of exosomes (Fig.1 B). Significantly, eFat from patients with AF secreted higher amounts of exosomes compared with controls (p<0.001), which confirmed by Nanoparticle Tracking Analysis (NTA) (Fig.1 A). The levels of exosomal pro-inflammatory and pro-fibrotic cytokines were higher in exosomes from patients with, compared with those without, AF (Fig.1 C, D). Measurements of micro RNA (miRNA) by real-time PCR showed lower levels of anti-fibrotic miRNA-133a (p=0.2), and higher levels of pro-fibrotic miRNA-146b (p=0.2) in exosomes from patients with, compared with those without, AF (Fig.1 E, F)

Conclusion
We show, for the first time, that exosomes from eFat of patients with AF have a unique pro-inflammatory and pro-fibrotic profile. We suggest a novel mechanism that links eFat to AF and eFat exosomes as novel biomarkers and potential therapeutic targets for AF.
P2590A liver-derived secretory protein, selenoprotein P causes pressure overload-induced cardiac hypertrophys
Authors: Usui S , Takashima S , Inoue O , Goten C , Takeda Y , Yamaguchi K , Murai H , Kaneko S , Takamura M 
Published: October 2019

Abstract

Background
Hepatokine selenoprotein P (SeP) contributes to insulin resistance and hyperglycemia in patients with type 2 diabetes. Inhibition of SeP protects the heart from ischemia reperfusion injury and serum levels of SeP are elevated in patients with heart failure with reduced ejection fraction.

Objective
We investigated the role of SeP in the regulation of cardiac remodeling in response to pressure overload.

Methods and results
To examine the role of SeP in cardiac remodeling, transverse aortic constriction (TAC) was subjected to SeP knockout (KO) and wild-type (WT) mice for 2 weeks. Hepatic expression of SeP in WT was significantly increased by TAC. LV weight/tibial length (TL) was significantly smaller in SeP KO mice than in WT mice (6.75±0.24 vs 8.33±0.32, p<0.01). Lung weight/TL was significantly smaller in SeP KO than in WT mice (10.46±0.44 vs 16.38±1.12, p<0.05). TAC-induced cardiac upregulation of the fetal type genes, including atrial and brain natriuretic factors, was significantly attenuated in SeP KO compared to WT. Furthermore, azan staining revealed that there was significantly less interstitial fibrosis in hearts after TAC in SeP KO than in WT mice. To determine whether hepatic overexpression of SeP affects TAC-induced cardiac hypertrophy, a hydrodynamic injection method was used to generate mice that overexpress SeP mRNA in the liver. Hepatic overexpression of SeP in SeP KO mice lead to a significant increase in LV weight/TL and Lung weight/TL after TAC compared to that in other SeP KO mice.

Conclusions
These results suggest that cardiac pressure overload induced hepatic expression of SeP and the absence of endogenous SeP attenuated cardiac hypertrophy, dysfunction and fibrosis in response to pressure overload in mice. SeP possibly plays a maladaptive role against progression of heart failure through the liver-heart axis.
P2592Combining home monitoring temporal trends and baseline patient risk profile for predicting impending heart failure hospitalizations. Results from the SELENE HF (BIO.Detect HF IV) study
Authors: D'Onofrio A , Solimene F , Calo' L , Calvi V , Viscusi M , Melissano D , Russo V A , Rapacciuolo A , Campana A , Bonfanti P , Caravati F , Zanotto G , Gronda E , Gargaro A , Padeletti L 
Published: October 2019

Abstract

Background/Introduction
The lack of a validated method to efficiently combine information provided by Remote Monitoring (RM) of implantable defibrillators (ICD) and patient clinical profile has limited the use of RM in the prevention of worsening heart failure episodes.

Purpose
Our objective was to develop and validate an index combining RM temporal trends and a baseline risk score for predicting the first HF hospitalization after device implantation.

Methods
We prospectively enrolled 918 patients (81% male, median age 69, interquartile interval [QI], 61/76; Seattle Heart Failure Score [SHFS], 0.17, QI, −0.40/0.75) with indication to ICD (56%), or ICD with cardiac resynchronization therapy (44%). The Home Monitoring (HM) system was activated in all patients after implant to collect several technical and HF-related variables daily. Investigators were blinded to HM reports, and only received automatic alerts for critical technical issues. The primary endpoint was the first adjudicated HF hospitalization. The cohort was a posteriori 1:1 randomized in derivation and validation groups stratified by device type and primary endpoint occurrence. The SHFS was used for baseline risk assessment.

Results
During a median follow-up of 23 months (QI, 14/36), 62 first HF hospitalizations were adjudicated. In the derivation group, the index was constructed by combining the SHFS and temporal trends of 24-hour and rest mean heart rates, ventricular ectopic beat frequency, arrhythmic atrial burden, heart rate variability, physical exercise, and thoracic impedance. Variable selection was based on an automatic stepwise procedure, after applying appropriate transformations in variable-specific time frames to maximize the area under the receiver operating characteristics curve (AUC). The resulting index was associated to an AUC of 0.88 and an Odds Ratio of 2.72 (confidence interval [CI] 1.97–3.75, p<0.001) for index unitary increase. In the index validation test, first HF hospitalizations were predicted with a sensitivity of 73.3% (CI, 54.1%-87.7%), a median alerting time of 55 days (QI, 20/68), false alert rate of 0.75 (CI, 0.70–0.81) patient-year, and 95.1% false-alert-free days.

Conclusion
HM temporal trends of selected variables and the SHFS may be combined to timely and efficiently predict the first HF hospitalization after implant, with less than 1 expected per-patient false alert per year.

Acknowledgement/Funding
BIOTRONIK SE & Co. KG, Berlin, Germany
P2602Inhaled iloprost improves echocardiographic myocardial performance during exercise in heart failure with preserved ejection fraction
Authors: Huang C Y , Wu C K , Lin L Y 
Published: October 2019

Abstract

Introduction
The pathophysiology of HFpEF is complicated and treatments that improve outcomes in HFrEF have no substantial benefits in HFpEF. Impairments in LV global longitudinal strain (GLS) and LV diastolic function parameters have been regarded as novel echocardiographic markers to predict cardiovascular events in HFpEF. Preliminary trials indicate that iloprost, an inhaled prostacyclin analougue, improves exercise hemodynamics in both patients with pulmonary artery hypertension and pulmonary hypertension associated with HFpEF.

Purpose
We aim to investigate the impact of inhaled iloprost on LV global longitudinal strain, LV diastolic function and RV function during exercise in HFpEF population.

Methods
34 patients diagnosed with HFpEF were included with exclusion of severe pulmonary, coronary artery, valvular heart and pericardial diseases. Subjects were randomized 1:1 to inhalation of iloprost or placebo. Transthoracic echocardiography was performed at rest and after 6-minute supine bicycle exercise at 20-Watt workload. We utilized tissue speckle tracking by QLAB software to derive LV GLS and global strain rate during LV isovolumetric relaxation period (SRIVR). E/e', E/SRIVR, tricuspid regurgitation pressure gradient (TRPG), tissue Doppler imaging of RV lateral tricuspid annulus and tricuspid annular plane systolic excursion (TAPSE) were measured to evaluate changes of myocardial performance.

Results
LV GLS during exercise significantly enhanced after iloprost use. E/SRIVR, a novel predictor of LV filling pressure, was significantly decreased. E/e' was also lower in iloprost group by trend. Improvements in RV function and degree of pulmonary hypertension during exercise with iloprost were observed in this study.
Echocardiographic myocardial function endpoints during 20-Watt excercise between iloprost and placebo groups Iloprost (N=17) Placebo (N=17) P value LV global longitudinal strain, % −4.96±1.20 −0.75±3.00 <0.001 E/SRIVR, cm 206.41±113.55 454.13±262.98 0.005 E/e' mean 10.77±2.39 14.41±12.14 0.235 TAPSE, cm 2.62±0.62 2.37±0.56 0.221 TRPG, mmHg 28.37±12.47 44.25±9.29 <0.001 TDI lateral tricuspid annulus, cm/s 16.41±4.61 14.77±2.92 0.222
Effects of iloprost at rest and exercise

Conclusions
Our study is the first to demonstrate that, in patients with HFpEF, inhaled iloprost favorably enhances LV GLS reserves, decreases LV diastolic filling load, reduces pulmonary hypertension and thereby improves RV function during exercise.

Acknowledgement/Funding
This work was supported in part by the National Science Council of the Republic of China, Taiwan (NSC107-2314-B-002-265-MY3)
P2604Clinical features associated with the development of diastolic dysfunction
Authors: Bots S H , Verschoor G B , Rutten F H , Onland-Moret N C , Hofstra L , Berdowski J , Tulevski I I , Somsen G A , Den Ruijter H M 
Published: October 2019

Abstract

Background/Introduction
Treatment for heart failure with preserved ejection fraction (HFpEF) is still elusive, which is a serious problem given the fact that it affects approximately 8 million people in Europe. Diastolic dysfunction (DD) is considered a precursor of HFpEF and could serve as a target for prevention. However, it is yet unclear which clinical features are associated with the development of diastolic dysfunction in men and women.

Purpose
To determine which clinical features are associated with the development of diastolic dysfunction in men and women visiting a cardiology outpatient clinic.

Methods
All individuals who visited one of the 13 Cardiology Centers Netherlands locations at least twice between April and 2007 and February 2018 for an echocardiographic evaluation were eligible for inclusion. Participants with incomplete data on diastolic function parameters or diastolic dysfunction at baseline were excluded. Information on age, sex, body mass index (BMI), systolic blood pressure (SBP), blood lipid levels, kidney function, cardiac history, co-morbidities and cardiovascular drug use was obtained for all participants. Diastolic function was scored based on E/e', relative wall thickness (RWT) and left-atrial dimension indexed by body surface area (LAD/BSA). The score allotted zero points for E/e' ≤8, RWT ≤0.41 and LAD/BSA ≤2.3, one point for E/e' between 9–14, RWT >0.42 and LAD/BSA >2.3, and two points for E/e' ≥15. Development of DD was defined as an increase in diastolic function score between the first and second echo. Missing data on determinants (max 26%) was imputed using multiple imputation. A stepwise logistic regression based on AIC was applied to evaluate the association between selected clinical features and DD. All analyses were performed in R.

Results
The study population comprised 1301 patients with a mean age of 56 (± 11) years and 46% were women. The median time between echo appointments was 631 (IQR: 381–1132) days and 549 patients developed DD (42%). After stepwise regression, the final model included age, sex, BMI, SBP, triglycerides and hypertension. DD was less likely to occur in men compared with women (OR=0.62, 95% CI: 0.57–0.67), and more likely in patients with hypertension (OR=1.29, 95% CI: 1.18–1.42) after adjustment. The adjusted risk for DD increased with triglyceride level (OR=1.24, 95% CI: 1.19–1.29), age (OR=1.04 per year, 95% CI: 1.03–1.04), BMI (OR=1.03 per kg/m2, 95% CI: 1.01–1.04) and SBP (OR=1.01 per 1 mmHg, 95% CI: 1.006–1.011) (Figure 1).
Figure 1

Conclusion(s)
Women and those with hypertension were at higher risk of developing DD compared to their male or normotensive counterparts. Age, triglyceride levels, BMI and SBP were also independently associated with an increased risk for DD. Prevention efforts focussing on life style changed and possibly lipid and blood pressure lowering drugs may reduce the risk of developing DD.
P2607Quick nutritional assessment and prognosis in outpatients with heart failure with mid-range ejection fraction
Authors: Zamora E , Gonzalez B , Rivas C , Diaz V , Velayos P , Lupon J , De Antonio M , Domingo M , Moliner P , Santiago-Vacas E , Cachero M , Joaquim C , Alonso N , Santesmases J , Bayes-Genis A 
Published: October 2019

Abstract

Background
Nutritional status is an important prognostic factor in patients with heart failure (HF) beyond body mass index, although its prognostic value in patients with mid-range left ventricular ejection fraction (HFmrEF) is not completely elucidated. In a pilot study we observed that the Mini Nutritional Assessment Short Form (MNA-SF) was the best approach for the screening of nutritional status in HF outpatients over others screening tools.

Purpose
To assess the prognostic role of malnutrition or risk of malnutrition in HFmrEF outpatients after the implementation of the MNA-SF screening tool in a routine way in a multidisciplinary HF.

Methods
The MNA-SF screening tool was administered during the global nurse evaluation of patients. The scoring ranges from 0 to 14, being 0 to7 as malnutrition status, 8 to 11 as at risk of malnutrition and 12 to 14 as normal nutritional status. For the present study those patients with malnutrition and at risk of malnutrition were merged and considered abnormal nutritional status. All-cause death was the primary end-point. Univariate and multivariate (backward conditional stepwise) Cox regression analyses were performed.

Results
Since October 2016 to November 2017, 153 HFmrEF patients were studied (mean age 68.8±11.7 years, 72.5% men, body mass index 28.4±4.4, LVEF 44% ± 3, NYHA class I 5.9%, II 86.3%, and III 7.8%). According to the MNA-SF 25 patients were (16.3%) fulfilled criteria of malnutrition (4) or where at risk of malnutrition (21). During a mean follow-up of 17.4±6.1 months, 23 patients died (15%). In the univariate analysis, nutritional abnormal status was significantly associated with all-cause death (HR 2.93 [1.23–7], p=0.02). In the multivariate analysis which included age, sex, NYHA functional class, body mass index, ischemic aetiology of HF and years of duration of HF, abnormal nutritional status remained significantly associated with all-cause mortality (HR 3.64 [1.39–9.54], p=0.009), together with NYHA functional class (HR 7.93 [2.69–23.4], p<0.001) and years of HF duration (HR 1.10 [1.04–1.16], p=0.001).

Conclusions
Nutritional status assessed with the screening MNA-SF was an independent predictor of all-cause death in ambulatory patients with HFmrEF – beyond BMI – together with NYHA functional class and HF duration.
P2620PIONEER-HF criteria ready for the prime time? Data from REDINSCOR II registry
Authors: Vidal-Perez R , Varela-Roman A , Gomez-Otero I , Pascual-Figal D , Delgado Jimenez J , Agra-Bermejo R , Cordero-Fort A , Ferrero-Gregori A , Alvarez-Garcia J , Worner Diz F , Segovia Cubero J , Cinca Cuscullola J , Fernandez Aviles F , Mazon-Ramos P , Gonzalez-Juanatey J R 
Published: October 2019

Abstract

Background
New treatment strategies are needed to improve the prognosis in acute heart failure (AHF), recently PIONEER-HF results have been published showing in a selected group of patients a potential use of sacubitril/valsartan with safety in this scenario

Purpose
To evaluate the impact of PIONEER-HF potential indication in daily practice after AHF hospitalization at discharge

Methods
We included a subgroup of 909 patients consecutively admitted with AHF between October 2013 and December 2014 from a national multicentre, prospective registry with the complete data for this analysis. In the trial left ventricular ejection fraction (LVEF) ≤40% and natriuretic peptides at admission with values of NT-ProBNP≥1600 pg/ml were needed to be included. The clinical and analytic stability at discharge to safely start sacubitril/valsartan was considered as MDRD estimated Glomerular Filtration Rate≥30 mL/min/1.73 m2, Systolic Blood Pressure ≥100 mmHg and Potassium ≤5.2 mmol/L.

Results
The mean age was 72.1±12.01 years. Of these, 373 (38.8%) were female, 734 (76,6%) were hypertensive, 462 (48.2%) had diabetes and 282 (29.9%) coronary artery disease. At admission atrial fibrillation was found in 403 patients (40.1%) and 409 (45%) had reduced LVEF. The mean levels of NT-ProBNP 7259.4±9437.1 pg/ml. In this group of patients, the in-hospital mortality was 28 (2.9%) and the 1 year follow up mortality was 197 (20.5%) and the heart failure rehospitalizations in 1 year were 303 (31,5%). In table 1 the percentage of patients that fulfil the needed criteria for the application of PIONEER HF is shown. In our registry 235 patients (25.9%) could be potential users of sacubitril/valsartan after the acute phase of hospitalization
Table 1 Elements to stablish indication Number of patients (%) NT-ProBNP ≥1600 pg/ml at admission 730 (80.3%) MDRD estimated GFR ≥30 mL/min/1.73 m2 at discharge 798 (87.8%) Systolic Blood Pressure ≥100 mmHg at discharge 755 (83.1%) Serum Potassium ≤5.2 mmol/L at discharge 856 (94.2%) Clinical and analytic stability at discharge 636 (70%) Left ventricular ejection fraction ≤40% 409 (45%) PIONEER HF Criteria 235 (25.9%) GFR: Glomerular Filtration Rate.

Conclusions
In our cohort of AHF patients around 1 out 4 could be treated with sacubitril/valsartan at discharge if we apply the PIONEER HF criteria in a contemporary setting, this finding could have potential implications in the prognosis and current costs of care in a population with high morbidity and mortality.

Acknowledgement/Funding
Heart Failure Program of the Red de Investigaciόn Cardiovascular del Instituto de Salud Carlos III, Madrid, Spain (RD12/0042) and FEDER
P2621Clinical safety and efficacy of tolvaptan for acute phase therapy in patients with low-flow severe aortic stenosis
Authors: Mitsui M , Kataoka A , Nara Y , Nagura F , Kawashima H , Hioki H , Nakashima M , Watanabe Y , Yokoyama N , Kozuma K 
Published: October 2019

Abstract

Background
Conventional diuretic therapy for low-flow (LF) severe aortic stenosis (SAS) often has an inadequate effect or causes hemodynamic instability. Tolvaptan is used for acute heart failure in addition to conventional diuretics in Japan, and it does not cause intravascular dehydration.

Purpose
This study aimed to retrospectively investigate the safety and efficacy of tolvaptan in the acute phase patients with SAS and compared LF-SAS with normal-flow (NF) SAS.

Methods
56 consecutive SAS patients are analyzed. The primary endpoints were adverse clinical events (death, worsening heart failure, worsening renal failure, fatal arrhythmia, cardiogenic or hypovolemic shock, and use of inotropic agents) and the volume of urine and fluid balance within 48 hours of tolvaptan administration (Figure).

Results
Among 56 patients, 16 had LF-SAS (29%), and 40 had NF-SAS (71%). Severe adverse clinical events were not observed 48 hours after tolvaptan administration. In both groups, the urine volume significantly increased after tolvaptan administration in comparison to 24 hours before tolvaptan administration (both, p<0.01). There were no changes in the urine volume during the initial 24 and 48 hours. In the LF-SAS group, tolvaptan resulted in a significant decrease in fluid balance during the initial 24 and 48 hours compared to 24 hours before tolvaptan administration (p<0.05).
Treatment and data collection protocols

Conclusion
Adding tolvaptan to conventional treatment leads to an increase in urine output and a decreased fluid balance without hemodynamic instability in patients with LF-SAS.

Acknowledgement/Funding
None
P2623Measurement of liver fibrosis marker: type IV collagen 7S among patients with acute heart failure and its relationship with the Enhanced Liver Fibrosis (ELF) score
Authors: Aida K , Nagao K , Kajitani K , Tamura A , Kobayashi T , Yukawa H , Kanazawa T , Kobayashi Y , Takahashi N , Nakagawa E , Ito H , Hayashi F , Makita T , Inada T , Tanaka M 
Published: October 2019

Abstract

Background
Hemodynamic disturbance in acute heart failure (HF) can cause injury to extra-cardiac organs such as the liver. Organ injury in HF might evoke a profibrotic response, which could adversely affect the prognosis.

Methods
Among 189 patients with acute HF, we simultaneously determined the liver fibrosis marker, type IV collagen 7S (P4NP 7S) and the Enhanced Liver Fibrosis (ELF) Score consisting of tissue inhibitor of metalloproteinases 1 (TIMP-1), amino-terminal propeptide of type III procollagen (PIIINP) and hyaluronic acid (HA) on admission and at discharge.

Results
During hospitalization, P4NP 7S and ELF score significantly decreased from 7.1 ng/mL to 6.1 ng/mL (P<0.001) and 10.39 to 10.13 (P<0.001), respectively. P4NP 7S and ELF score were correlated with each other on admission (r=0.4, P<0.001) and at discharge (r=0.4, P<0.001). %Change of (Δ) P4NP 7S during hospitalization was correlated with ΔBNP and ΔELF score (r=0.3, P<0.001 and r=0.4, P<0.001, respectively). Among the components of ELF score, PIIINP and HA were correlated with P4NP 7S on admission (r=0.5, P<0.001 and r=0.3, P<0.001, respectively) and at discharge (r=0.4, P<0.001 and r=0.3, P<0.001, respectively). ΔP4NP 7S was also correlated with ΔTIMP-1, ΔPIIINP and ΔHA (r=0.3, P<0.001, r=0.4, P<0.001 and r=0.3, P<0.001, respectively). Each patient was followed up up to 365 days after discharge. 69 patients died or were hospitalized for HF. When the patients were divided into two groups according to the median value of each marker at discharge, the cumulative 1-year incidences of all cause death or HF hospitalization were 32.0% and 45.5% in P4NP 7S-low and P4NP 7S-high group, respectively (log-rank P=0.051) and 43.2% and 34.9% in ELF score-low and ELF score-high group, respectively (log-rank P=0.44). After adjustment by the clinically relevant factors including age, sex, hemoglobin, sodium and left ventricular ejection fraction, P4NP 7S showed independent prognostic value (adjusted hazard ratio: 1.12, P=0.02), while ELF score did not (adjusted hazard ratio: 1.04, P=0.79).

Conclusion
Parallel elevation of P4NP 7S and ELF score were documented during acute phase of HF. P4NP 7S at discharge may identify patients at high risk for subsequent HF related events.