bluuebunny/crossref_metadata_2025_split huggingface dataset:
P2587Cardiosomal microRNAs are essential in post-infarction myofibroblast phenoconversion
Authors: Sardu C , Shu J , Matarese A , Santulli G 
Published: October 2019

Abstract

Background
Circulating microRNAs (miRNAs) are actively transported, via inclusion in extracellular microvesicles/exosomes (herein named cardiosomes since they are deriving from cardiomyocytes), allowing protection from degradation and underlying cell-cell communications.
After myocardial infarction (MI), quiescent cardiac fibroblasts can acquire an activated phenotype, and a recognized marker of such activation is the expression of α-smooth muscle actin (α-SMA); such cells are commonly known as myofibroblasts.

Hypothesis
We hypothesize that cardiosomal miRNAs play a pivotal role in the activation of myofibroblasts following ischemic injury.

Methods
Using an established murine model of MI, obtained via permanent ligation of the left anterior descending coronary artery, we tested our hypothesis by measuring in primary isolated fibroblasts and cardiosomes the expression levels of a set of miRNAs, which we found to be upregulated in cardiomyocytes post-MI and to be involved in myofibroblast phenoconversion.

Results
Bioinformatic studies validated by biological assays identified three cardiomyocyte-specific miRNAs (namely miR-92a, miR-195, and miR-494) that are upregulated following cardiac ischemia and are also known to regulate α-SMA expression. We demonstrated that these miRNAs are upregulated in fibroblasts post-ischemia and are also contained in cardiosomes; to ensure that these miRNAs were confined inside cardiosomes, the samples were treated with RNase, showing that the level of miRNAs was not affected by RNase treatment, unless in presence of the detergent Triton X-100. The activation of myofibroblasts was confirmed by the increased expression of α-SMA. Using a luciferase assay, we also validated that miR-92a, miR-195, and mir-494 target the 3'UTR of α-SMA and regulate its transcription. Moreover, we observed that primary isolated cardiac fibroblasts were activated both when incubated with cardiosomes isolated from ischemic cardiomyocytes and when cultured in conditioned medium of post-MI cardiomyocytes, whereas no significant effects were detected following incubation with cardiosomes or medium from sham cardiomyocytes. Strikingly, myofibroblast phenoconversion was markedly attenuated when GW4869, an inhibitor of neutral sphingomyelinase 2 responsible for cardiosomes secretion, was added to cultured post-MI cardiomyocytes.

Conclusion
Taken together, our findings indicate that three cardiomyocyte-specific miRNAs (miR-92a, miR-195, and miR-494) are crucial in the activation of myofibroblasts.
P2593Evaluation of an ambulatory heart failure service - a 2 years' experience
Authors: Doleman F , Santon M , Clewes J , Laithwaite C , McIntosh R , Ahmed H , Ahmed N 
Published: October 2019

Abstract

Background
Heart failure accounts for 1–2% of health care expenditure in the National Health Service in the United Kingdom. Approximately 60–70% of that cost is in hospitalization for treatment. Various methods have been employed to reduce hospitalization in chronic heart failure; however effectiveness and safety of these methods have yet to be evaluated. Our ambulatory heart failure unit, run by specialist heart failure nurses, seeks to reduce admissions to hospital for heart failure by administering intravenous (I.V) diuretics in a day unit setting for ambulatory patients.

Purpose
We have reviewed data from December 2016 to December 2018 of patients using the ambulatory heart failure services in our hospital and evaluated its safety and effectiveness.

Methods
Retrospective evaluation of data collected from the ambulatory heart failure unit over a 24-month period as well as hospital data on admissions and length of stay of heart failure patients. Qualitative data was also collected from patients using the ambulatory heart failure unit.

Results
Since the opening of the ambulatory heart failure unit in December 2016, we have had 393 patient episodes. Referrals were largely from the community (265, 67%) however 128 (33%) patients were referred from an inpatient setting. Patients were treated for a mean of 12 days with intravenous furosemide infusion. The minimum dose of furosemide used was 120mg over 1 hour whereas maximum dose was 360mg over 2 hours. This translated into 4351 hospital bed days saved in a 24-month period. 144 (37%) of patients had heart failure with preserved ejection fraction (EF >40%), and 239 (61%) had heart failure with reduced ejection fraction (EF <40%).
28 patients (7%) referred to the unit were deemed inappropriate for unit and required admission. A further 35 patients (9%) were admitted to hospital for other illnesses whilst being treated on the unit due to various reasons. 3 patients (0.8%) died in the community during the period they were receiving care on the unit. Of the 63 patients (16%) admitted to hospital 23 (6%) died during that hospital admission. The number of all cause mortality of our patients was 26 (7%) during the time they were treated on the unit.
Whilst the number of heart failure hospital admissions remained similar, the average length of stay in hospital for heart failure dropped by 0.99 days. Patient feedback on the unit was excellent, with patients feeling more independent and in control of their health.

Conclusions
The ambulatory heart failure unit reduces the burden on the hospital by reducing the length of stay of heart failure patients and may be preferred by patients. Intravenous diuretics on a day case basis are safe, as evident by unchanged overall mortality of heart failure patients.
P2596Right ventricular function after anthracycline therapy: specificities of myocardial necrosis markers
Authors: Quinaglia T Q , Ferreira De Souza T , Bianchini Cardoso F , Silva L M , Toledo C , Neilan T , Antunes-Correa L , Herold M J , Coelho-Filho O R 
Published: October 2019

Abstract

Background
Anthracycline therapy may induce left ventricle (LV) dysfunction. However, few studies investigated how it may affect the right ventricle (RV).

Purpose
The goal of this study was to assess RV systolic function and biomarkers that may predict early dysfunction in breast cancer patients treated with anthracyclines.

Methods
Twenty-seven women with breast cancer (51.8±8.9 years), underwent CMR prior, and up to 3-times after doxorubicin with matching measurements of biomarkers: high-sensitive troponin T (TnT), creatinine-kinase MB isoenzyme (CK-MB) and C reactive protein (CRP).

Results
Before anthracyclines, all subjects had normal LVEF (69.4±3.6%) and RVEF (55.1±9%) and LV and RV EF correlated significantly (ρ=0.42; p=0.031). At 351–700 days after anthracycline, LVEF and LV mass index declined to 58±6% (P<0.001) and 36±6 g/m2 (P<0.001) (table). RVEF also decreased, reaching 46±8% at 231,4 days after (P<0.001), but lost the correlation with LVEF seen at baseline (r=0.22; P=0.068). RVEF showed strong negative association with serum CK-MB (r=−0.4, p=0.004) and no significant correlation with TnT (r=−0.18, p=0.28) or CRP (r=0.03, p=0.932) (figure). In patients with a peak TnT of >10 pg/ml the change of RVEF overtime was significant (Regression Splines coefficients for RVEF: 1.0, p=0.731–peak TnT ≤10pg/ml; 2.51, p<0.001–peak TnT >10 pg/ml). LVEF was not associated with CK-MB (p=ns).
Baseline and Follow-Up CMR Findings Median days after anthracycline Pre-DOX (79,146] (146,231] (231,350] (350,700] N 27 16 19 14 16 LVEF, % 69.4±3.6 61.1±7.6† 55.99±5.0† 53.8±8.4† 57.5±6.1† LVEDV index, ml/m2 60.2±9.9 64.3±9.6 66.7±17.7 * 56.9±18.5 59.2±12.6 LVESV index, ml/m2 18.3±4.0 24.7±7.3# 29.0±7.3† 26.2±9.7† 25.3±8.2† LV mass index, g/m2 51.4±8.0 45.3±3.8† 43.2±4.9† 39.9±5.4† 36.0±6.1† RVEF, % 55.1±9.4 51±8.1 48±8.5 46±8.5 50±7.4 RVEDV index, ml/m2 45.07±6.6 46.5±11.31 47.35±9.16 41.14±9.7 46.16±7.3 RVESV index, ml/m2 20.45±5.4 22.31±5.8 24.77±6.6 21.96±6.4 22.24±4.7 Data are presented as mean ± SD. LV: left ventricle; RV: right ventricle; EF: ejection fraction; EDV: end diastolic volume; ESV: end systolic volume (average±SD). *Significantly different from Pre-DOX level (p<0.05 from linear mixed effects model). #Significantly different from Pre-DOX level (p<0.01 from linear mixed effects model). †Significantly different from Pre-DOX level (p<0.001 from linear mixed effects model).
RVEF and correlate variables

Conclusions
RVEF reduction does not follow LVEF changes after anthracyclines and CK-MB may be a more specific biomarker to assess RV dysfunction. A higher peak cTnT could predict a greater change in RVEF during follow-up.
P2599Echo color doppler evaluation of renal hemodynamic during acute heart failure
Authors: Sacchi A , Galassi M , Brugioni F , Ricco' B , Lami F , Messora R , Bortolotti M , Pinelli G , Turrini F 
Published: October 2019

Abstract

Background
Acute heart failure (AHF) is often accompanied by impairment in renal function. A profound derangement of normal abdominal haemodynamic is always present during this clinical phase.

Methods
14 patients (6 F – mean age 80 – mean EF 0.39) admitted for acute heart failure underwent cardiac and renal Echo Doppler examination at day 1-3-5 of Hospital stay. Parameters of arterial and venous flow within cortical right kidney were recorded. Venous Doppler Profile (VDP) was classified as: continuous (C), pulsatile (P), biphasic (B) or monophasic (M) according to the growing degree of derangement. Arterial resistive index (RI) >0.8 was considered elevated. Correlation between renal hemodynamic (and its changes) with biohumoral and echo parameters was sought.

Outcome
At day 1 VDP was M or B in 8 patients (57%) and in four (50%) of them dropped to C or P at day 5. RI was elevated in 8 patients at day 1 while only in 4 at day 5. VDP and RI were not related to EF or BNP values. One patient died before day 5, no other worsening heart failure episodes occurred. Two patients (14%) developed acute kidney injury but their VDP and RI were normal and did not change. Three patients (21%) did not improve their BNP (decrease >30%) but this was not associated with VDP or RI changes. Elevated derived pulmonary artery systolic pressure (>40 mmHg) was present in 6 out of 8 patients (75%) with M or B VDP and in all 4 patients with both elevated RI and M or B VDP.
Venous Pattern Day 1 Day 3 Day 5 Continous 2 8 5 Pulsatile 4 2 4 Biphasic 2 1 2 Monophasic 6 3 2 Arterial RI >0.8 8 6 4 BNP, pg/ml 1060±1180* 372±281* 424±213* Creatinine, mg/dl 1.4±0.6 1.5±0.6 1.3±0.6 Hb, g/dl 12.1±2.3 12.3±3.6 13.2±2.3 *p>0.05.

Conclusions
This is the first study exploring changes in renal hemodynamic by echo Doppler during AHF. With respect to previous studies among stable patients, our preliminary data shows a higher proportion of deranged renal venous and/or arterial pattern. After diuretic therapy a trend towards improvement in VDP was recorded. No clear association with other clinical and hemodynamic parameters seems evident.
P2605Liver stiffness assessed by fibrosis-4 index; noninvasive marker using serum biomarkers is associated with right ventricular function and cardiovascular prognosis in HFpEF
Authors: Nakashima M , Sakuragi S 
Published: October 2019

Abstract

Background
Liver stiffness is reported to be associated with right atrial pressure and worse prognosis of heart failure. Fibrosis-4 (FIB4) index (age (years) × aspartate aminotransferase (IU/L)/platelet count (109/L) × square root of alanine aminotransferase (IU/L)) is known as a useful and simple marker for evaluating liver stiffness. However, the association between FIB4 index and prognosis in heart failure with preserved ejection fraction (HFpEF) was not elucidated.

Purpose
This study aimed to clarity the association between FIB4 index and right ventricular (RV) function and major adverse cardiac events (MACE) of HFpEF.

Method
From February 2012 to December 2015, 132 subjects diagnosed as HFpEF after hospitalization of acute decompensation were enrolled (79 years, 59 male). Subjects performed thoracic surgery or percutaneous coronary intervention within half a year and died before discharge were excluded. All subjects were measured FIB4 index and tricuspid annular plane systolic excursion (TAPSE) to assess RV function before discharge. In addition, patients were classified into two groups: high-(≥3.01, n=52) and low-FIB4 index groups (<3.01, n=80). MACE incidence during the follow-up period were compared between these groups.

Results
Patient with high-FIB4 index were older and higher level of blood pressure. There was no difference in prevalence rates of history of liver disease. In multivariate Linear regression analysis, FIB4 index was significantly association with TAPSE independently confounding factors. Kaplan-Meier analysis showed that patients with high-FIB4 index experienced more CV events during the 1734 days of follow-up (42.3% vs 26.2%, p=0.028) (figure).
Kaplan-Meier curve freedom from MACE

Conclusions
FIB4 index is associated with RV dysfunction and a high risk of future CV event of HFpEF.
P2622Use of intravenous vasodilators in patients hospitalized with acute heart failure: insights from Tokyo cardiovascular care unit network database
Authors: Shiraishi Y , Kohsaka S , Katsuki T , Harada K , Miyamoto T , Matsushita K , Iida K , Takei M , Fukuda K , Yamamoto T , Nagao K , Takayama M 
Published: October 2019

Abstract

Background
Despite recommendations from clinical practice guidelines, there is scant evidence confirming the effects of vasodilators on clinical outcomes in patients with acute heart failure (AHF).

Purpose
We sought to investigate the effects of intravenous vasodilators on clinical outcomes and to identify the potential patient populations that would benefit from its use.

Methods
Data of 26 212 consecutive patients urgently hospitalized for AHF between 2009 and 2015 were extracted from a multicenter data registration system (Tokyo Cardiovascular Care Unit Network Database, including 72 institutions within the Tokyo metropolitan area in Japan). Patients who did not present with typical AHF episodes, including those without pulmonary congestion on physical and/or chest X-ray and serum B-type natriuretic peptide level <500 pg/ml, as well as those who had hypotension and/or hypoperfusion (systolic blood pressure [SBP] <100 mmHg) as dominant presentation, were excluded. Propensity scores were calculated with multiple imputation and 1:1 matching performed between patients with and without vasodilators. The primary endpoint was in-hospital mortality and the secondary endpoints were length of intensive/cardiovascular care unit (ICU/CCU) stay and hospital stay.

Results
Overall, 8 863 patients were included in the present analysis; they were predominantly male (57%) with a median age of 79 (interquartile range: 70–86) years. Compared with the group without vasodilator use, the vasodilator group had higher SBPs and heart rates and higher frequency of assisted ventilation use, but lower frequency of intravenous diuretics use. After propensity score matching, there were no significant differences in in-hospital mortality rates (7.8% vs. 8.9% in patients without vasodilators, p=0.16) or in length of ICU/CCU stay (5.8 days vs. 5.4 days, p=0.44) and hospital stay (22.7 days vs. 23.8 days, p=0.22) between the groups. However, in subgroup analyses, favorable impacts of vasodilator use on in-hospital mortality were observed among patients who had higher SBPs and among those who had no atrial fibrillation upon admission (Figure). In addition, vasodilators were likely to be more effective in AHF patients with SBP increasing; while levels below 140 mmHg of SBP appeared to be associated with an increased risk for mortality among patients treated with vasodilators compared with those without vasodilators.
Figure 1

Conclusions
In patients with AHF, vasodilator use was not universally associated with improved in-hospital outcomes; however, its effect was dependent of individual clinical presentation. Detailed phenotyping might aid tailoring of treatment strategies for patients with AHF.

Acknowledgement/Funding
the Tokyo Metropolitan Government
P2629Early benefits of empagliflozin in patients with type 2 diabetes with heart failure are not offset by increased adverse events: results from the EMPA-REG OUTCOME trial
Authors: Pellicori P , Pernille Ofstad A , Fitchett D , Zeller C , Wanner C , George J , Zinman B , Brueckmann M , Lindenfeld J 
Published: October 2019

Abstract

Background
The cardiovascular (CV) benefits of sodium-glucose co-transporter-2 (SGLT2) inhibitors in patients with type 2 diabetes (T2D) have been demonstrated in long-term clinical trials. In the EMPA-REG OUTCOME trial, the SGLT2 inhibitor empagliflozin (EMPA), compared with placebo (PBO), significantly reduced the risk of CV death and hospitalisation for heart failure (HHF) in patients with T2D and established CV disease, with a median follow-up time of 3.1 years.

Purpose
To investigate the early benefits and safety associated with use of EMPA in patients enrolled in the EMPA-REG OUTCOME trial according to heart failure (HF) status at baseline.

Methods
We evaluated the effects of treatments on glycated haemoglobin (HbA1c) levels and on the clinical endpoints of HHF, HHF or CV death, and HHF or all-cause mortality (ACM), as well as the occurrence of adverse events (AEs), at 12 weeks, 6 months, and 1 year after randomisation. Outcomes data were explored descriptively at 12 weeks, and assessed by Cox regression models adjusting for baseline risk factors at 6 months, and 1 year, whereas safety data were explored descriptively. Effects on HbA1c were evaluated using a Mixed Model Repeated Measures (MMRM) model.

Results
A total of 7020 participants, 706 (10%) with investigator-reported HF at baseline, were randomised to PBO, or two different doses of EMPA (10 mg or 25 mg once daily). In patients with HF at baseline, the adjusted mean differences in HbA1c between pooled EMPA and PBO at 12 weeks, 6 months, and 1 year after randomisation were −0.55, −0.54 and −0.53%-point, respectively, p<0.001 vs PBO for all, with similar results in those without HF (p for interactions 0.822, 0.939 and 0.539 at 12 weeks, 6 months and 1 year, respectively). Already at 12 weeks, patients assigned to EMPA had a lower frequency of all evaluated clinical outcome events (HHF, HHF or CV death, HHF or ACM) compared with PBO, regardless of HF status. This effect was sustained and significant at 6 months and 1 year in those with and without HF (see Figure). During the same time frame, the rates of AEs were generally higher in those with HF than without HF, but were not increased by the use of EMPA. At 1 year, any AE occurred in 206 (84.4%) and 1694 (81.1%) patients with and without HF, respectively, on PBO vs 363 (78.6%) and 3246 (76.8%) patients with and without HF on EMPA; any serious AE at 1 year occurred in 79 (32.4%) and 447 (21.4%) patients with and without HF on PBO vs 105 (22.7%) and 764 (18.1%) of those with and without HF on EMPA.

Conclusions
In the EMPA-REG OUTCOME trial, EMPA led to early beneficial effects on morbidity and mortality outcomes in patients with T2D with or without HF, which were not offset by an increased risk of AEs.
P2659Difference of prognostic impact of Killip classification in ACS patients with or without hemodialysis
Authors: Takasaki A , Kurita T , Masuda J , Dohi K , Hoshino K , Tanigawa T , Saito Y , Kitamura T , Kakimoto H , Setsuda M , Makino K , Ichikawa T , Ito M 
Published: October 2019

Abstract

Background
Cardiovascular deaths are more frequently in hemodialysis (HD) patients compared to general population. However, difference of prognosis of acute coronary syndrome (ACS) patients with or without HD were not well evaluated.

Purpose
The purpose of this study was to evaluate the clinical and prognostic characteristics of ACS patients with HD compared to that of ACS patients without HD.

Methods
We investigated 3427 ACS patients including 63 HD and 3364 non-HD patients between 2013 and 2017 using date from Mie ACS registry, a retrospective and multicenter registry. The primary outcome was defined as all-cause mortality.

Results
HD patients showed significantly higher prevalence of diabetes mellitus, past treatment of coronary artery disease, history of myocardial infarction and Killip ≥2 compared to non-HD patients (p<0.05, respectively). During the follow-up periods (median 719 days), 425 (12.4%) patients experienced all-cause death. HD patients demonstrated the higher all-cause mortality rate compared to that of non-HD patients during the follow-up (11.9% versus 38.1%, p<0.001, chi square). Kaplan Meier survival curves demonstrated that HD and non-HD patients with Killip 1 showed similar 30-day mortality, and Killip ≥2 patients also showed similar prognosis (Left side of figure). On the other hand, all cause mortality at 2 years were higher in Killip 1 HD patients compared to Killip 1 non-HD patients and similar between Killip 1 HD patients and Killip ≥2 non-HD patients in the 30 days landmark analysis (Right side of figure). In addition, cox regression analyses for all cause mortality demonstrated that HD was a strongest independent prognostic factor not of 30-day mortality but of after 30-day mortality with hazard ratio of 4.09 (95% confidential interval: 2.32–7.21, p<0.001).
Figure 1

Conclusion
Careful management are required in chronic phase for ACS patients with HD even in Killip 1 classification.
P2689Irregular protrusion area is associated with incidence of cardiac events after implantation of new generation drug-eluting stents - optical coherence tomography study
Authors: Yanagawa K , Nishino M , Nishino M , Nakamura H , Nakamura H , Matsuhiro Y , Matsuhiro Y , Yasumoto K , Yasumoto K , Tanaka A , Tanaka A , Matsunaga Y , Matsunaga Y , Nakamura D , Nakamura D , Yano M , Yano M , Yamato M , Yamato M , Egami Y , Egami Y , Shutta R , Shutta R , Tanouchi J , Tanouchi J 
Published: October 2019

Abstract

Background
Several studies using optical coherence tomography (OCT) have shown that the prevalence of irregular protrusion was associated with the incidence of adverse cardiac events. However, the correlation between cardiac events and protrusion area is not well investigated.

Method
One hundred twenty-nine consecutive patients with 138 clesions with 2nd and 3rd generation drug-eluting stents (DES) which had pre-stenting and post-stenting OCT imaging between April 2016 and April 2018 were evaluated. We compared baseline characteristics, procedure findings and OCT findings including minimum stent area, protrusion type and maximum protrusion area between target lesion revascularization (TLR) group and non-TLR group.

Results
TLR occurred in 12 (9.3%) in 129 patients. The baseline characteristics and procedure findings were similar between TLR group and non-TLR group. Univariate analysis revealed that maximum irregular protrusion area was significantly larger (0.51 [0.00–0.63] vs 0.00 [0.00–0.27], p=0.036) in TLR group than non-TLR group. Receiver operating characteristic curve analysis revealed that the suitable cutoff value of maximum irregular protrusion area were 0.43mm2 for TLR. In multivariate analysis using the parameters with p value<0.10 determined by univariate analysis, maximum irregular protrusion (≥0.43mm2) and minimum stent area (MSA) were independently correlated with TLR (table).
Odd's ratio (95% CI) P value Major irregular protrusion (≥0.43mm2) 17.3 (3.63–82.6) <0.001 MSA 2.13 (1.15–3.93) 0.002

Conclusion
Major irregular protrusion (>0.43mm2) in post-stenting OCT findings may be a powerful predictor of TLR in the patients with new generation DES.