bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stabilin-1+/SMA- macrophages in diagnostics of postinfarction tissue inflammation associated with adverse cardiac remodeling in patients with myocardial infarction
Authors: Gombozhapova A , Rogovskaya Y , Rebenkova M , Kzhyshkowska J , Ryabov V 
Published: November 2020

Abstract

Introduction
Molecular biomarkers of monocytes/macrophages identified to date have provided advanced diagnostic capabilities. We have accumulated a large amount of knowledge related to the role of innate immune response in the development of postinfarction cardiac remodeling. However, there is no significant advancement in clinical studies.

Purpose
The purpose was to assess prospects of macrophage biomarkers in diagnostics of postinfarction tissue inflammation associated with adverse cardiac remodeling in patients with myocardial infarction (MI).

Methods
The study included 41 patients with MI type 1, died in 2013–2014. We used a biobank of tissue samples for analysis. Group 1 (n=24) comprised patients who died within 72 hours of MI (the inflammatory phase), group 2 (n=17) comprised patients who died 4–28 days after MI (the regenerative phase). Macrophage infiltration in the heart was assessed by double immunofluorescence. We used stabilin-1 as a marker of M2 macrophages, while α-smooth muscle actin (α-SMA) was considered as a marker of cell transdifferentiation. Cells were counted in the infarct (IA) and non-infarct area (NIA). Morphological determination of adverse cardiac remodeling was based on the ratio of heart size, in particular, length/width ratio that was &lt;1.1.

Results
We identified subpopulations of stabilin-1+/α-SMA− and stabilin-1+/α-SMA+ macrophages. In the IA the number of stabilin-1+/α-SMA− macrophages was lower during the inflammatory phase than during the regenerative phase (Table 1). The calculation of sensitivity and specificity of stabilin-1+/α-SMA− macrophages in the NIA for predicting of adverse cardiac remodeling has shown following: AUC=0.96, p&lt;0.001. The cut-off value was 18 cells/mm2. The ROC curve is presented in Figure 1.

Conclusions
We identified that number of stabilin-1+/α-SMA− macrophages in the NIA ranged from 0 to 18 cells/mm2 was associated with adverse cardiac remodeling. The presence of stabilin-1+/α-SMA+ macrophages could indicate persistent tissue inflammation and possibility of macrophage transdifferentiation and plasticity. Our study supports prospects for implementation of macrophage biomarkers in clinical practice that might become a breakthrough in the development of new methods for management of MI and following complications.
Figure 1

Funding Acknowledgement
Type of funding source: None
Thigh intramuscular fat predicts the prognosis in patients in non-ischemic cardiomyopathy with reduced ejection fraction
Authors: Yoshida T , Shibata A , Tanihata A , Hayashi H , Ichikawa Y , Ishikawa H , Yamaguchi Y , Kitada R , Ehara S , Izumiya Y , Yoshiyama M 
Published: November 2020

Abstract

Background
Skeletal muscle atrophy is an independent prognostic predictor for patients with chronic heart failure, and the concept of sarcopenia is drawing attention. Furthermore, the importance of not only muscle mass but also intramuscular fat (IMF) has been pointed out. However, there is a lack of consensus on the implications of ectopic fat for the prognosis in patients with non-ischemic cardiomyopathy.

Purpose
We investigated whether ectopic fat in the thigh affects the prognosis with non-ischemic cardiomyopathy.

Methods
We recruited 105 patients who were diagnosed with non-ischemic cardiomyopathy by cardiac catheterization and echocardiographic date between September 2017 and November 2019. Finally 73 patients with reduced EF (EF 40% or less) enrolled in this prospective study. Functional status was evaluated by using cardiopulmonary exercise test at baseline. All patients were measured quantity of epicardial fat and thigh IMF percentage (%IMF) using computed tomography scan. Demographic, laboratory and echocardiographic date were collected from the patients' medical records. Clinical endpoints were unexpected readmission.

Results
During the follow-up period 18 patients had adverse events. The %IMF was significantly higher in the group with adverse events than without (5.57±5.70 and 3.02±2.44%, respectively; p&lt;0.01). Spearman correlation coefficient analysis showed a modest correlation between %IMF and lower limb extension strength (Spearman r=−0.280; p=0.0315), but there was no significant correlation between %IMF and exercise tolerance such as anaerobic threshold and peak oxygen uptake. Patients were divided into 2 groups according to the median values of %IMF. Kaplan-Meier analysis demonstrated that events were significantly higher in the high %IMF group (log-rank p=0.033). Multivariate Cox regression analysis adjusted for left ventricular end-diastolic diameter and peak ventricular oxygen consumption found %IMF as an independent factor of adverse events (hazard ratio 1.545; 95% confidential interval 1.151–2.087; p=0.004).

Conclusions
In non-ischemic cardiomyopathy patients with reduced EF, %IMF may have important adverse consequences such as increased cardiac-related events.
Kaplan-Meier curves

Funding Acknowledgement
Type of funding source: None
Sacubitril/valsartan improves ventilation stability in patients with chronic heart failure
Authors: Sciarrone P , Borrelli C , Giannoni A , Gentile F , Aimo A , Vergaro G , Emdin M , Passino C 
Published: November 2020

Abstract

Background
Sacubitril/valsartan (SV) ameliorates symptoms and prognosis in patients with heart failure and reduced ejection fraction (HFrEF), but the reasons for such effects are unclear. The impact of SV on ventilation has never been investigated. In HFrEF, apneas are highly prevalent both at daytime and nighttime and are associated with increased mortality.

Purpose
We hypothesize that treatment with SV could favourably stabilize ventilation by reducing the severity of central apneas in patients with HFrEF.

Methods
51 patients with HFrEF (mean age 67±9 years, mean left ventricular ejection fraction, LVEF 27±7%) and apneas defined by an apnea-hypopnea index, AHI≥5 (median 16, interquartile range 8–28) events/hour, eligible to treatment with SV and previously on optimal medical therapy for HFrEF, were enrolled. An extensive evaluation including cardiac ultrasound and a 24-hour cardiorespiratory monitoring was performed.

Results
After six months of treatment with SV, left ventricle systolic and diastolic function, mitral regurgitation (MR), left atrial volume (LAVI) and systolic pulmonary artery pressure (sPAP) were improved. Severity of apneas was reduced by 50%, 65% and 36% throughout the 24-hour, at daytime and nighttime, respectively.

Conclusion
Besides its known efficacy on cardiac remodeling, SV positively decreases the apneic burden in patients with HFrEF.

Funding Acknowledgement
Type of funding source: Private company. Main funding source(s): Roche Diagnostics unrestricted grant
U-shaped association of sphingosine-1-phosphate level with mortality in chronic systolic heart failure
Authors: Xue Y , Ma Q , Chen S , Wang X , Ma A 
Published: November 2020

Abstract

Background
The immunomodulatory molecule sphingosine-1-phosphate (S1P) has received attention in the cardiovascular field due to its significant cardioprotective effects, as revealed in animal studies. Until now, it has been unclear what is the normal range of S1P in chronic heart failure patients and whether it is related to long term prognosis.

Purpose
The purpose of our study was to identify the distribution characteristics of S1P in systolic heart failure patients and the prognostic value of S1P for long-term prognosis.

Methods
We recruited 210 chronic systolic heart failure patients from June 2014 to December 2015. Meanwhile 54 healthy people in the same area were selected as controls. Plasma S1P was measured by mass spectrometry. Patients were grouped according to the baseline S1P level quartiles, and restricted cubic spline plots described a U-shaped association between S1P and all cause death. Cox proportional hazard analysis was used to determine the relationship between category of S1P and all-cause death. Survival curves were using the Kaplan-Meier method and the log-rank test was used for comparison.

Results
Compared with the control group, the plasma S1P in chronic heart failure patients demonstrated a higher mean level (1.269 μmol/L vs 1.122 μmol/L, P=0.006) and a larger standard deviation (0.441 vs 0.316, P=0.022). After a follow-up period of 31.7±10.3 months, the second quartile (0.967–1.192μml/L) with largely normal S1P levels had the lowest all-cause mortality and either an increase (HR=3.87, 95% CI 1.504–9.960, P=0.005, adjusted HR=3.134, 95% CI 1.211–8.111, P=0.019) or a decrease (HR=3.271, 95% CI 1.277–8.381, P=0.014, adjusted HR=1.90, 95% CI 0.711–5.083, P=0.200) predicted a worse prognosis.

Conclusions
Plasma S1P levels in systolic heart failure patients are related to the long-term all-cause mortality with a U-shaped correlation. Through restoring abnormal levels to a normal range instead of simply up regulation or down regulation, S1P may have the potential to be a therapeutic target for reducing the risk of death in patients with heart failure in the future.

Funding Acknowledgement
Type of funding source: Public grant(s) – National budget only. Main funding source(s): Ministry of Science and Technology of the People's Republic of China. Ministry of Finance of the People's Republic of China.
Head-to-head comparison of MAGGIC-HF, SHFM and BCN-Bio HF scores
Authors: Codina P , De Antonio M , Domingo M , Santiago-Vacas E , Zamora E , Santesmases J , Subirana I , Buchaca D , Diez-Quevedo C , Boldo M , Rivas C , Velayos P , Nunez J , Lupon J , Bayes-Genis A 
Published: November 2020

Abstract

Background
Three heart failure (HF) web-based risk scores are currently used in clinical practice. Two only include clinical variables; one adds biomarkers, known to refine pathophysiological pathways in HF and to improve mortality prediction.

Objective
To assess inter-score agreement and to compare mortality prediction discrimination between MAGGIC-HF risk score, Seattle HF Model (SHFM) and Barcelona Bio-HF Risk Calculator (BCN Bio-HF), which includes both clinical and biomarker variables (NTproBNP).

Methods
Out of 1745 consecutive patients with HF from different etiologies admitted at our Unit from May 2006 to November 2018, 1689 with NTproBNP measurement at first visit were included. Absolute and consistency intraclass correlation coefficient (ICC) at individual level among the three risk estimation tools was assessed. Bland Altman graphics were used to illustrate the differences between scores across the broad spectrum of mortality risk. Discrimination of the three prediction tools was compared by AUC of the ROC curves for 1-, 3- and 5-year all-cause mortality. Patients used previously to derivate the BCN Bio-HF were excluded.

Results
Patients age 66.3±13.3 years, 70.4% men, LVEF 36.4%±14.4, ischemic etiology 43.7%. Absolute ICC was poor for the three tools (from 0.18 [–0.006 to 0.35] to 0.53 [0.42 to 0.62], while consistency ICC was slightly better (from 0.28 [0.24 to 0.33] to 0.57 [0.53 to 0.60], being highest the ICC of MAGGIC-HF and BCN Bio-HF. Correlation was better among scores in low-mortality risk profile patients but clinical scores tended to infraestimate the risk in comparison with the BCN Bio-HF in high-risk patients (Figure). Discrimination was numerically better with the BCN Bio-HF at every time risk (Table), significantly better when compared with SHFM.

Conclusions
In comparison with other clinical scores, the BCN Bio-HF calculator predicted better higher mortality risk. Correlation was globally poor for the three tools at individual level, although improved in the low risk patients. Discrimination tended to be numerically better with the BCN Bio-HF calculator, reaching statistical significance when compared with the SHFM.
Bland Altman agreement among tools

Funding Acknowledgement
Type of funding source: None
The impact of frailty and aging on prognosis in patients with heart failure with preserved ejection fraction – insights from PURSUIT-HFpEF registry
Authors: Okada M , Inoue K , Onishi T , Iwakura K , Yamada T , Yasumura Y , Tamaki S , Hayashi T , Yano M , Hikoso S , Sakata Y 
Published: November 2020

Abstract

Introduction
Frailty and aging are two common conditions both associated with increased vulnerability to stressful events with high risk of adverse outcomes.

Purpose
To evaluate the association between frailty and aging and their impacts on clinical outcome in patients with heart failure with preserved ejection fraction (HFpEF).

Methods
Analysis was performed from a prospective multicenter observational registry for HFpEF (PURSUIT-HFpEF Registry) conducted in the Osaka region of Japan. A total of 757 patients hospitalized for acute heart failure (diagnosed by using Framingham criteria) met the inclusion criteria: a left ventricular ejection fraction ≥50% and brain natriuretic peptide ≥100pg/ml. We included 483 patients (age, 80±9 years; men, 45%; atrial fibrillation, 35%) whose follow-up data after survival discharge were available. Patients' frailty and aging were evaluated using the clinical frailty scale (CFS) and age quartiles (Q1: &lt;76 years (n=122), Q2: 76–82 years (n=111), Q3: 82–87 years (n=127), Q4: &gt;87 years (n=123)), respectively. The primary clinical endpoint was defined as the composite of death, re-hospitalization for heart failure, and cerebrovascular accident.

Results
The median (interquartile range) CFS rating was 3 (2–5), and there was a little correlation between CFS rating and age (r2=0.16, p&lt;0.001). The prevalence of frailty, defined as a CFS rating &gt;4 (n=132), was positively correlated with age quartiles (Q1: 9.0%, Q2: 21.4%, Q3: 29.9%, Q4: 48.0%, p&lt;0.001). During the median follow-up period 396 days (interquartile range, 344–698) after discharge, the clinical endpoint was observed in 172 patients. The incidence was higher in patients with frailty than those without it (49.6% vs. 30.4%, log-rank p&lt;0.001). It was also correlated with age quartiles (Q1: 23.0%, Q2: 34.2%, Q3: 36.2%, Q4: 48.8%, log-rank p=0.001). Multivariate Cox regression analysis revealed that frailty (hazard ratio, 1.52; 95% confidence interval, 1.09–2.10; p=0.013) and age (hazard ratio per quartile increase, 1.24; 95% confidence interval, 1.07–1.43; p=0.004) were both associated with the clinical endpoint. Subgroup analysis in 352 patients without frailty also revealed the significant impact of age on the endpoint (1.26; 1.06–1.51; p=0.008). However, in 131 patients with frailty, there was no significant impact of age on the endpoint (1.16; 0.90–1.51; p=0.25).

Conclusions
Frailty was common and was associated with aging in HFpEF patients. Although they were both associated with unfavorable events, aging was no longer a significant predictor of adverse outcomes under the frailty conditions.

Funding Acknowledgement
Type of funding source: Private company. Main funding source(s): Roche Diagnostics K.K. and Fuji Film Toyama Chemical Co. Ltd.
Real world heart failure epidemiology and outcome: a population-based analysis of 1,990,162 heart failure patients
Authors: Leszek P , Zaleska-Kociecka M , Was D , Witczak K , Bartolik K , Rolska-Wojcik P , Brukalo K , Maruszewski B , Kleinork A 
Published: November 2020

Abstract

Background
Heart failure (HF) is the leading cause of death and hospitalization in developed countries. Most of the information about HF is based on selected cohorts, the real epidemiology of HF is scarce.

Purpose
To assess trends in the real world incidence, prevalence and mortality of all in-and outpatients with HF who presented in public health system in 2009–2018 in Poland.

Methods
It is a retrospective analysis of 1,990,162 patients who presented with HF in Poland in years 2009–2018. It is a part of nationwide Polish Ministry of Health registry that collects detailed information for the entire Polish population (38,495,659 in 2013) since 2009. Detailed data within the registry were collected since 2013. HF was recorded if HF diagnosis was coded (ICD-10).

Results
The incidence of HF in Poland fell down from 2013 to reach 127,036 newly diagnosed cases (330 per 100,000 population) in 2018 that equals to 43.6% drop. This decrease was mainly driven by marked reduction in females (p&lt;0.001; Fig. 1A) and HF of ischaemic etiology (HF-IE vs HF-nonIE, Fig. 1B. p&lt;0.001). The HF incidence per 100,000 population decreased across all age groups with the greatest drop in the youngest (Table 1).
The prevalence rose by 11.6% to reach 1,242,129 (3233 per 100,000 population) in 2018 with significantly greater increase in females and HF-IE (both p&lt;0.0001, Fig. 1C and D, respectively). The HF prevalence per 100,000 population increased across all age groups except for the 70–79 years old. (Table 1).
Mortality increased by 28.5% to reach 142,379 cases (370 per 100,000 population) in 2018. The rise was more pronounced among females (p=0.015, Fig. 1E) and in HF-IE (p&lt;0.001, Fig. 1F). The HF mortality per 100 000 population increased across all age groups, except for the 50–59 subgroup (Table 1).

Conclusions
Heart failure incidence plummeted in years 2013–2018 in Poland due to drop in newly diagnosed HF-IE. Despite that fact, the prevalence and mortality increased with rising trends in HF-IE.
Figure 1. Incidence, prevalence, mortality trends

Funding Acknowledgement
Type of funding source: Public grant(s) – EU funding. Main funding source(s): The project is co-financed by the European Union from the European Social Fund under the Operational Programme Knowledge Education Development and it is being carried out by the Analyses and Strategies Department of the Polish Ministry of Health
Increasing home-time for patients with heart failure in Sweden 1992–2008
Authors: Ekestubbe S , Fu M , Giang K.W , Lindgren M , Rosengren A , Schioler L , Schaufelberger M 
Published: November 2020

Abstract

Background
Heart failure (HF) reduces survival and is one of the most common causes of hospitalizations in the elderly, imposing a major economic burden on the health care system, with frequency of rehospitalizations often used in interventional and observational studies in patients with HF. Home-time is a novel end-point measuring time spent alive and out of hospital and is easier for both clinicians and patients to relate to. Given the advances in treatment of HF over the last decades we postulated that an increase in home-time would follow.

Purpose
To investigate whether home-time for patients with HF has changed over the last decades in Sweden and if home-time differs between patients of working age and those retired, or between men and women.

Methods
Patients aged 18–84 years with a first hospitalization for HF in Sweden between 1992 and 2008 were identified using the National Inpatient Register which was linked to the Swedish Cause of Death Register. Information on rehospitalizations and mortality was collected and followed over a time period of 4 years. The patients were divided into two age groups: (i) &lt;65 years and (ii) &gt;65 years. The cut off 65 years was chosen being the official age of retirement over the study period in Sweden.

Results
A total of 324,907 patients were included in this study, mean age 73.5 years (standard deviation 9.3). Only 15.6% were &lt;65 and 45.1% were women. In total, average home-time was 70.1% of the total follow up time, 2.1% of time was spent in hospital while, during a mean of 27.9% of the 4 year-period, patients were no longer alive. A small increase in home-time was observed over the study period. The older age group spent 67.7% at home compared with 83% in the younger group. After taking differences in mortality into account, the difference in home-time was no longer significant, with 92.7 and 95.8% home-time for the older and younger age groups, respectively. Over the entire study period older men had less home-time compared with older women. Since 1998 the reverse was true in younger men and women, where younger men had more home-time than younger women. Home-time increased for all subgroups over the study period with the most pronounced increase for younger men (see figure 1).

Conclusion
Home-time for patients in Sweden increased over the study period and the increase was more marked for younger patients, where men spent more time at home than women.
Figure 1

Funding Acknowledgement
Type of funding source: Public grant(s) – National budget only. Main funding source(s): The Swedish state (ALF), The Swedish Heart and Lung Foundation, Västra Götaland Region, The Göteborg Medical Society
Coronary sinus oxidative stress markers allow for accurate assessment of the prognosis in patients with advanced heart failure awaiting transplantation
Authors: Szczurek W , Gasior M , Skrzypek M , Antonczyk K , Bielka A , Dziobek B , Zembala M , Szygula Jurkiewicz B 
Published: November 2020

Abstract

Background
Oxidative stress is a cause of cardiac diseases and contribute to apoptosis, cardiac remodeling, cardiac growth and repair. The end-stage heart failure (HF) is associated with ischemia-reperfusion, increased neurohumoral activity, cytokine stimulation and presence of inflammatory cells. Above factors are stimuli which generate free radicals and can induce oxidative stress in the heart and cause damage to essential myocardial structures and function. However, the role of oxidative stress in end-stage HF has not been fully understood.

Purpose
This study aimed to evaluate the prognostic value of the oxidative stress markers in ambulatory patients with end-stage HF awaiting heart transplantation (HT) during a 1.5 year follow-up period.

Method
The study was a prospective analysis of 85 optimally treated adult patients with end-stage HF, who were added to the HT waiting list at the Cardiology Department between 2015 and 2016. At the time of enrollment to the study routine laboratory tests, cardiopulmonary exercise test, echocardiography, spirometry and right heart catheterization were performed in all patients. During right heart catheterization, 10 ml of coronary sinus blood was additionally collected to determine total oxidant status (TOS) and total antioxidant capacity (TAC) levels. TOS and TAC were measured by Erel's method. The endpoint was all-cause mortality during a 1.5 years follow-up. The Medical University of Silesia's local Institutional Review Board approved the study protocol, and all patients provided informed consent.

Results
Median age of the patients was 53.0 (43.0–56.0) years and 90.6% of them were male. During the observation period, the mortality rate was 40%. The area under the receiver operating characteristics (ROC) curves indicated an acceptable discriminatory power of TAC (AUC: 0.780 [CI: 0.677–0.883]; sensitivity 56%, and specificity 90%); and excellent power of TOS (AUC: 0.9530 [CI: 0.9279–0.9781]; sensitivity 88%, and specificity 94%) for 1.5 years mortality. Patients with a low TAC level (≤1.10) had a significantly worse 1.5-year survival compared to the group with a high TAC level (&gt;1.10) (1.5 year survival: 20.8% versus 75.4%; (long rank p&lt;0.001). Similarly, patients with a high TOS level (≥3.11) had a significantly worse survival compared to the group with a low TOS level (&lt;3.11) (1.5- year survival: 9.1% versus 92.3%; p&lt;0.001).

Conclusion
TAC with acceptable prognostic power and TOS with excellent prognostic power allows assessment of the prognosis in end-stage HF during a 1.5 year follow-up period.

Funding Acknowledgement
Type of funding source: Public Institution(s). Main funding source(s): Medical University of Silesia, Katowice, Poland