bluuebunny/crossref_metadata_2025_split huggingface dataset:
Therapeutic role of Prostaglandin E2 receptor 4 stimulation in inflammatory cardiomyopathy
Authors: Takakuma A.T , Nishii M.N , Saji R.S , Sakai K.S , Matsumura R.M , Ogawa F.O , Takeuchi I.T 
Published: October 2021

Abstract

Background
Prostaglandin E2 receptor 4 (EP4) plays a crucial role in inflammatory diseases. Inflammatory cardiomyopathy often leads to refractory heart failure.

Purpose
We aimed to evaluate the role of EP4 in the development of inflammatory cardiomyopathy.

Methods
Experimental autoimmune myocarditis (EAM) was induced by immunization with cardiac myosin in balb/c mice. EP4 selective antagonist (CJ-42794, Cayman Chemical: 30 mg/kg/day), EP4 selective agonist (20 mg/kg/day), both, or vehicle alone was daily administrated after the immunization. Cardiac function and dimensions were assessed by echocardiography. Blood pressure and heart rate were assessed with tail-cuff method. Cardiac inflammation and fibrosis were immunohistologically examined. Molecular examination was performed by RT-PCR and immunoblotting.

Results
Cardiac dysfunction and dilatation were worsened on day 21 in EP4 antagonist-treated group compared with in the vehicle-treated group, accompanied by an increase in cellular infiltration area (21.7±1.9 vs. 11.0±2.7%, P=0.0367, respectively). Conversely, cardiac dysfunction and dilatation were improved in EP4 agonist-treated group compared with in the vehicle-treated group (Left ventricular fractional shortening: 69±3% vs. 40±4%, P&lt;0.0001; Left ventricular systolic dimension: 0.7±0.1mm vs. 1.9±0.3mm, P=0.0007; respectively). These parameters did not show significant differences between both-treated group and the vehicle-treated group. The protective effect of EP4 stimulation in EAM was also kept on day 56. Moreover, cardiac fibrosis area as well as mRNA expressions of Type III collagen and brain natriuretic peptide in the bulk hearts was significantly reduced on day 56 in EP4 agonist-treated group compared with in the vehicle-treated group (12.3±2.4% vs. 24.7±3.0%, P=0.0278, respectively). Cardiac expression of phosphorylated smad 2/3 protein as well as TGF-β1 mRNA did not show significant differences between the 2 groups, while cardiac expression of RORgammat protein, the master regulator of Th17 immunity was increased in the EP4 antagonist-treated group.

Conclusions
EP4 activation negatively regulated the induction of cardiac autoimmunity, which alleviated cardiac dysfunction, dilatation, and fibrosis. EP4 may be a therapeutic target for preventing the development of inflammatory cardiomyopathy.

Funding Acknowledgement
Type of funding sources: None.
Mortality and long-term outcomes of palliative inotropes in ischemic and non-ischemic cardiomyopathy
Authors: Tolia S , Khan M , Khan S , Alexander D , Soltys M , Kamba K , Brennan S , Adhikari S , Hussain S , Joshi A , Sciamanna C , Narang N , Pillarella J , Cotts W , Andrade A 
Published: October 2021

Abstract

Background
Palliative inotropes are frequently utilized for symptom management in patients with end stage heart failure who are unable to undergo durable advanced heart failure therapies. With the advent of improved medical management and early intervention, palliative inotropes may allow for improved patient outcomes than seen previously. In this study, we aim to investigate the survival and outcomes of palliative inotrope therapy and its impacts on ischemic versus non-ischemic cardiomyopathy.

Methods
We retrospectively analyzed 220 patients with American Heart Association Stage D heart failure who were discharged with palliative inotrope therapy after January 1, 2010. Patients who underwent mechanical circulatory support (MCS) or those who underwent heart transplant were excluded. Those with a history of coronary artery disease, myocardial infarction, history of percutaneous intervention, or coronary artery bypass grafting were assigned to ischemic cardiomyopathy (ICM), while patients without these findings were assigned to non-ischemic cardiomyopathy (NICM). Statistical analysis was completed using Chi-Square and Student's t-tests, wherein p&lt;0.05 was considered statistically significant.

Results
Of the 220 patients, 87 had NICM as opposed to 133 with ICM. Mean age was found to be higher among patients with ICM (70 [62–79]) compared to NICM (65 [55–72], p-value &lt;0.01). No significant difference was seen in total days on inotrope therapy (p=0.6). While more patients in both groups were placed on milrinone as opposed to dobutamine, there was no difference between patients with ischemic and NICM (p=0.66 and 0.51 respectively). Although a greater number of patients with NICM had been lost to follow up, admitted to hospice, or expired at 2 years (p&lt;0.01), survival at 3 months, 1 year, and 2 years showed no difference between both groups. No difference was seen in number of hospitalizations or clinic visits in one year. Both groups had similar complication rates with intravenous-access related PICC line infections and new arrhythmias. (See Table).

Conclusion
Despite more frequent use of durable mechanical support devices, many patients who are deemed unsuitable for invasive measures are treated with palliative inotrope therapy. We have found that there is no significant difference in survival, complications, and outcomes of patients on palliative inotropes among ischemic and NICM. These findings show the versatility of palliative inotrope therapy in end stage heart failure. Further studies with larger populations need to be evaluated.

Funding Acknowledgement
Type of funding sources: None.
Low serum chloride level gives renin-angiotensin system inhibitor a prognostic impact in heart failure patients with preserved ejection fraction
Authors: Shirotani S , Jujo K , Kishihara M , Watanabe S , Endo N , Takada T , Abe T , Minami Y , Hagiwara N 
Published: October 2021

Abstract

Background
Hypochloremia is associated with a poor prognosis of heart failure (HF) patients. This phenomenon is sustained even in HF with preserved ejection fraction (HFpEF). Serum chloride level is known to be affected by serum renin secretion; however, this relationship is one of the least investigated field in HF patients. Renin-angiotensin system (RAS) inhibitor is recommended as a first-line medication for HF patients with reduced left ventricular ejection fraction, but no prior studies of RAS inhibitors have achieved to improve the prognosis of HFpEF patients.

Purpose
We investigated the relationship between baseline serum chloride level and the prognostic impact of RAS inhibitor in HFpEF patients.

Methods
This is an observational study including 1,913 consecutive patients who admitted to hospital due to worsening of HF and discharged alive in a single university hospital. After excluding patients who received regular hemodialysis and whose left ventricular ejection fraction were under 50%, 506 HFpEF patients were ultimately analyzed. They were categorized into tertiles by serum chloride levels at discharge (T1: −100 mEq/L, T2: 101–104 mEq/L, T3: 105- mEq/L), and patients in each category were further divided into subgroups depending on the prescription of RAS inhibitor at discharge (RAS inhibitor group and Non-RAS inhibitor group). The primary endpoint of this study was death from any cause.

Results
During the observation period with 479 days of median follow-up, 77 (15.2%) died. Patients in the RAS inhibitor group had significantly better prognosis than those in the Non-RAS inhibitor group in T1 category (Log-rank: p=0.003, Figure). In contrast, there was no statistical difference in the mortality between the RAS inhibitor group and Non-RAS inhibitor group in T2 and T3 categories (Log-rank: p=0.15, p=0.81, respectively, Figure). Multivariate Cox regression analysis in T1 category revealed that taking RAS inhibitor at discharge was independently associated with a lower mortality rate, even after the adjustment of diverse covariates (hazard ratio: 0.40, 95% confidence interval: 0.20–0.80).

Conclusion
In this observational study, the administration of RAS inhibitor was associated with an improved prognosis of HFpEF patients only in low serum chloride level at discharge. Therapeutic strategy focusing on the chloride level may be one of the promising options to find the light on a unintervenable prognosis of HFpEF.

Funding Acknowledgement
Type of funding sources: None.
Changing demographics, temporal trend in waitlist and post-transplant outcomes after heart transplantation in the United States: analysis of unos database 1991–2019
Authors: Akintoye E , Alvarez P , Shin D , Egbe A , Panos A , Briasoulis A 
Published: October 2021

Abstract

Background
The landscape of heart transplantation (HT) has changed significantly with respect to patient selection, surgical techniques, and patient outcomes. We sought to investigate temporal trends in patient characteristics, waitlist and post-transplant outcomes after HT in the U.S.

Methods
We queried the national database of the United Network of Organ Sharing (UNOS) to identify adults listed for HT in the U.S. between 1991 and 2019. Patients were divided into four eras based on the three time points in which changes were made to the patient selection/allocation policy (1999, 2006, and 2018), and patient characteristics as well as waitlist and post-transplant outcomes were evaluated for each era.

Results
Between 1991 and 2019, a total of 95,179 patients were added to the waitlist for HT in the U.S. Compared to era 1, patients listed in era 4 were older (mean age: 52.4 years), more female (27.6%) and ethnic minorities (40%), and with higher-risk comorbidities (28.8% diabetes, 35.6% obese). Over the study period, there were 22,070 waitlist deaths and 61,687 transplants.
Compared to the preceding era, there was significant decrease in waitlist mortality in the last 2 eras (e.g., sub-hazard ratio for era 4 vs era 3 =0.37, 95% CI=0.32–0.44). For each year, only 27.1% to 40.5% of those on the waitlist were transplanted. Among those who were transplanted, there was increase in the rates of in-hospital stroke (2.8% in era 1 to 3.7% in era 4), renal failure requiring dialysis (7.2% to 17.1%), and hospital length of stay (14 to 17 days), p-values&lt;0.001 for all. However, this has not negatively impacted short-term survival when compared to the preceding era (1-year graft survival = 89.7% in era 4). Based on a projection model, we predict a 47% increase in living adult heart transplant recipients to to 44,366 in 2040.

Conclusion
There have been significant changes in the characteristics of patients listed for HT in the U.S., including an increasing proportion of high-risk co-morbidities. Although the transplant volume has increased, the wide supply-demand gap persisted. The last 2 changes in the allocation policy in 2006 and 2018 achieved their primary objective of reducing waitlist mortality.

Funding Acknowledgement
Type of funding sources: None.
B-lines by lung ultrasound is associated with pulmonary symptoms and cardiac function in acute malaria: a prospective cohort study
Authors: Wegener A , Holm A , Gomes L , Lima K , Matos L , Vieira I , Kaagaard M , Souza R , Marinho C , Sorensen T , Silvestre O , Brainin P 
Published: October 2021

Abstract

Background
Malaria patients are at risk of cardiopulmonary complications, but diagnosis and management are difficult in resource limited environments. B-lines by lung ultrasonography (LUS) can identify pulmonary alterations, however, little is known about the usefulness in malaria.

Purpose
We aimed to investigate the occurrence of B-lines in acute malaria patients at baseline and at follow-up, and whether they are associated with shortness of breath and impaired left ventricular ejection fraction (LVEF).

Methods
Adult patients with non-severe acute malaria were prospectively enrolled from June to December 2020 in community healthcare clinics in a remote area. Patients were age- and sex-matched to controls without a prior history of malaria. We examined patients prior to anti-malaria treatment and at follow-up. Malaria treatment was administered according to national guidelines. Patients were excluded if they were pregnant, had concomitant infections or recent chest trauma. Patients underwent LUS (8-zones), echocardiography and peripheral blood smear. Measurements were blinded to clinical variables and outcomes.

Results
We included a total of 99 patients (median age 40±15 years, 55% men). Patients suffered from Plasmodium vivax (n=75), P. falciparum (n=22), and a mix of the two (n=2) and median parasite density was 1,595 parasites/mL (interquartile range [IQR] 528–6,585/mL). Follow-up was completed in 71 patients and the median follow-up time was 31 days (IQR 27–40 days).
Patients with acute malaria had significantly more B-lines at baseline than matched controls (P-value&lt;0.001) and fewer B-lines at follow-up (P-value&lt;0.001) (Figure 1). In acute malaria patients, number of B-lines at baseline correlated significantly with shortness of breath (OR 1.20, [1.04 to 1.39], P-value=0.01) and with LVEF (adjusted for age and sex: +8% [+1% to +15%], P-value=0.016 per 1% decrease in LVEF). There was no correlation between number of B-lines and parasite density (+2% [−5% to +11%], P-value=0.53 per 1000 increase in parasite density).

Conclusion
B-lines detected by LUS are more frequent in patients with acute malaria than in age- and sex-matched controls and decrease in response to treatment. B-lines also correlate with shortness of breath and lower LVEF at baseline. Because LUS is a quick and accessible examination, it may potentially facilitate risk stratification and therapeutic decisions regarding cardiopulmonary complications in patients with acute malaria.

Funding Acknowledgement
Type of funding sources: Foundation. Main funding source(s): Danish Heart Association
Cardiac allograft vasculopathy and acute rejection surveillance in the same procedure through a single vascular access. High volume center experience
Authors: Arellano Serrano C , Oteo Dominguez J.F , Garcia Touchard A , Fernandez Diaz J.A , Del Trigo Espinosa M , Mitroi C , Hernandez Perez F.J , Gomez Bueno M , Goicolea Ruigomez J , Segovia Cubero J 
Published: October 2021

Abstract

Introduction
Cardiac Allograft Vasculopathy (CAV) and Acute Rejection (AR) surveillance after a Heart Transplant (HT) is based on the performance of Coronary Angiography (CAG) that requires arterial access and Endomyocardial Biopsy, normally Ventricular Right (RV-EMB), which requires venous access. Depending on the clinical indication, HT patients are referred to the cath lab to perform both procedures in the same day. We evaluated the effectiveness and safety of performing a Left Ventricular Endomyocardial Biopsy (LV-EMB) and a CAG with a single artery access.

Methods
We retrospectively analyzed HT patients referred to cath lab for surveillance of AR and CAV on the same day between January 2018 and March 2021. We compared the procedures performed with two accesses (Group 1; CAG + RV-EMB) versus procedures made with a single artery access (Group 2; CAG + LV-EMB).

Results
121 Procedures were performed within the indicated period, 96 (79.3%) belong to the double access group and 25 (20.7%) to the single access group. All procedures were successful and without major complications. There were only 2 cases of insufficient sample, one for each group. Baseline characteristics in both groups and AR or CAV presence were similar (table). Total procedure time (52.00±15.30 vs 33.36±18.69min) and fluoroscopic time (10.70±4.89 vs 6.84±1.82 min) were significantly shorter in the single access group (p&lt;0.001 in both). The most used arterial access in group 2 was the right radial artery (15; 60%) followed by the right femoral artery (5; 20%).

Conclusions
Performing an endomyocardial biopsy and coronary angiography through a single arterial access is as effective and safe as with double access, arterial and additional venous. Procedure time and fluoroscopic time is significantly less when it is performed through the same access.

Funding Acknowledgement
Type of funding sources: None.
Right ventricular dysfunction but not left ventricular ejection fraction is associated with length of stay in acute heart failure
Authors: Berrill M , Ashcroft E , Baltabaeva A 
Published: October 2021

Abstract

Background
Acute heart failure (AHF) remains a substantial healthcare burden worldwide. It is therefore important to identify triaging markers which are associated with length of stay (LOS). Attention from an echocardiographic perspective often centres on the left-ventricular ejection fraction (LVEF). The role of right ventricular (RV) function and pulmonary hypertension (PHT) remains less certain.

Methods
We investigated LOS in 440 consecutive patients presenting in AHF. We also identified those admitted ≥5 days – the cut-off date when reimbursement for AHF-related hospital care is reduced significantly in England. All patients underwent bedside echocardiography within 24 hours of recruitment, prior to intensive diuresis. Patients were followed up for 2 years. We analysed the association between echo parameters with LOS in 414 patients who survived to discharge. We also compared those admitted ≥5 and &lt;5 days.

Results
The average LOS for survivors was 7.7±5.7 days; 216 (52.2%) stayed ≥5 days, with 198 (47.8%) discharged &lt;5 days. LVEF was not correlated with LOS; Spearman's ρ −0.062 (p=0.207). RV fractional area change (ρ −0.108 [p&lt;0.03]), tricuspid annulus plane systolic plane excursion (ρ −0.166 [p&lt;0.001]) and systolic pulmonary artery pressure (ρ −0.161 [p&lt;0.001]) were all correlated with LOS. In patients with longer LOS, greater BNP, diabetes and chronic kidney disease were more prevalent. 2-year all-cause mortality was 41.0% in those admitted ≥5 days and 27.1% for &lt;5 days (Hazard ratio 1.57; 95% CI 1.13–2.19 [p=0.007]).

Discussion
RV dysfunction and severe PHT, not LVEF, were correlated with increased LOS in 414 consecutive patients discharged from an admission with AHF. These patients will place a disproportionate cost on health care resources. These hypothesis generating results suggest early echo assessment to quantify RV dysfunction may help to risk stratify patients with AHF and re-design hospital tariffs.

Funding Acknowledgement
Type of funding sources: Private company. Main funding source(s): Abbott Laboratories Table and KM curve
Use of echocardiography and heart failure mortality from registry data in Japan
Authors: Okushi Y O , Kusunose K K , Ise T I , Yamaguchi K Y , Yagi S Y , Fukuda D F , Yamada H Y , Soeki T S , Wakatsuki T W , Sata M S 
Published: October 2021

Abstract

Background
There are several recommendations for the use of echocardiography in acute hospitalized HF. Echocardiography requires a high degree of skill on the part of the examiner, and the skill may be more improved in larger volume centers.

Purpose
In this study, we investigated whether the use and volume of echocardiography is associated with in-hospital mortality from the real world registry database of heart failure (HF) hospitalizations.

Methods
This study was based on the Diagnosis Procedure Combination database in the Japanese Registry of All Cardiac and Vascular Datasets (JROAD-DPC). We categorized the 739 hospitals into 3 groups according to the number of echocardiographic studies performed annually (first tertile: &lt;2500 cases, second tertile: 2500–4500 cases, third tertile: &gt;4500 cases) and compared the groups of patients who were first admitted to the categorized hospitals with heart failure between April 2015 and March 2016. We estimated the odds ratios and their 95% confidence interval for in-hospital mortality using multivariable models. The variables of multivariable analysis were selected by stepwise method.

Results
A total of 80,496 HF patients were hospitalized, and 73.2% were examined for echocardiography. We found that the use and volume of echocardiography exams were associated with significantly lower odds of all-cause hospital mortality in heart failure (adjusted OR: 0.48 for use of echocardiography and 0.78 for the third tertile; both P&lt;0.001).

Conclusions
The use of echocardiography was associated with decreased odds of hospital mortality in HF. The volumes of echocardiographic examinations were also associated with hospital mortality; thus, this study suggests that the skill of echocardiography may be improved in the large volume center and provide good outcomes in HF.

Funding Acknowledgement
Type of funding sources: Public Institution(s). Main funding source(s): Japan Society for the Promotion of Science (JSPS) Flowchart of this studyOdds ratio of in-hospital mortality
Prognostic value of a new systemic inflammation-nutrition index in patients admitted with acute decompensated heart failure; a comparison with malnutrition
Authors: Yamada T , Watanabe T , Morita T , Kawasaki M , Kikuchi A , Kawai T , Seo M , Nakamura J , Kayama K , Fukunami M 
Published: October 2021

Abstract

Background
Systemic inflammation plays a critical role in the outcomes of heart failure. Malnutrition is also associated with poor outcome in heart failure patients. It has been recently reported that advanced lung cancer inflammation index (ALI), which is calculated as body mass index × serum albumin / neutrophil to lymphocyte ratio (NLR), is an independent prognostic marker in several types of cancer. However, there is no information available on the prognostic impact of ALI in patients admitted with acute decompensated heart failure (ADHF), especially in comparison with malnutrition.

Methods and results
We studied 263 ADHF patients discharged with survival. At the discharge, we measured ALI. Malnutrition was assessed by prognostic nutritional index (PNI) and controlling nutritional status score (CONUT). During a follow up period of 5.1±4.3 yrs, 67 patients had cardiovascular death (CVD). ALI was significantly smaller in patients with than without CVD (32.5±18.2 vs 52.2±30.2, p&lt;0.0001). At multivariate Cox regression analysis, ALI was significantly associated with CVD, independently of prior heart failure hospitalization, systolic blood pressure and eGFR, although PNI and CONUT showed the association with CVD at unvariate analysis. By receiver-operator curve analysis, AUC of ALI was 0.733 (0.664–0.803), which was significantly greater than that of PNI (0.664 [0.590–0.739]) and CONUT (0.591 [0.509–0.672]). Patients with lowest tertile of ALI (&lt;32.0) had a increased risk of mortality than middle tertile (NLR=32.0–53.6; HR 2.06 [1.15–3.71]) and highest tertile (ALI&gt;53.6: HR 5.80 [2.60–12.94]) (48% vs 21% vs 9%, p&lt;0.0001, respectively).

Conclusion
ALI, a systemic inflammation-nutrition index, is more useful prognostic marker than malnutrition in patients admitted with ADHF.

Funding Acknowledgement
Type of funding sources: None.