bluuebunny/crossref_metadata_2025_split huggingface dataset:
Outcomes of pediatric ventricular assist device in the United States: an analysis of the national inpatient sample database
Authors: Hamzah M , Hejazi Y , Mostafa G , Macrae D 
Published: November 2023

Abstract

Background
Infants and children with advanced heart failure, refractory to medications, are frequently supported with ventricular assist devices (VAD).

Purpose
To describe the patient characteristics of those who were supported with VADs and describe the factors associated with mortality with use of VAD in the USA.

Methods
We conducted a retrospective analysis of a large administrative database, the National Inpatient Sample (NIS) dataset for the years 2010 to 2018. We identified pediatric patients (0–18 years of age) who had implantation of VAD during the hospitalization. Patient characteristics and outcomes were compared between survivors and those who died during the hospitalization.

Results
We identified 1620 patients with VAD procedure in the years we studied. Of them, 324 patients (20%) died during the hospitalization. The trend of utilizing VAD was increasing during the years of the study (Fig. 1). Mortality trend over the study years is presented in figure 2. In multivariable regression analysis, patients with VAD who died were more likely to be less than 1 year of age (OR=4.14, 95% CI:2.29–7.50, p &lt; 0.001), on mechanical ventilation for more than 96 hours (OR=10.71, 95% CI: 6.69–17.14=5, p &lt; 0.001), had liver failure (OR 19.88, 95% CI:10.15-38.95, p&lt;0.001). Those who survived to hospital discharge were more likely to have orthotopic heart transplantation (OR=19.08, 95% CI: 8.12-44.81, p&lt;0.001) and were diagnosed with dilated cardiomyopathy (OR=5.08, 95% CI: 3.38-7.63, p&lt;0.001).

Conclusion
VAD in pediatric population is increasingly being used in the United States as a bridge to recovery or transplantation. During study period, in hospital mortality trended down significantly. Younger patient's age; less than one year, liver failure and &gt;96 hours mechanical ventilation are considerable risk factors for mortality. Prospective studies are needed to account for confounders, and further classify risk factors based on underlying structural heart disease and clinical status at time of hospital admission.
Dissociation of LA volume and deformation is a hallmark of ATTR-CA
Authors: Satyavolu B , Ozbay B , Rearick C , Soman P , Sade L E 
Published: November 2023

Abstract

Background
Transthyretin Cardiac amyloidosis (ATTR-CA) is associated with an infiltrative left atrial (LA) cardiomyopathy.

Purpose
We sought to identify unique characteristics of LA cardiomyopathy in CA compared to non-amyloid states of left ventricular hypertrophy (LVH).

Methods
In suspected patients, a diagnosis of ATTR-CA was made by a positive Tc-99m PYP in conjunction with negative serum/urine studies for a clonal plasma cell dyscrasia. Endomyocardial biopsy was performed when clinically indicated. All patients underwent complete transthoracic echocardiography (TTE) with speckle tracking strain imaging. Left ventricular (LV) strain, LA reservoir strain (LASr) and LA volume index (LAVI) were measured. LA stiffness index was estimated by the ratio (E/e’)/LASr. ATTR-CA patients were compared to patient with non- CA LVH (interventricular septal thickness &gt; 1.2 cm). Atrial fibrillation (AF) during the TTE was noted. Logistic regression and Cox-regression analyses were performed to find the independent determinant of ATTR-CA and outcome predictors, respectively.

Results
We studied 98 patients with ATTR-CA (44 with AF) and 62 patients with non-CA LVH (35 with AF). ATTR-CA patients had a higher prevalence of relative apical sparing (RAS) (79% vs 20%, p&lt;0.0001), reduced LASr (9.8±4.8% vs 14.0±7.2%; p&lt;0.001) and high LA stiffness (2.5±0.2 vs 1.4±0.9; p&lt;0.001) irrespective of AF. Surprisingly, LAVI of ATTR-CA patients was significantly lower than non- CA LVH patients (44±15 ml/m2 vs 51±24 ml/m2; p=0.046). Consequently, LAVI correlated strongly with LASr in non-amyloid LVH group (r= -0.52, p&lt;0.001) whereas no correlation was observed in ATTR-CA (p&lt;0.05) (Figure 1). Patients with ATTR-CA had the lowest LASr and highest LA stiffness regardless of AF (Figure 2). Importantly, LASr determined ATTR-CA among all study subjects independently of RAS (p&lt;0.001) and emerged as a predictor of composite endpoint including all-cause mortality, hospitalization from heart failure and stroke in ATTR-CA patients (p=0.037).

Conclusion
ATTR-CA is characterized by severely reduced LASr and increased LA stiffness, yet LA dilatation is relatively less severe when compared to other causes of LVH. LASr seems promising to make the differential diagnosis of ATTR-CA and is of prognostic importance.Figure 1Figure 2
Role of NTproBNP and donor-derived cell-free DNA in the diagnosis of acute rejection in heart transplant recipients: a prospective study
Authors: Jimenez-Blanco Bravo M , Crespo Leiro M , Marco Clement I , Lozano Jimenez S , Donoso V , Ortiz Bautista C , Farrero M , De Antonio M , Diaz Molina B , Diez Lopez C , Rangel Sousa D , Salterain N , Garrido Bravo I , Segovia Cubero J 
Published: November 2023

Abstract

Background
Donor-derived cell-free DNA (dd-cfDNA) has shown a good ability to rule out rejection in heart transplant (HT) recipients, but there is scarce information on the utility of NTproBNP (and the combination of both biomarkers) in this setting.

Methods
We prospectively obtained levels of both biomarkers in all patients included in the FreeDNA-CAR study (NCT 04973943), just before performing surveillance endomyocardial biopsies (EMB) at 0.5, 1, 2, 3, 4, 6 and 12 months post-HT. Primary end-point was the correlation between dd-cfDNA and NTproBNP levels.

Results
A total of 206 HT patients from 12 different centers were included (mean age 54±12 years, 74% male), with a median of 5.6 EBM per patient. After excluding visits with missing data, 883 pairs of EBM-both biomarkers were available for analysis.
ACR, defined as grade ≥2R, was present in 37 EMB (4.2%), and AMR ≥1 in 16 EMB (1.8%). Median (IQR) NTproBNP values for each ACR group were: 0R 1067 pg/ml (454-2563), 1R 1300 pg/ml (562-3298) and 2R-3R 1780 pg/ml (943-4880) and median dd-cfDNA values: 0R 0.08% (0.038-0.178), 1R 0.105% (0.04-0.34), 2R-3R 0.22% (0.058-0.7). Regarding AMR, median NTproBNP in pAMR0 was 1200 pg/ml (504-2840) and in pAMR≥1 2230 pg/ml (806-4256) (Figures 1A and 1B).
Using a GEE (generalized estimating equation) approach to account for repeated measures in each individual, a statistically significant correlation between both biomarkers was found, with a coefficient of 0.001 (CI95% 0.0006-0.002), meaning that for every increase of 100 units of NTproBNP, %dd-cfDNA increased in 0.001, p &lt;0.001 (Figure 2).
Moreover, in a multivariable analysis, both biomarkers were associated with the risk of acute rejection, with an OR 1.48 (CI95% 1.04-2.11), p=0.03 for dd-cfDNA, and OR 1.007 (IC95% 1.001-1-013) p=0.017 for each additional 100 pg/ml of NTproBNP.

Conclusion
In a cohort of HT patients in their first post-transplant year, dd-cfDNA and NT-proBNP levels were associated with acute rejection and showed a good correlation between them. Further studies are needed in order to determine if the combination of both biomarkers could improve individual performance and increase the number of EMB that could be safely eliminated.Median (IQR) NTproBNP levels (pg/ml)Linear prediction of dd-cfDNA
Donor-derived cell-free DNA as a new biomarker for acute rejection in heart transplant recipients: results from the freedna car study
Authors: Jimenez-Blanco Bravo M , Crespo Leiro M , Garcia Cosio M D , Hernandez Perez F J , Lopez Villela R , Ortiz Bautista C , Farrero M , Zegri Reiriz I , Diaz Molina B , Diez Lopez C , Rangel Sousa D , Salterain N , Garrido Bravo I , Segovia Cubero J 
Published: November 2023

Abstract

Background
There is an increasing body of evidence supporting the potential utility of donor-derived cell-free DNA as a non-invasive biomarker that could allow surveillance of rejection without the need of repeated endomyocardial biopsies (EMB) in heart transplant (HT) recipients.

Methods
Free-DNA CAR was a multicenter, observational, prospective study, performed between 2019 and 2022 (NCT 04973943). All patients underwent per-protocol surveillance EMB at 0.5, 1, 2, 3, 4, 6 and 12 months post-HT. Dd-cfDNA levels were determined prior to each EMB, using Next Generation Sequencing technology. Primary end-point was the association between dd-cfDNA levels and the presence of clinically relevant rejection defined as ACR grade ≥2R and/or pAMR≥1.

Results
The cohort included 206 patients from 12 HT centers (mean age 54 ± 12 years, 74% male), with a total of 1006 pairs of EMB-dd-cfDNA determinations. ACR ≥2 was present in 44 EMB (4.4%) and AMR ≥1 in 17 EMB (1.7%). Two samples had simultaneous ACR≥2 and pAMR≥1.
Patients with clinically relevant rejection had dd-cfDNA levels significantly higher than those without, 0.189% (0.058-0.6) vs 0.097% (0.04-0.24), p=0.0049 (Figure 1A, with %dd-cfDNA logtransformed as log2(x+0.01) in order to reduce the skewness). Median (IQR) dd-cfDNA values for each group are shown in figure 1B.
Using GEE (generalized estimating equation) models in order to account for repeated individual measures, a trend to significant association between %dd-cfDNA and rejection was found (OR 1.25, IC95% 0.95-1.64) (Figure 2), even though it did not reach statistical significance (p = 0.109).
In the subgroup of samples evaluated for ACR (n =991, after excluding 15 samples that did not have ACR but had AMR ≥1), there was also a significant difference between those with and without rejection: 0.205% (0.06-0.65) in ACR≥2 vs 0.097 (0.04-0.24) in ACR 0-1, p = 0.0097.
Area under the ROC curve for the composite endpoint was 0,61. A 0.15% dd-cfDNA threshold showed a negative predictive value of 96%, which could allow to safely eliminate 61% of EMB.

Conclusions
Dd-cfDNA appears to be an excellent biomarker to rule out ACR and AMR. Its high negative predictive value could allow to eliminate a significant percentage of surveillance EMB currently performed in HT recipients.Median (IQR) dd-cfDNA values
Cardiac rejection diagnosis using serum mRNA encoding proteins related to fibrotic process
Authors: Rosello-Lleti E , Perez Carrillo L , Benitez Ramos M , Gimenez Escamilla I , Delgado Arija M , Gonzalez I , Portoles M , Tarazon E 
Published: November 2023

Abstract

Background
Finding a standardized, non-invasive method of diagnosis of rejection is still a challenge in the field of heart transplantation. A novel alternative for allograft rejection diagnosis is the detection of biomarkers present in serum. Cardiac fibrosis appears to be present in patients who are experiencing cardiac allograft rejection. Thus, the process of fibrosis could offer a wide range of candidate molecules to explore as possible biomarkers.

Purpose
This study aimed to determine the expression of fibrosis-related coding mRNAs in serum of patient with cardiac rejection and evaluate the diagnostic capacity as potential biomarkers for the non-invasive detection of mild (grade 1R) and moderate/severe (grade ≥2R) cellular rejection.

Methods
We included consecutive serum samples from transplant recipients undergoing routine endomyocardial biopsies. Non-coding RNA sequencing analysis (Illumina HiSeq 2500) was performed on 40 samples, 28 diagnosed with acute cellular rejection (Grade 1R, n=16; and Grade ≥2R, n=12) and 12 samples without cardiac rejection.

Results
We detected 228 mRNA related to fibrosis in serum, which 38 presented differential expression in patients with cardiac rejection of Grade ≥2R. We obtained 16 molecules that showed excellent diagnostic ability in moderate-severe rejection (AUC &gt; 0.800). We highlight RELB that was able to detect mild rejection (AUC=0.734, p&lt;0.05). We stand out TNS1 (AUC=0.972), COL4A2 (AUC=0.958) and JAK1 (AUC=0.944), p&lt;0.0001, for its relevant diagnostic capacity of acute cellular rejection.

Conclusions
We propose serum mRNA levels of genes encoding fibrosis related proteins as potential biomarkers of cardiac rejection. We highlight the role of RELB due to its excellent diagnostic capacity for acute cellular rejection correlating with the severity of the episode.
Clinical relevance and outcome of routine endomyocardial biopsy to detect rejection after heart transplantation
Authors: Kieviet L , Szymanski M K , Van Der Meer M G , Van Der Kaaij N P , De Jonge N , Van Laake L W , Oerlemans M I F 
Published: November 2023

Abstract

Background
After heart transplantation (HTx), endomyocardial biopsies (EMBs) are the gold standard to monitor cardiac allograft rejection. However, a clear consensus on the optimal frequency and duration of EMB monitoring is lacking.

Purpose
Since the first HTx in 1985 in our center, EMB protocols have gradually changed to a low-frequency schedule. We assessed the diagnostic yield and complication rate of the three different EMB protocols used during the past 37 years.

Methods
In this retrospective, single centre, observational study, all biopsy data of routine EMBs after HTx between 1985 and 2022 were collected for analysis. Patients with symptom-driven biopsies or follow up in another hospital were excluded. The total number of biopsies, type of rejection and complications were evaluated.

Results
In a total of 431 patients (69.6% male, mean age at transplant 48±13 years), 6692 routine surveillance EMB procedures were performed. The average number of biopsy procedures per patient was 25.1±8.1 for protocol 1 (n=44, 1985-1994), 17.0 ±3.6 for protocol 2 (n= 213, 1994-2009) and 11.3±2.6 for protocol 3 (n=174, 2009-2022). Cellular rejection was detected in 8.93%, of which grade I, II and III cellular rejections were seen in 7.32%, 1.58% and 0.03%, respectively. The frequency of ≥ ISHLT grade 2R requiring additional treatment was 1.61% and decreased over time with each EMB protocol (2.80%, 1.72%, and 0.76%). Complication rate was 1.63%, mainly consisting of puncture of the carotid artery (57.9%). Independent of the EMB protocol used, the majority of rejections occurred within the first six months after HTx (68.7%).

Conclusion
Complications of EMB after HTx are rare. Cellular rejection mostly occurs within the first 6 months after HTx. The incidence of clinically relevant cellular rejection (≥ISHLT grade 2) has declined over time, partly due to improved immunosuppressive therapy. A conservative approach using a low-frequency EMB schedule seems feasible and safe.Cellular rejection per protocol
Left atrial stiffness evaluation in beta-thalassemia major patients
Authors: Patsourakos D , Aggeli C , Gatzoulis K , Dimitroglou Y , Koukos M , Gialleli F , Tsioufis K 
Published: November 2023

Abstract

Introduction
Diastolic dysfunction is the earliest cardiac abnormality in β-thalassemia major (β-TM) patients and HFpEF is the predominant cardiac phenotype in symptomatic β-TM patients. Left atrial stiffness index (LASI) has been proved to have prognostic value in HFpEF patients.

Purpose
In our study we aimed to evaluate LASI in β-TM patients and assess its relation with conventional indices of diastolic function.

Methods
Sixty β-TM patients and twenty-nine controls were included in this cross-sectional study. Left ventricular ejection fraction (LVEF), early mitral inflow velocity to basal septal early diastolic velocity ratio (E/e'), left atrial volume index (LAVI), tricuspid valve regurgitation velocity (TVR) and left atrial deformation at reservoir phase (LASr) were calculated. T2* was used for myocardial iron load estimation. LASI was calculated as the [E/e’]/[LASr] ratio. Patients with LVEF &lt;50% were excluded. LAVI, E/e’ and TVR were used as criteria of diastolic dysfunction.

Results
LASI was greater in patients compared to controls (0.30 ± 0.22 vs 0.18 ± 0.06, p = 0.003). Patients with diastolic dysfunction (n = 16) had greater LASI than patients without (n = 20) (0.49 ± 0.35 vs 0.21 ± 0.05, p = 0.001) as well as lower LASr (34.0 ± 15.6% vs 42.1 ± 6.7%, p = 0.043). Patients with indeterminate diastolic status (n = 24) had LASI = 0.26 ± 0.08 and LASr = 45.5 ± 13.6%. No correlation was found between LASI and T2* (p = 0.221).

Conclusions
β-TM patients with echocardiographic evidence of diastolic dysfunction have increased LASI. Myocardial iron load did not correlate with left atrial stiffness. A significant portion of β-TM patients have indeterminate diastolic function based on conventional criteria and novel indices, such as LASI or LASr, could be useful for reclassification of these particular patients.
Cost-effectiveness of HerzMobil Tirol, a multidimensional post-discharge disease management program for heart failure patients Economic evaluation along a one-year observation period
Authors: Poelzl G , Egelseer-Bruendl T , Jahn B , Arvandi M , Puntscher S , Santamaria-Navarro J , Pfeifer B , Rissbacher C , Modre-Osprian R , Siebert U 
Published: November 2023

Abstract

Methods
We conducted a cost-effectiveness analysis along a retrospective cohort study of the routine DMP in the province of Tyrol, Austria (HerzMobil Tirol, DMP-HMT) with a propensity score matched cohort of 257 individuals in the usual care (UC) and 251 in the DMP group and a one-year follow up (2016-2019). We determined the effectiveness (hospital-free life expectancy, event-free life years and life years gained, and number of avoided rehospitalizations), costs (DMP, rehospitalizations) and the incremental cost-effectiveness ratio (ICER) of DMP-HMT vs. UC. Data preparation included two steps, missing value imputation and adjustment for remaining confounding due to imperfect matching. We performed a nonparametric sensitivity analysis with bootstrap sampling (n=5,000 replications), sensitivity analyses on costs of HF-rehospitalizations after events that are highly irrelevant for the stated research question and on costs per disease-related diagnosis (DRG) score for rehospitalizations.

Results
The base-case analysis showed that, on average, DMP-HMT results in 42 additional hospital-free life days, 0.54 event-free days to the next cardiovascular event, 40 additional life days, and 0.12 avoided hospitalizations per person compared to UC. The average DPM costs are EUR 1,916 per person. Mean rehospitalization costs are EUR 5,551 in HMT and EUR 6,943 in UC. The ICER of DMP-HMT compared to UC is EUR 4,773 per life-year gained outside the hospital. In a sensitivity analysis, DMP-HMT was also cost saving when "high irrelevant costs" related to the DMP were replaced with average costs. The ICER decreases with increasing costs per DRG score.

Conclusions
Our economic evaluation along the cohort study showed that the DMP HerzMobil Tirol is cost-effective compared to UC based on the one-year time follow up horizon. The DMP was cost-saving in a sensitivity analysis correcting for "high irrelevant costs". Our findings promote widespread adoption of telemedicine assisted DMP for HF. Further research is needed on the long-term assessment of benefits and costs beyond the study period using a decision-analytic model and considering upcoming real-world evidence.
Effectiveness of transitional-care programmes according to the sex of patients with heart failure managed in integrated care systems: a study with longitudinal real-world data in 77,554 patients
Authors: Alcober Morte L , Torres B , Vela E , Cleries M , Corbella M , Jose N , Ramos R , Ras M , Enjuanes C , Comin-Colet J 
Published: November 2023

Abstract

Background
Integrated heart failure (HF) programs are the recommended setting for management of patients with HF. In this setting, several sex differences in outcomes and medical resource use have been described. However, the whether the effectiveness of such HF programs may differ according to sex has not been evaluated.

Purpose
To analyze the effect of sex on health outcomes before and after a pragmatic implementation of an intensive transitional care nurse-based HF management program integrating hospital and primary care and resources for patients with HF at a high risk of events in a health-care area of 209,255 inhabitants.

Methods
We included all individuals consecutively admitted to hospital with at least one ICD-9-CM code for HF as primary diagnosis and discharged alive in Catalonia (7,794,749 inhabitants) during 2015-2019. We considered 3 periods: pre-implementation (2015-2016), transition (2017) and consolidation (2018-2019). We compared outcomes between patients of the implementation area and the rest of Catalonia stratified by sex.

Results
We included 77,554 patients in the study: 3,396 in the implementation area and 74, 158 in the rest of Catalonia. 35,895 (46.3%) were male and 41,659 (53.7%) female. Death occurred in 37,469 (48.3%), clinically related readmission in 41,709 (53.8%) and HF readmission in 29,755 (38.4%). In the population in which the HF program was implemented (HUB-Delta area), multivariate adjusted Cox proportional hazards analyses (Table 1) showed reduction in all-cause death, clinically related readmission and HF readmission both in the transition period (2017) and in the consolidation period (2018-2019) in both men and women. As shown in Figure 1 (left column), compared to the rest of Catalonia, the implementation of the programme in the HUB-Delta area significantly improved outcomes in patients with HF during the consolidation period and these benefits (central and right column) were equally observed in both sexes. The reduction of mortality was more prominent among females (26% of relative change) compared to males (9.3% of relative change). Whereas, clinically related readmission and HF readmission improved more in males (15.7% and 20.7% relative change respectively in males and 7% and 12.6% in females.

Conclusions
Implementation of a transitional intensive care nurse-based HF management program improves clinical outcomes in both males and females. The benefits in prevention of readmission seemed to be more prominent among men while women experienced a higher benefit in terms of mortality. These differences should be considered in the planning of future programs and their causes should be further analysed.Table 1Figure 2