bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effect of kidney dysfunction on introducing guideline-derived medical therapy and on mortality among hospitalized patients with heart failure with reduced ejection fraction
Authors: Muk B , Banfi-Bacsardi F , Majoros Z S , Vagany D , Borsanyi T , Lee S , Pilecky D , Duray G Z , Kiss R G , Nyolczas N 
Published: October 2022

Abstract

Introduction
Chronic kidney disease (CKD) is one of the main limiting factors of introducing and uptitrating guideline-derived medical therapy (GDMT) among patients with heart failure with reduced ejection fraction (HFrEF). Only few studies evaluated the success of implementation of pharmacotherapy in HFrEF and its effect on prognosis across the whole spectrum of CKD stages.

Aim
To analyze the implementation differences of mortality reducing triple therapy (ACEi/ARB/ARNI + BB + MRA) by severity of CKD among hospitalized HFrEF patients. Furthermore, we evaluated the association between mortality and CKD stages.

Patients and methods
257 consecutive, hospitalized HFrEF patients' data were analyzed retrospectively, who had been hospitalized at the Heart Failure Unit of a tertiary cardiological centre in 2019–2021 (male: 74%, age: 65 [56–73] years, ischemic: 45%, diabetes: 40%, hypertension 58%, atrial fibrillation 46%, LVEF: 25 [20–30] %, NT-proBNP at admission: 6086 [2757–11994] pg/ml). Median eGFR was 58 [39–74] ml/min/1.73 m2, 53% of patients had eGFR &lt;60 ml/min/1.73 m2 (CKD stage: G1 – eGFR &gt;90 ml/min/1.73 m2: 15%, G2 – eGFR = 60–90 ml/min/1.73 m2: 32%, G3A – eGFR = 45–59 ml/min/1.73 m2: 20%, G3B – eGFR = 30–44 ml/min/1.73 m2: 21%, G4 – eGFR = 15–29 ml/min/1.73 m2: 9%, G5 – eGFR &lt;15 ml/min/1.73 m2: 3%). 1% of patients was on dialysis.
The success of implementing triple-therapy depending on CKD stages was investigated with Chi-square test, while mortality differences were analyzed with Kaplan-Meier method.

Results
The severity of CKD led to significantly (p&lt;0.0001) lower implementation rate of triple-therapy (CKD stage G1–G2–G3A–G3B–G4–G5: 92 vs. 87 vs. 81 vs. 74 vs. 29 vs. 43%). However, only the ratio of RASi use showed significant difference (p&lt;0.0001) among CKD subgroups (stage G1–G2–G3A–G3B–G4–G5: 100 vs. 100 vs. 92 vs. 87 vs. 42 vs. 43%), while BB (CKD stage G1–G2–G3A–G3B–G4–G5: 92 vs. 88 vs. 88 vs. 81 vs. 71 vs. 71%; p=0.162) and MRA (CKD stage G1–G2–G3A–G3B–G4–G5: 97 vs. 98 vs. 96 vs. 93 vs. 83 vs. 100%; p=0.0899) implementation was independent of renal function. All-cause 6-month mortality was 14% in the whole population. 6-months mortality rates proved to be higher (p=0.0083) in patients with more severe CKD (stage G1–G2–G3A–G3B–G4–G5: 8 vs. 11 vs. 8 vs. 20 vs. 35 vs. 29%).

Conclusions
Patients with advanced HFrEF and concomitant CKD are not equally treated with GDMT, even though kidney dysfunction is not an absolute contraindication of cornerstone HFrEF therapies. HFrEF patients with more severe CKD have poorer prognosis, thus implementation of mortality- and morbidity reducing drug therapy according to the guidelines is essential.

Funding Acknowledgement
Type of funding sources: None.
Effects of empagliflozin in patients with heart failure and preserved ejection fraction according to baseline diuretic use: results from the EMPEROR-Preserved trial
Authors: Butler J 
Published: October 2022

Abstract

Background
In the EMPEROR-Preserved trial, empagliflozin reduced the risk of hospitalizations for heart failure (HHF) or cardiovascular (CV) death in patients with heart failure and preserved ejection fraction (HFpEF). Almost one in five patients in the trial were not on baseline diuretic therapy.

Purpose
To evaluate the efficacy and safety of empagliflozin according to baseline diuretic treatment, as well as change in diuretic therapy after initiation of empagliflozin.

Methods
Patients were categorized into subgroups as no diuretic and furosemide-equivalent diuretic dose of &lt;40, 40 and &gt;40mg and were compared for first HHF or CV death, HHF, CV death, total HHF, change in eGFR slope, and change in Kansas City Cardiomyopathy Questionnaire – Clinical Summary Scores (KCCQ-CSS) between patients on empagliflozin vs. placebo. Changes in diuretic therapy in the two treatment groups were also compared.

Results
Amongst 5815 patients with data on diuretic dose, 1179 (20%) were on no diuretic, 2039 (35%) were on &lt;40mg, 1700 (29%) were on 40mg, and 897 (15%) were on &gt;40mg at baseline. Patients on higher diuretic doses at baseline were more likely to be diabetic, had a higher body weight and NT-proBNP, and lower estimated glomerular filtration rate (eGFR) on average. Patients on higher diuretic doses also had worse health status based on NYHA class and KCCQ-CSS estimates. The reduction of the risk of CVD or HHF, total HHF, preservation of eGFR, and KCCQ-CSS improvement with empagliflozin were consistent across all doses of diuretics (Table 1). The findings for all outcomes were consistent in patients on diuretics (any dose) vs. not on diuretics. Treatment with empagliflozin was associated with decreased rates of initiation (HR: 0.73 [0.59,0.90; p=0.004) or intensification (HR: 0.74; [0.65, 0.84]; p&lt;0.001) of diuretics, while there were increased rates in permanent discontinuation of diuretics (HR: 1.46 [1.17, 1.82]; p&lt;0.001) or diuretic dose reduction (HR: 1.22 [1.06, 1.42]; p=0.007). The incidence of adverse events were similar between treatment arms, irrespective of baseline use of diuretics. Volume depletion events were more common with empagliflozin amongst patients treated with diuretics (7.4 vs 5.7 events per 100 patient-years for empagliflozin vs placebo).

Conclusion
Empagliflozin improved clinical outcomes and health status in patients with HFpEF irrespective of baseline use of diuretics. Additionally, empagliflozin was associated with increased de-escalation or discontinuation of diuretics and decreased chances of initiation or intensification.

Funding Acknowledgement
Type of funding sources: Private company. Main funding source(s): Boehringer Ingelheim & Eli Lilly and Company Diabetes Alliance
Association of heart rate with heart failure outcomes and the effects of empagliflozin in patients with preserved ejection fraction – EMPEROR-Preserved trial
Authors: Boehm M , Anker S D , Mahfoud F , Filippatos G , Ferreira J P , Pocock S J , Brueckmann M , Linetzky B , Schueler E , Wanner C , Zannad F , Packer M , Butler J 
Published: October 2022

Abstract

Background and objective
High resting heart rate (HR) associates with cardiovascular death (CVD) and heart failure hospitalisation (HFH) in patients with reduced ejection fraction (HFrEF), but data are sparse in patients with preserved (HFpEF) or mildly reduced (HFmrEF) ejection fraction. Empagliflozin reduced the risk of CVD and HFH in HFpEF in the EMPEROR-Preserved trial. This study analyses the influence of HR on outcomes in patients with left ventricular ejection fraction (LVEF) &gt;40% in EMPEROR-Preserved and evaluates the effects of empagliflozin across HR categories.

Methods
Patients (n=5988) with HFpEF (LVEF &gt;40%) were categorised to HR &lt;70 beats per minute (bpm), 70–75 bpm and &gt;75 bpm. The composite of CVD or HFH (primary outcome), first HFH, CVD, recurrent HFH and all-cause mortality were studied in the HR groups and in patients separated by sinus rhythm (SR) or atrial fibrillation (AF) and true HFpEF (EF ≥50%) or HFmrEF (EF 40–49%).

Results
Empagliflozin did not influence HR over time. At HR &gt;75 bpm, the primary outcome (hazard ratio: 1.31, 1.13–1.52, p=0.0003), time to first HFH (hazard ratio: 1.25, 1.04–1.49, p=0.02), recurrent HFH (hazard ratio: 1.29, 1.05–1.60, p=0.02), CVD (hazard ratio: 1.49, 1.21–1.84, p=0.0001) and all-cause mortality (hazard ratio: 1.49, 1.28–1.73, p&lt;0.0001) were increased compared to HR of &lt;70 bpm with HR 70–75 bpm showing intermediate results. The influence of HR on the primary outcome was only observed in SR (p trend=0.005), but not in AF (p trend=0.55). Patients with true HFpEF (≥50%) or HFmrEF (40–49%) showed similar effects. The treatment effects of empagliflozin to reduce the primary outcome, time to first HFH and recurrent HFH were not modified by HR.

Conclusions
HR in SR, but not in AF, predicts heart failure outcomes in HFpEF and HFmrEF, but the effects of empagliflozin were not modified by HR.

Funding Acknowledgement
Type of funding sources: Private company. Main funding source(s): Boehringer Ingelheim & Eli Lilly and Company Diabetes Alliance
The effectiveness of ARNI medication in patients, non-responder to cardiac resynchronization therapy
Authors: Szabo K , Sandorfi G , Nagy L T , Nagy L , Clemens M , Toth A , Borbely A , Polik Z S , Raduly A , Csanadi Z 
Published: October 2022

Abstract

Introduction
Almost 30% of patients are non-responders to cardiac resynchronization therapy (CRT) with no improvement of heart failure (HF) symptoms and left ventricular ejection fraction (LVEF). Angiotensin Receptor Neprilysin Inhibitor (ARNI), a novel class of medication resulted in a significant improvement in HF with reduced ejection fraction (HFrEF) in recent trials. No data has been reported on the clinical effectiveness of ARNI in the specific HF patient cohort of CRT non-responders (CRT-NR).

Objective
Herein, we compared the efficacy of ARNI medication in a general HF patient population and in CRT-NR patients.

Method
CRT-NR patients on ARNI therapy initiated at least 6 months after CRT implantation in years 2019–2021 were enrolled. Criterium for CRT-NR was a no, or less than 10% improvement in LVEF measured with echocardiography 6 months post-implantation. HF patients on ARNI therapy from our HF Clinic were used as controls. Changes in LVEF, in NYHA functional class and in the level of NT-proBNP were compared before ARNI therapy initiation and 6 months thereafter in both groups.

Results
70 patients (age: 66,03±9.06 years, 9 women) were enrolled in the CRT-NR and 135 patients (age 62,36±11.26 years; 31 women) in the control group. LVEF increased from 25,25±5.70% to 29,47±6.73% (p&lt;0.001), NYHA class decreased from 2,74±0.55 to 2.03±0.68 (p&lt;0.001) and NT-proBNP from 3884.21±2503.95 to 2676,16±1745.94 (p&lt;0.001) in CRT-NR patients after a 6-month treatment with ARNI. Similar improvement was demonstrated in all parameters in the control group: LVEF increased from 26,64±6.47% to 29,91±6.64% (p&lt;0,001), NYHA class decreased from 2,97±0.54 to 2,18±0.58% (p&lt;0,001) and NT-proBNP from 5355,17±1731.71 to 2062,66±1919.07 (p&lt;0,001). During a mean follow-up of 20,55±11,36 months mortality rates were 17,14% in the CRT-NR group, and 18,51% in the control group.

Conclusion
ARNI therapy resulted in significant improvement in functional class, LVEF and HF biomarker level in CRT-NR patients, similarly to what was observed in a general HF patient cohort with no CRT.

Funding Acknowledgement
Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Project no. TKP2021-EGA-18 has been implemented with the support provided from the National Research, Development and Innovation Fund of Hungary, financed under the TKP2021-EGA funding scheme.
Clinical determinants and barriers to cardiac rehabilitation enrolment of patients with heart failure with reduced ejection fraction
Authors: Alexandre A , Campinas A , Schmidt C , Magalhaes S , Preza-Fernandes J , Silveira J , Gomes C , Santos M , Torres S 
Published: October 2022

Abstract

Introduction
Cardiac rehabilitation (CR) is a recommended treatment for patients with heart failure with reduced ejection fraction (HFrEF). Despite the robust evidence supporting its safety and benefits, there is an incomplete understanding of the reasons of the underutilization of CR programs in HFrEF. These reasons are complex and probably encompass healthcare system- and patient-level barriers.

Purpose
To study the clinical determinants and barriers to enrolment in a CR program for HFrEF patients.

Methods
We conducted a study of consecutive heart failure patients followed at a dedicated HFrEF cardiology clinic from January 2019 to April 2021. Patients were divided according to previous enrolment in CR program. Data were collected from electronic health records, and in case of missing data patients were asked by telephone about the reason for not participating in CR using a structured and validated questionnaire for this purpose.

Results
Of 228 patients with HFrEF, 60% had not been enrolled in a CR program; they were older (63 vs 58 years; p&lt;0.01) and more likely to have comorbidities such as hypertension (56% vs 41%; p=0.03) or concomitant chronic obstructive pulmonary disease (20% vs 8%; p=0.01). Conversely, patients enrolled in CR programs were more likely to have a previous history of acute myocardial infarction (34% vs 20%; p=0.02). Regarding heart failure-related clinical features (NYHA functional class, LVEF, ICD/CRT), we did not find any significant differences between groups. The main reasons for not being enrolled in CR programs were: no medical referral (31%), concomitant medical problems (27%) such as musculoskeletal problems, patient refusal (11%) and geographical distance to the hospital (9%).

Conclusion
Despite the high proportion (40%) of HFrEF patients who underwent CR program compared to previous studies, the enrolment to CR can be further improved. The main barriers are related to health professionals (no referral), healthcare system (geographical distance to the hospital) and patients (concomitant noncardiac problems). Innovative strategies should target these factors to increase the delivery of CR program in HFrEF.

Funding Acknowledgement
Type of funding sources: None.
Progression of aerobic and anaerobic thresholds in cardiac rehabilitation: heart failure vs coronary artery disease
Authors: Custodio P M , Santos A R , Moreno L , Mendes M 
Published: October 2022

Abstract

Background
Cardiac rehabilitation (CR) aims at the maintenance and potential recovery of cardiovascular function through an exercise program. Programs may be started with cardiopulmonary exercise test (CPET) in order to assess aerobic and anaerobic thresholds (VT1 and VT2), and to optimize the exercise prescription. In our center, most CR programs are in-hospital for the first 3–6 months, after which patients undertake another CPET to evaluate the progression and follow up with a home-based training schedule.

Aim
To compare the progression in aerobic and anaerobic thresholds after CR program in patients with heart failure (HF) or post-acute event in coronary artery disease (CAD). Stratify the results based on ejection fraction to see which patients show the most benefit.

Methods
A retrospective single center study using data from patients that were included in a CR program between January 2016 and December 2020. Patients without measurable ventilatory thresholds 1 and 2 (VT 1 and VT2) at both CPET were excluded as were those that didn't complete the CR program. VT 1 and VT2 progression was compared among patients referred to the CR program due to HF and CAD.
A sub-analysis was performed based on having reduced ejection fraction (rEF) (&lt;50% on echocardiogram).

Results and discussion
A total of 136 patients were included (57,51±13,47 YO; 80,9% (n=110) male; 44,2% (n=60) had reduced ejection fraction. 46 patients were referred to CR due to HF and 90 due to CAD. Most patients referred to CR due to CAD underwent complete revascularization (82,2%) beforehand. The average time between the acute coronary event and the beginning of the CR program was 208 days. Even though the stunned myocardial phase would be expected to be resolved by the time the CR program was started, patients with CAD showed the steepest progression in VT1 and VT2 thresholds. Patients with CAD with preserved ejection fraction are the subgroup with the most robust progression in VT1 and VT2 when compared with rEF. This difference was statistically significant when the two etiologies were compared (p value = 0,047 for VT1 and 0,031 for VT2) – Table 1.

Conclusion
Patients with CAD and preserved ejection fraction exhibit the faster progression in aerobic and anaerobic thresholds in CR when compared to HF patients.

Funding Acknowledgement
Type of funding sources: None.
Comparative effectiveness of exercise-based cardiac rehabilitation for heart failure: a Bayesian network analysis of 44 randomized trials and 5896 patients
Authors: Jiang L , Wan R X , Li J T , Yan Y 
Published: October 2022

Abstract

Introduction
The prevalence of heart failure (HF) is increasing nowadays. Exercise-based cardiac rehabilitation (CR) reduces mortality and further improves the outcome of patients with HF. However, the effect of different types of CR on HF remains unclear. Data comparing these CR have not been synthesized. Thus, the purpose of this study is to determine the relative efficacy of different types of exercise-based CR for individuals with HF using a Bayesian network meta-analysis.

Methods
We followed a pre-specified protocol (PROSPERO: CRD42021278351). We conducted a systematic literature review of any randomized controlled trials which evaluated exercise-based CR for patients with HF. Databases including Embase, Medline, the Cochrane Central Register of Controlled Trials, and Web of Science were screened up to 31 December 2021. The primary outcomes focus on functional capacity (peak oxygen uptake and 6-minute walk distance) and health-related quality of life (hr-QOL). The main analysis was complemented by network subanalysis, standard pairwise comparisons, and subgroup and sensitivity analyses. The pooled estimates were quantified as mean differences (MD) or standardized mean difference (SMD)where appropriate, at 95% confidence intervals (CI).

Results
We identified 44 randomized controlled trials with a total of 5896 HF participants. Among 23 studies that compared exercise-based CR and usual care, participants in center-based CR (CBCR) had improvement of peak oxygen uptake (MD: 2.30 mL/kg per minute; 95% CI, 0.43–4.40) and 6-minute walk distance (MD: 33 meters; 95% CI, 11.00–58.00).18 studies that compared exercise-based CR with usual care showed that CBCR and cardiac telerehabilitation (CTR) had greater improvements in hr-QOL (SMD: −0.38; 95% CI, −0.49 to −0.15 and SMD: −0.18,95% CI, −0.36 to −0.00 respectively). Treatment ranking indicated CTR has the highest probability (46.0%, 50.2%) of being the most effective CR for peak oxygen uptake and hr-QOL elevation respectively. CBCR was similarly indicated as the most effective treatment for 6-min walk distance (38.7%).

Conclusion
Exercise-based CR programs provide broader cardiovascular benefits compared with UC. CBCR significantly improved functional capacity. CBCR and CTR have favorable effects on hr-QOL.

Funding Acknowledgement
Type of funding sources: Public Institution(s). Main funding source(s): China Scholarship Council
General practitioners’ perceptions of pharmacists working in general practice: a qualitative interview study
Authors: Hurley Eoin , Walsh Elaine , Foley Tony , Heinrich Clara H , Byrne Stephen , Dalton Kieran 
Published: October 2022

AbstractBackgroundPharmacists are being increasingly employed as part of general practice teams globally, and their input has been associated with several clinical and economic benefits. However, there is a paucity of research focussing on general practitioners’ (GPs’) perceptions of pharmacist integration into practices in countries where this novel role for pharmacists is yet to become commonplace.ObjectiveTo explore GPs’ perceptions of integrating pharmacists into general practices and to identify the behavioural determinants of GPs integrating pharmacists into practices.MethodsSemistructured interviews were conducted with GPs practising in Ireland, who were sampled using a combination of purposive, convenience, and snowball sampling. Interviews were audio-recorded and transcribed verbatim, which then were analysed using conventional content analysis and directed content analysis employing the Theoretical Domains Framework (TDF).ResultsSeventeen GPs were interviewed between November 2021 and February 2022. Seven TDF domains were identified as predominant in influencing GPs’ perceptions of pharmacist integration into general practices. These perceptions were mostly positive, especially regarding patient outcomes, cost savings, and improving access to care. However, there were concerns about funding the role, affecting others’ workloads, and pharmacists’ training needs to work in practices.ConclusionThis study’s theory-informed insight provides a deeper understanding of GPs’ perceptions of pharmacists working in general practice and behaviours which can be targeted to help optimize integration. These findings should be utilized in future service development to preempt and address GPs’ concerns ahead of pharmacist integration, as well as to inform the development of general practice-based pharmacist roles going forward.
Facial Trustworthiness Perception Across the Adult Life Span
Authors: Pehlivanoglu Didem , Lin Tian , Lighthall Nichole R , Heemskerk Amber , Harber Alexandria , Wilson Robert C , Turner Gary R , Spreng R Nathan , Ebner Natalie C 
Published: October 2022

Abstract

Objectives
Trust is crucial for successful social interaction across the life span. Perceiver age, facial age, and facial emotion have been shown to influence trustworthiness perception, but the complex interplay between these perceiver and facial characteristics has not been examined.

Method
Adopting an adult life-span developmental approach, 199 adults (aged 22–78 years) rated the trustworthiness of faces that systematically varied in age (young, middle-aged, and older) and emotion (neutral, happy, sad, fearful, angry, and disgusted) from the FACES Lifespan Database.

Results
The study yielded three key results. First, on an aggregated level, facial trustworthiness perception did not differ by perceiver age. Second, all perceivers rated young faces as the most trustworthy, and middle-aged and older (but not young) perceivers rated older faces as least trustworthy. Third, facial emotions signaling threat (fear, anger, and disgust) relative to neutral, happy, and sad expressions moderated age effects on facial trustworthiness perception.

Discussion
Findings from this study highlight the impact of perceiver and facial characteristics on facial trustworthiness perception in adulthood and aging and have potential to inform first impression formation, with effects on trait attributions and behavior. This publication also provides normative data on perceived facial trustworthiness for the FACES Lifespan Database.
Toward Quantification of Agitation in People With Dementia Using Multimodal Sensing
Authors: Davidoff Hannah , Van den Bulcke Laura , Vandenbulcke Mathieu , De Vos Maarten , Van den Stock Jan , Van Helleputte Nick , Van Hoof Chris , Van Den Bossche Maarten J A 
Published: October 2022

Abstract

Background and Objectives
Agitation, a critical behavioral and psychological symptom in dementia, has a profound impact on a patients’ quality of life as well as their caregivers’. Autonomous and objective characterization of agitation with multimodal systems has the potential to capture key patient responses or agitation triggers.

Research Design and Methods
In this article, we describe our multimodal system design that encompasses contextual parameters, physiological parameters, and psychological parameters. This design is the first to include all three of these facets in an n &gt; 1 study. Using a combination of fixed and wearable sensors and a custom-made app for psychological annotation, we aim to identify physiological markers and contextual triggers of agitation.

Results
A discussion of both the clinical as well as the technical implementation of the to-date data collection protocol is presented, as well as initial insights into pilot study data collection.

Discussion and Implications
The ongoing data collection moves us toward improved agitation quantification and subsequent prediction, eventually enabling just-in-time intervention.