bluuebunny/crossref_metadata_2025_split huggingface dataset:
Epicardial adipose tissue is associated with an increased risk of mortality and hospitalizations in patients with heart failure with preserved ejection fraction
Authors: Grubler M , Binder C , Duca F , Kronberger C , Polednicek M , Rettl R , Hartmann A , Beitzke D , Loewe C , Dona C , Badr-Eslam R , Hengstenberg C , Kastner J , Bergler-Klein J , Kammerlander A A 
Published: November 2023

Abstract

Background
Accumulating evidence suggests that epicardial adipose tissue (EAT) plays a critical role in heart failure (HF). Previous studies raised the possibility of an association with mortality and hospitalizations, but data in preserved ejection fraction (HFpEF) is sparse.

Purpose
To investigate the association of epicardial fat measured by cardiac magnetic resonance imaging (CMR) with the combined end point of heart failure hospitalizations and cardiovascular death in patients with heart failure with preserved ejection fraction

Methods
In this secondary analysis of a prospective cohort study recruiting participants with HFpEF between July 2012 and March 2018 at a tertiary care centre. Patients with cardiac amyloidosis were excluded. The combined primary endpoint of this analysis consists of heart failure hospitalizations and cardiovascular mortality. The statistical analysis plan consisted of a Cox proportional hazard regression adjusted for multiple potential confounders. Adjustments were predefined and selected by their clinical relevance. EAT volume was measured using a modified Simpson rule, EAT area was measured in the four-chamber view. EAT was defined from visceral (immediately adhering the myocardium) to the parietal layer of the pericardium. Epi-pericardial tissue was excluded. We used dark blood steady-state free precision (SSFP) at end-diastole. If unavailable we used bright blood SSFP or true fast imaging with steady-state free precession.

Results
We studied 206 patients (69% women, mean age 71±9 years, median N-terminal prohormone of brain natriuretic peptide [NT-proBNP]: 1090 IQR 420 – 1997pg/mL). During mean follow-up of 78±35 months, 78 patients (37%) died of a cardiovascular cause. In multivariate analysis adjusting for age, gender, atrial fibrillation, left-ventricular ejection fraction (EF), right ventricular (RV) end-diastolic volume index, RVEF and NT-proBNP, EAT was significantly associated with a higher risk of the composite outcome (HR 1.07 [95% CI 1.02-1.12], P = 0.007). Additional adjustments for hepatic-, renal- and pulmonary function as well as metabolic biomarkers did not materially change the results. There was no statistically significant association with pulmonary pressures on right heart catheterization.

Conclusions
EAT accumulation is associated with increased risk for mortality and hospitalizations in patients with HF with preserved ejection fraction. This finding supports the rational for future interventional studies of EAT in HFpEF.

Conclusions
EAT accumulation is associated with increased risk for mortality and hospitalizations in patients with HF with preserved ejection fraction. This finding supports the rational for future interventional studies of EAT in HFpEF.
By using the new hemodynamic definition of pulmonary hypertension in patients with left heart disease the prognostic value of different phenotypes might be lost
Authors: Bech-Hanssen O , Astengo M , Karason K , Bollano E 
Published: November 2023

Abstract

Background and aims
In the 2022 ECS/ERS pulmonary hypertension (PH) guidelines the threshold for increased pulmonary vascular resistance (PVR) was lowered from 3 to 2 Wood Units (WU). Consequently, in patients with PH due to left heart disease, the proportions of patients with combined pre- and postcapillary PH (CpcPH) will increase while the proportion with isolated post-capillary PH (IpcPH) will decrease. In the present study we investigate in patients with left heart disease the impact of this revision in terms of hemodynamic profile, right ventricular (RV) function and prognostication. Methods. Two-hundred and two patients consecutively referred for heart transplant or heart failure work-up were included with right heart catheterization and echocardiography within 48 hours. RV dysfunction was graded using a novel echocardiographic score allocating one point each for (1) systolic pulmonary artery pressure (PAP) &gt;40 mmHg, (2) reduced tricuspid annular plane systolic excursion (TAPSE&lt;17 mm), (3) RV area dilatation, (4) moderate/severe tricuspid regurgitation and (5) reduced inferior cava collapsibility. For assessment of prognostication, we studied the end-point of all-cause mortality. Results. One-hundred and seventy-three patients (86%) had left ventricular ejection fraction &lt;40%. Eighty-nine patients (44%) underwent heart transplantation and the median (25%; 75% percentile) follow-up time (years) was 1.8 (0.35; 6.7). Sixty patients (30%) had mean PAP&lt;20 mmHg, thus no PH. Ninety-six patients (48%) had IpcPH using PVR 3 WU as threshold. Lowering the threshold to PVR 2 WU decreased the corresponding proportion to 24%. The degree of backward failure (PA wedge pressure), forward failure (cardiac index) or RV dysfunction (RVD score) did not significantly differ by the change in hemodynamic definition (Table). With the previous hemodynamic definition, the Kaplan-Meier curves demonstrated increased mortality in CpcPH patients compared with IpcPH (Figure B). Using the new definition this difference was not present (Figure B). Conclusions. The revised hemodynamic definition of PH significantly increases the proportion with CpcPH, but does not significantly alter the hemodynamic or RV function profiles in left heart disease patients with IpcPH or CpcPH phenotype. However, our findings indicate that by using the new hemodynamic definition of IpcPH and CpcPH phenotype the prognostic value of this hemodynamic classification might be lost.Table
Sleep-disordered breathing is associated with fibrosis and impaired diastolic function
Authors: Wester M , Hegner P H , Tafelmeier M T , Lebek S L , Provaznik Z P , Floerchinger B F , Schmid C S , Maier L S M , Arzt M A , Wagner S W 
Published: November 2023

Abstract

Background
Emerging evidence is linking sleep-disordered breathing (SDB) to diastolic dysfunction. SDB-induced hypoxia may stimulate the development of cardiac fibrosis which then causes diastolic dysfunction. We investigated the association between SDB and myocardial collagen and PDGF mRNA levels and how collagen mRNA levels are linked to parameters of diastolic dysfunction.

Methods
RA biopsies were collected from 31 patients undergoing elective coronary artery bypass grafting in the prospective observational study CONSIDER-AF. Tissue mRNA levels of collagen type I (Col1A), PDGFα, and PDGFβ were quantified using real-time qPCR on ViiA 7 real-time PCR system. NT-pro-BNP levels were measured in the serum via ELISA blots. The apnea-hypopnea-index (AHI) was registered in portable SDB-monitoring. Echocardiography was performed to assess diastolic function.

Results
First, we investigated an association of SDB and cardiac fibrosis. AHI was correlated with tissue mRNA levels of Col3a (p = 0.0239, Fig A), PDGFα (p = 0.0414, Fig B), and PDGFβ (p = 0.0024, Fig C). Then, we investigated an association between cardiac fibrosis and diastolic dysfunction. Tissue mRNA levels of Col3A were inversely correlated with lateral (p = 0.0196, Fig D) and septal E’ (p = 0.0006, Fig E) as a marker for diastolic relaxation. Higher ratios of E/E’mean were correlated with increased tissue mRNA levels of Col3A (p = 0.0368, Fig F). NT-pro-BNP which is a diagnostic criterion for heart failure with preserved ejection fraction was correlated with Col3 levels (p = 0.0247, Fig G).
Discussion: Our findings indicate that SDB is linked to fibrosis which is associated with diastolic dysfunction.
Heart failure with improved ejection fraction: patients' characters and predictors for improvement
Authors: Segev A , Avrahamy B , Fardman A , Regev O , Younis A , Grupper A 
Published: November 2023

Abstract

Introduction
Heart failure with improved ejection fraction (HFimpEF) is a relatively new definition, which presents a diagnostic and therapeutic challenge. Little is known about these patients' characteristics and predictors for EF improvement.

Purpose
Characterizing the profile of HFimpEF patients and evaluate predictors for EF improvement within heart failure with reduced ejection fraction (HFrEF) patients.

Methods
The cohort included ambulatory HFrEF patients (EF≤40%) who had two consecutive echo exams at least 6 months apart in a single tertiary medical center. Patients who improved their EF from ≤40% to &gt;40% and by ≥10% (improved group) were compared to those who did not (not-improved group). Clinical, electrocardiographic and echocardiographic data were collected and compared between the groups.

Results
A total of 567 HFrEF patients (72% male, 54.3±14.4 years old) were analyzed. Patients without EF improvement (n = 393) were more likely to be male, had more comorbidities and had higher rates of ischemic cardiomyopathy (ICMP), compared with the improved group (n = 174) (Table). Lack of improvement in EF was also associated with lower EF and higher left and right ventricular diameters in the first echo.
In a multivariate analysis model adjusted to all statistically significant variables in the univariate analysis, predictors for lack of EF improvement were male sex (adjusted odds ratio [OR] 1.63, 95% CI 1.02-2.61; P = 0.041), ICMP (OR 3.98, 95% CI 2.03-7.81; P&lt;.001), larger left ventricular end diastolic and end systolic diameters (OR 2.07, 95% CI 1.44-2.98 and OR 1.84, 95% CI 1.36-2.5, respectively; P&lt;.001 for both) and enlarged right ventricle (OR 1.93, 95% CI 1.11-3.36; P = 0.02), while higher EF at baseline was a positive predictor for improvement (OR 0.95, 95% CI 0.92-0.98; P = 0.001) (Figure). Interestingly, NYHA functional class was not associated with EF improvement (OR 1.16, 95% CI 0.87-1.55; P = 0.306).
Hospitalization and mortality rates were both higher in the not-improved group (median of 1 (IQR 1-2) vs. 0 (IQR 0-1); P&lt;.001 and 24% vs. 13%; P = 0.001, respectively). Patients in both groups were generally treated with high rates of guideline directed medical therapy (GDMT) for HFrEF. Although no correlation was found between GDMT and EF improvement, these drugs were associated with reduced hospitalization and mortality rates in both groups.

Conclusions
Improvement in EF among HFrEF patients may be predicted by the HF etiology and echocardiographic parameters. HFimpEF patients have better prognosis compared to HFrEF patients. While GDMT was not associated with EF improvement, it improved outcomes in both HFimpEF and HFrEF regardless of EF.
Clinical predictors of right ventricular dysfunction and association with adverse outcomes in peripartum cardiomyopathy
Authors: Imran T F , Ataklte F , Lopez D , Mohebali D , Bello N A , Gaziano J M , Djousse L , Coglinease E , Arany Z , Sabe M , French K , Poppas A , Wu W , Choudhary G 
Published: November 2023

Abstract

Background
Peripartum cardiomyopathy (PPCM) is a type of pregnancy associated heart failure with reduced ejection of unknown etiology that is associated with significant morbidity and mortality in young women. It is a leading cause of peripartum maternal death in the United States, with mortality as high as 25% in some cohorts, and accounts for approximately 50% of cases of maternal cardiogenic shock.

Purpose
We sought to identify factors associated with right ventricular (RV) dysfunction and elevated RV systolic pressure (RVSP) and association with adverse outcomes in PPCM.

Methods
We conducted a multi-center cohort study to identify subjects with PPCM with the following criteria: LVEF &lt; 40%, development of heart failure within the last month of pregnancy or 5 months of delivery and no other identifiable cause of heart failure with reduced ejection fraction. Outcomes included a composite of 1) major adverse events (need for extra-corporeal membrane oxygenation, ventricular assist device, orthotopic heart transplantation or death) or 2) recurrent heart failure hospitalization.

Results
In all, 229 women (1993 to 2017) met criteria. Mean age was 32.4 ± 6.8 years, 28% were of African descent, 50 (22%) had RV dysfunction, and 38 (17%) had RVSP &gt; = 30mmHg. After a median follow-up of 3.4 years (IQR 1.0-8.8), 58 (25%) experienced the composite outcome of adverse events. African descent, family history of cardiomyopathy, LVEF, and RVSP were significant predictors of RV dysfunction (Table 1).
Using Cox proportional hazards models, we found that women with RV dysfunction were three times more likely to experience the adverse composite outcome: HR 3.21 (95% CI: 1.11-9.28), p = 0.03 in a multivariable model adjusting for age, race, body mass index, preeclampsia, hypertension, diabetes, kidney disease and LVEF. Women with RVSP &gt;= 30mmHg had a lower probability of survival free from adverse events (log rank p = 0.04) (Figure 1).

Conclusion
African descent and family history of cardiomyopathy were significant predictors of RV dysfunction. RV dysfunction and elevated RVSP were significantly associated with a composite of major adverse cardiac events. This at-risk group may prompt closer monitoring, genetic testing, or early referral for advanced therapies.Table of predictorsSurvival curves
The effect of empagliflozin on ketone bodies in patients with heart failure with reduced ejection fraction (Empire HF)
Authors: Larsen J H , Jensen J , Andersen C F , Hoejlund K , Kistorp C M , Poulsen M I , Tuxen C , Gustafsson F , Koeber L , Schou M , Moeller J E , Omar M 
Published: November 2023

Abstract

Background
The thrifty-substrate hypothesis suggests that Sodium-Glucose Cotransporter-2 (SGLT2) inhibitors increase plasma levels of ketone bodies and create a salutary switch in myocardial fuel metabolism.

Purpose
We investigated the effect of SGLT2 inhibitor on plasma beta-hydroxybutyrate in patients with heart failure and reduced ejection fraction (HFrEF).

Method
This is a post hoc analysis of the Empagliflozin in Heart Failure Patients with Reduced Ejection Fraction (Empire HF) trial, an investigator-initiated, double-blind, randomized, placebo-controlled trial which enrolled 190 stable HFrEF patients with a left ventricular ejection fraction (LVEF) of ≤40%. Patients were randomly assigned (1:1) to empagliflozin 10 mg once daily, or matching placebo. Analyses were performed in patients with complete data using a linear-mixed effect-model with log-transformed beta-hydroxybutyrate, adjusted for baseline beta-hydroxybutyrate value, age, sex, and type 2 diabetes.

Results
A total of 188 (99%) patients had available data. The groups were well-matched with respect to baseline characteristics. Mean age was 64 (SD, 11) years; LVEF was 29 (SD, 8) %, 13% had type 2 diabetes, New York Heart Association (NYHA) class II was found in 78%. Median plasma levels of beta-hydroxybutyrate were 0.10 (inter quartile range (IQR) 0.05–0.18) mmol/l at baseline, and 0.11(IQR 0.07–0.2) mmol/l at follow-up in the empagliflozin group. In the placebo group, baseline and at follow-up concentrations were 0.10 (0.06–0.17) mmol/l and 0.09 (0.05–0.15) mmol/l, respectively. Empagliflozin increased plasma levels of beta-hydroxybutyrate compared to placebo (adjusted between-groups treatment effect; Ratio of change 1.45 [95%confidence interval (CI); 1.12–1.87], p = 0.005 (Figure 1). The effect of empagliflozin on beta-hydroxybutyrate outcomes was consistent across multiple subgroups analyses including baseline median age, sex, N-terminal-pro B-type natriuretic peptide (NT-proBNP) cut-off 600 pg/mL, treatment with sacubitril–valsartan or beta-blockers, measured glomerular filtration rate (GFR) level, hemoglobin A1c (HbA1c) level, and concomitant type 2 diabetes (all P interaction&gt;0.05).

Conclusion
In patients with HFrEF, predominantly without diabetes, short-term treatment with empagliflozin increased the levels of beta-hydroxybutyrate. The absolute changes were modest and the exact contribution of ketone bodies to the cardiovascular benefits of SGLT2 inhibitors requires further clarification.Figure 1Table 1
Accelerometer-measured physical activity in patients with heart failure and reduced ejection fraction: determinants and relationship with patient-reported health status
Authors: Larsen J H , Andersen C F , Omar M , Kistorp C M , Tuxen C D , Gustafsson F , Koeber L , Poulsen M I , Broend J C , Moeller J E , Schou M , Jensen J 
Published: November 2023

Abstract

Background
Accelerometer-measured physical activity is an increasingly used endpoint in heart failure (HF) trials.

Purpose
We aimed to investigate the determinants of accelerometer-measured physical activity and to establish the minimal clinically important difference (MCID).

Methods
Post-hoc analysis of the Empire HF trial, including stable outpatients with HF with reduced ejection fraction (HFrEF). Physical activity was quantified as average accelerometer counts per minute (CPM) with higher values representing higher activity. Associations between activity level and important clinical variables [age, sex, body mass index, N-terminal pro-brain natriuretic peptide, left ventricular ejection fraction (LVEF), atrial fibrillation, and anemia], as well as patient-reported health status (Kansas City Cardiomyopathy Questionnaire, KCCQ) were assessed.

Results
Complete data were available in 180 (95%) patients (86% male, mean age 65 years, mean LVEF 30%). Baseline median physical activity level was 1318 CPM (Q1-Q3 1111–1585). At baseline, age and anemia were independently associated with activity level (β-coefficients: -10 CPM per year age increase [95% CI -16 to -5.1], p = 0.00015, and -126 CPM for presence of anemia [95% CI -9.1 to -244], p = 0.035). Moreover, a significant independent association was observed between activity level and all KCCQ summary scores (β-coefficient point estimates of 3.7, 4.6, and 4.9 CPM, all p&lt;0.02). For 12-week changes, only the KCCQ-clinical summary score (CSS) was associated with activity level, with a mean increase of 17.5 CPM [95% CI 1.5 to 34.0], p = 0.032, for every clinically relevant 5-point increase in KCCQ-CSS, corresponding to the MCID.

Conclusion
In patients with HFrEF, high age and anemia were independently associated with lower accelerometer-measured physical activity. Moreover, clinically relevant 5-point increases in Kansas City Cardiomyopathy Questionnaire clinical summary scores at 12 weeks were associated with an increase of 17.5 activity counts per minute, thus representing the minimal clinically important difference.Table 1.Baseline characteristicsFigure 1
Role of beta-3 adrenergic receptor polymorphism TRY64ARG in heart failure
Authors: Jimenez Rodriguez G , Elizalde-Silva J L , Manzur-Sandoval D , Cota-Apodaca L , Ramos-Enriquez A , Bucio-Reta E , Lazcano-Diaz E , Baeza-Herrera L , Santos-Martinez L , Gonzalez-Ruiz F , Gaytan-Garcia C , Hernandez-Gonzalez G L , Rojas-Velasco G 
Published: November 2023

Abstract

Introduction
The TRY64ARG polymorphism of the beta-3 adrenergic receptor has been associated with the onset and maintenance of hypertension, diabetes and obesity, its role in heart failure has not been studied.

Objectives
To examine the role of the TRY64ARG beta-3 adrenergic receptor in the improvement of left ventricular ejection fraction (LVEF) in patients with Heart Failure due to ischemic heart disease.

Methods
This study is a retrospective analysis based on a 5-year follow-up of patients with heart failure with decreased LVEF due to ischemic heart disease.

Results
We studied a sample of 338 patients with decreased LVEF collected from our Genetic database during the period of time from January 2012 to December 2016. In the scrutiny 26 patients did not have complete data for analysis, resulting in a final sample of 312 patients with a minimum follow-up of 5 years. The mean age was 58.9 years (SD 14), 72% of the population were men (n = 244), the frequency of hypertension was 168 (53.85%), diabetes 119 (38.14%), obesity (18.27%). The definition of LVEF improvement was defined as an incremental in more than 15%. There was no statistical difference in the medical treatment and revascularization methods. Patients with the TRY64ARG β3 adrenergic polymorphism present less improvement in the LVEF (42% vs 58%, p&lt; 0.001).

Conclusions
The expression of the TRY64ARG polymorphism of the beta-3 adrenergic receptor in patients with HF and low LVEF is related to a lack of incremental LVEF at 5 years.
Efficacy and safety of intravenous iron repletion in patients with heart failure: a systematic review and meta-analysis
Authors: Vukadinovic D , Abdin A , Boehm M 
Published: November 2023

Abstract

Introduction
AFFIRM-AHF and IRONMAN demonstrated lower rates of the combined endpoint recurrent heart failure (HF) hospitalizations and cardiovascular death (CVD) by using intravenous (IV) ferric carboxymaltose (FCM) and ferric derisomaltose (FDI), respectively in patients with HF and iron deficiency (ID) utilizing prespecified COVID-19 analyses.

Material and methods
We meta-analyzed efficacy, between trial heterogeneity and data robustness for the primary endpoint and CVD in AFFIRM-AHF and IRONMAN. As sensitivity analysis, we analyzed data from all eligible exploratory trials investigating FCM/FDI in HF.

Results
FCM/FDI reduced the primary endpoint (RR = 0.81, 95% CI 0.69-0.95, p = 0.01, I2 = 0%), with the number needed to treat (NNT) being 7. Power was 73% and findings were robust with fragility index (FI) of 94 and fragility quotient (FQ) of 0.041. Effects of FCM/FDI were neutral concerning CVD (OR = 0.88, 95% CI 0.71-1.09, p = 0.24, I2 = 0%). Power was 21% while findings were fragile with reverse FI of 14 and reversed FQ of 0.006. The sensitivity analysis from all eligible trials (n = 3,258) confirmed positive effects of FCM/FDI on the primary endpoint (RR = 0.77, 95% CI 0.66-0.90, p = 0.0008, I2 = 0%), with NNT being 6. Power was 91% while findings were robust (FI of 147 and FQ of 0.045). Effect on CVD was neutral (RR = 0.87, 95% CI 0.71-1.07, p = 0.18, I2 = 0%). Power was 10% while findings were fragile (reverse FI of 7 and reverse FQ of 0.002). Rate of infections (OR = 0.85, 95% CI 0.71-1.02, p = 0.09, I2 = 0%), vascular disorder (OR = 0.84, 95% CI 0.57-1.25, p = 0.34, I2 = 0%) and general or injection-site related disorders (OR = 1.39, 95% CI 0.88-1.29, p = 0.16, I2 = 30%) were comparable between groups. There was no relevant heterogeneity (I2&gt;50%) between the trials for any of the analyzed outcomes.

Conclusions
Use of FCM/FDI is safe and reduces the composite of recurrent HF hospitalizations and CVD without benefit on CVD. Findings concerning composite outcomes exhibit a high level of robustness without heterogeneity between trials with FCM and FDI.Summary