bluuebunny/crossref_metadata_2025_split huggingface dataset:
Repetitive LevosimenDan infusions fOR patients with advanced chronic heart failure in the vulnerable post-discharge period: the multinational randomized LeoDOR trial
Authors: Polzl G , Altenberger J , Comin-Colet J , Delgado J , Fedele F , Garcia-Gonzales M J , Gustafsson F , Masip J , Papp Z , Stoerk S , Ulmer H , Vrtovec B , Wikstrom G , Zima E , Bauer A 
Published: November 2023

Abstract

Background
Studies of the repetitive use of intravenous levosimendan suggested a beneficial effect in patients with advanced heart failure (HF). It was the aim of the LeoDOR trial to test the efficacy and safety of intermittent levosimendan therapy in the vulnerable phase following a hospitalization for acute HF.

Methods
In this multicenter, double-blind, three-armed trial with an enrolment period from 3-2018 to 6-2021, patients with advanced HF were randomized 2:1 at the end of an index hospitalization for acute HF to intermittent levosimendan therapy or placebo for a period of 12 weeks. Levosimendan was administered according to center preference either as 6-hour infusion at a rate of 0.2 mcg/kg/min every 2 weeks, or as 24-hour infusion at a rate of 0.1 mcg/kg/min every 3 weeks. The primary efficacy assessment after 14 weeks was based on a global rank endpoint consisting of three hierarchical groups: Tier 1 = time to death or urgent heart transplantation or implantation of a ventricular assist device; Tier 2 = time to non-fatal HF requiring i.v. vasoactive therapy; Tier 3 = time-averaged proportional change in NTproBNP from baseline to week 14.

Results
Due to a forced interim interruption of the study as a result of the COVID-19 pandemic, the planned number of patients could not be recruited. The final modified intention-to-treat (mITT) analysis included 145 patients (93 in the combined levosimendan arm, 52 in the placebo arm). Patient characteristics were well balanced between treatment and placebo arms (mean age 69.3±9.7 vs 67.9±10.1, proportion of women 22.6% vs 21.2%, HF-hospitalizations in previous 12 months 1.9±1.4 vs. 1.7±1.1, NTproBNP at baseline 4740 ng/L (IQR 2235 – 9016) vs 5380 ng/L (IQR 2287 – 8204). There were no marked differences regarding HF medication and implanted devices.
Compared with placebo, intermittent levosimendan had no significant effect on the primary endpoint (mean rank score 71.8 for the levosimendan group vs 75.1 for the placebo group; p = 0.65). However, there was a strong signal towards a higher incidence of the individual clinical components of the primary endpoint (tier 1 plus tier 2) in the levosimendan group vs the placebo group both after 14 weeks (HR 2.94, 95%CI 1.13–7.70; p = 0.028) and 26 weeks (HR 1.65 95%CI 0.87 – 3.12; p = 0.123). The number of investigator-reported adverse events during and immediately after drug application was 12.4% in the levosimendan group vs 11.8% in the placebo group (p = 0.905).

Conclusion
Our findings do not support the use of intermittent levosimendan to improve post-hospitalization clinical stability in patients who were recently hospitalized with HF and reduced LVEF. Further studies are warranted to find the correct use of levosimendan in advanced heart failure patients.
Clonal hematopoiesis has prognostic value in dilated cardiomyopathy independent of age and clone size
Authors: Sikking M , Stroeks S L V , Henkens M T H , Raafs A G , Cossin B , Van Deuren R , Steehouwer M , Riksen N P , Van Den Wijngaard A , Brunner H , Hoischen A , Verdonschot J A J , Heymans S R B 
Published: November 2023

Abstract

Background
Clonal hematopoiesis (CH) gives rise to mutated leukocyte clones, that may induce cardiovascular inflammation, and thereby impact the disease course in cardiovascular diseases such as atherosclerosis and ischemic heart failure. The term clonal hematopoiesis of indeterminate potential (CHIP) is used when the variant allele frequency (VAF; a marker for clone size) in blood is ≥2%. The impact of CH clones in non-ischemic dilated cardiomyopathy (DCM) remains largely undetermined. Moreover, the impact of small clone sizes (VAF &lt;0.5%) remains unknown in cardiovascular diseases in general.

Objectives
To establish the prognostic impact of CH in DCM down to small CH clone sizes.

Methods
CH was determined using an ultrasensitive single-molecule Molecular Inversion Probe technique that allows detection of clones down to a VAF of 0.01%. Cardiac death and all-cause mortality were predicted using receiver operating characteristic curve-optimized VAF cut-off values.

Results
520 DCM patients were included. 109 patients (21%) had CH driver mutations, of which 45 had a VAF of ≥2% and 31 had a VAF of &lt;0.5%. The median follow-up duration was 6.49 years [interquartile range 4.69 - 9.71]. DCM patients with CH had a higher risk of cardiac death (HR 2.33 using a VAF cut-off of 0.36%, 95% confidence interval 1.24 - 4.40) and all-cause mortality(HR 1.72 using a VAF cut-off of 0.06%, 95% confidence interval 1.10 - 2.69), independent of age, sex, left ventricle ejection fraction and New York Heart Association classification.

Conclusion
CH predicts cardiac death and all-cause mortality in DCM patients with an optimal threshold for clone size of 0.36% and 0.06%, respectively. Therefore, CH may be prognostically relevant independent of clone size in patients with DCM.Clonal hematopoiesis characteristicsClonal hematopoiesis prognosis
Diuretic use and outcomes in patients with HFrEF: Insights from the VICTORIA trial
Authors: Ezekowitz J A , Alemayehu W , Edelmann F , Ponikowski P , Lam C S P , O'connor C M , Butler J , Homering M , Corda S , Mcmullan C J , Westerhout C M , Voors A A , Mentz R J , Armstrong P 
Published: November 2023

Abstract

Background
In the Vericiguat Global Study in Subjects with Heart Failure with Reduced Ejection Fraction (VICTORIA) trial, vericiguat, compared with placebo, reduced the risk of cardiovascular death (CVD) and heart failure hospitalization (HFH) in patients enrolled shortly after a worsening heart failure (WHF) event. We examined the clinical outcomes and efficacy of vericiguat as it relates to the background use of loop diuretics in this population of patients with WHF.

Methods
We calculated the total daily loop diuretic dose equivalent to furosemide dosing at randomization and categorized these as &lt;40, 40, and &gt;40 mg total daily dose (TDD). The primary composite outcome of CVD or HFH and its components were evaluated as clinical outcomes and expressed as adjusted hazard ratios (adjHR) and 95% confidence intervals (95% CI). Post-randomization rates of change in TDD and safety were also examined.

Results
Of 4434 patients with diuretic dose information available at randomization, 647 (14.6%) were on &lt;40 mg, 1633 (36.8%) were on 40 mg, and 2154 (48.6%) were on &gt;40 mg TDD. Patient characteristics revealed those patients taking &gt;40 mg TDD were more often in NYHA Class III/IV, diabetic, and had higher NT-proBNP, lower eGFR, less triple guideline-based HF therapy, and a higher MAGGIC risk score. The composite event rate of CVD or HFH per 100 patient years (pt-yrs) progressively increased with higher doses of diuretics: 29.8 per 100 pt-yrs for 40 mg TDD: adjHR 1.23 (95%CI 1.02-1.49); 48.1 per 100 pt-yrs for &gt;40 mg TDD adjHR 1.50 (95%CI 1.25-1.81), relative to &lt;40 mg TDD (22.5 per 100 pt-yrs). Results were similarly observed for the components of the composite endpoint (Figure). There was no significant interaction for the efficacy of vericiguat vs placebo for any outcome examined according to TDD at randomization (p-interaction &gt;0.72, 0.57 and 0.64 for the primary endpoint, CVD and HFH). Diuretic dose changes post-randomization were assessed in 3684 eligible patients (followed for a median duration of 14.2 months). By treatment group, there were similar rates of up-titration (26.7 and 29.4 per 100 pt-yrs), down-titration (13.8 and 15.4 per 100 pt-yrs), and stopping of diuretic use (23.4 and 24.2 per 100 pt-yrs) observed for vericiguat and placebo groups, respectively.

Conclusions
The amount of loop diuretic TDD at randomization was associated with a higher risk phenotype commensurate with worse outcomes. However, the efficacy of vericiguat was preserved across this range of different loop diuretic doses used by patients with recent WHF in VICTORIA.
Effect of eplerenone according to duration of heart failure in EMPHASIS-HF: It is never too late to start an MRA in HFrEF
Authors: Matsumoto S , Kondo T , Jhund P S , Swedberg K , Veldhuisen D J , Vincent J , Pocock S J , Pitt B , Zannad F , Mcmurray J J V 
Published: November 2023

Abstract

Background
In the Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure trial (EMPHASIS-HF), the mineralocorticoid receptor antagonist (MRA) eplerenone reduced both the risk of death and heart failure (HF) hospitalization in patients with HF and reduced ejection fraction (HFrEF) and mild symptoms. However, many patients are still not prescribed an MRA and physicians may be reluctant to add another treatment in patients with longstanding HF who appear to be "stable" on their current therapy.

Purpose
As little is known about how the effect of MRA therapy varies by the duration of HF, we examined the efficacy of eplerenone according to time from HF diagnosis among patients in EMPHASIS-HF. The primary trial outcome was the composite of a first hospitalization for HF or cardiovascular death.

Methods
Three patient groups of similar size were created according to the duration of HF: &lt;1 year, ≥1 to &lt;5 years, and ≥5 years. Outcomes were analysed using Cox regression and the Kaplan-Meier estimate. Treatment effects were examined according to HF duration category and also using the duration of HF as a continuous variable.

Results
The number of patients in each group was: 975 (&lt;1 year), 769 (1 - &lt;5 years), and 988 (≥5 years), respectively. Patients with longer duration of HF were older and more frequently had an ischaemic aetiology of HF. Additionally, a longer duration of HF was associated with lower eGFR levels, wider QRS duration, and a higher proportion of atrial fibrillation at baseline. The rate of the primary outcome (per 100 person-year) increased with HF duration: 9.8 (95% CI: 8.4-11.4) for &lt;1 year, 13.5 (11.6-15.7) for 1 - &lt;5 years, and 17.6 (15.6-19.8) for ≥5 years. Similar trends were seen in all other outcomes (Figure 1). The hazard ratios for the effect of eplerenone compared to placebo on the primary outcome were 0.57 (95% CI: 0.42-0.79) for &lt;1 year, 0.81 (0.60-1.10) for 1- &lt;5 years, and 0.61 (0.48-0.78) for ≥5 years; P for interaction = 0.24. The benefits of eplerenone were also consistent across the duration of HF examined as a continuous variable (Figure 2). For the primary outcome, The number needed to treat (NNT) over the duration of the trial, for the primary outcome, was 14 for &lt;1 year, 13 for 1 - &lt;5 years and only 10 for ≥5 years duration.

Conclusions
Patients with a longer duration of HF had worse clinical status and a higher rate of events, but the benefit of eplerenone was consistent in people with longer-standing HF and HF of shorter duration. These data suggest that it is never too late to start an MRA in patients with HFrEF.
Figure 1. Outcomes according to heart failure duration category
Abbreviations: CV cardiovascular; HF heart failure
Figure 2. Treatment effects according to the duration of heart failure
Abbreviations: CV cardiovascular; HF heart failureFigure 1Figure 2
Mitochondrial function is abnormal in circulating blood monocytes of patients with chronic heart failure
Authors: Sabbah H , Gupta R C , Singh-Gupta V , Castle K , Lanfear D E 
Published: November 2023

Abstract

Background
Cardiac mitochondrial function is abnormal in heart failure (HF) and is likely to contribute to disease progression. We previously showed that in dogs with HF mitochondrial functional abnormalities exist in both failing cardiomyocytes and in circulating blood monocytes, and to similar extent. This finding suggested the possibility that mitochondrial function in circulating monocytes can serve as a surrogate for cardiac mitochondrial function. We also showed that mitochondrial abnormalities exist in cardiomyocytes of patients with chronic HF.

Purpose
In the present study we sought to test the difference between patients with advanced HF and age-matched controls in terms of circulating monocyte mitochondrial function.

Methods
We examined circulating blood monocytes from 10 patients evaluated in our advanced HF clinic and with left ventricular ejection fraction &lt;35%. compared to 10 age-matched control persons without cardiac disease (CON). Peripheral blood samples (15 ml) were obtained from each participant and monocytes were isolated using standard Ficoll-Paque gradient centrifugation. Isolated monocytes were suspended in Agilent XF-DMEM base buffer for quantification of mitochondrial function with Seahorse XFe96 analyzer. The following key mitochondrial functional parameters were determined: basal respiration (BASEresp), ATP production-linked respiration (ATPresp), maximal respiration (MAXresp) and respiratory capacity (RC).

Results
BASEresp, ATPresp, MAXresp and RC were significantly lower in monocytes of patients with HF compared to NL subjects (BASEresp 2.7 ± 0.7 vs. 5.2 ± 1.6, p&lt;0.05; ATPresp 10.0 ± 0.8 vs. 15.9 ± 1.0, p&lt;0.05; MAXresp 36.5 ± 5.9 vs. 69.3 ± 3.8, p&lt;0.05; RC 26.5 ± 5.5 vs. 53.5 ± 3.5, p&lt;0.05).

Conclusions
Mitochondrial dysfunction is present in circulating blood monocytes of patients with chronic HF. These findings coupled to those in dogs with HF suggest the possibility that determination of mitochondrial function in peripheral monocytes may identify those patients with HF with cardiac energetic deficiencies. If validated this technique could help illuminate how cardiac energy deprivation relates to disease progression and potentially enable targeted therapies directed at mitochondria dysfunction.
Relationship between the right ventricular function and MECKI score in patients with advanced heart failure
Authors: Acar R D , Halil G S , Deger S , Akbal O Y , Dogan C , Efe S C , Kirali K 
Published: November 2023

Abstract

Background
Three- dimensional echocardiography (3DE) is an attractive technique for assessment of RV wrapping around the conical left ventricle and MECKI score is a strong predictor of prognosis in patients with advanced heart failure.

Purpose
We aimed to evaluate the relationship between the right ventricular function obtained by 3DE and MECKI Score in patients with advanced heart failure.

Methods
The Metabolic Exercise test data combined with Cardiac and Kidney Indexes (MECKI) score was calculated by an online free calculator using parameters peak oxygen uptake (% predicted value) and VE/CO2 slope values obtained by CPET, blood samples such as hemoglobin, sodium, MDRD and left ventricular ejection fraction (LVEF).(1)

Results
The 43 patients with sinus rhythm who were candidates for heart transplantation or left ventricular assist device (LVAD) therapy between June 2022 and January 2023 were included in the study. The majority of the patients were male (% 81). The mean 3D LV EF was % 22 ± 3.8, the mean value for peak VO2 max obtained by CPET was 15 ± 5.8 ml/kg/min and the median value for VE/CO2 slope was 34 (24-99). When the right ventricular parameters were compared according to the median value of 34, the right ventricle was larger and parameters of the right ventricular systolic function were worse in patients with the higher VE/CO2 slope values. (Figure 1). The mean value for percentage of predicted peak VO2 max was % 52 ± 16 and the median for the MECKI Score was 9.3 (1.8-86). By univariate and multivariate regression analyses, only the 3D RV basal diameter was found independently associated with peak VO2 max. Also, the VECO2 slope was found independently associated only with 3D RV TAPSE. Also these two parameters, 3D RV basal diameter and 3D RV TAPSE were found independent predictors of MECKI score. In ROC analysis, the cut off value 40.9 mm for 3D RV basal diameter to predict MECKI score with sensitivity and specificity were % 90 and % 68 , respectively (AUC:0.792). Also, AUC was 0.784 for the cut off value of 7.7 mm for 3D RV TAPSE with the sensitivity % 90 and specificity % 81. (Figure 2).

Conclusion
The major findings in this study were RV basal diameter was an independent predictor of the peak VO2 max value and RV 3D TAPSE was an independent predictor of the VECO2 slope. These results suggest that, while the basal diameter of the right ventricle, in other words, the size of the right ventricle effects peak oxygen consumption, the O2 transport and utilization, 3D TAPSE, namely systolic function of the right ventricle effects the ability to remove C02 from the whole body. Also these two parameters were found independent predictors of the MECKI score which is a strong predictor of prognosis in patients with advanced heart failure.Figure 1Figure 2
Prognostic impact of lung ultrasound detected B-Line on hospitalized ischemic HFmrEF patients
Authors: Zhu Y L , Zhang H , Zhou Y Y , Chen F Q , Li N , Peng X , Wu M X , Huang H B , Zhang L L , Liao M , Xiao S H A , Chen Y L , Chen S H , Liu Z C , Zeng J P 
Published: November 2023

Abstract

Background
The prognostic impact of lung ultrasound derived B-Line (LU-BL) in heart failure patients with mildly reduced left ventricular ejection fraction (HFmrEF) remains elusive. We evaluated the correlation between LU-BL and prognosis in HFmrEF patients.

Methods
This study screened consecutive hospitalized HFmrEF patients in our hospital between January 2015 and August 2020 with LU-BL results at admission. LU-BL results at admission were available in 610 HFmrEF patients, and majority patients were diagnosed as ischemic HFmrEF (574, 94.1%). We thus observed the prognostic impact of LU-BL on ischemic HFmrEF patients. Patients completed at least one year of clinical follow-up through telephone, clinical or community visits after discharge. The primary endpoint was defined as the composite endpoint of cardiovascular (CV) death or heart failure hospitalization (CV event) at 90 days and 1-year post discharge.

Results
CV event at 90 days were significantly higher with higher LU-BL number (0; 1-2; 3-9; ≥10: 12.8%, 11.9%, 14.3% and 28.9%, P&lt;0.001). Kaplan-Meier curves showed LU-BL &gt;6 was associated with increased CV event at 90 days (Log rank P&lt;0.001) and at 1 year (Log rank P = 0.029). After adjusted for clinical and echocardiographic covariates, multivariable Cox regression analysis showed that LU-BL&gt;6 (HR 1.036, 95% CI 1.011-1.062, P = 0.005) and LU-BL &gt;11 (HR 1.882, 95% CI 1.225-2.891, P = 0.004) were independently associated with increased CV event rate at 90 days. The lowest CV event rate at 90 days post discharge was identified in patients with LU-BL&lt;11 and free of diabetes (10.4%). Presence of diabetes was associated with 2-fold higher CV event rate at 90 days post discharge in ischemic HFmrEF patients with LU-BL ≤11 (20.3%).

Conclusions
LU-BL&gt;6 and 11 is independently related worse cardiovascular outcome at 90 days post discharge in ischemic HFmrEF patients. Diabetes is a fundamental risk factor of worse cardiovascular outcome within 90 days post discharge in ischemic HFmrEF patients with LU-BL&lt;11.LU-BL and outcome of ischemic HFmrEF
The prognostic association of atrial fibrillation on heart failure hospitalizations after acute myocardial infarction
Authors: Yandrapalli S , Achanta A , Malik A H , Aronow W S , Zaman S , Januzzi J L , Wasfy J H 
Published: November 2023

Abstract

Aims
The association of atrial fibrillation (AF) with heart failure (HF) specific hospitalizations after acute myocardial infarction (AMI) is unclear. We aim to study the association of AF and 6-month HF hospitalization after an AMI in a large American cohort.

Methods and Results
Adult survivors of a AMI hospitalization without cardiogenic shock were identified from the 2019 US Nationwide Readmissions Database. The unadjusted association of AF (pre-existing and denovo) with baseline characteristics and primary outcome of rate of 6-month HF admission, and secondary outcomes of fatal HF admission, composite of HF peri-AMI or a 6-month HF admission, and a composite of 6-month HF or death during a non−HF-related admission was evaluated using chi square tests or t-tests, and independent associations of AF on outcomes were evaluated using multivariable logistic regression. Cox proportional hazards models were used to identify the association of AF on cumulative incidence risk on HF readmission.
Of 262,390 AMI survivors, AF was present in 18.0%. By 6-months, HF hospitalization occurred in 5.4% of all patients. AF was associated with a higher adjusted risk for 6-month HF admission (OR 1.42, 95% CI: 1.34-1.50). In the adjusted time-to-event analysis, AF was associated with a higher risk for 6-month HF readmission (HR 1.39, 95% CI 1.31-1.46, P&lt;0.001). AF was associated with a higher risk for fatal HF and the composite outcomes.

Conclusions
AF was present in 1 in 6 AMI survivors without cardiogenic shock and AF was associated with a higher risk of HF hospitalization in the subsequent 6-month period.Cumulative Incidence CurvesOutcomes Table
Echocardiography-based risk score predicts cardiovascular outcomes in ischemic heart failure patients with reduced ejection fraction
Authors: Liu D , Hu K , Wagner C , Kreipl M , Sokalski V , Lau K , Lengenfelder B , Ertl G , Frantz S , Nordbeck P 
Published: November 2023

Abstract

Background
Ischemic heart disease (IHD) is the most common cause of heart failure (HF) and serves as an important prognostic factor across the whole HF spectrum. Prognostic assessment is important for optimal patient care, and a number of prediction models or prognostic scores have been developed in the past years for risk stratification of HF patients.

Purpose
Present study aimed to develop a comprehensive echocardiography-based score algorism for risk assessment of ischemic heart failure (IHF) patients with reduced left ventricular ejection fraction (&lt;50%).

Methods
This study included 1355 IHF patients with ejection fraction &lt;50%, the median clinical follow-up was 25 months. Multivariable Cox hazard models were used to assess the associations between echocardiography variables [including 13 standard parameters and global longitudinal strain (GLS)] and major adverse outcomes [including all-cause mortality, cardiovascular (CV) death, and CV related hospitalization].

Results
Rates of all-cause mortality, CV mortality, and combined CV events including death and hospitalization, were 29.2%, 18.2%, 41.1%, respectively. Right ventricular mid-cavity diameter (RVD)&gt;38mm, mitral annular plane systolic excursion (MAPSE)&lt;8mm, tricuspid annular plane systolic excursion (TAPSE)&lt;12mm, transmitral early flow velocity to mitral annular velocity ratio (E/E´)&gt;14.5, systolic pulmonary artery pressure (sPAP)&gt;38mmHg, and absolute GLS&lt;8% were identified as independent echocardiographic indexes for worse clinical outcome in the multivariable Cox models. An echocardiography-based risk score (Echo Risk Score, ranged from 0 to 6 points) was established based on these markers and patients were classified into 3 risk groups: a score of 0 to 1 as low-risk, 2 to 3 as intermediate-risk, and 4-6 as high-risk. After adjustment for all clinical covariates, high-risk patients faced 2 to 3-fold increased risk of all-cause mortality (HR 2.42, 95% CI 1.81-3.24), CV mortality (HR 2.75, 95% CI 1.88-4.02), and combined CV events (HR 1.84, 95% CI 1.43-2.36) compared with low-risk patients. Incremental predicting efficacy was evidenced after the addition of Echo Risk Score either to the model including clinical risk factors or to the model including clinical risk factors and N-terminal prohormone of brain natriuretic peptide (all P&lt;0.001, Figure 1).

Conclusions
This new echocardiography-based risk score is significantly and independently associated with all-cause mortality and CV mortality or hospitalization in ischemic heart failure patients with reduced ejection fraction. Future studies are warranted to validate the predicting efficacy of this echocardiography-based risk score in ischemic heart failure patients with reduced ejection fraction.Figure 1