bluuebunny/crossref_metadata_2025_split huggingface dataset:
In-hospital initiation of Vericiguat and short-term cardiovascular function improvement in heart failure patients with worsened renal function
Authors: Lou B , Yuan Z Y , She J Q 
Published: October 2024

Abstract

Background and Aims
Vericiguat, a novel soluble guanylate cyclase (sGC) stimulator, is approved for treating heart failure (HF) with reduced ejection fraction (HFrEF). This study aims to assess the short-term improvement in cardio-function resulting from in-hospital initiation of Vericiguat among patients with chronic kidney dysfunction (CKD), utilizing real-world data from a single-center experience in western China.

Method
Data were obtained from the Biobank of our hospital, spanning from January 2023 to December 2023. A total of 213 HF patients with Vericiguat initiation were screened for eligibility. Echocardiography was employed to evaluate cardio-function after 1- and 3-month short-term follow-up in each patient. Statistical analyses were conducted using one-way ANOVA (followed by Geisser-Greenhouse correction and Tukey’s multiple comparison) to assess significance between different timepoints.

Results
Among the 213 patients randomized in this study, baseline characteristics were compared based on estimated glomerular filtration rate (eGFR) ≤ 30 (worsened renal function group, WRF, n = 20) and &gt;30 mL/min/1.73 m2 (n = 193). No significant differences were observed in age, gender, and other biochemical parameters expect hemoglobin and creatine between the two groups (Table 1). Analysis of cardiac function after 1- and 3-month follow-up revealed a promising increase in left ventricular ejection fraction (EF) (37.2% vs. 43.9%, Mean diff -6.7, 95% CI -12.78 to -0.62, p = 0.03), fractional shortening (FS) (20.9% vs. 25.3%, Mean diff -4.42, 95% CI -8.57 to -0.27, p = 0.04), and a significant decrease in left ventricular end-diastolic dimension (LVEDD) (65.0mm vs. 60.6mm, Mean diff 4.35, 95% CI 0.33 to 8.38, p = 0.03) after 3-month follow-up compared to Vericiguat initiation in WRF patients. However, no significant changes were observed between the beginning and 1-month follow-up in echocardiographic measurements (Figure 1).

Conclusion
In this real-world single-center study, Vericiguat demonstrated effectiveness in short-term improvement of cardiac function among HF patients with worsened renal function. The long-term efficacy in reducing major cardiovascular events in this subgroup, based on real-world experience, warrants further exploration.
Tafamidis treatment for transthyretin amyloid cardiomyopathy: results from an open-label, early-access, long-term study extension in an all-comers population
Authors: Crespo-Leiro M G , Hanna M , Damy T , Delgado D , Ebede B , Angeli F S , Maurer M S , Garcia-Pavia P , Drachman B M 
Published: October 2024

Abstract

Background
In the pivotal Tafamidis in Transthyretin Cardiomyopathy Clinical Trial (ATTR-ACT NCT01994889), tafamidis significantly reduced mortality and cardiovascular hospitalization in patients with transthyretin amyloid cardiomyopathy (ATTR-CM). Given the high clinical unmet need and the favorable benefit-to-risk profile of tafamidis, there was a justification to provide patients with an option for early access to treatment as part of the ATTR-ACT long-term extension study (LTE; NCT02791230).

Purpose
To assess long-term safety in an all-comers population receiving early access to tafamidis.

Methods
Following protocol amendment (20 July 2018), patients with ATTR-CM, not previously enrolled in ATTR-ACT, and without commercial access to tafamidis, were enrolled in the LTE early-access study arm in 13 countries. Patients received open-label, once-daily tafamidis free acid 61 mg for up to 60 months, until they gained product access by prescription or study discontinuation by the sponsor. All-cause and cardiovascular (CV)-related mortality, CV-related hospitalization, and treatment-emergent adverse events (TEAEs) were assessed.

Results
Of 1481 patients enrolled in the early-access cohort, 1476 received at least one dose of tafamidis and were included in the analysis. Mean (SD) age at enrollment was 76.5 (7.8) years old, 37.5% were ≥80 years old, and 88.8% were male. Most patients (85.6%) had wild-type ATTR-CM, and 14.9%, 52.9%, 30.8%, and 1.3% were in New York Heart Association (NYHA) Class I, II, III, and IV, respectively. Over a mean (SD) follow-up period of 17.7 (13.8) months, all-cause and CV-related mortality rates were 23.4% and 13.8%, respectively (Table). Mean frequency of CV-related hospitalization per year was 0.28 (0.60). Serious TEAEs and TEAEs leading to discontinuation of the study were observed in 0.6% of patients (both); no new safety signals were identified.

Conclusions
Findings from the early-access cohort of the ATTR-ACT LTE highlight the safety of tafamidis treatment in an all-comers ATTR-CM patient population.
Understanding the benefits of renin-angiotensin-aldosterone system inhibitors and influence of hyperkalaemia on their prescription: a UK survey of healthcare professionals' views and practice
Authors: Wasef M , Birkhoelzer S , Cowan E , Turner C , Lopes L , Sardo P , Howe S , Kalra P R 
Published: October 2024

Abstract

Background
Renin–angiotensin–aldosterone system inhibitors (RAASi) improve outcomes in heart failure with reduced ejection fraction (HFrEF) and they should be increased to the maximally tolerated dose. However, their use is often hindered by hyperkalaemia leading to discontinuation or down titration.

Purpose
Assess perceptions of primary and secondary healthcare professionals regarding benefits of RAASi according to indication and, in the context of developing hyperkalaemia, to identify barriers to optimal utilisation, and to explore options for improving management protocols, specifically in HFrEF.

Methods
An electronic survey was distributed in primary and secondary care setting in Hampshire, UK, to evaluate knowledge about benefits of RAASi, clinical response to varying level of potassium (K+), and decision-making using several clinical scenarios. Hyperkalaemia was graded into mild (serum K+ 5.5 – 5.9 mmol/L), moderate (serum K+ 6.0 – 6.4 mmol/L) or severe (serum K+ ≥ 6.5 mmol/L).

Results
Between November 2021 and January 2023, 300 questionnaires were completed by 274 (91%) physicians (varying grades of seniority), 22 (7%) non-medical prescribers, and 4 (1%) pharmacists. 80% were working in secondary care across different specialities (31 working in cardiology and 15 in nephrology). The majority were aware of prognostic benefit of angiotensin converting enzyme inhibitors (ACEi) in patients with HFrEF although this was lower for mineralocorticoid receptor antagonists (MRA) (Fig 1). Fewer than 2/3 of respondents were aware of impact of ACEi on symptoms. In the presence of mild hyperkalaemia, 75% and 88% of healthcare professionals would stop or reduce ACEi and MRA, respectively. In moderate or severe hyperkalaemia, this increased to 96% and 97%, respectively (Fig 2A-B). When considering the scenario of a patient with HFrEF who had ACEi stopped due to K+ 5.9 mmol/L, the potassium at which the responder would consider re-starting the ACEi ranged from 77% when potassium level &lt; 5.5 mmol/L to 1% in moderate or severe hyperkalaemia (Fig 2C). 74% of healthcare professionals were familiar with local hyperkalaemia management protocol and 93% supported dedicated training on RAASi dose adjustment and hyperkalaemia management.

Conclusion
This survey, across a broad range of healthcare professionals, shows uncertainties around knowledge of benefits of RAASi in patients with HFrEF and there is sizeable variation in the prescribing response to degrees of hyperkalaemia. Given the voluntary nature of the survey, it is plausible that these data are biased towards individuals with greater understanding. Regardless, there is a need for continued education with a goal of improving patient-centred care.
Intermittent levosimendan infusions for advanced heart failure: a systematic review and meta-analysis of randomized controlled trials
Authors: Elsaeidy A S , Ghaly R , Soliman Y , Abuelazm M , Amin A M , El-Gohary M , Elshenawy S , Seri A R , Abouzid M , Abdelazeem B 
Published: October 2024

Abstract

Background
Intermittent intravenous infusions of levosimendan have been shown to provide benefits in patients with advanced heart failure (AHF), preventing HF rehospitalization and mortality.

Purpose
We aim to investigate the efficacy of intermittent intravenous levosimendan infusion in patients with AHF.

Methods
A systematic review and meta-analysis synthesizing evidence from randomized controlled trials (RCTs) obtained from PubMed, Embase Cochrane, Scopus, and WOS until September 2023. We used the random-effects model to report dichotomous outcomes using risk ratio (RR) and continuous outcomes using mean difference (MD), with a 95% confidence interval (CI). Finally, we implemented a trial sequential analysis (TSA) to improve the reliability of our results.

Results
We included 15 RCTs with 1,181 patients. Intermittent levosimendan was significantly associated with an improved left ventricular ejection fraction (LVEF) compared to placebo (MD: 6,39, 95% CI [3.04, 9.73], P= 0.002; I2=75, P=0.0005), with cumulative Z-score of change after ≤ 1 week passing the monitoring boundaries favors the levosimendan but did not cross the required information size. Additionally, there was a significant improvement in the all-cause mortality rate favoring levosimendan (RR: 0.60, 95% CI [0.40, 0.90], P= 0.01; I2=9, P=0.36). However, There was no difference between intermittent levosimendan and placebo in all-cause rehospitalization rate (RR: 0.75, 95% CI [0.46, 1.22], P= 0.25; I2=70, P=0.04) or event-free survival rate (RR: 0.97, 95% CI [0.72, 1.30], P= 0.84; I2=63, P=0.03).

Conclusion
In patients with AHF, intermittent levosimendan significantly improved LVEF and all-cause mortality rate. However, there was no effect on rehospitalization or event-free survival.Figure 1.LVEF and TSAFigure 2.Mortality, Rehospital, Surviva
Echocardiographic evaluation of cardiac remodelling in a cohort of patients with heart failure and reduced ejection fraction treated with dapagliflozin
Authors: Bonini J , Cantone A , Dal Passo B , Ballarini T , Sanguettoli F , Arzenton M , Maio D , Campo G , Serenelli M 
Published: October 2024

Abstract

Background
Several mechanisms have been proposed to explain SGLT2 inhibitors’ (SGLT2i) beneficial effects in patients with heart failure (HF), but their exact mode of action in this setting is not fully understood. Pivotal randomised clinical trials regarding this class of drugs in HF setting have not reported echocardiographic data regarding potential cardiac positive remodelling.

Objectives
To assess the effects of dapagliflozin treatment initiation on cardiac remodelling in patients with HF and reduced ejection fraction (HFrEF), with a focus on left ventricular performance and atrial volumetry.

Methods
In this retrospective observational study, we analysed data from 94 patients with HFrEF in whom dapagliflozin had been prescribed as part of HF treatment optimization. Inclusion criteria were: age &gt; 18 years; ongoing optimal medical therapy (OMT) for HF according to 2021 ESC HF guidelines (except for SGLT2i); transthoracic echocardiogram within 30 days of baseline assessment demonstrating a left ventricular (LV) ejection fraction (EF) &lt;40%; comprehensive assessment at 6 months with clinical, laboratory and echocardiographic data.

Results
Patients (mean age 71.7 ± 9.8, 76% males, coronary artery disease as HFrEF main aetiology in 66%) showed significant cardiac remodelling after dapagliflozin initiation, specifically in terms of stroke volume index (SVi, +9.7 ml/m2, p&lt;0.001), LVEF (+5.1%, p&lt;0.001), LV end-diastolic volume (LV EDV) index (-8.4 ml/m2, p&lt;0.001), left atrial (LA) volume index (-3.9 ml/m2, p=0.026), and LV mass index (LVMi, -12.9 gr/m2, p=0.004). BNP tended to significantly decrease (-168.6 ng/L, p=0.025). Percentage of patients with an indication for ICD implantation in primary prevention went from 36.2% to 8.5%, p&lt;0.001. We did not observe significant differences in terms of mitral regurgitation (MR) grading at follow-up (in particular, the proportion of patients with severe MR remained approximately stable: 7% vs 4%, p=0.86). We did not observe any change in diastolic function measured by E/e’ ratio (mean difference -0.6; 95% CI -2.2 to 0.9, p=0.41).

Conclusions
Treatment with dapagliflozin resulted in positive remodelling in our cohort of patients with HFrEF in terms of chamber volumes, contractility parameters (and this was not explained by an improvement in MR severity) and LVMi. There was a significant decrease in natriuretic peptide as well as in the proportion of patients with primary prevention ICD indication. Our findings highlight the need of further data to fully elucidate the exact mechanism that leads to LA and LV positive remodelling with SGLT2i.Figure 1.Change in TTE Parameters
Efficacy of acetazolamide as adjunct therapy in improving fluid management in patients with acute congestive heart failure: a systematic review and meta-analysis of randomized controlled trials
Authors: Narciso I , Ribeiro A P R , Faria N , Carvalho L , Terres M T T , Malagutti B C M , Mendes B S M 
Published: October 2024

Abstract

Introduction
Persistent congestion in acute congestive heart failure despite conventional treatments highlights the need for innovative therapeutic approaches. Evaluating acetazolamide as adjunctive therapy for reducing volume overload is significant. Our meta-analysis examines randomized clinical trials to assess acetazolamide's efficacy in improving fluid management in acute congestive heart failure.

Methods
We systematically searched Embase, PubMed, and the Cochrane Library in January 2024 for randomized controlled trials comparing the addition of acetazolamide to diuretic therapy versus standard diuretic therapy in patients with acute congestive heart failure. Article selection was conducted independently by two authors. Statistical analyses, including the weighted mean differences (MD) and assessment of heterogeneity using the I² statistic, were performed using R software version 5.4.1.

Results
Three studies comprising 596 patients were included. Of these, 297 (50%) received acetazolamide as adjunctive diuretic therapy, while 299 (50%) received standard diuretic therapy with a loop diuretic. Among participants, 385 (65%) were male, with a mean age of 72.76 years (±11.13). Acetazolamide adjunctive therapy led to an increase in natriuresis at day 2, expressed in milimoles (mmol), (MD 80.30; 95% CI [45.10-115.51]; p&lt;0.00001; I2=29%), and a trend towards higher natriuresis volume, expressed in liters (L), at day 2 (MD 0.56; 95% CI [-0.37-1.48]; p=0.24; I2=87%), although the latter lacked statistical significance.

Conclusions
Our findings suggest that acetazolamide adjunctive therapy may have potential benefits in improving fluid management and possibly enhancing clinical outcomes in patients with acute congestive heart failure. Further research is warranted to validate these findings and explore the long-term effects of acetazolamide therapy.
Estimated plasma volume in heart failure with reduced ejection fraction: ACE inhibitors versus angiotensin receptor/neprilysin inhibitor in follow up
Authors: Varga S , Antolkovic L , Zeljkovic I , Pavlovic N , Jordan A , Pavlov M , Vitlov P , Rudan D , Novak A , Lisnjic P , Manola S , Jurin I 
Published: October 2024

Abstract

Background
Estimated plasma volume status (ePVs) has been considered a biological surrogate for congestion and has been shown to be associated with post-discharge outcomes in patients with heart failure with reduced ejection fraction (HFrEF). The plasma volume status can be easily estimated by the index of the PVs according to the haemoglobin and haematocrit levels.

Purpose
The aim of the study was to examine the change in ePVs and N-terminal pro B-type natriuretic peptide (NT-proBNP) levels during the 12-month follow up of HFrEF patients treated with ACE inhibitors (ACEi) and angiotensin receptor/neprilysin inhibitor (ARNI).

Methods
We included all patients treated or diagnosed with HFrEF in our hospital from May 2021 to February 2022 and prescribed with either ACEi or ARNI among complete guideline-directed medical therapy (GDMT). We used Strauss-derived Duarte formula [ePVs= (100-Hct%) ÷ Hb] to estimate PVs during the initiation of GDMT and after 12-month follow up.

Results
This registry-based study included 619 patients with HFrEF, out of which 278 were prescribed with ACEi (ACEi group) and 273 with ARNI (ARNI group). There were no differences between the groups regarding age (ACEi 68 vs. ARNI 67 years, p=0.09), however, ACEi group had significantly more women (30% vs. 26% of patients, p=0.02). Patients in ACEi group were more likely to have ischemic cardiomyopathy (61 vs. 49%, p&lt;0.01), higher estimated glomerular filtration rate (72 vs. 64 L/min/1.73m², p=0.01), while patients in ARNI group were more likely to be NYHA III class (40 vs. 48%, p=0.04). Initial ePVs (4.23 for ACEi vs. 4.20 for ARNI, p=0.46), NT-proBNP levels (3357.5 for ACEi vs. 2786 for ARNI, p=0.08), and left ventricular ejection fraction (median 35% for ACEi vs. 35% for ARNI, p=0.49) did not significantly differ between the groups. After the 12-month follow up, the change in ePVs was similar between the groups (-0.22 for ACEi vs. -0.19 for ARNI, p=0.93). Reduction of NT-proBNP levels was more prominent in ACEi group (1750.5 vs. 858.5 pg/mL, p=0.01). Mortality rate did not differ between the groups during 12-month follow up (9.71% in ACEi vs. 8.42% in ARNI, p=0.60).

Conclusion
In HFrEF patients both ACEi and ARNI reduced ePV and NTproBNP levels during 12-month follow up. ACEi were more potent in reducing NT-proBNP levels. Despite the more prominent reduction in NT-proBNP levels, no significant difference was observed in mortality rate during follow up between the groups.
Ventricular tachycardia burden in heart failure with reduced ejection fraction - can we rely on optimized medical therapy
Authors: Rode F , Zeljkovic I , Novak A , Jordan A , Vitlov P , Puskadija M , Blivajs A , Serman A , Sipic T , Pavlovic N , Manola S , Jurin I 
Published: October 2024

Abstract

Introduction
Implantation of cardioverter-defibrillator and/or resynchronization (ICD and CRT-D) devices is aimed to prevent sudden cardiac death, fatal complication of heart failure with reduced ejection fraction (HFrEF). Guidelines propose a period of 3 months receiving maximally titrated guideline-directed medical therapy (GDMT) prior to implantation. Ventricular tachycardia (VT) burden in HFrEF has been related to worse outcomes. The effect of GDMT up-titration on VT incidence after device implantation has not yet been fully clarified.

Purpose
The main goal of this study is to examine the effects of GDMT evidence-based target doses on VT and appropriate device therapy (ADT) incidence in patients with HFrEF implanted with ICD or CRT-D.

Methods
This registry-based study included patients with HFrEF who were implanted with ICD or CRT-D from January 2021 to November 2023, with at least one follow-up. Titration of GDMT and incidence of VT/ADT were evaluated. We compared VT/ADT incidence in target dose group to incomplete titration group of each drug class. We also compared GDMT titration and VT/ADT incidence in CRT-D to ICD group. The Fisher exact test was used to evaluate the differences between groups.

Results
Data on 132 patients were collected (mean age 63±26 years, 16% female). Median follow-up time from device implantation was 201 (30-748) days. Target doses were reached for 24.4% beta blockers (BB), 37.8% angiotensin receptor neprilysin inhibitors (ARNI), 73.5% mineralocorticoid receptor antagonists (MRA), 89.5% sodium-glucose contransporter-2 inhibitors (SGLT2I), and 18.8% of complete GDMT. Total VT and ADT incidence was 32.6% and 12.9%, respectively. In target doses vs. incomplete doses groups, VT incidence was 34.4% vs. 32.0% (p=.83) for BB, 28.0% vs. 35.4% (p=.45) for ARNI, 32.0% vs. 34.3% (p=.84) for MRA, 30.1% vs. 50.0% (p=.23) for SGLT2I and 33.3% vs. 32.4% (p=1) for complete GDMT. ADT incidence was 18.8% vs. 11.0% (p=.36) for BB, 12.0% vs. 13.4% (p=1) for ARNI, 12.4% vs. 14.3% (p=.77) for MRA, 11.0% vs. 21.4% (p=.39) for SGLT2i, and 16.7% vs. 12.0% (p=.51) for complete GDMT. In CRT-D vs. ICD group, 31.5% vs. 19,2% (p=.15) BB, 44.4% vs. 33.3% (p=.21) ARNI, 79.6% vs. 69.2% (p=.16) MRA, 98.1% vs. 83.3% (p&lt;0.05) SGLT2I; and 20.4% vs. 16.7% (p=.65) of complete GDMT were maximally titrated. VT incidence was significantly lower in CRT-D group (18.5% vs. 42.3%, p&lt;0.05). ADT was also lower, but without statistical significance (9.3% vs. 15.4%, p=.43).

Conclusions
Up-titration of any individual drug or complete GDMT to the evidence-based target dose did not directly correlate with a decrease in VT or ADT incidence. Cardiac resynchronization therapy provides more room for target GDMT doses, particularly of BB. We notice only a modest trend in up-titration of GDMT in patients with CRT-D, who had significantly lower incidence of VT.