bluuebunny/crossref_metadata_2025 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

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 >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

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

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 < 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

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

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 > 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) <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<0.001), LVEF (+5.1%, p<0.001), LV end-diastolic volume (LV EDV) index (-8.4 ml/m2, p<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<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

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<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

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<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

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<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<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.
Effects of sodium-glucose cotransporter 2 inhibitors on pulmonary hemodynamics in chronic heart failure patients with a pulmonary artery pressure sensor
Authors: Santiago-Vacas E , Rovira-Sole J , Codina P , Carrete A , Borrellas A , Domingo M , Ruiz-Cueto M , Cediel G , Camblor A , Gonzalez B , Velayos P , Crespo E , Pulido A , Lupon J , Bayes-Genis A
Published: October 2024

Background

Approximately 50% of patients with chronic heart failure (HF), either with preserved or reduced left ventricular ejection fraction (LVEF), have secondary pulmonary hypertension, which results in poorer prognosis. In previous studies, sodium-glucose cotransporter 2 inhibitors (SGLT2i) have shown a reduction in cardiovascular death, HF hospitalization and pulmonary artery pressure (PAP) in patients with HF, regardless of LVEF, but exact mechanisms remain unclear.

Purpose

The main objective of this study is to analyse effects of SGLT2i on PAP in patients with chronic HF followed by a PAP sensor (CardioMEMS HF system). The secondary objective is to analyse effects in subgroups of LVEF.

Methods

We included chronic HF patients (regardless of LVEF) with previously implanted a PAP sensor, from July 2019 to February 2023. SGLT2i had been added in fourth position in patients with reduced LVEF, since they were previously on optimal HF treatment as chronic patients. Changes in PAP, renal function and N-terminal pro B-type natriuretic peptide (NTproBNP) were compared between two periods of time: "30 days before" and "30 days after" SGLT2i initiation. Patients were then classified in two groups: group 1 (LVEF ≤40%) and group 2 (LVEF >40%) and repeated same analyses.

Results

Overall, 61 patients were screened, and 17 finally were included, mean age 71.7 ± 9.6 years, 64.7% were men, mean LVEF was 49.4 ± 17.5%, 23.5% had ischaemic aetiology and 64.7% were in NYHA class III (Table 1). There were more men in group 1 than in group 2 (p=0.043), without other differences in basal characteristics between groups (Table 1). Dapagliflozin (10mg daily) was initiated in 14 patients (82.4%), 5 from group 1 and 9 from group 2 (p=1.000), and empagliflozin (10mg daily) in 3 patients (17.6%), 1 from group 1 and 2 from group 2 (p=1.000). Before SGLT2i, mean diastolic PAP (dPAP) was 17.3 ± 5.6 mmHg and median NTproBNP was 2841.5 (289-10515) pg/mL. SGLT2i significantly reduced dPAP; average dPAP ("30 days after" period) was 1.5 mmHg lower (95% CI, 0.26-2.74; p=0.021) compared to "30 days before" period (Figure 1). SGLT2i also reduced systolic PAP (-2.2 mmHg), mean PAP (-1.7 mmHg), NTproBNP (-183 pg/mL) and creatinine (-0.2 mg/dL), but not statistically significant. SGLT2i reduced PAP, NTproBNP and creatinine too in group 1 (6 patients), but did not achieve statistical significance. Reductions were as well observed in group 2 (11 patients), and SGLT2i significantly reduced dPAP (-2.04 mmHg) (95% CI, 0.31-3.77; p=0.025).

Conclusions

In patients with chronic HF and a PAP sensor, SGLT2i, added to previous HF treatment, significantly reduced dPAP. PAP reductions were observed regardless LVEF, but results were more robust in patients with LVEF >40%.Figure 1
The efficacy of IV iron in anemic heart failure patients: a systemic review and meta-analysis of randomised controlled trials
Authors: Desouki M R A , Abdelaziz A , Khatatbeh A A , Ramadan S , Rasheed W M , Eldamanhory M H , Aref Alqurm A K , Heiba A H , Aly Zaher A A , Mostafa Elsayed D E , Abdelazeem B , Lavie C J , Slipczuk L
Published: October 2024

Introduction

Iron deficiency in the context of heart failure is a multifaceted concern, where the intricate interplay between diminished iron stores, impaired absorption mechanisms, and reduced recycled iron in the reticuloendothelial system adds a layer of complexity to patient management. Initial attempts to address this issue with oral iron treatments have been questioned due to its poor absorption. Intravenous iron therapy is now preferred, as it has been shown to reduce heart failure hospitalisations and cardiovascular mortality. However, there is a lack of randomised studies specifically focused on heart failure patients, highlighting the need for more targeted investigations.

Purpose

The aim of this review is to provide reliable evidence from published randomised controlled trials (RCTs) regarding the beneficial effect of IV iron in heart failure patients.

Methods

We systematically searched PubMed, Web of Science, Scopus, and Cochrane Central, and EMBASE from inception until December 2023. We included randomised controlled trials (RCTs) comparing the effect of IV iron in heart failure patients versus placebo. The primary outcomes were 6MWT mean change, ferritin concentration mean change, transferrin saturation mean change and worsening heart failure. All data were pooled as either Mean difference in the random effect model with the corresponding SD or pooled as RR and 95% CI for dichotomous data.

Results

Twelve RCTs involving 6800 patients were included in the analysis. The overall effect on the measured primary outcomes was in favour of IV iron in terms of 6MWT mean change (MD= 34.45, 95% CI [ 29.58 to 39.31], P=<0.0001), ferritin concentration mean change (MD= 219.18, 95% CI [ 208.7 to 229.66], P=<0.0001), transferrin saturation mean change (MD= 9.77, 95% CI [ 8.14 to 1.39], P=<0.0001) and worsening heart failure (RR= 0.46, 95% CI [ 0.31 to 0.69], P=0.002).

Conclusion

The introduction of the IV iron therapy to heart failure patients showed a beneficial effect in terms of the measured haematological and cardiovascular metrics, which include 6MW test mean change, ferritin concentration mean change, and worsening heart failure.6MWT mean changeFerritin mean change
Utilization and safety of digoxin in patients with chronic heart failure and atrial fibrillation with rapid ventricular rate
Authors: Berge K , Schirmer H , Kleiven Ø , Grundtvig M , Gullestad L , Orn S , Myhre P L
Published: October 2024

Background

Digoxin can reduce symptoms and the risk of tachycardia-induced cardiomyopathy in patients with heart failure (HF) and concomitant atrial fibrillation (AF) with rapid ventricular rate. The effect of digoxin in HF and AF has not been tested in randomized controlled trials, and observational data have shown conflicting results linking digoxin to increased mortality in AF, though the nature of observational data makes it prone to bias and results difficult to interpret.

Purpose

To assess the utilization of digoxin in patients with HF and AF, and its association with New York Heart Association (NYHA) functional class and survival.

Methods

We used data from the Norwegian HF registry that collected data from all Norwegian HF clinics between 2013-2022. Data was collected from the first and last visit during optimizization of HF medical therapy. Associations with mortality status from Statistics Norway were assessed in unadjusted time-to-event analysis, and after adjustment for age, sex, body mass index, estimated glomerular filtration rate, aldosterone antagonists, renin-angiotensin-aldosterone system inhibitors, and beta blockers.

Results

The study included 4,877 HF patients, consisting of 4,067 (83.4%) with ejection fraction (EF) ≤40% and 810 (16.6%) with EF >40%.. The mean age was 67.7±12.0 years; 25.1% were women, and 27.3% had NYHA functional class III/IV. At the first visit, 1,339 (27.5%) patients had AF and 829 (61.9%) of these were treated with ≥50% of the beta-blocker target dose. AF with a ventricular rate ≥100 bpm was present in 277 (20.1%) patients, and 188 (67.9%) of these were on ≥50% beta-blocker target dose. Similarly, 262 (19.6%) of all AF patients and 44 (15.9%) of those with a ventricular rate ≥100 bpm were treated with digoxin. After optimization of HF medical therapy (median duration 140 [Q1–Q3 82–237] days), 1,039 (21.3%) patients had AF. Among these, 227 (21.9%) were treated with digoxin, including 9 (18.0%) patients with ventricular rate ≥100 bpm. Patients with AF who were started on digoxin experienced during the optimization period a larger decline in heart rate compared to those who were not (mean change -23.7±17.2 vs. -5.7±16.7 bpm, p=0.001), and more often an improvement in NYHA functional class (45% vs 30%, p=0.018). During median 779 [Q1–Q3 386–1,334)] days of follow-up after the last optimization visit, digoxin use was associated with lower mortality in HF patients with AF in unadjusted analysis (HR 0.67 [0.46–0.97]). After adjustment for baseline characteristics and other HF medical therapies, the association with mortality was attenuated and no longer significant (HR 0.96 [0.65–1.42]).

Conclusion

Digoxin was infrequently used in patients with HF and AF with rapid ventricular rate but was associated with a greater decrease in heart rate and improvement in NYHA functional class. The use of digoxin appears safe and was not associated with increased mortality.
Long-term safety and efficacy of antibody ALXN2220 for depletion of cardiac amyloid transthyretin: results of treatment beyond 12 months in the open-label extension of study NI006-101
Authors: Van Der Meer P , Lairez O , Donal E , Aus Dem Siepen F , Kristen A , Damy T , Quarta C , Mercuri M , Nitsch R M , Grimm J , Rey S , Tichy M , Kahr P C , Hock C , Garcia-Pavia P
Published: October 2024

Introduction

ALXN2220 (formerly NI006) is an investigational human monoclonal antibody in development for the treatment of transthyretin-mediated amyloid cardiomyopathy (ATTR-CM). ALXN2220 is designed to deplete cardiac amyloid transthyretin (ATTR) deposits in patients with ATTR-CM on top of standard of care. Data from the first-in-human, ascending dose study NI006-101 show that ALXN2220 is safe and well tolerated. A reduction of surrogate markers of cardiac amyloid load and cardiac biomarkers was observed in participants receiving doses of ≥ 10mg/kg of ALXN2220 over a period of 12 months of treatment.

Purpose

Long-term safety, tolerability and efficacy of ALXN2220 treatment beyond 12 months was studied in a prolonged Open-Label Extension (OLE) of the NI006-101 study.

Methods

Participants completing 12 months in dose cohorts ≤ 30 mg/kg were allowed to receive additional 6 to 12 monthly open-label ALXN2220 infusions with up-titration of all participants to 30 mg/kg. Cardiac biomarkers were measured centrally, and serial cardiac imaging was performed with echocardiography and cardiac MRI or scintigraphy.

Results

Out of 27 participants completing 12 months, 23 (18 ATTRwt, all male, median age 70 years at screening (range 28-83)) continued treatment in the prolonged OLE. Median number of infusions of ALXN2220 received and median time followed across the full study were 20 infusions (range 11-24) and 125 weeks (range 83-153). Overall adherence to treatment was high in the prolonged OLE, 97% of planned infusions administered, 87% of participants received all planned doses. No severe or serious adverse events were considered related to ALXN2220 or resulted in the discontinuation during OLE, and no events of cytokine release syndrome or thrombocytopenia were observed. None of the participants had anti-drug antibodies throughout the trial. Cardiac biomarkers (NT-proBNP, troponin) and cardiac imaging indicated continued treatment effects beyond 12 months and supported the up-titration of participants who previously received lower doses of ALXN2220.

Conclusions

Up-titration and long-term treatment at a dose level of 30 mg/kg in the OLE was safe and well tolerated, with overall good adherence to treatment. Cardiac imaging and cardiac biomarker data indicated continued treatment effects beyond 12 months and supported the up-titration of patients to 30 mg/kg.
Acetazolamide for patients with acute decompensated heart failure: a systematic review and meta-analysis of randomised controlled trials
Authors: Kritya M , Lingamsetty S S P , Fatima S R , Gewehr D M , Pastrana S H , Huang W , Doma M , Naji Z , Hamdanieh M , Martignoni F V
Published: October 2024

Background

The role of acetazolamide as an adjunct to standard loop diuretic therapy in patients with acute decompensated heart failure (ADHF) remains uncertain.

Purpose

We undertook a systematic review and meta-analysis to ascertain the efficacy and safety of acetazolamide plus standard of care (SOC) in patients with ADHF.

Methods

In January 2024, we systematically searched PubMed, Embase, and Cochrane for randomised controlled trials (RCTs) comparing acetazolamide plus SOC versus SOC alone in patients with ADHF. Effective decongestion was defined as per the definition of each individual study. We pooled risk ratios (RR) and standardized mean difference (SMD) with 95% confidence intervals (CI) for binary and continuous outcomes, respectively. Statistical analyses were performed using Review Manager version 5.4.1.

Results

We included 4 RCTs comprising 634 patients, of whom 318 (50.1%) were randomised to acetazolamide plus SOC. The mean age was 77.1 years and 64.2% were male. Nearly half of the patients (n=320; 50.5%) had impaired left ventricular ejection fraction at baseline. Most patients had a New York Heart Association functional class III or higher, ranging from 75 to 91% in each study. In the pooled analysis, acetazolamide plus SOC significantly increased the proportion of patients with clinical decongestion at day 3 compared with SOC alone (RR 1.36; 95% CI 1.10 to 1.68; p=0.005; Figure 1A). There was no significant difference between groups in natriuresis at day 1 (SMD 0.46; 95% CI -0.01 to 0.94; p=0.06; Figure 1B) or worsening renal function (RR 1.71; 95% CI 0.73 to 3.98; p=0.22; Figure 1C).

Conclusion

In this meta-analysis of RCTs among patients admitted with ADHF, acetazolamide plus SOC significantly improved the proportion of patients with clinical decongestion at day 3 relative to SOC alone, without significantly affecting renal function or natriuresis.Figure 1
Effects of dapagliflozin according to QRS duration across the spectrum of LVEF: An analysis of DAPA-HF and DELIVER
Authors: Abdin A , Kondo T , Boehm M , Jhund P S , Vaduganathan M , Lam C S P , De Boer R , Kosiborod M N , Desai A S , Kober L , Ponikowski P , Martinez F A , Hernandez A , Solomon S , Mcmurray J
Published: October 2024

Aims

To document the prevalence of QRS prolongation in patients with HFrEF and HFmrEF/HFpEF, the association between QRS duration and outcomes, and the effect of dapagliflozin according to QRS duration across the spectrum of LVEF.

Methods

A pooled analysis of the DAPA-HF and DELIVER trials, excluding patients with a paced rhythm and CRT was conducted. The information collected was used to categorize patients according to QRS duration based on the cutpoints used in the CRT trials, as follows: QRS <120 ms, QRS 120-149 ms, and QRS ≥ 150 ms. The data were analyzed according to these categories and using QRS duration as a continuous variable.

Results

Overall, 4004 patients had HFrEF, and 5820 had HFmrEF/HFpEF. QRS duration (ms) was <120 in 7039 patients (71.7%), 120–149 in 1725 (17.6%), and ≥150 in 1060 patients (10.8%). The median follow-up time was 23 months. The rate of the primary composite outcome of CV death or worsening HF was 9.2 (95%CI 8.7-9.7), 14.3 (13.0-15.7), and 15.9 (14.1-17.9) per100 patient-years in the <120, 120–149, and ≥150 ms groups, respectively. This gradient in event rates was observed both in HFrEF and HFmrEF/HFpEF. Dapagliflozin, compared with placebo, reduced the risk of the primary outcome, consistently, across the QRS duration subgroups: hazard ratio (95% CI) 0.75 (0.67-0.85), 0.79 (0.65-0.96) and 0.89 (0.70-1.13) in the <120, 120–149, and ≥150 ms groups, respectively (P for interaction 0.28). The effect of dapagliflozin on the primary outcome was consistent across the QRS duration regardless of HF phenotype i.e., HFrEF or HFmrEF/HFpEF.

Conclusion

Prolongation of QRS duration is associated with worse outcomes irrespective of HF phenotype. Dapagliflozin reduced the risk of the primary outcome, regardless of QRS duration, in DAPA-HF and DELIVER.KM curves according to QRS durationEffect of dapagliflozin on outcomes
Impact of left ventricular lead position on echocardiographic response after upgrading from right to biventricular pacing - Insights from the BUDAPEST CRT Upgrade Trial
Authors: Merkely B , Merkel E D , Hatala R , Szigeti M , Behon A , Veres B , Lakatos B K , Osztheimer I , Geller L , Zima E , Molnar L , Kutyifa V , Kovacs A , Kosztin A
Published: October 2024

Introduction

Left ventricular (LV) lead position is strongly associated with the long-term outcome of patients undergoing de novo cardiac resynchronization therapy (CRT) implantation. However, data is scarce about patients who undergo upgrade CRT from right ventricular (RV) pacing.

Aims

To investigate the impact of the LV lead location on the primary outcome of heart failure (HF) hospitalization, all-cause mortality, or echocardiographic reverse remodelling in the BUDAPEST CRT Upgrade trial cohort.

Methods

Heart failure patients with reduced ejection fraction (HFrEF), with previously implanted pacemaker (PM) or implantable cardioverter defibrillator (ICD) and intermittent or permanent RV pacing, who were randomly assigned to the CRT-D arm (n=215) and those who were cross-overs from the ICD arm (n=27) were investigated. Short-axis position (anterior / posterior / lateral) of the LV lead was assessed. Primary endpoint encompassed HF hospitalization, all-cause mortality, and the end-systolic volume (ESV) decrease less than 15% from baseline to 12 months follow-up. Echocardiographic response was evaluated by percent change of ESV and LVEF.

Results

LV lead location was available for 223 patients (age 72.8 ± 8 years, 14% female, 38% diabetic, 49% with prior myocardial infarction, 30% with prior ICD) with a median follow-up time of 12.4 months. There was no difference in the occurrence of the primary endpoint by the lead positions (anterior vs. lateral OR 0.33; 95%CI 0.09-1.22, p=0.10, anterior vs. posterior OR 0.58; 95%CI 0.14-2.50, p=0.47). However, LVEF change was more pronounced in those with lateral LV lead location compared with anterior position (adjusted LVEF difference 7.43%, 95%CI 1.25 – 13.62; p=0.02), while those with posterior leads did not differ from the anterior ones (adjusted LVEF difference 3.00%, 95%CI -3.92 – 9.93; p=0.39). Decrease in ESV was also more remarkable with a lateral position as compared to the other locations (lateral vs. anterior adjusted ESV difference -0.17 mL, 95%CI -0.32 – (-0.01); p=0.03, posterior vs. anterior adjusted ESV difference -0.09 mL, 95%CI -0.26– 0.08; p=0.31).

Conclusion

Upgrade CRT results in better outcomes as compared to ICD alone; however, lateral LV lead position is associated with the most beneficial mid-term echocardiographic response as compared to other short-axis locations. This finding may translate into better clinical outcomes in the long term.
Outcomes of intra-aortic balloon pump in patients with advanced heart failure and cardiogenic shock undergoing heart transplantation
Authors: Bellini V , Fatori D , De Mateo F G , Loureiro G J F , Macatrao M F , Bernoche C , Kopel L , Lage S G
Published: October 2024

Background

Intra-aortic balloon pump (IABP) is generally used as a short-term device to maintain adequate organ perfusion in patients with cardiogenic shock (CS). However, whether IABP improves clinical outcomes as a bridge therapy for heart transplant (HTx) remains controversial.

Purpose

Evaluate the survival rate 30 days after heart transplant (HTx) in patients with advanced heart failure (HF) and CS using IABP pre transplant compared to non-IABP group.

Methods

We retrospectively analyzed consecutive patients with advanced HF and CS, admitted in the cardiac intensive care unit (ICU) of a tertiary university center, between 2009 and 2020, who underwent HTx. Study group included patients submitted to IABP implantation before HTx, and a non-IABP group submitted to HTx without left ventricular mechanical support. Propensity Score Matching was used to pair the groups according to relevant clinical covariates. The primary outcome of survival rate 30 days after HTx was estimated by the Kaplan-Meier method.

Results

326 were enrolled, 199 in IABP group and 127 in non-IABP group. For non-IABP and IABP group, respectively, the most frequent etiology was Chagas disease (29,9% and 47,2%, p=0,006) followed by idiopathic cardiomyopathy and ischemic cardiomyopathy, the majority of patients were male (63% and 61,3%, p=0,760), the mean age was 46,9 ± 14,4 and 46,5 ± 12 years (p=0,791) and mean left ventricular ejection fraction was 25,9 ± 9,5% and 23,5 ± 5,9% (p=0,010). The Simplified Acute Physiology Score 3 (SAPS 3) at ICU admission was compared in both groups, which was 36,8% ± 17,8% in non-IABP group and 32,6% ± 18,6% in IABP group (p=0,042). At 30 days after HTx, there was no statistical difference in overall survival (p=0,459) between the groups (IABP: 18,1% mortality; non-IABP: 14,2% mortality). Survival rate after HTx was also similar in patients with Chagas disease compared to the other etiologies in both study groups (IABP group: p=0,221; non-IABP group: p=0,421).

Conclusion

In patients with advanced HF and CS submitted to HTx, the survival rate 30 days after HTx was equivalent in the IABP and non-IABP groups. In patients with Chagas disease the survival was also similar compared to other etiologies in both groups.Characteristics according to groupsKaplan-Meier survival estimates
Ventricular arrhythmia characteristics after left ventricular assist device implantation
Authors: Li X , Qing P , Du J , Zou L , Zhou X T , Chen H B , Duan F J , Yu L T , Yao Y , Wang X Q , Hu S S
Published: October 2024

Background

Ventricular arrhythmia (VA) characteristics in patients with advanced heart failure (HF) and left ventricular assist devices (LVADs) are currently poorly studied.

Methods

Patients with advanced HF implanted with third-generation LVADs during 2019-2023 were enrolled, and six-month post-LVAD VA events were retrospectively analyzed. Baseline characteristics, 6-month VA events, Holter monitoring and ambulatory blood pressure were also analyzed. Post-LVAD VA events were categorized as new right bundle-branch block (RBBB) superiorly directed VA and prior VA recurrence.

Results

Fifty-four advanced HF patients (90.7% male, 50.0±13.7 years old) who underwent LVAD (CH-VAD: n=23; Evaheart2: n=10; Corheart6: n=21) were consecutively enrolled in this study. Twenty-two patients suffered post-LVAD VA events (15 new RBBB superiorly directed VA, 7 prior VA recurrence), and 94.4% of the patients were hemodynamically stable. A total of 46.3% of the patients presented with a 50% reduction in VA burden, and amiodarone use decreased from 25.9% to 16.7%. The nighttime mean arterial pressure (MAP) and maximum inferior venous cava (IVC) diameter had opposite predictive effects on the new RBBB VA, and the post-LVAD left ventricular ejection fraction (LVEF) was negatively correlated with the prior VA recurrence. Multivariate analysis revealed that a higher nighttime MAP/IVC ratio (OR 2.24, 95% CI 2.22-4.52; P=0.025) and a lower post-LVAD LVEF (OR 0.75, 95% CI 0.57-0.99; P=0.048) were independently related to the new RBBB superiorly directed VA and prior VA recurrence, respectively.

Conclusion

The overall VA burden decreased after LVAD implantation. Volume deficiency and poor post-LVAD cardiac function were associated with different VA patterns.Changes in VAs pre- and 6 monthsVA distributions of patients
A meta-analysis of the efficacy and safety of exercise-based cardiac rehabilitation in patients with left ventricular assist devices
Authors: Abuelazm M , Ibrahim A , Amin A , Khan U , Rezq H , Elbenawi H , Abdelnabi M , Shaban M , Abouzid M , Abdelazeem B
Published: October 2024

Background

Left Ventricular Assist Devices (LVADs) and heart transplantation stand out as the two well-established and effective therapeutic approaches for managing patients with advanced heart failure. Exercise-based cardiac rehabilitation (EBCR) has been demonstrated to improve functional capacity in patients with LVAD.

Purpose

We aim to assess the efficacy and safety of EBCR in patients with LVAD. Also, to compare high-intensity (HIT) versus moderate-intensity (MIT) EBCR regimens in patients with LVAD.

Methods

A systematic review and meta-analysis synthesizing evidence from randomized controlled trials (RCTs) studies obtained from PubMed, Embase Cochrane, Scopus, and WOS until January 2024. We used the fixed-effects model to report dichotomous outcomes using risk ratio (RR) and continuous outcomes using standardized mean difference (SMD) with a 95% confidence interval (CI).

Results

Six RCTs with 160 patients were included. There was no significant difference between EBCR and standard care regarding peak VO2 change [SMD: 0.24 with 95% CI (-0.14, 0.62), P= 0.21] and six-minute walk distance (6-MWD) change [SMD: 0.28 with 95% CI (-0.11, 0.66), P= 0.16]. Also, there was no significant difference between HIT and MIT exercise regarding peak VO2 change [SMD: 0.20 with 95% CI (-0.41, 0.82), P= 0.52] and 6-MWD change [SMD: 0.07 with 95% CI (-0.54, 0.69), P= 0.81]. Moreover, EBCR was associated with a significant decrease in the incidence of any adverse events when compared to usual care with [RR: 0.80 with 95% CI (0.65, 0.99), P= 0.04], while there was no significant difference between HIT and MIT exercise regarding the incidence of any adverse events [RR: 0.38 with 95% CI (0.02, 9.22), P= 0.55].

Conclusion

EBCR did not improve functional capacity in patients with LVAD, with no significant effect on peak VO2 or 6-MWD.