bluuebunny/crossref_metadata_2025 huggingface dataset:
Quality of life in patients with heart failure and improved ejection fraction: one-year follow-up with ARNI and SGLT2i
Authors: Tadic S , Ilic A , Stojsic-Milosavljevic A , Stefanovic M , Miljkovic T , Bjelobrk M , Kovacevic M , Milovancev A , Petrovic M , Popov T , Stojsic S
Published: October 2024

Introduction

A baseline Heart Failure (HF) with reduced Ejection fraction (HFrEF) <=40% that improved for >=10 points and a second measured left ventricle ejection fraction (LVEF) >40%, can be considered as HF with improved ejection fraction (HFimpEF). The novel therapy for HFrEF and HFimpEF are sacubitril/valsartan (ARNI- angiotensin receptor/neprilysin inhibitor) and Sodium-glucose cotransporter-2 inhibitors (SGLT2i).

Purpose

Our study aimed to evaluate ARNI and SGLT2i therapy on the health status of HFrEF patients, as well as the prognostic impact of HFimpEF in terms of quality of life and outcomes (mortality and rehospitalization due to HF) during a one-year follow-up.

Methods

In this prospective study, we included 376 hospitalized HFrEF patients, in whom ARNI and SGLT2i were initiated into regular therapy. A 12-item Kansas City Cardiomyopathy Questionnaire (KCCQ-12) was performed at discharge and after one year. The primary prognostic endpoints were all-cause mortality and HF rehospitalization.

Results

Initially, about two-thirds of the study population were men (71%), mean age of 61.0±11.5 years, mean LVEF 27.5±5.2 % and mean KCCQ overall summary (KCCQ-OS) score of 48.5±12.5, while quality of life KCCQ-QoL 37.4±10.2. After one year LVEF was increased by 35.6±7.1 %. The total number of 143 patients (38%) met the criteria for HFimpEF, with the improvement of mean LVEF (45.2±8.6 %., p<0.001). Overall, HFimpEF patients experienced an average 5.3 ± 18.6-point improvement in the KCCQ-OS compared with 2.5 ± 17.4 points for non-HFimpEF group (differences in mean changes of 2.9 [95% CI: 1.4 to 4.7). This is largely due to improvements in the domain of KCCQ-QoL (5.8 ± 29.7 points vs. 2.9 ± 22.2 points, respectively). During one year of follow-up, combined SGLT2i + ARNI therapy was represented statistically significantly more in HFimpEF compared to the non-HFimpEF group (86% vs. 34%, p<0.0005), where 45% took only one medicine and 21% none. The HFimpEF group had a significantly better outcome in terms of all-cause mortality (2.8% vs. 18.9%, p<0.005) and HF rehospitalization (3.5% vs. 40%, p<0.0001). The one-year KCCQ-12 was independently associated with outcomes; the hazard ratio for the integrated endpoints (mortality and HF rehospitalization) was 1.08 (95% CI: 1.05–1.11, p = 0.005).

Conclusions

In routine clinical practice, initiation of the ARNI and SGLT2i therapy was associated with significant improvements in the health status of HFrEF patients, but also change to HFimpEF. The one-year quality of life in patients with heart failure and improved ejection fraction was superior to baseline and compared to the non-HFimpEF group. HFimpEF was associated with a better outcome. All HF patients should undergo KCCQ-12 because it is an independent predictor of outcome.
Empagliflozin: unlocking new potentials in heart failure decongestion
Authors: Khan F , Jamal Khan A
Published: October 2024

Background

Managing acute heart failure (AHF) remains a formidable challenge in cardiology, primarily due to the limitations of conventional decongestive therapies. This study explores the efficacy of Empagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, in decongestion management for AHF.

Methods

Conducted in a tertiary care setting, this prospective cohort study involved 450 patients, divided equally into an Empagliflozin group and a control group receiving standard care. The study assessed changes in body weight, clinical congestion scores, hematocrit levels, and NT-proBNP levels as primary outcomes over a period of 90 days. Safety and adverse events related to Empagliflozin were also monitored.

Results

Empagliflozin led to a significant reduction in body weight (mean difference at Day 15: −1.95 kg, P<0.0001), and clinical congestion scores (mean difference at Day 15: −0.35, P=0.0050). Hematocrit levels increased significantly (mean increase at Day 15: 1.65%, P<0.0001), and NT-proBNP levels showed a more substantial decrease in the Empagliflozin group compared to the placebo. Safety profiles were consistent with previous studies, showing no significant increase in adverse events.

Conclusion

Empagliflozin demonstrates a substantial improvement in decongestion management in AHF patients, offering a promising alternative to traditional therapies. The findings indicate potential broader applications in heart failure management and support the need for updated clinical guidelines incorporating Empagliflozin as a therapeutic option in AHF.
Continuation of beta-blockers at discharge is associated with improved outcome in patients with HFpEF and concomitant moderate aortic stenosis
Authors: Shumkova M , De Oliveira E O , Hrubyak L H , Beles M B , Bertolone D T B , Ratti A R , Adeo L A , Viscusi M V , Barbato E B , Wyffels E W , Vanderheyden M V , Van Camp G V C , Herman R H , Bartunek J B , Penicka M P
Published: October 2024

Background

In patients with severe aortic stenosis or decompensated heart failure with preserved ejection fraction (HFpEF), beta-blockers are usually discontinued despite the absence of unequivocal evidence. The data on the effect of beta-blockers in patients with moderate aortic stenosis (MAS) are scarce.

Aim

To investigate the relationship between beta-blocker use and outcome in patients with MAS, who were hospitalized for decompensated HFpEF.

Methods

The current study includes 61 patients admitted for decompensated HFpEF with concomitant MAS. The mean age of the population was 82.7±7.59 years old and 41% were females. The diagnosis MAS was established on criteria including aortic valve area between 1-1.5 cm², mean gradient - 20-39 mmHg, and max velocity between 3-3.9 m/s. For those with borderline measurements, the Doppler Velocity Index (DVI) was calculated (DVI < 0.25 indicates severe aortic stenosis). All echocardiographic data were assessed by an experienced echocardiographer. Patients with previous aortic valve replacement and a severe mixed of multivalvular disease were excluded.

Result

The median follow-up was 52 months (interquartile range 34-63 months). During this period 38 patients (62.3%) died from any cause while 42 (68.9%) individuals experienced a composite endpoint, of all-cause death or hospitalization due to worsening HFpEF. In survivors, we observed higher prescription of beta-blockers at hospital discharge (66% vs. 34%, p<0,05) and better diastolic function than in patients with endpoints. In multivariate Cox regression analysis the use of beta-blockers (HR = 0,27; 95% CI 0,13-0,57; p<0.01) and better diastolic function, defined as higher septal e` (HR=0,76; 95% CI 0,61-0,94; p=0.01) were identified as independent predictors for both - survival and composite endpoint (Figure 1). Advanced age was recognized as an associated factor for outcomes.

Conclusion

In the present study, continuation of beta-blockers at discharge was independently associated with better survival in patients with decompensated HFpEF and concomitant MAS. It remains to be addressed in future studies, whether or not beta-blockers should be started in these patients or if there is any prognostic interaction between beta-blockers and aortic valve intervention for MAS.Figure 1.Kaplan-Meier survival curve
Reduced stroke volume by resting 2-dimensional echocardiography negatively affects survival in patients with abnormal ejection fraction
Authors: Ciampi Q , Cortigiani L , Zagatina A , Kasprzak J D , Wierzbowska-Drabik K , Haberka M , Djordjevic-Dikic A , Rigo F , Gaibazzi N , Pitino A , Tripepi G L , Rodriguez-Zanella H , Villari B , Pellikka P A , Picano E
Published: October 2024

Background

Abnormal (<50%) ejection fraction (EF) is a cornerstone of risk stratification and therapy, but also an imperfect proxy of left ventricular (LV) cardiac pump function, better assessed with stroke volume (SV).

Aim

To assess the value of SV in stratifying risk of patients with abnormal EF.

Methods

In a prospective, observational, multicenter study, we recruited 746 patients (age 66± 11 years, 536 males, 72%, 359 with previous myocardial infarction, 48%) with chronic coronary syndromes (CCS) and EF <50% referred for resting transthoracic echocardiography with technically successful 2-dimensional volumetric echocardiography in 17 accredited laboratories. We quantitatively assessed LV end-diastolic volume (EDV) and end-systolic volume (ESV) by Simpson’s biplane method. EF (EDV-ESV/EDV) and SV (EDV-ESV) were calculated from LV volumes. The outcome end-point was all-cause death.

Results

EF was 39±9%, SV 48±20 ml. There were 100 all-cause deaths during a median follow-up of 796 days (interquartile range 420-1286 days). Receiver-operating curve analysis identified SV≤31.4 ml/b as the best cut-off for predicting mortality. At multivariable analysis, after adjustment for age and prior myocardial infarction, EF <40% and SV ≤31.4 ml/b were significantly associated with decreased survival (HR 2.09, 95%, confidence intervals 1.09-4.01, p=0.024). The annual mortality was lowest (3.19%) in the group with mildly reduced (40-49%) EF and normal (>31.4 ml) SV, and highest (8.30%) in patients with both reduced EF and abnormal SV: see figure.

Conclusion

Patients with CCS and abnormal EF are a prognostically heterogeneous group, and the mortality rate is almost 3-times worse in patients with reduced EF and abnormal SV compared to patients with mildly reduced EF and normal SV. A simple resting volumetric two-dimensional echocardiography can offer an efficient risk stratification, beyond EF, with no extra imaging or analysis time.Figure
Comparative outcomes between empagliflozin and dapagliflozin in heart failure: real world multi-center cohort study
Authors: Bu S , Ahn H S , Jung M H , Lee D , Hwang Y M , Cho J S , Yi J E , Kim H , Kim S , Kim S H
Published: October 2024

Introduction

Heart failure (HF) is a significant global health concern, and sodium-glucose cotransporter-2 (SGLT2) inhibitors, such as dapagliflozin and empagliflozin, have emerged as important therapeutic options. However, their comparative effectiveness in a real-world population remains uncertain.

Purpose

The purpose of this multicenter, population-based cohort study was to investigate and compare the outcomes associated with dapagliflozin and empagliflozin use in patients with heart failure. We sought to understand whether these SGLT2 inhibitors had differential effects on cardiovascular events in a real-world setting.

Methods

We analysed data from a clinical data warehouse encompassing seven medical centers. Subjects diagnosed with heart failure between January 2021 and November 2023, who were prescribed dapagliflozin or empagliflozin, were included. We conducted one-to-one propensity-score matching, ensuring that the dapagliflozin and empagliflozin groups were comparable in baseline characteristics. The primary outcome was a composite of cardiovascular (CV) death or hospitalization for HF, analysed as the first event occurring after starting each medication. Secondary outcomes included individual components, all-cause death, and CV hospitalization.

Results

Propensity-score matching made a balanced cohort of 6,281 patients (3,111 in the dapagliflozin group and 3,170 in the empagliflozin group). The median follow-up duration was 16.0 months. In the propensity-score matched cohort, dapagliflozin and empagliflozin showed no significant difference in the primary outcome (8.8% versus 7.8%, hazard ratio [HR] 0.91, 95% confidence interval [CI] 0.77-1.08, p=0.276). Similar findings were observed in secondary outcomes. Subgroup analysis revealed potential benefits of empagliflozin in patients with diabetes mellitus (DM) (7.8% versus 5.6%, HR 0.73, 95% CI 0.55-0.98, p=0.039).

Conclusion

This study suggests that dapagliflozin and empagliflozin have similar clinical outcomes in the management of heart failure in a real-world setting. However, empagliflozin showed result in improving outcomes for HF patients with DM. Further research is warranted to validate these findings and guide clinical decision-making in the individualized management of heart failure.Baseline characteristicsSubgroup analysis
Effects of anakinra on patients with heart failure below and above 60 years of age
Authors: Golino M , Moroni F , Canada J , Del Buono M G , Hogwood A , Denicolai M , Van Tassell B , Abbate A
Published: October 2024

Background

Anakinra, an interleukin-1 (IL-1) blocker, is being explored in heart failure (HF) to improve cardiorespiratory fitness (CRF). CRF declines with increasing age.

Purpose

We aimed to determine the influence of anakinra on CRF in aging patients with HF.

Methods

We analyzed data from 73 patients with HF (55 [51-62] years, 37 (51%) female) treated with anakinra 100 mg subcutaneously daily. Patients were stratified into two groups according to a predetermined cut-off age of 60 years. We measured peak oxygen consumption (peak VO2) and C-reactive protein (CRP), a surrogate for IL-1 activity.

Results

We included 49 (67%) patients with age <60 years and 24 (33%) with age ≥60 years. The duration of treatment with anakinra was 4 [2-12] weeks. Age was negatively correlated with peak VO2 at baseline and during treatment with anakinra (Spearman’s Rho= -0.375, p=0.001 and Rho= -0.334, p=0.004, respectively). Younger patients had higher baseline peak VO2 (15.2 [12.4–17.7] vs 12.4 [10.3–14.3] mLO2·kg-1·min-1, p=0.001) but similar CRP (6.6 [3.6-16.6] vs 5.1 [2.7-11.2] mg/L, p=0.18). In both groups, anakinra decreased CRP (<60 years: from 6.6 [3.6–16.6] to 1.5 [0.9–3.8] mg/L, p<0.001; ≥60 years: from 5.1 [2.7–11.2] to 1.0 [0.5–3.4] mg/L, p<0.001)(Figure 1A) and increased peak VO2 (<60 years: from 15.2 [12.4–17.7] to 16.0 [14.0–18.7] mLO2·kg-1·min-1, p=0.036; ≥60 years: from 12.4 [10.3–14.3] to 13.7 [11.7–15.8] mLO2·kg-1·min-1, p<0.001)(Figure 1B). No significant differences in interval changes were observed between the groups.

Conclusions

Older patients with HF have a greater impairment in CRF than younger patients, yet they appear to benefit similarly from treatment with anakinra.Figure 1
Efficacy of sotagliflozin by diabetes duration: a secondary analysis of SCORED
Authors: Aggarwal R , Bhatt D , Szarek M , Davies M , Banks P , Pitt B , Steg G
Published: October 2024

Background

Sotagliflozin is a sodium-glucose cotransporter (SGLT) 1 and SGLT2 inhibitor. SCORED randomized patients with type 2 diabetes (DM) and high cardiovascular (CV) risk to sotagliflozin or placebo.

Purpose

We evaluated if diabetes duration affects HF and CV outcomes when comparing sotagliflozin with placebo in SCORED, as diabetes duration can modify CV risk.

Methods

SCORED enrolled patients with DM (hemoglobin A1c ≥7%), chronic kidney disease (glomerular filtration rate of 25-60 mL/minute per 1.73 m2), and CV risk factors. Patients were randomized to sotagliflozin compared with placebo.

Patients in SCORED were stratified by diabetes duration, into categories of <10 years, 10-19 years, or ≥20 years. The primary endpoint was total CV death, hospitalization for HF, or urgent visit for HF. Secondary endpoints were total hospitalization for HF or urgent visit for HF, as well as total CV death, nonfatal myocardial infarction, and nonfatal stroke (MACE).

Outcomes were assessed using marginal proportional hazard models stratified according to HF criteria and geographic region where non-CV death was a competing terminal event. Subgroup analyses were assessed with natural cubic splines of interaction between treatment and continuous diabetes duration.

Results

In SCORED, 10,579 (99.9%) of 10,584 patients had complete data on diabetes duration, with 2412 (22.8%), 4424 (41.8%), 3743 (25.9%) having diabetes duration of <10, 10-19, and ≥20 years respectively. Median (Q1, Q3) diabetes duration was 16.4 years (10.4, 22.4 years), while mean hemoglobin A1c was 8.6%, 8.7%, and 8.7% respectively by diabetes duration.

The rate of the primary endpoint was lower in the sotagliflozin group (5.6 events per 100 patient-years [p-y]) compared with the placebo group (7.5 events per 100 p-y) (HR: 0.74; 95% CI: 0.63, 0.88). Event rates among diabetes duration subgroups indicated that rates in both the placebo group and relative treatment benefit increased with increasing diabetes duration, with 5.6 vs 5.8 events per 100 p-y, 6.1 vs 7.4 events per 100 p-y, and 4.6 vs 8.5 events per 100 p-y for diabetes duration <10, 10-19, and ≥20 years respectively. Spline analysis indicated increasing treatment benefit with increasing duration when modeled continuously (Figure Panel A; PSpline=0.02). Similar findings were observed for the secondary HF outcome of hospitalization for HF or urgent visit for HF, with increased treatment benefit with duration (Figure Panel B; PSpline=0.10).

Total MACE was lower in the sotagliflozin group (4.8 events per 100 patient-years) than in the placebo group (6.3 events per 100 patient-years) (HR: 0.77; 95% CI: 0.65, 0.91), without significant difference in relative treatment benefit by duration (Figure Panel C; PSpline=0.30).

Conclusions

Sotagliflozin improved HF and MACE outcomes in patients with high CV risk, with increasing treatment benefit for HF outcomes among patients with longer diabetes duration.
Elegibility for Sacubitril/Valsartan in italian clinical practice: insights from the OPTIMA-HF registry
Authors: Paolillo S , Marzano F , Nardi E , Gargiulo P , Agostoni P , Calabro' P , Sinagra G , Indolfi C , Montisci R , Guarnaccia F , Cameli M , Brunetti N , Aloisio A , Carugo S , Perrone-Filardi P
Published: October 2024

Background/Introduction

Guidelines strongly recommend patients with heart failure with reduced ejection fraction (HFrEF) be treated with multiple medications proven to improve clinical outcomes, as tolerated. Among them, angiotensin receptor blocker/neprylisin inhibitor (ARNi) are the foundation of neuro-hormonal blockade in patients with HFrEF, however the degree to which gaps in this medication use and dosing persist in outpatient practice is unclear.

Purpose

To assess the proportion of patients with HFrEF who are eligible for ARNi based on the PARADIGM-HF trial criteria and the association between eligibility and baseline characteristics.

Methods

The OPTIMA-HF (Optimization of Therapy in the Italian Management of Heart Failure) registry included outpatients in Italy with chronic HFrEF receiving at least 1 oral medication for management of HF. Patients were characterized by baseline use and dose of angiotensin-converting enzyme inhibitor (ACEI)/angiotensin II receptor blocker (ARB)/ARNI, beta-blocker, mineralocorticoid receptor antagonist (MRA) and sodium glucose co-transporter II inhibitor (SGLT2i). Patient-level factors associated with medication use were examined.

Results

Outpatients with HFrEF from 29 ambulatory cardiology practices and university hospitals in the OPTIMA-HF registry recruited between January 2022 and September 2023 were included. Of 1291 patients, 1018 (79%) met the PARADIGM-HF criteria and 949 of them (93%) were on ARNi. Of the enrolled patients, 342 (27%) were not on ARNi, however only 129 (38%) did not met the PARADIGM-HF inclusion criteria for ARNi prescription. Reasons for not meeting PARADIGM-HF criteria were no beta-blocker background therapy (22%), hyperkalemia (4%), hypotension (15%), chronic kidney disease (65%) and hyperkalemia (79%).

In a logistic regression model not being on ARNi was associated with older age, chronic kidney disease, not being on cardiac resynchronization therapy, lower systolic blood pressure, lower BMI, and higher PAPs (Figure), representing the picture of a more fragile patient net of compliance with the PARADIGM-HF criteria.

Conclusions

Among outpatients with HFrEF in the OPTIMA-HF Registry, 79% met the PARADIGM-HF criteria. Strategies to improve guideline-directed use of HFrEF medications remain urgently needed, and these findings may inform targeted approaches to optimize outpatient medical therapy.
Right ventricular failure following left ventricular assist device implantation
Authors: Laimoud M , Maghirang M J , Hakami E , Mohamed T
Published: October 2024

Background

Left ventricular assist device (LVAD) therapy is a lifesaving option for patients with medical therapy-refractory advanced heart failure.(1) Right ventricular failure (RVF) is a cause of major morbidity and mortality after LVAD implantation.(2,3) Our objective was to get the outcomes and predictors of RVF in adult patients undergoing LVAD implantation.

Methods

This retrospective study enrolled 73 adult patients with LVAD (Heart Mate III) implantation, of them 24(32.9%) patients had RVF after LVAD implantation.

Results

The patients with RVF had statistically significant more frequencies of acute kidney injyry (p<0.001), new need for dialysis(p<0.001), RVAD insertion (p<0.001), total mortality (p=0.012) and on-VAD mortality(p=0.018) with prolonged ICU stay (p<0.001) compared to the non-RVF group respectively. The pre-LVAD pulmonary vascular resistance(PVR) ≥3 WU (OR:2.4, 95%CI: 1.52-7.38, p=0.04) and diastolic pulmonary gradient(DPG) ≥ 7 mmHg (OR:6.4,95%CI: 5.49-18.6, p<0.001) were the independent predictors of RVF after LVAD implantation. Cox proportional regression analysis revealed that RVF was associated with increased risk of death (HR:3.12,95%CI:1.42-6.85, p=0.005).

Conclusion

Early RVF post-LVAD carries significant risks of mortality and multiple morbidities. Concomitant BiVAD implantation needs to be considered in patients with elevated DPG and PVR to avoid post-LVAD RVF.The significant variables of patients.Kaplan-Meier curves of the 2 groups.
Derivation and validation of a multicenter model to identify candidates for advanced HF therapies with high potential to achieve post-LVAD reverse cardiac remodeling
Authors: Maneta E , Taleb I , Kyriakopoulos C , Psotka M , Birks E , Guglin M , Silvestry S , Mehra M , Alharethi R , Fang J , Sideris K , Karra R , Kanwar M , Shah P , Drakos S
Published: October 2024

Background

A subset of advanced heart failure (HF) patients can experience significant improvement in their cardiac structure and function while on left ventricular assist device (LVAD) support, which is among the prerequisites for LVAD weaning.

Purpose

We sought to develop and validate a predictive personalized tool to identify candidates for advanced HF therapies with a high potential to achieve significant improvement in myocardial structure and function post-LVAD. This tool can aid clinicians and patients considering advanced HF therapies options.

Methods

A total of 884 consecutive LVAD patients were enrolled. The derivation and validation cohorts included 509 patients (from three institutions) and 375 patients from another four institutions), respectively. The primary outcome was "significant reverse remodeling", defined as left ventricular ejection fraction (LVEF) ≥40% and LV end-diastolic diameter ≤6 cm within one year on LVAD support. Bootstrap imputation and LASSO variable selection were used to derive a predictive model which was externally validated.

Results

Patients were predominantly white (78%), male (80.1%), 57±14 years old. Overall, 12.8% patients were identified as responders. Four variables associated with reverse remodeling were included in the multivariable model achieving a C-statistic of 0.72 (95% CI: 0.66-0.79) in the derivation and 0.75 (95% CI: 0.67-0.84) in the validation cohort (Figure). We created a calculator for individualized prediction of the probability of cardiac recovery and when applied to the studied population, we identified patients with 0.2%-67.6% chance of significant reverse remodeling (see Figure for patient example).

Conclusions

The Multicenter Recovery Calculator is a predictive tool that provides individualized probability of significant reverse remodeling. This tool may help clinicians and patients to maximize the benefits of both heart transplant and LVAD. Specifically, it may serve to (a) improve patient selection for LVAD as bridge to recovery and (b) benefit transplant waitlist outcomes by prioritizing allocation of donor allografts to patients without a high potential for cardiac reverse remodeling.
Impact of HF etiology on the sustainability of favorable response after LVAD weaning: A VAD Wean Registry analysis
Authors: Maneta E , Kyriakopoulos C , Dranow E , Wever-Pinzon O , Cogswell R , Schultz J , Schwartzman A , Shah K , Macgowan G , Schueler S , Zimpfer D , Jorde U , Selzman C , Patel S , Drakos S
Published: October 2024

Background

A subset of heart failure (HF) patients can experience significant improvement of their cardiac structure and function while on left ventricular assist device (LVAD) support.

Purpose

We sought to investigate the impact of HF etiology on the durability of cardiac improvement and favorable outcomes after LVAD weaning.

Methods

We studied 324 HF patients enrolled in the international multicenter VAD Wean Registry who received a durable continuous-flow LVAD and underwent device support weaning (Figure 1). Indications for VAD weaning included: structural/functional cardiac improvement meeting institutional criteria for "myocardial recovery" (responders) or LVAD-related complications accompanied by variable degrees of cardiac improvement (partial responders). Patients were divided into seven categories based on HF etiology: ischemic cardiomyopathy (CM) (n=30), post-myocarditis CM (n=65), peripartum CM (n=53), valvular CM (n=12), chemotherapy-induced CM (n=14) and idiopathic CM (n=150). The primary outcome was 2-year survival free of transplant or LVAD re-implantation. The secondary outcome was the LVEF, measured by echocardiography at 3, 6, 12 and 24 months post-LVAD weaning.

Results

Patients with idiopathic, peripartum and post-myocarditis CM had higher rate of 2-year survival free of transplant or LVAD re-implantation compared to patients with chemotherapy-induced CM (Figure 2-Panel A) (p-values: 0.009, 0.004, 0.001, respectively). Patients with post-myocarditis CM were also more likely to achieve the primary outcome compared to those with ischemic CM (ICM) (p-value, 0.009). The LVEF changes over time are depicted in the Figure 2-Panel B.

Conclusions

In this multicenter analysis the etiology of HF appears to impact the durability of favorable response after LVAD weaning. The degree of reverse remodeling achieved before VAD weaning and its impact on the durability of response in different HF etiologies warrants further investigation in studies with larger patient population and power.
Impact of digoxin on gastrointestinal bleeding following left ventricular assist device implantation: a systematic review and meta-analysis
Authors: Rahhal A , Habib M B , Alani H , Chapra A , Mahfouz A , Alyafei S , Carr C , Alkhulaifi A , Omar A
Published: October 2024

Introduction

Gastrointestinal bleeding (GIB) is a common complication post Left Ventricular Assist Device (LVAD) implantation for patients with advanced heart failure. Recent observational evidence suggested a potential association of digoxin use and GIB reduction post LVAD; however, the proposed benefit remains uncertain. Therefore, we conducted a systematic review and meta-analysis to assess the impact of digoxin use on GIB post LVAD.

Methods

We performed a systematic review and meta-analysis following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We searched PubMed and EMBASE for the studies published in English exploring GIB with chronic digoxin use following LVAD implantation, till 15/01/2024. Two independent reviewers assessed the quality and risk of bias of the included studies. A random-effect model was used to combine data. The primary outcome was all-cause GIB associated with digoxin use in comparison to non-digoxin use. Heterogeneity was assessed using Q test and I2, with I2 > 50% indicating marked heterogeneity.

Results

A total of three peer-reviewed observational studies (n= 14277) were included in the analysis of the primary outcome. More than 50% of patients received ACE inhibitors/angiotensin receptor blockers. Digoxin use post LVAD was associated with similar GIB incidence in comparison to non-digoxin use (Odds Ratio [OR]= 0.61; 95% CI, 0.33-1.14, I2= 81%, P=0.12), as shown in Figure 1. Interestingly, one study of 199 recipients of LVAD reported significantly lower gastrointestinal angiodysplasia-induced GIB with digoxin use (3% versus 13%, P=0.039).

Conclusion

Among patients with advanced HF requiring LVAD implantation, the use of digoxin demonstrated similar effectiveness of GIB prevention compared to non-digoxin use. Future studies needed to explore the potential use of digoxin for gastrointestinal angiodysplasia-induced GIB.Figure 1.Forest plot of gastrointestina
Comparative analysis of multi-organ failure trajectories reflected by the MELD-3.0 following heart transplantation and heartmate 3 implantation
Authors: Ptak J , Sokolski M , Przybylski R , Cielecka M , Boluk A , Bochenek M , Byszuk P , Wisniewski K , Waloszczyk M , Makiela M , Szwajkowski M , Gontarczyk J , Mania R , Zakliczynski M
Published: October 2024

Background

Multi-organ failure (MOF) frequently complicates advanced heart failure (HF), substantially impacting patient prognosis. The Model of End-Stage Liver Disease 3.0 (MELD-3.0) scale, encompassing liver and kidney function parameters, is a valuable tool for assessing the severity of organ dysfunction.

Purpose

This study aims to elucidate the trajectory of MOF in individuals undergoing either heart transplantation (HTx) or left ventricular assist device (LVAD) - HeartMate 3 implantation, utilizing the MELD-3.0 scale, over a 1-year follow-up period.

Methods

A comprehensive analysis was conducted, examining data from 1 month preceding to 1 year subsequent to the HTx or LVAD implantation. The MELD-3.0 score was calculated using the average values of international normalized ratio, bilirubin, creatinine, sodium, and albumin levels during this timeframe. Comparative assessments of the average MELD-3.0 scores were performed between the HTx and LVAD groups at 1 month pre-procedure, as well as at 1 week, 1 month, 3 months, 6 months, and 1 year post-procedure.

Results

The analysis included 107 patients undergoing HTx and 31 patients undergoing HMi, with a median age of 54 years (47-62), 85% were male. There was no difference in MELD-3.0 between HTx and LVAD patients in the pre-procedure period: 12.3 (7.3-15.9) vs 13.1 (7.7-16.6), p=0.95. There was also no difference in MELD-3.0 at 1 week and 1 month post-procedure. However, in the 3rd month, the difference gained statistical significance: 7.3 (4.6-9.4) vs 13.8 (11.5-19.7), p<0.01 and continued to be significant in the next follow-ups: 12-month 5.4 (3.1-10.2) vs 11.1 (6.7—15.1), p<0.01, comparing respectively HTx vs LVAD. In both groups of patients, a significant decrease in MELD-3.0 score from 3-month follow-up when compared to 1 month preceding the procedure was observed. Within 12 months post-procedure, 30 patients (22%) died (19 in HTx group and 11 in LVAD group), 8 LVAD patients (26%) had HTx.

Conclusion

The utilization of the MELD-3.0 scale reveals significant differences in the trajectory of multi-organ failure between HTx and LVAD patients. Both forms of advanced HF therapy result in an improvement of liver and kidney condition, while HTx patients' benefits are larger and last longer, highlighting the distinct impacts of this intervention on organ function.MELD 3.0 score in time
Electrical heart failure treatment in the Goldilocks zone: cardiac contractility modulation proves equally effective for heart failure control in HFrEF patients with mid-range QRS durations
Authors: Fastner C , Varma N , Rao I , Falk P , Remppis B A , Cranke G , Najarian K , Kane T , Burkhoff D , Akin I , Kuschyk J
Published: October 2024

Background

Current guidelines recommend a four pillar therapy for heart failure with reduced ejection fraction (HFrEF). A subgroup of patients, namely those with a QRS duration (QRSd) ≥150 ms, may also qualify for cardiac resynchronization therapy. However, a 30% CRT non-responder rate persists, with patients with narrower QRSd (i.e., QRSd <150 ms) and non-left bundle branch block receiving less benefit. At present, cardiac contractility modulation (CCM) has only been established in patients with QRSd <120 ms. Given these limitations, new options for additional device therapy are urgently sought for those patients who face drug-refractory HFrEF and with intermediate QRSd of 120-149 ms.

Purpose

Primarily to evaluate the impact of CCM on HF-related hospitalizations and secondarily on left ventricular EF (LVEF) as well as quality of life (by Minnesota Living with Heart Failure Questionnaire (MLWHF) score and New York Heart Association (NYHA) class) in a real-world population of HFrEF patients with QRSd 120-149 ms, compared to QRSd <120 ms.

Methods

CCM-REG enrolled 503 HF patients receiving CCM with a follow-up of up to 2 yrs. HF-related hospitalization rates were available for 1 yr pre-implant. Safety was assessed by comparison of actual versus MAGGIC score predicted mortality.

Results

455 patients were studied for these analyses. Among 111 subjects with QRSd 120-149 ms (mean QRSd 130±8 ms, age 68±10 yrs, 20% female, LVEF 29±9%, 82% NYHA class III), CCM diminished HF-related hospitalization rate by 72% (pre- vs. post-implant 0.90 vs. 0.25 events/per patient-yr over 2 yrs; p<0.001; Figure). LVEF improved by 7±8% (p=0.01 vs. baseline), MLWHFQ score by 10±23 pts (p=0.01 vs. baseline), and NYHA class by 0.5±0.7 classes (<0.001 vs. baseline). The effect size was similar to that in the QRSd <120 ms patients. Mortality within first year was 19% in QRSd 120-149 ms patients and thus not significantly different from the MAGGIC score prediction.

Conclusions

CCM significantly improved HF control in symptomatic HFrEF patients with moderately prolonged QRSd 120-149 ms. The effect was similar to patients with QRSd <120ms.Reduction in hospitalization rates
One-year prognostic value of right ventricular to pulmonary arterial coupling in patients hospitalized for acute coronary syndrome: insights from the ADDICT-ICCU study
Authors: Nogarede C , El-Beze N , Schurtz G , Dib J C , Delmas C , Bouleti C , Roule V , Boccara A , Trimaille A , Boccara F , Toupin S , Dillinger J G , Henry P , Pezel T , Fauvel C
Published: October 2024

Background

Tricuspid annular plane systolic excursion over systolic pulmonary artery pressure (TAPSE/sPAP) assessed by echocardiography is a good non-invasive approach for right ventricular to pulmonary artery (RV-PA) coupling assessment. Although the prognostic value of this ratio is well known in many cardiovascular diseases, its prognostic value in acute coronary syndrome (ACS) is not established.

Purpose

To assess one-year prognostic value of TAPSE/sPAP among patients hospitalised for ACS.

Methods

In the prospective multicentric ADDICT-ICCU study, all consecutive patients hospitalized for ACS (either Non ST-Elevation Myocardial Infarction or ST-Elevation Myocardial Infarction) over two weeks in April 2021 at 39 centres across France were included. The TAPSE/sPAP ratio was measured using the first echocardiography performed within the first 24 hours of hospitalisation. The primary composite outcome was one-year major adverse cardiovascular event (MACE) including: all-cause death or urgent hospitalisation for acute cardiovascular reason (acute heart failure, urgent myocardial revascularisation). C-tree analysis was used to find the optimal TAPSE/sPAP cut-off to predict the primary outcome.

Results

Among the 772 ACS patients (age 64±12 years, 74% males) included, 113 (15%) experienced 1-year MACE. The best cut-off for TAPSE/sPAP to predict 1-year MACE was 0.67 mm/mmHg. Patients with TAPSE/sPAP ≤0.67 mm/mmHg were more likely older (p<0.001), with previous atrial fibrillation (p<0.001), a higher length of hospitalization in ICCU (p<0.001), a higher NTproBNP (p=0.001) and a worse LVEF value (p<0.001). At one-year, all-cause death occurred in 27 (14%) patients with TAPSE/sPAP ≤0.67, compared to 7 (2.5%) with TAPSE/sPAP>0.67 (p<0.001), and 32 (16%) patients with TAPSE/sPAP ≤0.67 were hospitalised for acute cardiovascular reason against 20 (7%) with TAPSE/sPAP >0.67 (p=0.006). After adjustment for all traditional prognosticators, TAPSE/sPAP <0.67 mm/mmHg remained independently associated with the primary outcome (Table1): model 1 (comorbidities): HR 2.82, 95%CI[2.92-4.38], p<0.001, model 2 (echocardiography): HR=2.38, 95%CI [1,40-4,03], p<0.001). Patients with TAPSE/sPAP ≤0.67 mm/mmHg had worse event-free survival for the primary outcome: HR=2.92, 95%CI[1.98-4.29], p<0.001).

Conclusion

TAPSE/sPAP, a noninvasive approach for RV-PA coupling, was independently associated with 1-year MACE in patients hospitalised for ACS, even after adjustment with traditional prognosticators, including LVEF.Fig2.Multivariable Cox analysis
The impact of exogenous ketone body suppletion on energy and pH balance in skeletal muscle during exercise in chronic heart failure patients: a prospective randomized double-blind cross-over study
Authors: Voorrips S N , Jeneson J A L , Renken R J , Vijver M A T , Sibeijn-Kuiper A J , Zijlstra S N , Van Veldhuisen D J , Van Der Meer P , Westenbrink B D
Published: October 2024

Background

Heart Failure (HF) is characterized by impediments in exercise capacity. Disruptions in the energy metabolism of skeletal muscle contribute to this condition. Pre-clinical and clinical evidence showed that reductions in carbohydrate and FA metabolism in HF may be partially overcome by a compensatory increase in ketone body oxidation and suggest that suppletion of ketone bodies (KB) may improve energy metabolism in HF.

Purpose

We tested the effect of exogenous KB suppletion on energy and pH balance during cycling exercise using 31P Magnetic Resonance (MR) Spectroscopy of the exercising quadriceps muscle in patients with HF.

Methods

In a randomized, double-blind, placebo-controlled cross-over study, 14 stable HF patients with reduced ejection fraction and diminished exercise capacity underwent maximal exercise testing in a MR scanner fitted with a cycling ergometer after KB or placebo treatment. Phosphocreatine (PCr) and inorganic phosphate (Pi) resonance amplitudes and frequencies were measured continuously in the quadriceps muscle during rest, exercise and recovery using in-vivo 31P MR spectroscopy (Figure 1).

Results

Patients had a median age of 66 [53 – 75] years, were 14% female, had a median LVEF of 37% [27 – 40] and circulating NT-pro BNP levels of 411 [182 – 946] pg/mL. Peak oxygen uptake (VO2) was 18.2 [15.2 – 20.3] ml/kg/min, which is 68% [62 – 78%] of predicted. After treatment, exercise performance in terms of cycling duration and workload were comparable between treatment arms (Figure 2). Quadriceps acidification during exercise was larger after KB suppletion compared to placebo (ΔpH: -0.2 [-0.3 - -0.1] vs -0.1 [-0.3 - -0.1] respectively; p=0.041) while quadriceps energy depletion during exercise was not altered by treatment (ΔPi/PCr 0.77 [0.55 – 2.51] vs 0.66 [0.46 – 0.81] respectively; p=0.087). Post-exercise mitochondrial oxidative function was similar between treatment arms (KB: PCr resynthesis rate 48 sec [25 – 59] versus placebo: 42 sec [36 – 63]; p=0.767).

Conclusions

Ketone body suppletion increased acidification and did not improve energy balance in skeletal muscle during exercise or mitochondrial function during recovery in patients with chronic HF. These results question the value of ketone bodies as treatment to boost muscular energy metabolism during exercise in HF.31P MRS Spectrum during exercise in HFExercise and energy parameters
Effect of baseline and one-year follow-up anemia status on long-term clinical outcomes in patients with heart failure
Authors: Kim H J , Kim M A
Published: October 2024

Background

Anemia is a significant comorbidity in heart failure (HF), influencing patient prognosis and quality of life. In patients with HF, fluctuations in anemia status can markedly impact long-term outcomes.

Purpose

The aim of this study was to evaluate the long-term prognosis of HF patients according to change in anemia status at the baseline and one-year follow-up.

Methods

Data were obtained from a multicenter cohort of patients hospitalized for acute heart failure (AHF) from 10 tertiary university hospitals between March 2011 to February 2014. Out of 5,625 AHF patients, the study population was consisted of 1,798 patients with available data on hemoglobin levels at baseline and one-year follow-up. Anemia is defined as hemoglobin levels below 13 g/dL for men and 12 g/dL for women. These patients were then categorized into four groups: group ‘anemia to anemia’; group 2 ‘no-anemia to anemia’; group 3 ‘anemia to no-anemia’; group4 ‘no-anemia to no-anemia’. Primary outcome was the composite incidence of cardiac death or HF readmission.

Results

Among 1,798 patients, 718 patients (39.9%) died during follow-up (mean 1169.1 ± 880.7 days, median 1057.5 days) and 816 patients (45.4%) developed primary outcome. The patients with baseline anemia had a worse clinical profile than those without anemia. The development of primary outcome tended to significantly decrease from group 1 to group 4 (55.6% vs. 48.1% vs. 40.2% vs. 36.3%, p for trend <0.001). In addition, the incidence of all-cause death, cardiac death, readmission due to cardiac cause, and HF readmission also tended to decrease significantly toward group 4. The cumulative cardiac death or HF readmission free survival rate showed significantly lowest in the group 1 (log-rank p-value < 0.001), and the survival rate increased from Group 1 to Group 4 (Figure). After adjusting for confounding factors, Cox regression analysis showed that anemia to anemia group was independently associated with a 1.368-fold increased risk of primary outcome compared to no-anemia to no-anemia group during follow-up (Hazard ratio [HR] 1.368, 95% confidence interval [CI] 1.110-1.701, p = 0.005). No-anemia to anemia group had also a 1.376-fold increased risk of primary outcome (HR 1.376, 95% CI 1.043-1.814, p = 0.024) compared with no-anemia to no-anemia group.

Conclusions

In conclusion, the risk of adverse clinical outcomes including cardiac death and HF readmission increased progressively in groups transitioning from no-anemia to anemia or consistently remaining anemic in AHF patients. Conversely, those who improved from anemia to non-anemia or remained non-anemic exhibited a decreased risk, highlighting the critical role of anemia status as a determinant of long-term prognosis. Clinicians should actively manage and monitor anemia as an essential component of treatment strategies to improve long-term outcomes in patients with HF.Kaplan-Meier Survival curve
Eicosanoids in coronary sinus negatively correlate with natriuretic peptides in heart failure with reduced ejection fraction: insights from Eicosanoids in Human Heart Failure Study
Authors: Kala P , Hnat T , Mikula J , Jezdikova K , Honek J , Kotaska K , Ostadal P
Published: October 2024

Background

The diagnostic and therapeutic potential of eicosanoids, metabolites of arachidonic acid with positive cardio-renal activity in preclinical heart failure models, remains unclear in human chronic heart failure with reduced ejection fraction (HFrEF).

Purpose

The aim of this part of a traslational Eicosanoids in Human Heart Failure Study was to investigate levels of eicosanoids in different body compartments and their relation to natriuretic peptides.

Methods

Eleven consecutive patients with HFrEF indicated to cardiac resynchronisation therapy (CRT) were enrolled to measure plasmatic 14,15-epoxyeicosatrienoic acid (14,15-EET) and 14,15-dihydroxyicosatrienoic acid (14,15-DHET) levels from venous, arterial, and coronary sinus (CS) blood samples and correlate them with N-terminal pro B-type natriuretic peptide (NT-proBNP) from the same compartments.

Results

In CS, NT-proBNP levels negatively correlated with plasmatic 14,15-EET levels (r = -0.63, p = 0.03) and positively with the DHET/EET ratio (r = 0.73, p = 0.02). This correlation was not found in the other compartments. Plasmatic 14,15-EET nor 14,15-DHET levels in measured compartments did not differ statistically (p = 0.21, p = 0,64, respectively). In individual patients, the levels of both eicosanoids correlated across all compartments. Peripheral plasma 14,15-EET levels in controls were lower compared to HF patients.

Conclusion

Peripheral venous eicosanoid (14,15-EET, 14,15-DHET) levels correlate and do not differ from arterial and CS levels in patients with HFrEF indicated to CRT. In CS, NT-proBNP levels negatively correlated with plasmatic 14,15-EET levels and positively with the DHET/EET ratio, an indirect soluble epoxide hydrolase activity parameter.Graphical AbstractFigures
The dynamics of urine sodium concentration after intra-venous furosemide in patients with acute heart failure
Authors: Fujimoto Y , Kitai T , Nasu T , Matsumoto S , Naruse Y , Hioki H , Shimizu M , Yonetsu T , Horiuchi Y , Matsue Y
Published: October 2024

Background

The urine sodium concentration measured at 2 hours after the administration of intravenous (IV) furosemide in patients with acute heart failure (AHF) is recommended as a marker to assess the responsiveness to IV furosemide. However, little is known regarding the dynamics of natriuresis in the very acute phase after IV furosemide and its association with prognosis in patients with AHF.

Purpose

The aim of this study is to investigate the dynamics of natriuresis in the very acute phase after IV furosemide and its prognostic implication in patients with AHF.

Methods

DIURESIS-AHF (Diuretic Resistance Measured by Sodium Excretion and Urine Output in Acute Heart Failure) is a multicenter, prospective, and observational study that evaluated the urine samples at the time of 0h, 1h, 2h, 6h, and 24h after the first administration of IV furosemide in hospitalized patients with AHF.

Results

After excluding 20 patients who needed additional IV furosemide within the first 6 hours, and 9 patients with missing data about 1h-spot urine sample, 84 patients with AHF (79±8 years, 55% men) were analyzed. Median N-terminal pro-brain natriuretic peptide levels at admission were 4722 [interquartile: 2616-8095] pg/mL, and median first IV furosemide doses were 20 [interquartile:20-20] mg. 29 combined event of all-cause death and heart failure rehospitalization were observed during a 1-year follow-up after registration. Urine sodium concentration corrected for urine creatinine concentration peaked 1 hour and decreased at 2 hours after IV furosemide. Kaplan-Meier curve analysis indicated that 1h urine sodium concentration below 50 mEq/L was significantly associated with a high incidence of composite endpoint (Log-rank P=0.033), and this association was retained even after adjusting for age and sex (hazard ratio, 2.37 [95% CI, 1.03-5.45]; P=0.042), but 2h urine sodium below 50 mEq/L was not associated with a poor prognosis (Log-rank; P=0.630).

Conclusions

Urinary sodium excretion after IV furosemide administration peaked at 1 hour after IV furosemide and decreased at 2 hours in patients with AHF. The urine sodium concentration below 50 mEq/L at 1 hour, but not 2 hours, was associated with adverse events.Urine Na trajectoriesKaplan Meier curves