bluuebunny/crossref_metadata_2025_split huggingface dataset:
Treatment strategy for heart failure patients with guideline-directed medical therapy intolerance: a real-world prospective study
Authors: Chen J L , Gao L , Zhang D Y 
Published: October 2024

Abstract

Background
Guideline-directed medical therapy (GDMT) reduces the incidence of worsening events in patients with heart failure (HF) with reduced ejection fraction (HFrEF). However, in actual clinical practice, a proportion of patients are unable to tolerate complete GDMT.

Purpose
This study aimed to assess the medication strategy for patients with HFrEF who are intolerant to GDMT.

Methods
A total of 110 patients admitted with acute HF were included in the study. The patients were non-randomly assigned to receive complete or incomplete GDMT after assessment by doctors before discharge from the hospital. All patients were followed up for 180 days. The primary composite endpoint was worsening HF-associated events, including death or rehospitalization due to HF, and the need for intravenous diuretic therapy. The secondary endpoints were the New York Heart Association functional class, blood pressure, and cardiac structure and function assessed by echocardiography.

Results
The main reasons for GDMT intolerance were renal insufficiency (41.8%) and hypotension (26.4%). GDMT-intolerant patients had lower eGFR (50.4 ml/min/1.73 m² vs. 70.9 ml/min/1.73 m²; p=0.002) compared with those who tolerated GDMT, and included more patients with chronic kidney disease (56.4% vs. 23.6%, p&lt;0.001) and higher NT-proBNP levels (5340 pg/ml vs 8080 pg/ml, p=0.039) at baseline. While patient mortality was similar between the two groups, the rate of worsening HF events was lower in patients with GDMT (hazard ratio: 0.736; 95% confidence interval: 0.389−1.393) and vericiguat treatment (p&lt;0.001). In terms of the secondary endpoint, patients who received GDMT showed greater improvements in cardiac structure and function although there was no statistical difference between the groups. In the prespecified subgroup analysis of the effects of vericiguat on the primary endpoint, the incidence of worsening HF events was reduced by vericiguat, regardless of whether the patient was comorbid with GDMT or not, or whether they had a previous history of HF (p-interaction= 0.519 and 0.227, respectively).

Conclusions
Patients with early in-hospital initiation of complete GDMT and continuous GDMT after discharge had better outcomes compared with patients who were intolerant to GDMT. Co-administration of vericiguat with or without GDMT may reduce the incidence of worsening HF events in HF patients within 180 days.Results of the primary endpoint
Serial changes of 99mTc- pyrophosphate uptake in patients with hereditary transthyretin amyloid cardiomyopathy treated with tafamidis
Authors: Yu A , Chen Y , Tsai C , Chao C , Su M , Chou C , Shun C , Hsueh H , Juang J , Lee M , Tseng P , Hsieh S , Lin Y , Cheng M 
Published: October 2024

Abstract

Objective
Transthyretin amyloid cardiomyopathy (ATTR-CM) arises from the deposition of amyloid in the heart, resulting in adverse outcomes. Tafamidis has demonstrated potential in slowing disease progression. Our research group, alongside others, has documented cases where decrease in cardiac tracer uptake were observed through bone scintigraphy after tafamidis treatment.[1-8] This study aims to assess the efficacy of Technetium-99m (99mTc)-pyrophosphate (PYP) scintigraphy in longitudinally monitoring tafamidis treatment for hereditary ATTR-CM over an extended follow-up period.

Methods
We retrospectively analyzed a prospective cohort of hereditary ATTR-CM patients treated with tafamidis (61 mg/day) retrospectively. A control group comprised hereditary ATTR-CM patients who hadn't received eplontersen, inotersen, tafamidis, or patisiran. 99mTc-PYP SPECT/CT scans were conducted at baseline and 1-3 years post-treatment, measuring visual score, planar heart to contralateral lung (H/CL) ratio, and volumetric heart to lung (H/L) ratio.

Results
Twenty hATTR-CM patients received tafamidis, with the other ten in the control group. After a 2-year follow-up, the tafamidis group experienced a significant decrease in volumetric heart to lung (H/L) ratio (3.817 to 3.011, p &lt; 0.001), while the control group showed no significant change (3.775 to 3.621, p = 0.121)(Figure 1B). Significant decreases in volumetric H/L ratio were noted in the first year of tafamidis treatment (-21.71%), with minimal changes in the subsequent two years (-0.77% in the second year and -2.41% in the third year)(Figure 2B).

Conclusion
A significant initial reduction in 99mTc-PYP uptake was observed in hereditary ATTR-CM patients during the first year of tafamidis treatment. However, this effect was not sustained in the subsequent two years. Further investigation is warranted to comprehend the long-term efficacy of tafamidis in these patients.Changes in 99mTc-PYP uptake at 2 yearsChanges between 1st, 2nd and 3rd year
A newly developed small-molecule ErbB4 agonist reduces reactive cardiac fibrosis and adverse ventricular remodelling after myocardial infarction in a sex-specific manner
Authors: Goovaerts B , Civati C , Feyen E , De Keulenaer G W , Segers V F M 
Published: October 2024

Abstract

Background
The beneficial effects of the neuregulin/ErbB pathway on the diseased heart have been well-established. The anti-fibrotic and cardioprotective aspects of neuregulin are largely attributable to the activation of the ErbB4 receptor. We recently developed a small-molecule selective ErbB4 agonist, which reduced collagen production in cultured fibroblasts and prevented oxidative-stress induced cardiomyocyte death in vitro.

Purpose
In order to evaluate the in vivo effects of this small-molecule ErbB4 agonist (referred to as compound, Cpd), we assessed its effect on left ventricular remodelling, cardiac fibrosis and cardiac function in a murine model of myocardial infarction (MI). Since there is a potential interaction between ErbB4 and the oestrogen receptor, we also aimed to evaluate whether these effects were sex-dependent. We hypothesised that Cpd would attenuate left ventricular remodelling, reduce cardiac fibrosis and help retain cardiac function in a sex-specific manner.

Methods
Mice were divided by sex and then further divided into three experimental groups: a sham group, an MI group receiving Cpd (MI/Cpd), and a control MI group receiving vehicle only (MI/Veh). MI was induced by ligating the left descending coronary artery. Seven days after MI, mice started treatment with either Cpd (2mg/kg/d) or its vehicle through subcutaneous osmotic minipumps. Cardiac ultrasound was performed weekly until mice were sacrificed after four weeks of treatment. Hearts were excised and stained with Masson’s trichrome to assess reactive cardiac fibrosis in the myocardium of the left ventricle, located remote from the infarction scar. A WGA-isolectinB4-DAPI immunofluorescent stain was performed to assess cardiomyocyte cross-sectional area in order to evaluate cardiomyocyte hypertrophy.

Results
In females (n=25), Cpd significantly decreased left ventricular end-diastolic volume compared to vehicle (LVEDV, Fig.1A, 80±23 µl vs.108±29 µl, p=0.045) and induced a slightly increased left ventricular ejection fraction (LVEF, Fig.1B, 32±12% vs. 22±9%, p=0.086). In addition, Cpd significantly reduced reactive interstitial fibrosis myocardium (Fig.1C, fibrotic area, 1.4±1.0% vs. vehicle: 3.8±3.1%, p=0.0363). In males (n=30), Cpd had no significant effects on either of the parameters mentioned above, (Fig.1E-G). There was no significant treatment effect in either group on cardiomyocyte cross sectional area (Fig.1D, Fig.1H).

Conclusion
Treatment with the novel small-molecule ErbB4 agonist attenuates left ventricular dilation and reactive interstitial fibrosis after MI in female mice, but not in males. These data support the premise that small molecule-induced ErbB4 activation is a potential new therapy for heart failure, especially in female patients. The mechanisms underlying the sex-dependent effects warrant further exploration.Figure 1
Beta-blocker use and outcomes in patients with heart failure and mildly reduced and preserved ejection fraction
Authors: Matsumoto S , Henderson A D , Boer R A D , Lam C S P , Martinez F A , Packer M , Redfield M M , Rouleau J L , Veldhuisen D J V , Vaduganathan M , Zannad F , Zile M R , Jhund P S , Solomon S D , Mcmurray J J V 
Published: October 2024

Abstract

Background
Concerns have been raised about the appropriateness of use and safety of beta-blockers (BBs) in patients with heart failure and mildly reduced (HFmrEF) and preserved ejection fraction (HFpEF). However, randomized trial evidence is still lacking.

Purpose
To perform an observational analysis of the association between BB use and clinical outcomes in a large dataset of patients with HFmrEF and HFpEF.

Methods
We pooled individual patient data from four large HFmrEF/HFpEF trials (I-Preserve, TOPCAT, PARAGON-HF, and DELIVER). The associations between baseline BB use and outcomes were analyzed. The primary outcome was the composite of cardiovascular death or HF hospitalization.

Results
Among the 16,951 patients included, the mean left ventricular ejection fraction (LVEF) was 56.8%, and 13,400 (79.1%) had HFpEF (LVEF ≥50%). Overall, 12,812 patients (75.6%) received a BB. The median bisoprolol-equivalent dose of BB was 5.0 (Q1-Q3: 2.5-5.0) mg with BB continuation rates of 95.1% at 1 year and 93.1% at 2 years (in patients who survived more than 1 and 2 years, respectively). Overall, the hazard ratio (HR) for the primary outcome did not differ between BB users and non-users (HR: 0.98 [95% CI: 0.91-1.05]) but among patients with HFmrEF, BB users had a lower HR (0.84 [95% CI 0.71-0.98]), whereas in HFpEF the HR was similar BB users and non-users (0.99 [95% CI 0.92-1.08]). However, after comprehensive adjustment for known prognostic variables, including NT-proBNP, BB use was associated with a better outcome in the overall cohort (HR 0.81 [0.74-0.88]), and this association was maintained across the range of LVEF (Figure 1). In subgroup analyses, the risk of the primary outcome was similar in BB users and non-users with or without a history of myocardial infarction, with or without a history of hypertension, or with or without a baseline heart rate &lt;70 bpm. By contrast, a better outcome with BB use was seen in patients with atrial fibrillation compared to those without atrial fibrillation (Figure 2).

Conclusions
Although this is an observational analysis of non-randomized treatment, there was no suggestion that BB use was associated with worse HF outcomes even after extensive adjustment for other prognostic variables.
Figure Legends
Figure 1. Association between beta-blocker use and outcomes across the range of LVEF. Risk in beta-blocker users versus non-users is shown as an adjusted continuous hazard ratio
Figure 2. Association between beta-blocker use and non-use in the overall population and clinically relevant patient subgroups, shown as an adjusted hazard ratio (HR). The outcome analyzed was the composite of CV death or HF hospitalization (primary outcome)Figure 1Figure 2
Long-term follow-up of the TRED-HF trial
Authors: Cheng L , Hammersley D , Ragavan A , Javed S , Mukhopadhyay S , Gregson J , Han J , Ware J , Tayal U , Pennell D J , Cleland J G F , Prasad S K , Halliday B P 
Published: October 2024

Abstract

Background
The TRED-HF trial (1) found that 44% of patients with recovered dilated cardiomyopathy (DCM) relapsed in the short term after withdrawal of medical therapy. The longer-term risk of relapse is uncertain.

Purpose
This follow-up aims to investigate the longer-term risk of relapse in patients with recovered DCM and any possible predictive factors.

Methods
TRED-HF trial participants were followed until May 2023. The primary outcome was DCM relapse defined as &gt;10% reduction in left ventricular (LV) ejection fraction to &lt;50%, doubling in N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) to &gt;400ng/L, or clinical recurrence of heart failure (HF). Therapy intensity for HF was calculated using QUAD scores. The incidence of relapse was calculated using Kaplan-Meier estimates. Predictors of relapse were investigated using Cox proportional hazard modelling.

Results
For all fifty-one patients, median follow-up from enrolment was 6 (IQR: 6-7) years. Overall, thirty-three patients (65%) relapsed with an estimated 5-year relapse rate of 61% (95% CI 45-73). Twenty patients relapsed during the randomised trial, nine of whom had a recurrent relapse during follow-up (Figure 1). Thirteen patients relapsed for the first time after completion of the trial; of those, one patient did not have therapy withdrawn during the trial, 8 had restarted low intensity HF therapy and 4 patients stayed on no therapy. Five patients stayed off HF therapy and did not relapse. The overall mean intensity of HF therapy was lower after the trial compared to enrolment (mean difference in QUAD score -6 [-8 to -4]; p&lt;0.001). A mean reduction in medication intensity was also seen at the point of relapse during the trial and during follow-up (Figure 2). Of relapses during follow-up, seven had identifiable triggers (arrhythmia (n=4), pregnancy (n=1), hypertension (n=1), infection (n=1)). Patients taking more HF medications at baseline or with higher baseline NT-pro-BNP were more likely to relapse. Corrected atrial fibrillation was associated with reduced future risk of relapse.

Conclusions
In patients with recovered DCM, the risk of relapse after therapy withdrawal increased with longer follow-up. Lower doses of HF medications and recurrent external triggers contributed to relapse. Few patients who stopped medications had sustained remission. Recovery of DCM after correction of AF was associated with a low risk of relapse provided atrial fibrillation did not recur.
Interplay between strain pattern-based classification of dyssynchrony and myocardial scar in CRT patients
Authors: Duchenne J , Calle S , Larsen C K , Devos D , Aalen J , Galli E , Mirea O , Puvrez A , Penicka M , Bogaert J , Donal E , Hopp E , Smiseth O A , Timmermans F , Voigt J U 
Published: October 2024

Abstract

Introduction
Echocardiography-derived septal strain patterns are valuable for predicting volumetric reverse remodelling and survival in patients undergoing cardiac resynchronization therapy (CRT). Nevertheless, presence of myocardial scarring in the left ventricle (LV) is known to attenuate CRT treatment response.

Purpose
This study aims to investigate the interplay between septal strain patterns and myocardial scarring in CRT candidates, and how they link to outcome after CRT.

Methods
In this prospective multicentre study, CRT candidates from five European institutions underwent pre-implantation assessments using speckle-tracking strain analysis on echocardiography and cardiac magnetic resonance imaging (CMR) with late gadolinium enhancement (LGE). Dyssynchrony was graded through analysis of septal strain curves, categorizing patients into five distinct patterns, denoted as strain Stage-0 through strain Stage-4 (Fig. A). LGE of the LV wall was quantitatively assessed using CMR (as a percentage). The study endpoints were volumetric reverse remodelling (volume responder = more than 15% decrease LV end-systolic volume) after one year, and all-time all-cause mortality.

Results
A total of 267 patients, with a mean age of 66±11 years (69% males, 90% left bundle branch block [LBBB]) presented with an average LV ejection fraction (EF) of 30±7%. With each stepwise increase in strain stage, global LV scarring decreased (p&lt;0.01; Fig. B) and the proportion of volume responders increased (all p&lt;0.0001; Fig. C). ROC curves demonstrated that the predictive power of strain stages for CRT volumetric response was not significantly improved when scarring percentage was added (AUC 0.78 [95% CI: 0.69-0.83] vs. 0.81 [95% CI: 0.71-0.90]; p&gt;0.05; Fig. D). In a multivariate cox regression model – including clinical characteristics that were significantly related to survival in univariate analysis – a patients’ strain stage was the only significant predictor of survival, also outperforming scar burden as determinant of outcome (HR 0.68; p=0.041; Fig. E).

Conclusions
Septal strain patterns show a strong association with the extent of reverse remodelling and outcome in CRT-treated patients. An inverse relationship is observed between pre-implant strain stages and the extent of myocardial scarring. However, scar burden did not provide incremental predictive value over the strain stages. Strain-pattern-based dyssynchrony assessment is a meaningful predictive marker which integrates information on myocardial dysfunction due to dyssynchrony as well as scar burden.
The role of fibrosis and inflammation for response and outcome prediction in candidates to cardiac resynchronization therapy: is response the right answer?
Authors: Beltrami M , Galluzzo A , Bonacchi G , Garofalo M , Checchi L , Perrotta L , Ricciardi G , Pieragnoli P , Palazzuoli A 
Published: October 2024

Abstract

Background
Cardiac resynchronization therapy (CRT) is an established treatment in selected patients suffering from heart failure with reduced ejection fraction (HFrEF). It has been proposed that myocardial fibrosis and inflammation could influence CRT "response" and outcome.

Purpose
Our study investigated the long-term prognostic significance of cardiac biomarkers in HFrEF patients with an indication for CRT.

Methods
86 consecutive patients referred for CRT implantation were retrospectively evaluated. The soluble suppression of tumorigenicity 2 (sST2), galectin-3 (Gal-3), N-terminal portion of the B-type natriuretic peptide (NT-proBNP), and estimated glomerular filtration rate (eGFR) were measured at baseline and after 1 year of follow-up. An echocardiographic reduction of LV end-systolic volume ≥15% was used to define a patient as responder to CRT. Multivariate analyses were performed to evaluate their correlation with the primary composite outcome of cardiovascular mortality and heart failure hospitalizations at a mean follow-up of 9 ± 2 years.

Results
44% of patients experienced the primary outcome. the mean baseline values of NT-proBNP, Gal-3, and sST2 were significantly higher compared with the patients without cardiovascular events. At the multivariate analyses, baseline Gal-3 [cut-off: 38.5 ng/ml, AUC: 0.63, p=0.03, (OR 7.13 [1.12;45.41], p=0.03), together with TAPSE&gt;17.5 mm (OR 10.86 [3.15;37.44], p&lt;0.001) significantly correlated with the structural response to CRT in several prediction models. Baseline Gal-3 [cut-off: 16.6 ng/ml, AUC: 0.91, p&lt;0.001, HR 8.33 (1.88–33.33), p = 0.005] and sST2 [cut-off: 35.6 ng/ml AUC: 0.91, p&lt;0.001, HR 333 (250–1,000), p = 0.003] significantly correlated with the composite outcome in the prediction models with high likelihood (Table). At Kaplan-Meyer curve patients with both high baseline sST2 and Gal-3 had the lowest survival probability (Figure). Among the parameters evaluated at 1-year follow-up, sST2, eGFR, and the variation from baseline to 1-year of Gal-3 levels showed a strong association with the primary outcome [HR 1.15 (1.08–1.22), p &lt; 0.001; HR: 0.84 (0.74–0.91), p = 0.04; HR: 1.26 (1.10–1.43), p ≤ 0.001, respectively]. Conversely, the echocardiographic definition of CRT response did not correlate with any outcome.

Conclusion
In HFrEF patients with CRT, sST2, Gal-3, and renal function were associated with the combined endpoint of cardiovascular death and HF hospitalizations at long term follow-up, while the echocardiographic CRT response did not seem to influence the outcome of the patients.
Beating the clock: the impact of heart failure duration on CRT efficacy
Authors: Grama E , Codina P , Ruiz-Cueto M , Camblor A , Borrellas A , Santiago-Vacas E , Domingo M , Bazan V , Aranyo J , Villuendas R , Zamora E , Lupon J , Bayes-Genis A 
Published: October 2024

Abstract

Background
Cardiac Resynchronization Therapy (CRT) stands as an established intervention for selected patients with heart failure (HF) presenting with a wide QRS complex. The optimal timing for CRT implantation remains uncertain. Current evidence suggests superior outcomes post-CRT in patients who have not been previously hospitalised for HF and those receiving the implant during their initial hospitalisation for HF.1

Purpose
The primary objective of this study is to investigate the long-term clinical outcomes following CRT implantation relative to the duration of HF previous to the implant. It was analysed in a cohort of consecutive patients from a HF Unit who met the criteria for CRT as recommended by the ESC guidelines (QRS duration ≥150ms, left bundle branch block morphology, and left ventricular ejection fraction (LVEF) ≤35% despite optimal medical therapy).

Methods
We evaluated all patients who received CRT from January 2011 through September 2022. Follow-up ended in September 2023. Patients with CRT indicated for ventricular pacing due to high-degree atrioventricular block were excluded. Patients were categorized into two groups based on the duration of HF progression prior to CRT implantation: more than 3 years and 3 years or less. The primary outcome was all-cause mortality (ACM). Secondary outcomes included a composite of ACM and HF hospitalisation and the proportion of patients who demonstrated a significant improvement in LVEF (defined as an increase of ≥10% from baseline and a subsequent measurement of LVEF ≥40%).

Results
The cohort consisted of 127 patients, mean age 65.8±10.7 years, 23.6% were women, mean LVEF was 28.4±8.6% and 36.2% had ischaemic aetiology (Table 1). 62 patients either died or were hospitalized for HF. Mean follow-up was 4.9±2.7 years. After adjusting for age, sex and baseline LVEF, patients with HF for more than three years before CRT implantation had a worse prognosis: HRs of 2.31 for ACM (p=0.016) and 2.13 for the combined endpoint of ACM+HFH (p=0.010) (Figure 1).
The proportion of patients with improved LVEF after CRT was significantly higher in the group with shorter HF duration (68.25%) compared to the group with longer HF duration (25%), p &lt;0.001.

Conclusions
Our findings reveal that patients with a shorter history of HF (less than three years) prior to CRT implantation exhibit significantly better clinical outcomes. These results highlight the role of early intervention with CRT in patients with HF, suggesting that shorter HF duration prior to CRT may lead to more favourable long-term outcomes.