bluuebunny/crossref_metadata_2025_split huggingface dataset:
Left bundle branch area pacing improves right ventricular function in heart failure with preserved ejection fraction: evidence from PROPHET trial
Authors: Su Y 
Published: November 2023

Abstract

Background
Left bundle branch area pacing (LBBAP) has emerged as a promising pacing strategy, especially for patients with heart failure. However, the impact of LBBAP on hemodynamics and cardiac function in heart failure with preserved ejection fraction (HFpEF) has not been investigated yet.

Aim
To investigate the hemodynamic response and change of cardiac function of LBBAP in patients with HFpEF.

Methods
This prospective cohort study enrolled patients with preserved left ventricular ejection fraction who were receiving LBBAP, and two cohorts (non-HFpEF cohort and HFpEF cohort) were built based on diagnosis of HFpEF. Hemodynamics before and after LBBAP were measured using right heart catheterization (RHC). And the changes of cardiac function were evaluated by transthoracic speckle tracking echocardiography (STE).

Results
30 consecutive patients were included in the study, with 17 patients in the non-HFpEF group and 13 patients in the HFpEF group. Preprocedural STE showed worsened right ventricular function in the HFpEF group indicated by global longitudinal strain rate, free-wall strain rate, fractional area change, Tricuspid annular pulmonary systolic excursion and Tei index. And RHC showed elevated right ventricular stroke work index (RVSWI, 8.6±4.1 non-HFpEF vs 15.0±5.6 HFpEF, P = 0.170). While post-LBBAP evaluation showed a more significant reduction in RVSWI in the HFpEF group (6.7±2.5 (reduction 22.1%) non-HFpEF vs 8.0±1.0 (reduction 46.7%) HFpEF, P = 0.043). Besides, post-LBBAP STE showed improvement of right ventricular function, despite no significant difference in the extent of improvement was found between groups.

Conclusion
LBBAP might be more beneficial to patients with HFpEF as it could improve right ventricular function by alleviating the workload of right ventricle. Long-term benefit of LBBAP in HFpEF requires further investigation.
Functional mitral regurgitation and ventricular arrhythmias in patients with cardiac resynchronization therapy
Authors: Yoshimura A , Suzuki A , Yoshida A , Kanai M , Hasegawa S , Kataoka S , Yazaki K , Saito C , Yagishita D , Domoto S , Shiga T , Ashihara K , Shoda M , Niinami H , Yamaguchi J 
Published: November 2023

Abstract

Introduction
In patients with heart failure (HF), the occurrence of ventricular arrhythmias (VAs) is associated with prognosis, and advanced HF can cause VAs. In HF patients developed moderate to severe functional mitral regurgitation (FMR), a transcatheter mitral valve repair therapy has significantly reduced the hospitalization and mortality rates compared to guideline-directed medical therapy. Although the mechanisms of arrhythmias are multiple, it is unclear whether FMR is involved in the development of VAs advanced HF patients.

Methods and results
We retrospectively examined 176 cardiac resynchronization therapy (CRT) patients (78% men, median age 67 years) without FMR before CRT implanted between 2010 and 2018. Worsening FMR was defined as developing moderate to severe FMR after CRT. During median follow-up of 40 (quartile range, 23-60) months, worsening FMR was detected in 26 (15%) patients at a median of 30 (quartile range, 12–75) months after CRT implantation. There was no difference in age, New York Heart Association functional class, QRS width before CRT and the rate of responders between patients with and without worsening FMR. Patients with worsening FMR had a tendency of larger left ventricular end-systolic dimension (58 [53-68] vs. 53 [47-60] mm, p&lt;0.10), a significantly higher rate of female (38% vs. 19%, p&lt;0.05) and a significantly larger left atrial volume index (LAVI) (63 [43-81] vs. 48 [35-62] ml/m2, p&lt;0.05). By multivariate logistic regression analysis, female gender (odds ratio 4.3) and baseline LAVI (odds ratio 1.04 per a ml/m2 increase) were independent factors associated with worsening FMR. There was a significantly higher incidence of HF hospitalization (50% vs 15%, log-rank P&lt;0.05) (Figure 1) and a higher incidence of VAs, defined as sustained ventricular tachyarrhythmias requiring implantable-cardioverter defibrillator therapy or external defibrillation, in patients with worsening FMR than patients without worsening FMR (65% vs 38%, log-rank P&lt;0.05) (Figure 2). Multivariate analysis showed that worsening FMR was independently associated with the development of VAs (hazard ratio 2.77, 95% confidence interval 1.13-6.83).

Conclusions
In patients with HF and CRT, female gender and baseline LAVI were associated with worsening FMR after CRT. We need to pay attention to changes in the FMR that can be associated with developing VAs after CRT implantation.
Characterization and prognostic impact of ischemic etiology in heart failure with reduced left ventricular ejection fraction
Authors: Perea Armijo J , Heredia Campos G , Lopez Aguilera J , Castillo Dominguez J C , Anguita Sanchez M 
Published: November 2023

Abstract

Introduction and objectives
Ischemic heart disease is the cause of 50-60% of cases of heart failure with reduced left ventricular ejection fraction (HF-rEF). The impact of ischemic etiology on left ventricular ejection fraction (LVEF) improvement and prognosis remains unclear. Our main objective was to analyze the differential clinical profile between ischemic and non-ischemic etiology, as well as its medium-to-long term prognosis.

Methods
Prospective study of a cohort of patients with HF-rEF in real clinical practice. A comparative analysis was performed between patients with HF-rEF of non-ischemic etiology (Group 1) and ischemic etiology (Group 2). Clinical, analytical, echocardiographic and therapeutic variables were analyzed, and the medium-to-long term impact in terms of mortality and hospital readmissions for HF was evaluated.

Results
409 patients were analyzed. 276 patients (67.5%) had non-ischemic etiology and 133 patients (32.5%) had ischemic etiology. Group 2 was older (65.8±13.3vs70.8±10.3;p&lt;0.001), more men (68.1%vs86.5%;p&lt;0.001), higher prevalence of arterial hypertension (62.3%vs76.7%;p = 0.004), diabetes mellitus (38.8%vs67.7%; p&lt;0.001), dyslipemia (52.4%vs82.7%;p&lt;0.001), chronic kidney disease (34.4%vs56.4%;p&lt;0.001), anemia (24.3%vs47.4%;p&lt;0.001) and vascular comorbidity (25.7%vs54.9%;p&lt;0.001) and lower prevalence of atrial fibrillation (56.2%vs44.4%;p = 0.025). In Group 2 there was a lower proportion of de novo HF (60.1%vs45.1%;p = 0.004) with longer HF evolution time (24.4±48.8vs61.5±89.3; p&lt;0.001), a lower proportion of patients improving LVEF at follow-up (51.6%vs21.1%;p&lt;0.001) and a higher baseline NTproBNP concentration [4463(IQR 1976-10431)vs5746(IQR 2336.5-13789);p = 0.039]. Regarding baseline treatment, in Group 1 there was a higher prescription of mineralocorticoid receptor antagonists (78.3%vs63.9%;p = 0.002) and less ICD implantation (6.5vs14.3%;p = 0.01), with no differences in the rest of the treatment. With a mean follow-up of 60 months, Group 2 had a higher readmission rate (39%vs50.3%;p&lt;0.01) and higher HF mortality (26.8%vs41%;p&lt;0.01), with differences from early stages.

Conclusions
Patients with HF-rEF of ischemic etiology associate a greater number of comorbidities, a lower percentage of de novo HF, longer time of HF evolution, lower percentage of LVEF improvement and higher baseline NTproBNP.
Effect of vericiguat on cardiovascular outcomes in patients with heart failure with and without diabetes: Insights from the VICTORIA trial
Authors: Khan S , Butler J , Young R , Lewis B S , Escobedo J , Refsgaard J , Reyes E , Roessig L , Blaustein R O , Lam C S P , Voors A A , Ponikowski P , Anstrom K J , Armstrong P 
Published: November 2023

Abstract

Objective
To investigate the impact of type 2 diabetes mellitus (T2D) on outcomes in patients with worsening heart failure with reduced ejection fraction (HFrEF) and to assess the efficacy of vericiguat in these patients.

Methods
Patients with HF and a left ventricular ejection fraction ≤45% were randomized to receive vericiguat or placebo in addition to standard therapy. The primary outcome was a composite of cardiovascular death or first hospitalization for HF (HHF). A Cox proportional hazards model was used to calculate hazard ratios (HR) and 95% confidence intervals (CI) to assess if the effect of vericiguat differed by history of T2D.

Results
Of the 5048 patients, 2369 (46.9%) had T2D. The risks of the primary outcome, HHF, and all-cause and cardiovascular death were already very high in those without T2D and even higher in patients with T2D. The beneficial effect of vericiguat on the primary outcome did not differ in patients with (HR, 0.91 [95% CI, 0.80–1.03]) or without (HR, 0.87 [95% CI, 0.76–0.99] (P-interaction = 0.64) T2D (Figure). No significant differences were noted among patients with and without T2D with respect to the effect of vericiguat on HHF and all-cause or cardiovascular death.

Conclusion
Notwithstanding the increased incidence of cardiovascular death and HHF conferred by T2D, in this post-hoc analysis of VICTORIA, vericiguat compared with placebo significantly reduced the risk of cardiovascular death or HHF in patients with worsening HFrEF regardless of T2D status.
Increased clonal hematopoiesis mutational burden and accelerated dynamic evolution of circulating clones in patients with ischemic heart failure
Authors: Kirschbaum K , Rieger M , Leistner D , Dimmeler S , Zeiher A , Cremer S 
Published: November 2023

Abstract

Background
Clonal hematopoiesis (CH) - defined as the age-related acquisition of mutations in hematopoietic stem cells giving rise to mutated circulating leukocytes - is associated with increased risk of death in patients with heart failure with reduced ejection fraction (HFrEF). While the mutational landscape of CH in peripheral blood (PB) of patients with HFrEF is well characterized, the mutational burden in bone marrow (BM) samples of patients with HFrEF as well as its dynamics over time have not been investigated.

Methods/Results
We analyzed matched BM and PB cells from 68 patients with ischemic HFrEF by deep error-corrected targeted sequencing of 56 CH-driver genes with a detection threshold of VAF ≥0.5%. In PB, 56/68 patients carried at least one CH mutation, whereas 63/68 patients had mutations in BM. The absolute numbers of detectable mutations were significantly higher in BM compared to PB (215 mutations vs 120 mutations; p&lt;0.0001) (Fig. 1A). Likewise, the cumulative VAF was significantly higher in BM compared to PB (3.83 +/- 0.5% vs 3.0% +/-0.7%; mean +/- SEM, p = 0.0025) (Fig. 1B). However, there was a strong correlation between mutation load in PB and BM (r = 0.54, p&lt;0.0001). Among the two most common mutations, DNMT3A mutations were either present in BM only or both compartments (PB only/BM only/ both compartments 2/12/10), whereas TET2 mutations were strikingly enriched in BM cells (PB only/BM only/both compartments 0/16/2).
To study the dynamic evolution of CH clones in patients with HFrEF, we serially analyzed PB samples from 19 patients. At baseline, 16/19 patients carried at least one mutation in a CH driver gene and a total of 31 mutations. After a median follow-up of 12 months, 19/19 patients had at least one detectable mutation and a total of 43 mutations were identified (mean number of mutations per patient 1.63 +/- 0.033 vs 2,26 +/- 0.27; mean +/- SEM, p = 0,0410), indicating an increased mutation load over time (Fig. 2A). Moreover, cumulative VAF increased from 1.59 +/-0.36 % to 2.01 +/- 0.38 %).

Conclusion
Patients with ischemic HFrEF display a high burden of CH mutations compared to values reported for healthy individuals, which is further amplified in the bone marrow compartment. Clones with new mutations arise rapidly in longitudinal samples of patients with HFrEF and clonal expansion occurs with high momentum. The overrepresentation of mutations in the BM is indicative for augmented DNA damage in the hematopoietic stem cells of patients with HFrEF, while the rapid expansion of mutated circulating clones over time suggests that heart failure itself may expedite the expansion of hematopoietic cells harboring CH-driver mutations.
Left ventricular thrombus in patients with heart failure with improved ejection fraction
Authors: Puwanant S , Peerawat Puwatnuttasit P P , Suksiriworaboot T S , Sinphurmsuksakul S S , Ariyachaipanich A A , Siwamoksatham S S , Boonyaratavej S B 
Published: November 2023

Abstract

Background
This study sought to: (1) determine the prevalence of LV thrombus at baseline and at the time of recovered ejection fraction (EF) in patients with heart failure with improved ejection fraction (HF-imp EF), (2) examine clinical and echocardiographic factors associated with the presence of LV thrombus, and (3) determine the prevalence of thromboembolic events when LVEF was improved and oral anticoagulant (OAC) was discontinued.

Methods and results
Patients with nonischemic HF-imp EF defined as a baseline LVEF of ≤ 40%, a ≥ 10% increase from baseline LVEF, and a second measurement (6 months apart) of LVEF of &gt; 40% were consecutively enrolled in advanced HF clinic in a tertiary center. Patients with recent myocarditis, recent coronary revascularization, active chemotherapy, hypertrophic cardiomyopathy, cardiac amyloidosis, and tachycardia induced cardiomyopathy were excluded. A total of 104 consecutive patients (age 51 ± 15 years; 66% were male) with HF-imp EF were included. Of these, 14 patients (14%) had LV thrombus at baseline. Baseline LVEDD, LVEF, and LV global longitudinal strain (GLS) were 61 ± 10 mm, 23 ± 15%, and -5.9 ± 3.3%, respectively. Younger age, absence of atrial fibrillation, receiving oral diuretics, lower LVEF, reduced LV GLS, and reduced RV free wall (FW) GLS were significantly associated with LV thrombus at baseline (p &lt; 0.05 for all) (Table 1). All patients (100%) with LV thrombus at baseline received oral anticoagulants (OAC). At the median follow-up of 27 months, 14 (100%) had complete resolution of LV thrombus when LVEF &gt; 40%. Of 14 patients, 11 (79%) who were in sinus rhythm discontinued OAC. After a median further follow-up of 27.4 months following OAC discontinuation, there was no thromboembolic event or all-cause mortality in these patients. One of 11 patients developed worsening LVEF and recurrent LV thrombus at 25 months after LVEF improvement (&gt; 40%).

Conclusions
Approximately 1 in 6 patients with HF-imp EF had LV thrombus at baseline. LV thrombus formation was associated with more impaired LV and RV systolic function and myocardial deformation implicating more thromboembolic milieu. Complete resolution of LV thrombus occurred in all patients who were on OAC therapy at the time of imp-EF. Discontinuation of OAC when LVEF &gt; 40% was safe. However, recurrent thrombus formation can occur when LV systolic function was deteriorated. Annual or bi-annual echocardiographic follow-up may be essential in these patients.
Prognostic value of left atrial strain in heart failure with reduced ejection fraction
Authors: Tas Ozbek B , Modin D , Sengloev M , Joergensen P G , Bruun N E , Fritz-Hansen T , Biering-Soerensen T 
Published: November 2023

Abstract

Background
The prognostic value of left atrial (LA) strain in patients with heart failure with reduced ejection fraction (HFrEF) has not been fully elucidated. Therefore, this study investigated the prognostic value of left atrial strain in HFrEF patients in relation to allcause mortality.

Methods
A total of 822 echocardiograms from HFrEF patients admitted to a heart failure clinic were analyzed offline. To calculate left atrial resevoir strain (LA RS) and left atrial contractile strain (LA CS), left atrial two-dimensional speckle tracking was performed in the 4-chamber, 2-chamber and 3-chamber view. The end-point was all-cause mortality. The association between left atrial strain parameters and outcome was examined using Cox regression.

Results
The median follow-up time was 40 months and follow-up was 100% complete. During follow-up, a total of 137 patients (16.7%) died of all causes. In a final multivariable model adjusted for clinical and echocardiographic parameters including global longitudinal strain, LA RS and LA CS were significantly associated with all-cause death during follow-up (LA RS, HR 0.96, 95% CI 0.92-0.99 p = 0.014, pr. 1% increase) (LACS, HR 0.95, 95% CI 0.92-0.98 p = 0.002, pr. 1% increase) (Table 1). When added to the final multivariable model, both LA RS and LA CS contributed with incremental prognostic value as determined by C-statistic (LA RS: C-stat difference 0.007, 95% CI 0.000-0.020, p = 0.050) (LA CS: C-stat difference 0.009, 95% CI 0.000-0.023, p = 0.030).

Conclusion
In HFrEF patients, LA RS and LA CS were associated with all-cause mortality and contributed with incremental prognostic value in addition to established prognostic measures.Table 1
The effect of iron deficiency treatment with intravenous ferric carboxymaltose on the arrhythmic burden of patients with HFrEF and cardiac implantable electronic devices
Authors: Tsarouchas A , Mouselimis D , Bakogiannis C , Papadopoulos C , Antoniadis A , Tsavousoglou C , Kelemanis I , Triantafyllou K , Strati E , Giannopoulos G , Fragakis N , Efthimiadis G , Vassilikos V 
Published: November 2023

Abstract

Background
The deleterious effect of iron deficiency (ID) on cardiomyocyte electrochemical stability is well-documented. In patients with heart failure and reduced ejection fraction (HFrEF), ID represents a key comorbidity associated with increased morbidity and mortality. Thus, it has been hypothesized that treating ID may lead to reduced incidence of arrhythmias in HFrEF patients.

Purpose
To study the effect of intravenous ferric carboxymaltose (IV FCM) treatment on the iron stores, arrhythmic burden, functional capacity and quality of life in HFrEF patients with ID and cardiac implantable electronic devices (CIEDs).

Methods
Patients with HFrEF, ID and CIEDs scheduled to receive IV FCM as per ESC guidelines were invited to participate. Follow-up lasted 12 months. The primary outcome was related to the amelioration of patients’ iron status. Secondary outcomes relative to arrhythmic burden included (i) the incidence of device-detected ventricular tachycardias (VTs) between the year before recruitment to the study and the follow-up period, (ii) patients’ Lown and Wolf classification as derived from 24hour Holter monitoring. Data related to non-invasive arrhythmic markers such as late potential, microvolt T-wave alternans and deceleration capacity were also available.

Results
This real-life cohort included 79 patients (84% male). Patients’ median age was 70.8 [IRQ:11.7] years. Median ferritin increased to 150 [125] ng/mL at 12 months (baseline 55 [68] ng/mL, P&lt;0.001). At their final visit, 45 (57%) patients no longer met the ESC criteria for iron deficiency (P&lt;0.001). The CIED-derived incidence of VT episodes decreased significantly after 12 months of IV FCM treatment (0.26±0.83 episodes per patient per year compared to 0.8±2.36, P = 0.048). Patients were also significantly likely to shift to a more favorable Lown and Wolf arrhythmic burden classification (P = 0.01). Patients’ late potential results and microvolt T-wave alternans also improved significantly (P = 0.01 for both tests).

Conclusion
The results of this real-life cohort analysis suggest significant reduction of the arrhythmic burden in HFrEF and ID after restitution of iron stores. Further studies are needed to further evaluate the impact of these results.
Heterogeneity of patients phenotyped as heart failure with mildly reduced ejection fraction
Authors: Kerkhof P L , Heyndrickx G R , Diaz-Navarro R A , Handly N 
Published: November 2023

Abstract

Background
Current phenotyping of heart failure (HF) is based on the ejection fraction (EF) criterion, resulting into three types including the mildly reduced (mr) category. Little is known about the heterogeneity of the volumetric (ie left ventricular [LV] size) and clinical characteristics (including myocardial oxygen consumption, MVO2) of patients who are assigned to the HFmrEF class.

Method
The metric EF combines details on end-systolic volume index (ESVi) and end-diastolic volume index (EDVi). Both volumetric measures can be presented in the volume regulation graph (VRG), allowing the graphical inspection of the behavior of EF under a variety of conditions, with stratification options based on age, sex or other clinically relevant determinants. To overcome the limitations intrinsic to ratio-based metrics such as EF, we introduced a logical EF-companion (EFCi), defined as the square root of (ESVi² + EDVi²). In other studies the EFCi has been shown to offer incremental value beyond the single use of EF.

Patients
LV volumes were determined by biplane angiocardiography in 190 HF patients (69 women), and retrospectively analyzed.

Results
Average ESVi values for mrEF are 57.9 and 60.2 mL/m² for men (n = 22) and women (n = 10), respectively. The distribution of {EDVi, ESVi} data pairs in the VRG is shown in Figure 1, stratified for women and men. Patients categorized as HFmrEF are indicated by separate markers, and located in the region between the lines that indicate the 40 and 50% limits for EF. The double arrowed yellow bar refers to the wide ESVi range (27 to 118 mL/m²) for the patients within this narrow EF bandwidth. As ESVi refers to the extent of (reverse) remodeling and is associated with MVO2, there is a clear need the consider ESVi or EFCi for patients, in addition to their nearly similar EF values. Figure 2 shows the distribution of EFCi (range 59.5 to 231.8 mL/m2) for all HFmrEF patients, and clearly illustrates the supplementary value of the companion to the ratio-based metric EF.

Conclusions
As the bandwidth for EF narrows, the specificity of EF decreases and the higher the need to rely on EFCi. Thus, in contrast to the current view indicating that HFmrEF patients form a well-defined rather homogeneous phenotype exhibiting comparable clinically relevant characteristics, we found a relatively pronounced heterogeneity within the HFmrEF phenotype group. Distinguishing individual patients within the HFmrEF phenotype can be realized by considering the newly introduced parameter EFCi. This approach resolves most of the criticism thus far expressed regarding limitations of EF. The proposed additional dimension beyond EF offers a more comprehensive description of these patients, and will allow a personalized analysis based on a more careful characterization. Further investigations are warranted to explore implications for patient management.Figure 1.VRG for HF patients (n = 190)Figure 2.HFmrEF vs EFCi (n = 32)