bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transvenous lead extraction in pediatric patients. Is it the same procedure in children as in adults?
Authors: Kutarski A , Miszczak-Knecht M , Brzezinska M , Birbach M , Polewczyk A M , Jachec W , Tulecki L , Polewczyk A , Tomkow K , Stefanczyk P , Nowosielecka D , Bieganowska K 
Published: October 2022

Abstract

Background
Fibrous tissue encapsulating the lead and causing venous occlusion makes lead removal more difficult.

Purpose
This study sets out to define the differences in transvenous lead extraction (TLE) between pediatric and adult patients.

Methods
We report a retrospective review of prospectively collected data on lead extraction in 63 children aged ≤18 years and 2659 adults ≥40 years of age. The two groups were compared with respect to risk factors, procedure complexity, effectiveness, and complications.

Results
The predominant systems were VVI in children and DDD in the adult group. Lead dysfunction and infection were the main indications for extraction in children and adults respectively. Risk factors: the number of leads extracted in one patient, multiple lead extraction and ICD leads were significantly more common in adults. The mean implant duration before TLE was longer in children (p=0.03). Dwell time of the oldest lead per patient and dwell time of the oldest extracted lead did not differ significantly. The duration (p=0.006) and mean extraction time per lead (p&lt;0.001) were longer in children. Technical difficulties during TLE were more common in the pediatric group (p&lt;0.001). Similarly, additional tools were more frequently used in children (p&lt;0.001). Major complications were more common, albeit not significantly, in children. Complete radiographic and complete procedural success were significantly lower in the children's group (p&lt;0.001).

Conclusions
TLE in children was frequently more complex, time consuming and arduous, and had lower procedural success. Lead removal in children is a different procedure than in adults.

Funding Acknowledgement
Type of funding sources: None.
Exercise ventilation inefficiency and dynamic tricuspid regurgitation in heart failure
Authors: Mondellini G , Rusconi I , Giustiniani A , Torta D , Novello G , Bursi F , Guazzi M 
Published: October 2022

Abstract

Background
Exercise ventilation inefficiency, i.e. increase slope of the relationship of ventilation (VE) vs carbon dioxide (VCO2) slope is a key prognostic indicator in heart failure (HF). Many determinants have been identified primarily related to the left heart and impaired reflexogenic control of VE. In parallel, the severity of tricuspid regurgitation (TR) at rest is increasingly recognized as an important determinant of functional status and prognosis. It is undefined whether VE inefficiency may be related to the dynamic TR during exercise.

Purpose
We tested the role of dynamic TR and its correlates to exercise VE inefficiency by combining cardiopulmonary exercise test (CPET) with echocardiography.

Methods
We prospectively studied stable HF patients with both reduced and preserved left ventricular ejection fraction (LVEF). Patients with severe pulmonary disease and those who underwent valve replacement or cardiac surgery were excluded. Mitral and tricuspid regurgitation degree were adjudicated accordingly to ESC Guidelines criteria.
Demographics and clinical characteristics along with laboratory parameters including electrolytes, biomarkers of congestion (NT-proBNP), renal and liver function, were collected at the time of CPET. Dynamic TR was defined as worsening of TR grade from rest to stress detected by Doppler analysis. VE/VCO2 slope and peak oxygen consumption (pVO2) were compared between patients with dynamic TR (Group 1) vs non-dynamic TR (Group 2).

Results
Among 56 patients (66±13 years, 64% men, mean LVEF of 50±14%, 35% ischemic) 12% showed at least moderate mitral regurgitation and 16% patients had at least moderate TR at rest.
TR jet velocity at rest and at peak exercise were associated with VE/VCO2 slope (r=0.36 and r=0.3 respectively, p value &lt;0.05, Figure 1). A dynamic TR pattern (Group 1) appeared in 28 (50%) patients. No differences in clinical characteristics, laboratory parameters, LV ejection fraction, prevalence and degree of mitral regurgitation at rest and at peak were found between the two groups.
Group 1 compared to Group 2 exhibited a lower right ventricular fractional area change at peak exercise (45% [41–50] vs 52% [44–62] p=0.03), lower median pVO2 (13.3 [10.4–17.5] vs 16.3 [13.9–21.8], respectively (p=0.04)) and higher VE/VCO2 slope (40.3 [33.1–44] vs 34.1 [29.2–38.8], p=0.01; Figure 2A and B).

Conclusions
Patients with a dynamic TR pattern during CPET imaging exhibit a worse VE efficiency that correlates with TR extent. These data prospect, for the first time, an interaction between dynamic TR and ventilatory pattern during exercise in HF whose relevance may translate in targeting the right heart appropriately.

Funding Acknowledgement
Type of funding sources: None.
Potential role of circulating exosome miRNAs in left ventricular remodeling of patients with ST-segment elevation myocardial infarction
Authors: Guan R , Zeng K , Liu Y Q , Liu C Y , Li J W , Zhang B , Jiang H Q , Gao M N , Zhang L U , Li J F , Zhang Q , Yang M O , Yang Y 
Published: October 2022

Abstract

Background
Left ventricular remodeling (LVR) in patients with ST-segment elevation myocardial infarction (STEMI) may lead to poor prognosis in which circulating exosome miRNAs play a critical role. The aim of the present study is to identify specific exosome miRNAs for LVR in patients with STEMI.

Method
Plasma exosome miRNAs were assessed in 20 patients (90% male, mean age of 66.95±1.65 years) 3–6 months after STEMI and 24 healthy individuals (83% male, mean age of 33.2±0.93 years) by using qPCR. Of the 20 patients, 8 had post-STEMI LVR according to echocardiographic evaluation, and the others did not. Clinical biochemical data including total cholesterol, HDL-C, LDL-C, LDH and NT-pro-BNP were collected from the patients with STEMI at same time as exosome miRNAs assessment. Specific exosome miRNAs for LVR were identified by using qPCR. Correlations between the dysregulated exosome miRNAs and the clinical biochemical parameters in patients with STEMI were analyzed using spearman correlation test.

Results
Five exosome miRNAs including hsa-miR-181a-3p (p&lt;0.05, fold change = 0.59), let-7d-3p (p=0.01, fold change = 0.51), hsa-miR-224-5p (p&lt;0.01, fold change = 0.11), hsa-miR-23a-3p (p&lt;0.01, fold change = 1.42) and miR-874-3p (p&lt;0.01, fold change = 0.48) were dysregulated in the post-STEMI patients comparing with the healthy individuals. Among them, the exosome miR-181a-3p (p=0.01, fold change = 0.09) and let-7d-3p (p=0.01, fold change = 0.16) were significantly lower expressed in patients with LVR compared to those without (Figure 1). There was no significant difference in expression of the other three miRNAs between patients with and without LVR. Exosome hsa-miR-874-3p positively associated with LDH (p&lt;0.01, r=0.50) in all the patients with STEMI. In vitro cell culture confirmed that the miR-874-3p mimics upregulated expression of apoptosis related gene BMF (p&lt;0.05, fold change = 1.7) in cardiomyocyte. Exosome hsa-miR-23a-3p and hsa-miR-224-5p positively correlated with both HDL-C (p&lt;0.01, r=0.61; p=0.02, r=0.50) and LDL-C (p=0.02, r=0.50; p&lt;0.05, r=0.52) in all patients with STEMI. No correlation between the dysregulated exosome miRNAs and cholesterol or NT-ProBNP was observed (Figure 2).

Conclusions
Circulating exosome miR-181a-3p and let-7d-3p might play a potential role in LVR in patients 3–6 months after STEMI. Exosome hsa-miR-874-3p might be associated with cardiomyocyte injury. Hsa-miR-23a-3p and hsa-miR-224-5p demonstrated an activity in regulation of lipid metabolism and biosynthesis in patients with STEMI.

Funding Acknowledgement
Type of funding sources: Public hospital(s). Main funding source(s): This work was supported by grants from the 3×3 Clinical Scientist Fund of Sun Yat-sen Memorial Hospital
The utility of splenic imaging parameters in cardiac magnetic resonance for the diagnosis of immunoglobulin light-chain amyloidosis
Authors: Lama N , Briasoulis A , Karavasilis E , Stamatelopoulos K , Kastritis E , Kelekis N 
Published: October 2022

Abstract

Objectives
Cardiac Magnetic Resonance (CMR) Imaging is a key test in the diagnosis of cardiac amyloidosis (CA). Extracardiac involvement is common in light chain (AL) amyloidosis and MRI findings may assist in its diagnosis. We sought to investigate the utility of splenic CMR parameters for the diagnosis of CA.

Methods
Thirty-four patients with AL amyloidosis and 32 patients with severe left ventricular hypertrophy in the setting of aortic stenosis (LVH-AS) who completed 3T cardiac MRI at the time of their diagnosis of AL or LVH-AS were assessed with T1, T2 (modified Look-Locker inversion recovery), Extracellular volume (ECV) mapping, and late gadolinium enhancement (LGE) imaging of the heart and spleen.

Results
Age, left ventricular mass index, wall thickness, ejection fraction, and splenic dimensions did not differ significantly between groups. All AL patients had cardiac involvement. T1 and T2 spleen mapping did not differ significantly between groups but AL patients had higher median ECV in the spleen than in LVH-AS (AL 46.9%, LVH-AS: 31%, p&lt;0.001), and significantly lower short tau inversion recovery (STIR) ratio (AL: 1.7, LVH-AS: 2.7, p&lt;0.001) both with very good diagnostic performance to diagnose AL. We identified 16 AL patients with spleen involvement and 16 without. Spleen ECV and “normalized” spleen ratio, defined as the ratio of spleen LGE to muscle values exhibited strong correlation and had excellent diagnostic performance to discriminate those with spleen involvement.

Conclusion
Our findings show that spleen CMR parameters can identify spleen involvement in AL patients and differentiate them from those without AL amyloidosis.

Funding Acknowledgement
Type of funding sources: None.
Usefulness of right ventricular longitudinal systolic strain to predict the progression to heart failure with preserved ejection fraction in hypertensive patients
Authors: Marketou M , Kampanieris E , Maragkoudakis S , Alifrangie A , Karagounis T , Zervakis S , Anastasiou I , Fragkiadakis K , Plevritaki A , Kassotakis S , Pateromichelakis T , Savva E , Kochiadakis G 
Published: October 2022

Abstract

Background
Accurate assessment of right ventricular (RV) systolic function is important, as it is an established prognostic marker in cardiac diseases. Speckle-tracking echocardiography is a sensitive tool for detection of subclinical left ventricular impairment in essential hypertension.

Purpose
Our aim was to investigate the usefulness of RV longitudinal peak systolic strain (LS) to predict the risk of future development of heart failure with preserved ejection fraction (HFpEF) in patients with essential hypertension

Methods
We performed a retrospective observational study that included 453 patients with essential hypertension (266 males, aged 63±18 years) and 175 normotensives (100 males, aged 66±15 years). Standard echocardiography was performed at the initial visit. 2D speckle tracking echocardiography with evaluation of longitudinal strain in each segment of the RV (basal: RVLS-B; mid: RVLS-M, apical: RVLS-A) and global RV free-wall strain (RVLS-G) were also performed. We studied the cases of new onset HFpEF in hypertensive patients.

Results
The median follow up was 85 months (22–122). RVLS-G, RVLS-B and RVLS-M were significantly impaired in hypertensives compared to controls (RVLS-G: −16.1±9.7 vs −20.0±5.1, RVLS-B: −11.7±3.7 vs −20.6±3.3, RVLS-M:-16.3±5.4 vs −20.7±4.9, p&lt;0.05 for all). No significant difference was detected for the RVLS-A (−20.1±3.8 for hypertensives vs −21.31±6.5 for controls, p=NS). Thirty two hypertensive patients developed HFpEF (7%). A cut-off RVLS-G worse than −17% was significantly associated with new onset HFpEF (p&lt;0.001) in those patients. A multivariate Cox regression analysis showed that RVLS-G had independent significant prognostic value for the risk of HFpEF (HR: 10.5, 95% confidence interval (CI): 7.3–25.4).

Conclusions
Essential hypertension leads to a decrease of RVLS which is strong predictor of a new onset HFpEF. Future studies are needed to assess the significance of these findings and the effect of treatment.

Funding Acknowledgement
Type of funding sources: None.
Impact of aortic regurgitation on long-term outcomes in heart failure with preserved ejection fraction
Authors: De Colle C , Paolisso P , Gallinoro E , Bertolone D T , Mileva N , Fabbricatore D , Valeriano C , Mancusi C , Collet C , Vanderheyden M , De Luca N , Van Camp G , Barbato E , Bartunek J , Penicka M 
Published: October 2022

Abstract

Background
Aortic Regurgitation (AR) may aggravate the clinical course in patients with heart failure and preserved ejection fraction (HFpEF) by increasing filling pressures and triggering LV remodelling.

Objective
To assess AR's prevalence and long-term prognostic implications in patients with HFpEF.

Methods
The study population consisted of 458 consecutive patients (age 77.5±9.2 y, 57.9% females) hospitalized with de novo or worsened HFpEF. Patients with more than moderate aortic and/or mitral valve disease were excluded. Data on cardiovascular death, HF re-hospitalization and their composite (MACE) were collected.

Results
Out of 309 (67.5%) patients with any AR, 156 (34.0%) and 153 (33.5%) had mild-AR and moderate-AR, respectively. The remaining 149 (32.5%) individuals had no-AR. Patients with versus without AR were significantly older with larger LV and LA volumes and a higher prevalence of diastolic dysfunction (all p&lt;0.05). During a median follow-up of 33±25 months, a total of 114 patients (24.9%) died from cardiovascular causes, 126 patients (27.5%) were re-hospitalized for HF, while 272 (59.4%) had the composite endpoint (MACE). In multivariable Cox regression analysis, any AR emerged as an only independent predictor of MACE (HR=1.90, 95% CI 1.26–2.87, p=0.002). Mild-AR and Moderate AR increased the risk of MACE by 77% and 92%, respectively, compared to the No-AR (Figure).

Conclusions
In patients with HFpEF, mild-to-moderate AR is highly prevalent, and it seems to identify individuals with worse long-term outcomes. This suggests that even mild AR should be considered a high-risk prognostic marker in patients with HFpEF.

Funding Acknowledgement
Type of funding sources: None.
The therapeutic potential of relaxin for heart failure with preserved ejection fraction
Authors: Salama G , Palma J , Gabris-Weber B , MacMahon B , Kuhn B , Dschietzig T , Romero G 
Published: October 2022

Abstract

Background and significance
Heart Failure (HF) is the leading cause of cardiovascular deaths and ∼50% of HF patients have HF with preserved ejection Fraction (HFpEF). HFpEF patients typically have co-morbidities such as atrial fibrillation (AF), diabetes, lung edema and hypertension. The latter is a predictor of mortality and is targeted to prolong survival given the lack of a direct therapy for HFpEF. To address this unmet public health problem, we investigate the therapeutic potential of the insulin-like hormone Relaxin (RLX) in a rat model of HFpEF that recapitulates most aspects of clinical HFpEF.

Methods
ZSF1 diabetic rats were placed on a high fat diet (HFD for 11-weeks) and echocardiograms were used to track HFpEF development. At week 20, osmotic mini-pumps were implanted to release vehicle (Na-acetate) or RLX (400μg/kg/day, 2-weeks). Hearts were then perfused with a voltage-sensitive dye (RH237) and a Ca2+ indicator (Rhod-2/AM) to optically map action potentials and Ca2+ transients and analyze arrhythmia phenotype. Left ventricular (LV) tissue sections were used for immune-fluorescence (IF) imaging for changes in fibrosis (collagen 1), connexin 43, Wnt1 and β-catenin in LV myocytes. Blood draws were taken to measure changes in serum NT-pro-ANP, ET-1 and RLX.

Results
ZSF1 rats on a HFD developed HFpEF with E/e' (an echo marker of diastolic dysfunction) decreasing to −24.4 from −17.9 MV (n=12) and was reversed to −18.6 MV by RLX (n=6, p&lt;0.0001). In HFpEF rats that received the vehicle (n=6), a premature stimulus (S1-S2= 40 ms) elicited: a) no arrhythmia b) non-sustained AF or c) sustained AF, with (1/3 of rats in each group). RLX blocked sustained supraventricular (n=0/12) and n=4/12 had non-sustained AF. RLX improved conduction velocity (CV), at short cycle lengths (150 ms) from 0.74 to 0.9 m/s (n=4/group). IF indicated that RLX increased Cx43 (26.8±0.03%, p&lt;0.0001, n=6), and β-catenin (52.8±0.05%, p&lt;0.0001) at intercalated disks. RLX reduced collagen deposition in HFpEF rats (25±0.04%, p&lt;0.04, back to normal) and caused a marked increase of cytosolic Wnt1 (47.3±0.06%, p&lt;0.0001). IF data are given as mean ± SEM.

Conclusions
The ZSF1 diabetic rat on a high-fat diet recapitulates most of the phenotypes associated with human HFpEF, including atrial arrhythmias, fibrosis, and lung edema. RLX treatment post-development of HFpEF reversed the pro-arrhythmic phenotype, increased conduction velocity particularly at fast heart rates, reversed fibrosis, reduced NT-pro-ANP and ET-1 in male rats. Most intriguing, RLX treatment activated Wnt1 and β-catenin indicating that the beneficial actions of RLX occur via genomic remodeling of the heart.

Funding Acknowledgement
Type of funding sources: Private company. Main funding source(s): Relaxera Pharmazeutische Gesellschaft mbH & Co. KGStubenwald-Allee 8a, 64625 Bensheim, Germany & Uhlandstraße 4-5, 10623 Berlin, Germany
SGLT2 inhibitors in real-world patients with heart failure with preserved ejection fraction
Authors: Tarantini R , Vecchi A L , Matteo F , De Ponti R , Mortara A 
Published: October 2022

Abstract

Introduction
The diagnosis and management of heart failure with preserved ejection fraction (HFpEF) is challenging since ejection fraction is normal, clinical signs are often lacking and there are few therapeutic options. Two randomized clinical trials have tested SGLT2i for the treatment of HFpEF: DELIVER (pending results) and EMPEROR-PRESERVED; the findings of the latter trial show that empagliflozin, a sodium-glucose cotransporter inhibitor (SGLT2i) reduces the risk of cardiovascular death or hospitalization for HF in patients with HFpEF regardless the presence of diabetes. The results of this clinical trial have allowed European Medicine Agency (EMA) to extend the indication also to the patients with HFpEF, however the characteristics of the trial population don't often correspond to real-word HF population.

Aims
This study aims to investigate the eligibility of the EMPEROR-PRESERVED and DELIVER trial to a real-world heart failure population comparing the baseline characteristics of our patients to the recruited patients of clinical trials.

Material and methods
In this retrospective, observational study, 206 HF outpatients were enrolled from September 2018 to September 2019. The percentages of eligible patients according to EMPEROR PRESERVED and DELIVER inclusion criteria were analyzed, then we analyzed the difference between the characteristics of our HFpEF population and trials population.

Results
72 patients (35% of HF population) had heart failure with preserved ejection fraction. The EMPEROR-PRESERVED criteria and DELIVER trial were applied to these patients: 13 (18.1%) and 12 (16.7%) patients respectively fulfilled all enrolment criteria, whereas considering only EMA label criteria (EF &gt;40% and eGFR &gt;20 ml/min) 71 patients (98.6%) were eligible. The eligible patients according EMA criteria were significantly younger (67.3±14.3) than EMPEROR-PRESERVED population (72±9, p&lt;0.001) and DELIVER population (72±10, p&lt;0.001). The ejection fraction was significantly lower (50.2±5.8 vs 54±8.8; p&lt;0.001) whereas eGFR was no significantly different (64.4±22.7 vs 60.6±19.8; p=0.17).

Conclusion
Only a small percentage of our heart failure with preserved ejection fraction population was eligible for SGLT2 inhibitors according trials criteria, whereas according to EMA label almost all patients are candidate to these drugs. Furthermore, these patients were younger than EMPEROR-PRESERVED and DELIVER population with lower EF. The difference of eligibility between trials and real population is related to inclusion criteria, in particular the trial patients had elevated NT-proBNP levels whereas in the real world this criterion isn't considered. There is a lack of data about real-world patients who are often different from trials population. National and international registries of HF population may resolve this issue.

Funding Acknowledgement
Type of funding sources: None.
Targeted discovery proteomics to identify clinical phenotypes in heart failure with preserved ejection fraction: a proteomics substudy of VITALITY-HFpEF
Authors: Defilippi C , Shah S J , Alemayehu W , Lam C S P , Butler J , Reimann S , O'Connor C M , Shah P , Westerhout C M , Armstrong P W 
Published: October 2022

Abstract

Background
Heart failure with preserved ejection fraction (HFpEF) is a heterogenous syndrome that may emerge from overlapping systemic processes associated with several medical co-morbidities, often within an inflammatory milieu. Identification of unique proteins associated with distinct phenotypes may yield insight into novel therapeutics.

Purpose
Determine if unique clusters of circulating proteins are associated with specific clinical characteristics in patients with HFpEF.

Methods
A targeted discovery proteomics approach with 358 unique proteins associated with cardiovascular disease and inflammation (Olink) was used at baseline in VITALITY-HFpEF among 789 participants with documented left ventricular EF ≥45% and recent decompensation (&lt;6 mos). Proteins were clustered applying the weighted correlation network analysis (WCNA). The associations of the clinical characteristics and frailty and clusters were estimated with linear regression adjusted for age and eGFR. Frailty was characterized as normal, pre-frail, and frail using the Fried criteria. KCCQ was the primary and 6-minute walk distance (6MWD) the secondary endpoint of VITALITY-HFpEF.

Results
Four unique clusters were identified containing 24, 66, 197, and 81 proteins, respectively. Figure 1 shows the adjusted association of the 4 protein clusters, shown with their hub proteins, with the clinical characteristics. The color (red: positive, green: negative relationship) and intensity indicate the magnitude of the standardized difference (relative to the variation [i.e., T-value]); p-value shown in boxes. Cluster 3, with tumor necrosis factor receptor 1 as a hub protein that mediates apoptosis and inflammation, was associated with greater frailty and physical limitation along with shorter 6MWD. In contrast, cluster 4, with protein C as a hub protein that regulates anticoagulation and exerts a protective function on endothelial cells, is associated with less frailty and younger age, and more frequently male sex. Cluster 2 was associated with only younger age and cluster 1 with no clinical characteristics.

Conclusions
Proteomics appear to identify specific clinical phenotypes associated with HFpEF. Further exploration of this approach may provide insight into the diverse pathophysiology characterizing this disorder and a more targeted approach to therapy.

Funding Acknowledgement
Type of funding sources: Private company. Main funding source(s): VITALITY-HFpEF was funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA and Bayer AG, Wuppertal, Germany.