bluuebunny/crossref_metadata_2025_split huggingface dataset:
Heart failure with preserved ejection fraction (HFpEF) pathophysiology study (IDENTIFY-HF): rise in arterial stiffness associates with HFpEF with increase in comorbidities
Authors: Ali D , Tran P , Weight N , Ennis S , Weickert M , Miller M , Cappuccio F , Banerjee P 
Published: October 2021

Abstract

Background
There has been a shift in paradigm proposing that comorbidities play a significant role towards the pathophysiology of the heart failure with preserved ejection fraction (HFpEF) syndrome. Further, HFpEF patients have abnormal macrovascular function, potentially contributing significantly in altered ventricular-vascular coupling in these patients. However, our full understanding of the role of comorbidities, arterial stiffness and it relationship with HFpEF remains incomplete.

Purpose
The IDENTIFY-HF study aims to shed light on the HFpEF pathophysiology and investigates whether gradually increase in arterial stiffness (in addition to ageing) due to increasing common comorbidities, such as hypertension and diabetes, is associated with HFpEF.

Methods
Arterial compliance was assessed in five groups (Groups A to E) matched for age, (≥70 years), sex and renal function: Group A; normal healthy volunteers without major comorbidities (control). Group B; patients with hypertension only. Group C; patients with hypertension and diabetes mellitus only. Group D; patients with HFpEF. Group E; patients with heart failure and reduced ejection fraction (HFrEF); the parallel group. Arterial compliance was assessed using pulse wave velocity (PWV), as the primary outcome measure and was compared between Group A to D. A separate comparison was made between Groups D and E. To avoid confounding factors, participants were asked to omit their morning blood pressure medication and abstain from caffeine for 12 hours prior to the study.

Results
From the 95 volunteers recruited, PWV was obtained in 94 subjects. The mean PWV in group A, B, C, D and E was 10.2-, 12.2-, 13.0-, 13.7- and 10.0 m/s respectively. After adjusting for covariance (age, sex, BMI and renal function), the mean difference between Group A (healthy volunteers) and D (HFpEF) was 2.14 m/s (p=0.023). Whilst the mean difference between the HFpEF and HFrEF group D and E respectively was 2.68 m/s (p=0.003).

Conclusion
Rise in comorbidities increases arterial stiffness, as measured by pulse wave velocity, which in turn significantly associates with HFpEF (p=0.023). It is therefore possible that the HFpEF syndrome may not be due to a primary cardiac pathology but rather an end-result of non-cardiac comorbidities affecting vascular resistance with perhaps some secondary cardiac involvement.

Funding Acknowledgement
Type of funding sources: Public Institution(s). Main funding source(s): 1)West Midlands Clinical Research Network, National Institute of Health Research, UK2)Research, Development & Innovation department of the University Hospitals Coventry & Warwickshire NHS Trust (RDI, UHCW), UK.
Systolic blood pressure visit-to-visit variability and clinical outcomes of heart failure with preserved ejection fraction
Authors: Zhang Q , Zhou B.Y , Ma Y.U , Hu Y.C , Li X.M , Cong H.L 
Published: October 2021

Abstract

Background
Previous studies have shown that increased systolic blood pressure visit-to-visit variability (SBP-VVV) is associated with higher risk for cardiovascular events in patients with hypertension, atrial fibrillation, and heart failure with reduced ejection fraction, However, no studies have reported the relationship between SBP-VVV and adverse outcomes in heart failure with preserved ejection fraction (HFpEF).

Methods
This was a post-hoc analysis of the TOPCAT trial, a multicentered, randomized, placebo-controlled trial of spironolactone in patients with HFpEF. SBP-VVV was assessed during the first year of the trial and clinical outcomes were analysed from the end of the first year to the end of the follow-up period. SBP-VVV was primarily assessed by SBP-SD, the standard deviation (SD) of the mean SBP across these six visits of every patient. The primary study outcome was the composite outcomes of cardiovascular death, hospitalization for heart failure or aborted cardiac arrest occurring after the first 12 months after randomization. The secondary outcomes included cardiovascular mortality, first HF hospitalization event, and all-cause mortality occurring beyond the first 12 months following randomization.

Results
Of the 2907 patients from the TOPACT trial, SBP-VVV was categorized into quartiles (1st, &lt;6.05; 2nd, 6.06–8.94; 3rd, 8.95–12.81; and 4th, ≥12.82 mmHg) and as a continuous variable. During the subsequent median follow-up of 2.48 years, 373 (12.8%) patients met the primary outcome. On multiple Cox regression, patients in the 4th quartile were at higher risk for a primary outcome (hazard ratio for 4th vs. 1st quartile, 1.79;, 95% CI, 1.28–2.49; P&lt;0.001). Patients in the 4th quartile were also at higher risk of HF hospitalization (hazard ratio for 4th vs. 1st quartile, 2.49; 95% CI, 1.54–4.02; P&lt;0.001) and all-cause mortality (hazard ratio for 4th vs. 1st quartile, 1.52; 95% CI, 1.08–2.15; P=0.017). SBP-SD as a continuous variable was also associated with an increased risk of all outcomes.

Conclusions
In patients with HFpEF, high SBP-VVV was associated with an increased risk of adverse outcomes, independent of baseline and on-treatment SBP.

Funding Acknowledgement
Type of funding sources: None. Relationship between SBP-SD and HR
Prognostic impact of left atrial function in heart failure with preserved ejection fraction in sinus rhythm vs. atrial fibrillation
Authors: Schoenbauer R , Kammerlander A.A , Duca F , Aschauer S , Koschutnik M , Dona C , Nitsche C , Loewe C , Hengstenberg C , Mascherbauer J 
Published: October 2021

Abstract

Background
Left atrial (LA) function is related with outcome in heart failure with preserved ejection fraction (HFpEF). However, how LA function contributes to outcome in the context of atrial fibrillation (AF) versus sinus rhythm (SR) remains unclear.

Purpose
To determine the prognostic impact of LA size and phasic function in patients with HFpEF in SR vs. AF.

Methods
We enrolled consecutive HFpEF patients and assessed indexed LA volumes (LAVi) and emptying fractions (LA-EF) on cardiac magnetic resonance (CMR) imaging. We prospectively followed patients and used Cox regression models to determine the association of LA size and function with a composite endpoint of heart failure hospitalization and cardiovascular death.

Results
A total of 188 patients (71% female, 70±8 y/o) were included of whom 92 (49%) were in persistent AF (Figure 1A). Patients in persistent AF were older (p=0.017) and had a worse NYHA functional class (p=0.003). Compared to SR, peak and minimal LAVi were increased and LA-EF impaired (each p&lt;0.001 respectively) in persistent AF patients (Figure 2A).
A total of 65 patients reached the combined endpoint during a follow-up of 31 (9–57) months. Multivariate Cox regression adjusted for established risk factors revealed that LA-EF was significantly associated with outcome in patients in SR (adj.HR 2.14; 95% CI [1.32–3.47] per 1-SD decline, p=0.002). In persistent AF, however, no LA imaging parameter was related to outcome (Figure 1B). By receiver operating characteristic curve and restricted cubic spline- analyses, we identified an LA-EF ≥40% as best indicator for favorable outcomes in patients with HFpEF and SR (Figure 2B). Persistent AF carried a similar risk for adverse outcome compared to impaired LA-EF (&lt;40%) in SR (log-rank, p=0.340) (Figure 1A).

Conclusions
In HFpEF patients in SR, impaired LA-EF is independently associated with worse cardiovascular outcome, which is similar to persistent AF. With disease progression including development of persistent AF, LA parameters lose their prognostic ability and thus, are not helpful for further risk stratification.

Funding Acknowledgement
Type of funding sources: None. Figure 1Figure 2
The role of left ventricular remodeling in functional mitral regurgitation: functional and prognostic implications in patients with heart failure
Authors: Sugimoto T , Boveri S , Bandera F , Barletta M , Alfonzetti E , Guazzi M 
Published: October 2021

Abstract

Background
Left ventricular (LV) dilatation plays a key role on functional mitral regurgitation (MR) in patients with heart failure (HF) and exercise MR causes an additional LV remodeling. This study sought to investigate the different phenotypes and prognostic impact of LV end-diastolic volume (EDV) and MR during exercise in HF patients of any left ventricular ejection fraction (LVEF) categorization.

Methods
201 HF patients with reduced (n=119), mildly-reduced (n=46), and preserved (n=36) EF underwent exercise with gas exchange analysis combined with echocardiography for assessment of MR and were divided by 3 groups according to EDV index tertiles (T1 &lt;70.1, T2 70.1–95.6, T3 &gt;95.6 ml/m2).

Results
There was no significant difference in age (67±12 years) and peak oxygen consumption (VO2: 13.1±3.7 ml/kg/min) among the 3 groups but VE/VCO2 slope was higher in T3 group (T1 31±7, T2 31±5, T3 37±11, P&lt;0.05). EDV index was positively correlated with VE/VCO2 slope (R=0.33, P&lt;0.001) and effective regurgitant orifice area (EROA) of MR at rest (R=0.27, P=0.01) and exercise (R=0.45, P&lt;0.001). During follow up, 48 patients had the composite end point of all cause death or HF hospitalization. The age and gender adjusted hazard ratio for the events in patients with MR &gt;2+ was 1.8 (P=0.049) at rest and 1.9 (P=0.026) at exercise. The age, gender, peak VO2, VE/VCO2 slope, and exercise MR &gt;2+ adjusted hazard ratio of EDV index 10 ml/m2 increase was 1.1 (P=0.041) and the ratio in patients with EDV index &gt;95.6 ml/m2, derived by ROC curve (AUC=0.69, P&lt;0.05), was 2.0 (P&lt;0.033, figure).

Conclusions
Functional MR with LV dilation combines with the worse exercise gas exchange phenotype. Given also the predictive role of a EDV index cutoff of 95.6 ml/m2 attention for chamber geometry during exercise might become an indicator of mitral valve reparation.

Funding Acknowledgement
Type of funding sources: None.
The impact of marathon running on atrial remodeling in male and female amateur athletes assessed by three-dimensional echocardiography
Authors: Lasocka Z.B , Dabrowska-Kugacka A , Kaleta-Duss A , Lewicka-Potocka Z , Faran A , Danilowicz-Szymanowicz L , Nowak R , Kaufmann D , Raczak G , Lewicka E 
Published: October 2021

Abstract

Introduction
Endurance athletes have an increased risk of atrial remodeling and atrial arrhythmias. However, data regarding atrial adaptation to physical exercise in non-elite athletes are limited. We aimed to assess exercise-induced alternations in atrial morphology and function in male and female amateur marathon runners, using real-time three-dimensional (3D) echocardiography.

Methods
The study group consisted of 40 male (39±8 years) and 27 female (40±7 years) amateur athletes. 3D echocardiography was performed 2–3 weeks before (Stage 1) and immediately after (Stage 2) the marathon run. Right (RA) and left atrial (LA) remodeling was assessed by volumetric measures, total ejection fraction (EF) and volume (EV). Speckle tracking was used to determine the temporal evaluation of atrial function by strain analysis.

Results
The main results are presented in Table 1. At rest, male athletes demonstrated greater RA size and decreased RA contractility, as assessed by EF and atrial strains, in comparison to females. At Stage 1, LA morphology and function did not differ significantly between genders. After the marathon, a remarkable increase in RA maximal volume (RAVmax, 32.9±8.6 vs. 36.4±8.2 ml/m2, p=0.016) and RAEF (49.5±9.7 vs. 57.3±9.2%, p=0.002) was observed only in female athletes (p&lt;0.05 for both interactions sex and stage). Whereas in male runners, LA measures, such as LAVmax (30.7±6.4 vs. 26.8±6.2 ml/m2, p=0.007), LAEF (56.7±4.3 vs. 52.7±5.3%, p=0.037) and LA conduit strain (LAScd, −18.7±8 vs. −13.6±8%, p=0.045), significantly decreased postrace. This observation was absent in females (p&lt;0.05 for all interactions sex and stage).

Conclusions
In amateur athletes, marathon running promotes biatrial remodelling with significant gender discrepancies. Females are more susceptible to exercise-induced morphological and functional changes of RA, while postrace alternations in males concern principally LA. 3D echocardiography of the atria is a useful indicator of exercise capacity, not only in elite, but also in amateur athletes.

Funding Acknowledgement
Type of funding sources: None.
Usefullness of 2D/3D-TEE for guiding transapical beating heart neochordae implantation in mitral regurgitation
Authors: Mahia P , Cobiella J , Carnero M , Enriquez D , De Agustin J.A , Macaya C , Maroto L 
Published: October 2021

Abstract

Background
Transapical beating-heart neochord implantation (Neochord) to repair mitral valve regurgitation has been demonstrated to be a safe and effective minimally invasive alternative to open surgical repair in selected patients with mitral leaflet prolapse. Successful neochordae implantation depends on accurate localization of the site of regurgitation and careful assessment of MV morphology.
The objective of this study is to demonstrate that 3D-transesophageal echocardiography (3D-TEE) has become a fundamental tool, essential in both the preoperative study and to guide the procedure and for follow-up.

Methods
All consecutive patients with severe symptomatic DMR due to prolapse or flail of one or both mitral leaflets that underwent the NeoChord procedure between March 2017-Jan 2021 were included. Patients were categorized according to MV anatomy by 3D-TEE; Type A isolated central posterior leaflet prolapse and/or flail, Type B posterior multi-segment prolapse and/or flail, Type C anterior and/or bi-leaflet prolapse or flail, Type D paracommissural prolapse and/or flail and/or significant leaflet and/or annular calcifications.

Results
43 patients were included. Median age was 67.7±13.4 y. Median EuroSCOREII 2.7%±1.91. There were 35 Type A patients (81.4%), 4 Type B (9.3%), 1 Type C (2.3%), and 3 Type D (7%). Type A was considered the more favorable morphology. 2D/3D TEE were employed for guiding the device from the apex of the left ventricle across the mitral annulus (Figure 1, A–C), orientation of the tip of the device with regards to the prolapsing segment of the leaflet positioning and leaflet grasping (Figure 1, D, E) and evaluation of the final length and tension of the neochordae to obtain a satisfactory mitral valve competence. (Figure 1, F). Procedural success was achieved in 38 patients (88,4%). 5 patients, 2 type A and 3 type D, underwent conversion to open surgery for immediate failure. 1 high-risk patient considered inoperable died before discharge. At 19 (IQR 13–23) months median follow-up, MR ≤II was present in 29 (76.3%). Overall 2 year survival was 100%. Freedom from reintervention was 89% for overall population.

Conclusions
TEE-Guided Transapical beating-heart neochord implantation is a feasible, low-risk technique. 2D and 3D TEE are the fundamental and essential diagnostic tools for the correct selection and monitoring of the procedure, as well as its possible complications.

Funding Acknowledgement
Type of funding sources: None. Figure 1
Prognostic value of sST2 in heart failure patients with diabetes
Authors: Castiglione V , Chiriaco' M , Aimo A , Januzzi J , Richards A.M , Lam C.S.P , Latini R , Anand I.S , Ueland T , Brunner-La Rocca H.P , Bayes-Genis A , De Boer R.A , Huber K , Emdin M , Vergaro G 
Published: October 2021

Abstract

Background
Soluble suppression of tumorigenesis-2 (sST2) is released in response to inflammation and vascular injury, and holds prognostic value in heart failure (HF). Type 2 diabetes (T2D) is characterized by a pro-inflammatory status and is highly prevalent among HF patients, with adverse impact on outcomes. The clinical value of sST2 in HF patients with T2D has never been characterized.

Purpose
We aimed to assess sST2 clinical correlates and prognostic value in HF patients with T2D.

Methods
Individual data of 3476 patients with stable chronic HF from 5 cohorts from the BIOS (Biomarkers In Heart Failure Outpatient Study) dataset were analysed, with available N-terminal fraction of pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity troponin T (hs-TnT), and sST2 levels.

Results
Mean age was 65±12 years (75% males). T2D was present in 1386 patients (40%), who had higher body mass index (BMI, 27 [24–30] vs. 26 [23–29] kg/m2, p&lt;0.001), lower estimated glomerular filtration rate (eGFR, 56±22 vs. 60±19 mL/min/1,73 m2, p&lt;0.001), higher sST2 (33 [24–47] vs. 27 [20–40] ng/mL, p&lt;0.001), NT-proBNP (1735 [742–3963] vs. 1450 [514–3299] ng/L, p&lt;0.001), hs-TnT (28 [16.2–51.5] vs. 17 [9–31] ng/L, p&lt;0.001) and high-sensitivity C-reactive protein (hs-CRP, 6 [2–11] vs. 4. [2–9] mg/L, p=0.003) (Figure). Differences between sST2 levels in patients with or without T2D were influenced by hs-CRP (p for interaction=0.010) and hs-TnT (p=0.031), but not by NT-proBNP and eGFR. At multivariate linear regression analysis, NT-proBNP, hs-TnT and hs-CRP were independently associated with sST2 levels in both T2D and non-T2D patients. Compared with patients without T2D, those with T2D showed higher 1-year all-cause mortality (12% vs. 10%, p=0.034), cardiovascular mortality (9% vs. 7%, p=0.011), and HF hospitalization rate (22% vs. 12%, p&lt;0.001). In a prognostic model including age, sex, eGFR, ischemic vs- non-ischemic aetiology, left ventricular ejection fraction class, New York Heart Association class, NT-proBNP, hs-TnT, and hs-CRP, sST2 retained independent prognostic value in both patients with or without T2D for 1-year all-cause and cardiovascular mortality, and 1-year HF hospitalization, with higher optimal cut-offs for mortality prediction in T2D vs. non-T2D (39 and 45 vs. 29 and 29 ng/mL respectively for 1-year all-cause and cardiovascular mortality).

Conclusions
sST2 is higher in HF patients with T2D and likely linked to a pro-inflammatory status. sST2 maintains its prognostic value both in diabetic and non-diabetic HF patients, independently of NT-proBNP, hs-TnT and hs-CRP.

Funding Acknowledgement
Type of funding sources: None. Figure 1
Clinical and prognostic significance of the inflammatory markers GlycA and GlycB in chronic heart failure of both ischemic and non-ischemic etiologies
Authors: Cediel Calderon G , Teis A , Codina P , Domingo M , Santiago-Vacas E , Spitaleri G , Zamora E , Santasmases J , Alonso N , Lupon J , Bayes-Genis A 
Published: October 2021

Abstract

Background
N-acetylglucosamine/galactosamine (GlycA) and sialic acid (GlycB) constitute evolving nuclear magnetic resonance (NMR) biomarkers of systemic inflammation. They have been increasingly studied and associated with cardiovascular (CV) disease and incident heart failure (HF), but little is known about its value in chronic HF population.

Purpose
We aimed to examine the association on long-term CV outcomes of GlycA and GlycB in chronic HF relative to aetiology.

Methods
We prospectively included a cohort of 429 HF patients admitted to an ambulatory HF Unit. Plasma GlycA and GlycB concentrations were determined using NMR spectroscopy. The primary endpoint was a composite of CV death and readmission due to HF. Competing risk regression models were performed with non-CV death as the competing event. Because an interaction existed between GlycA and GlycB with ischemic etiology (p&lt;0.01), we examined this further.

Results
The mean (SD) follow-up was 4.5±2.9 years. Median concentrations (IQR) for GlycA and GlycB were 5.4 (4.9–6.2) mmol/L and 1.9 (1.7–2.2) mmol/L, respectively. A total of 92 (41.1%) and 123 (60.0%) patients from non-ischemic and ischemic etiology, respectively, the clinical endpoint. In ischaemic HF patients (47.8%; n=205) both markers were not associated with the primary endpoint. Conversely, in non-ischemic HF patients (52.2%; n=224), GlycA and GlycB exhibited association with the primary endpoint in univariable and after multivariable adjustment (HR 1.14; 95% confidence interval [CI]: 1.02–1.28, p=0.018 and HR 1.91; 95% CI: 1.27–2.88, p=0.002; respectively. Figure 1 and 2). In this subgroup, a correlation analysis with well-known biomarkers (NT-proBNP, hs-TnT and ST2) only evidenced a positively and significantly correlation of GlycB with ST2 (r=0.26, p&lt;0.001). No association was found with NYHA functional class.

Conclusions
GlycA and GlycB represent an evolving approach of inflammation status with prognostic value of long-term CV related events in non-ischemic HF patients.

Funding Acknowledgement
Type of funding sources: None. Figure 1. Probability of MACE by GlycA tertilesFigure 2. Probability of MACE by GlycB tertiles
Right ventricular ejection fraction as predictor of outcome in acute heart failure using RV ellipsoid model. A retrospective analysis of a prospective cross-sectional study
Authors: Ashcroft E.A , Belsey J , Berrill M , John I , Baltabaeva A 
Published: October 2021

Abstract

Introduction
Echocardiography (TTE) is an essential imaging modality for assessment of RV function in acute heart failure. Established parameters are useful and easy to perform but fail to reflect on global volumes due to reliability on one acoustic window. It is therefore attractive to calculate RV volumes and ejection fraction using an ellipsoid model (RVEF/E) which has been validated against MRI in healthy adults but not in the HF patients.

Purpose
Predictive value of RVEF/E were compared with two established echo parameters of RV function over two-year follow-up period in patients with acute HF. Primary outcome measure was all-cause mortality.

Methods
Prospective cross-sectional study enrolling 418 consecutive patients with symptoms of acute HF according to a predefined study protocol. All patients underwent TTE assessment of RV function using Tricuspid Annular Plane Systolic Excursion (TAPSE) and RV fractional area change (RVFAC) and RVEF/E. RV Volumes calculated using formula, RVIT is RV inflow tract diameter, RVLAX is RV length and LVD is LV maximal diameter in 2 chamber view.
RVV=(3.14/6) x RVIT x RVLAX x LVD

Results
ROC analyses established an RVEF/E cut-off of 46.8%, TAPSE of 1.6cm and RVFAC of 38.2%. RVEF/E was able to separate patients with higher BNP level (p≤0.0001) and lower systolic BP (p≤0.002). As expected TAPSE and RVFAC were significantly reduced in patients with impaired RVEF. RVEF/E was found equal to TAPSE & RVFAC in predicting outcome (HR 1.48 vs HR 1.48, p≤0.01 vs p≤0.01) and provided benefit of RV volume estimation.

Conclusions
This is the first study to demonstrate that RVEF/E derived from ellipsoid model is not inferior to well established measures of RV function as a prognostic indicator of medium-term outcome in the acute HF.

Funding Acknowledgement
Type of funding sources: None. Kaplan Meier survival curvesBaseline characteristics