bluuebunny/crossref_metadata_2025_split huggingface dataset:
The influence of left-heart myopathy on the diagnosis and treatment of mitral valve stenosis: an in silico trial
Authors: Van Den Acker G , Dhont S , Van Loon T , Churchill T W , Timmermans F , Delhaas T , Bertrand P B , Lumens J 
Published: January 2025

Abstract

Background
The shift in mitral stenosis (MS) aetiology from rheumatic to calcific valve disease, commonly seen in elderly patients with cardiomyopathy, challenges the differentiation between valve- or tissue-related causes of haemodynamic abnormalities.

Purpose
This study examines the impact of left-heart myopathy on the echocardiographic assessment of MS severity and acute haemodynamic effects following mitral valve (MV) intervention.

Methods
The CircAdapt model of the human cardiovascular system was used to evaluate the effect of MS on cardiac haemodynamics in a virtual patient cohort with broad ranges of impaired left atrial (LA) function and reduced left ventricular (LV) compliance. Mean gradient (MG) and pressure half-time (PHT) were derived for MS severity assessment, alongside LV and LA pressure traces to quantify the haemodynamic consequence of MV intervention.

Results
Depending on myocardial abnormalities, the MG varied by only 10%, 5% and 5% for mild, moderate and severe MS, respectively. Reduced LV compliance resulted in disproportionately lower PHT causing overestimation of the PHT-derived MV area up to 1.43 cm2. Following virtual MV intervention for moderate to severe MS, mean left atrial pressure (mLAP) decreased by 50% in presence of healthy myocardium but only 4% for combined LV and LA dysfunction. In patients with reduced LV compliance, LV end-diastolic pressure remained elevated despite MV intervention.

Conclusions
The virtual patient cohorts indicate that the MG is a robust metric for MS severity regardless of left-heart myopathy, whereas PHT may reveal underlying impaired LV compliance. However, neither MG nor PHT predict changes in mLAP following intervention. Recognizing the significance of distinguishing between increased left-heart pressures driven by valvular or tissue factors is therefore crucial for clinical decision-making.
graphical abstract
methods
Left ventricular impairment in aortic stenosis and clinical and neurohormonal improvement after TAVI
Authors: Rychlewski J , Golanski G , Kubisz K , Aleksandrowicz K , Protasiewicz M , Kubler P , Kosowski M , Przewlocka-Kosmala M , Ponikowski P , Kosmala W 
Published: January 2025

Abstract

In view of the increasing prevalence of aortic stenosis (AS) in ageing populations, identifying predictors of favorable clinical response to transcatheter aortic valve implantation (TAVI) is of particular importance. Typically, more severe LV function impairment is believed to indicate less potential for improvement after eliminating the cause of disease. However in AS, the reversibility of myocardial damage and its correlation with the regression of symptoms after valve replacement are less explored. It is suggested that myocardial work (MW) indices correcting global longitudinal strain (GLS) for LV afterload may offer greater diagnostic insight in AS than traditional load dependent echo markers.

Aim
To investigate the associations of post-TAVI improvements in 6 min walk test (6MWT) and NT-proBNP with baseline values and changes after valve replacement in LV systolic and diastolic function parameters in patients with AS.

Methods
We evaluated 162 patients (77±9 years) with severe AS who underwent TAVI. Transthoracic echocardiography, blood sampling and 6MWT were performed before and 3 months after treatment. The following indices of MW were assessed: global work index (GWI), global constructive work (GCW), global wasted work (GWW), global work efficiency (GWE). Changes from pre- to post-TAVI (deltas) were calculated as the follow-up (3-months) value minus the baseline value.

Results
Based on the post-TAVI improvements in 6MWT and NT-proBNP, the population was divided into 3 subsets: high benefit group (HB): (delta 6MWT&gt;median [49 m] and delta NT-proBNPmedian), and intermediate benefit group (IB): (the remainder patients). Participants from the HB group were characterized by the most severe LV function impairment, highest BNP and shortest 6MWT at baseline, as well as the greatest improvements in cardiac function after TAVI. On the other hand, the LB subgroup did not demonstrate the most impaired LV function at baseline compared to the other subgroups (Table). Post-TAVI improvements in 6MWT and NT-proBNP were larger in patients with baseline GLS below 9% than above 9% (85 ± 76 m vs. 43 ± 75 m, p=0.011, and -8848 ± 9096 pg/ml vs. -1384 ± 2740 pg/ml, p=&lt;0.001, respectively), as well as in patients with baseline GCW below 1500 mmHg% than above 1500 mmHg% (83 ± 77 m vs. 43 ± 75 m, p=0.025, and -9245 ± 8798 pg/ml vs. -1447 ± 3038 pg/ml, p=&lt;0.001, respectively).

Conclusions
Post-TAVI improvements in 6MWT and NT-proBNP can be expected even in AS patients with severely impaired myocardial function. GLS, MW, and diastolic parameters do not effectively identify patients with more irreversible LV impairment who benefit less from TAVI. MW indices are not superior to GLS in tracking LV responses to TAVI.
Table
Incremental clinical value of the regurgitant fraction assessed by three-dimensional echocardiography in patients with secondary tricuspid regurgitation
Authors: Buta A , Gavazzoni M , Tomaselli M , Radu N , Heilbron F , Fisicaro S , Clement A , Delcea C , Rella V , Kawada Y , Badano L P , Muraru D 
Published: January 2025

Abstract

Background
Differently from the effective regurgitant orifice area (EROA) and regurgitant volume (RegVol), RegFr directly accounts for the size and the function of the right ventricle (RV).

Objectives
To assess the relationship between regurgitant fraction (RegFr) evaluated using three-dimensional echocardiography (3DE) and the outcome in patients with secondary tricuspid regurgitation (STR).

Methods
331 patients with at least mild STR were enrolled. RegFr was computed as ratio between the RegVol, calculated using the proximal isovolumic surface area (PISA) method by Doppler and the total stroke volume (SV) of the RV computed as difference between 3DE RV end-diastolic (RVEDV) and end-systolic (RVESV) volumes. To compare the association of EROA, RegFr and RegVol with outcome, we used a composite endpoint of heart failure hospitalization (HFH) and death for any cause.

Results
After a median follow-up of 20 months, 133 patients (40%) reached the combined endpoint. Among the quantitative parameters of STR severity, RegFr had the highest area under the curve at ROC analysis (AUC= 0.65, 95%CI: 0.59-0.71). At Cox regression, RegFr was associated with outcome both in the univariate analysis (HR 1.012, CI 1.003-1.020, p=0.006) and in multivariate, adjusted for several clinical and echocardiography correlates. By testing each single quantitative parameter of STR severity, only RegFr significantly increased the prediction of the basal model (p=0.007) and improved the risk-stratification of the patients on top of EROA (Net Reclassification Index: 0.2833, p=0.011). In the subgroup of patients with non-severe STR (i.e., EROA&lt;0.4 cm²), the RegFr identified the patients with significantly higher risk of events (cumulative incidence of the combined endpoint of 73% in patients with EROA&lt;0.4 cm2 but RegFr≥50% vs 51 % in patients with RegFr&lt;50%, p= 0.02).

Conclusions
Compared to EROA and RegVol obtained by PISA method, RegFr obtained by 3DE was more strongly associated with the outcome of patients with STR.
Aortic dP/dt as a new tool for prediction of aortic stenosis progression: a validation in a single-center cohort
Authors: Bello A , Paiva M , Freitas P , Gomes D A , Lopes P , Gama F , Guerreiro S , Ferreira A , Abecasis J , Trabulo M , Andrade M J , Ribeiras R 
Published: January 2025

Abstract

Introduction
Aortic pressure increase per time unit (dP/dt) has been recently shown to predict the risk of progression of aortic stenosis (AS), with a proposed cut-off of 600 mmHg/s (Panel A). Whether it applies to other populations remains to be elucidated.

Methods
In this single-center retrospective study, we included patients with isolated moderate AS who had performed a complete transthoracic echocardiography (TTE) assessment in our center between 2014 and 2022. The primary endpoint was progression to severe AS, as documented by follow-up TTE. Uni- and multivariate analysis with Cox regression was used to assess the predictive value of dP/dt.

Results
A total of 103 patients were included, with a median age of 78 years (IQR 71 - 83), of which 58 (56%) were male. Median follow-up was 2.2 years (QR 1.1-3.7) and mean left ventricular ejection fraction (LVEF) was 54 ± 7%. We identified a total of 75 (73%) patients with a dP/dt ≥ 600mmHg/s; the mean value for dP/dt 737 ± 269 mmHg/s.
Aortic dP/dt was independent of flow conditions, showing no correlation with stroke indexed volume (rho = 0.182; p = 0.08; r2 = 0.02) or LVEF (rho = 0.102; p = 0.31; r2 = 0.04).
After adjustment for aortic maximum velocity (aHR 2.46 [1.08 - 5.5; p = 0.033]) and baseline creatinine (aHR 1.21 [1.06 - 1.37; p = 0.04]), dP/dt remained an independent predictor of progression to severe AS (aHR per 100 mmHg/s: 1.18 [1.03 - 1.34; p = 0.017]).
The median time to AS progression was considerably shorter in patients with a dP/dt ≥ 600mmHg/s when compared with patients with a dP/dt &lt; 600 mmHg/s (2.6 years [95%CI 2.0 – 3.3] vs. 5.3 years [95%CI 4.1-6.5]; Log-Rank p value &lt; 0.001) (Panel B).
The dP/dt cut-off of 600 mmHg/s had a sensitivity of 81% (95%CI: 69-90%), a specificity of 44% (95%CI: 30-60) a positive predictive value of 67% (95%CI 60-73%) and negative predictive value of 63% (95%IC: 48-75%).

Conclusions
Aortic dP/dt was validated in a single-center cohort of moderate aortic stenosis patients as an independent predictor of accelerated disease progression. This finding may help tailor individualized follow-up strategies.
Prevalence of heart valve disease and left ventricular systolic dysfunction in a multi-ethnic, migrant community
Authors: Laskar N , Bhattacharyya S , Lloyd G 
Published: January 2025

Abstract

Introduction
Clinically significant valvular heart disease (VHD) affects 13.3% of individuals aged 75 and older, while left ventricular systolic dysfunction (LVSD) is seen in 2% of those aged 85 and older, and 3.5% of those aged 65 and older but most data comes from rural/suburban areas with predominantly Caucasian populations. Data on these diseases in urban, ethnically diverse areas with high migrant populations is lacking.

Purpose
This quality improvement project aimed to establish the prevalence of left-sided valve disease and LVSD by conducting community-based handheld echocardiography detection in an urban, multi-ethnic community.

Methods
Patients over 65 without known left-sided heart valve disease or heart failure, across four GP practices and one vaccination centre using handheld ultrasound device (Vscan Extend). The protocol included an abbreviated dataset with colour flow and three standard echocardiography views. All studies were reviewed and adjudicated by an independent expert. Those patients adjudicated to have important disease on handheld detection underwent subsequent comprehensive echocardiography.

Results
518 patients were evaluated. Ethnic distribution: 14.4% Caucasian, 51.6% Indian, 0.2% Chinese, 14% Pakistani, 9.7% African, 9.1% other. New diagnoses of left-sided HVD or LVSD were identified in (n=166 ) 32% and (n=10) 2% respectively. Mitral Regurgitation (MR) was most common (n =100, 19.3%), followed by aortic regurgitation (AR) (n =30, 5.8%), aortic stenosis (AS) (n =13, 2.5%), and mitral stenosis (MS) (n =2, 0.4%). LVSD was found in (n=10, 2%).
Comprehensive confirmatory echocardiograms were done in 73 patients. Of these mild VHD was observed in n =57 (78%), (mild AR n =27, 37%, mild MR n =31, 45%, and mild AS/aortic sclerosis n =12, 16%). Calcified mitral valve was found in n =3, (4%). Mild LVSD was in n =6, 8%.
Moderate to severe HVD was found in n= 12 (16.4%), (MR in 8%, AR in 5% and AS in 2.7%) and moderate to severe LVSD in n =3, 4%. Age predicted HVD (OR 1.09, 95% CI 1.06-1.13, p &lt;0.001) and LVSD (OR 1.07, 95% CI 1.01-1.13, p &lt;0.05) while Type 2 diabetes (OR 3.47, 95% CI 0.13-0.83, p &lt;0.05) and ischemic heart disease (IHD) (OR 5.41, 95% CI 2.26-13.11, p &lt;0.001) were predictors for LVSD. There was no relationship between ethnic group and the presence of HVD or LVSD (p values &gt;0.05).

Conclusion(s)
HVD and LVSD is common in this urban, multi-ethnic community. A Vscan based detection program found a prevalence of any VHD of 32% and LVSD of 2% . Of these 2.3% and 0.6% were moderate to severe (HVD and LVSD). Age was associated with both HVD and LVSD, while T2DM and IHD are associated with LVSD. There was no relationship between ethnicity and either HVD or LVSD.
Severity of HVD
Ethnicity Distribution
Differential genetic impact on the occurrence of atrial fibrillation in hypertrophic cardiomyopathy according to age
Authors: Chung H , Ryu S K , Rim S J , Choi E Y 
Published: January 2025

Abstract

Background
Atrial fibrillation (AF) is a common arrhythmia associated with adverse events in patients with hypertrophic cardiomyopathy (HCM).

Purpose
The objective of this study was to investigate whether genetic characteristics were associated with AF in HCM patients.

Methods
Of the 212 prospectively enrolled patients in the HCM genetic registry, 33 had initial AF, and the remaining 179 (126 males, 58 ± 13 years) were followed up for the development of new-onset AF.

Results
Of the 212 patients, 45 were diagnosed with AF before the final follow-up visit. Pathogenic and likely pathogenic sarcomere gene mutations were detected in 29.3% (49/167) of patients without AF and 40.0% (18/45) of patients with AF, without significant differences. MYH6 was more prevalent in the AF group (2/45, 4.4%) than in the non-AF group (0/167, p = 0.044), and TNNI3 tended to be more prevalent in the AF group (6/45, 13.3%) than in the non-AF group (8/167, 4.8%) (p = 0.051). Among patients younger than 65 years (n = 128), those with any sarcomere variants (pathogenic and variants of uncertain significance, n = 77) had a higher prevalence of overall AF (initial and new-onset, p = 0.045). The mutation-positive group had a higher left atrial volume index, lower a’, and higher prevalence of non-apical HCM in patients &lt;65 years. However, in patients ≥65 years, no significant difference was found between mutation-positive and -negative groups.

Conclusions
In younger HCM patients, the presence of sarcomere variants, including variants of uncertain significance, is related to a higher prevalence of AF.
Dapagliflozin prevents ejection fraction and fractional shortening reduction, reduces myocardial NF-KB expression and systemic pro-inflammatory biomarkers in models of doxorubicin cardiotoxicity
Authors: Quagliariello V , Paccone A , Maurea F , Palma G , Luciano A , Bruzzese F , Zito Marino F , Franco R , Montella M , Barbato M , Izzo F , Giacobbe I , Giordano V , Arianna R , Maurea N I C O L A 
Published: January 2025

Abstract

Background
Anthracycline-mediated adverse cardiovascular events are among the leading causes of morbidity and mortality in patients with cancer. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) exert multiple cardiometabolic benefits in patients with/without type 2 diabetes, chronic kidney disease, and heart failure with reduced and preserved ejection fraction. We hypothesized that the SGLT2i dapagliflozin administered before and during doxorubicin (DOXO) therapy could prevent cardiac dysfunction and reduce pro-inflammatory pathways in preclinical models.

Methods
Female C57Bl/6 mice were treated for 10 days with a saline solution or DOXO (2.17 mg/kg), DAPA (10 mg/kg), or DOXO combined with DAPA. ). Cardiac function studies, including EF, FS and radial/longitudinal strain were analysed through transthoracic echocardiography (Vevo 2100) . Systemic levels of ferroptosis-related biomarkers, galectin-3, high-sensitivity C-reactive protein (hs-CRP), and pro-inflammatory chemokines (IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-10, IL-12, IL17-α, IL-18, IFN-γ, TNF-α, G-CSF, and GM-CSF) were quantified. After treatments, immunohistochemical staining of myocardial and renal p65/NF-kB was performed.

Results
DAPA exerts cytoprotective, antioxidant, and anti-inflammatory properties in human cardiomyocytes exposed to DOXO by reducing iATP and iCa++ levels, lipid peroxidation, NLRP-3, and MyD88 expression. Pro-inflammatory intracellular cytokines were also reduced. In preclinical models, DAPA prevented the reduction of radial and longitudinal strain and ejection fraction after 10 days of treatment with DOXO. A reduced myocardial expression of NLRP-3 and MyD-88 was seen in the DOXO-DAPA group compared to DOXO mice. Systemic levels of IL-1β, IL-6, TNF-α, G-CSF, and GM-CSF were significantly reduced after treatment with DAPA. Serum levels of galectine-3 and hs-CRP were strongly enhanced in the DOXO group; on the other hand, their expression was reduced in the DAPA-DOXO group. Troponin-T, B-type natriuretic peptide (BNP), and N-Terminal Pro-BNP (NT-pro-BNP) were strongly reduced in the DOXO-DAPA group, revealing cardioprotective properties of SGLT2i. Mice treated with DOXO and DAPA exhibited reduced myocardial and renal NF-kB expression.

Conclusion
The overall picture of the study encourages the use of DAPA in the primary prevention of cardiomyopathies induced by anthracyclines in patients with cancer.
Incidence, predictors and outcomes associated with pacemaker implantation in transthyretin cardiac amyloidosis
Authors: Istratoaie S , Bourg C , Marut B , L'official G , Lacout M , Serrano E , Fargeaud D , Donal E 
Published: January 2025

Abstract

Background
Arrhythmias are poorly tolerated by patients with transthyretin cardiac amyloidosis (ATTR). The occurrence rate of pacemaker (PM) implantation among ATTR, along with its predictors and impact on outcomes has not been extensively investigated. Our objective was to analyze the patterns of permanent PM implantation and to identify predictors for future PM placement in ATTR patients.

Methods
Consecutive patients with wild-type ATTR diagnosed in one single center between 2016-2022 were included. The primary outcome of the study was PM implantation. Patients with pre-existing PM (n = 31) were excluded. The study population included 160 patients, 88% male, median age 82 (76, 85) years. Clinical, laboratory, electrocardiography (ECG) and comprehensive echocardiography data were analysed.

Results
During a median follow-up of 30.5 months, 37 (23.1%) patients underwent PM implantation. The main indications for PM implantation were complete atrioventricular (AV) block (9 patients, 24.3%) and advanced conduction impairment (9 patients, 24.3%). ECG demonstrated a more prolonged PR interval and increased QRS duration (both p&lt;0.001) with higher rate of first-degree AV block and right bundle branch block (both p=0.003) in patients requiring PM implantation. The echocardiogram showed greater wall thickness, a more dilated left atrium, along with biventricular dysfunction in the PM group. At multivariable analysis, first-degree AV block (HR=2.96, p=0.012), interventricular septum (IVS) thickness (HR=1.27, p=0.001) and biomarker-based staging system (HR= 2.43, p=0.008) were independently associated with PM implantation. PM implantation was associated with increased mortality or HF hospitalization.

Conclusions
In our cohort of ATTR patients, 23.1% required a pacemaker, primarily due to conduction system disease. Independent predictors for new pacemaker implantation included first-degree AV block, increased IVS thickness, and the biomarker-based staging system.
Systemic sclerosis is associated with coronary microvascular dysfunction assessed using echocardiographic coronary flow parameters: a meta-analysis
Authors: Jain H , Jain J , Alderhalli R , Singh J , Khaled K , Goyal A , Odat R M , Patel N , Scott I , Ahmed R 
Published: January 2025

Abstract

Background
Systemic sclerosis (SSc) is a connective tissue disease that is characterized by vascular dysfunction and extensive fibrosis. The current literature suggests a 15-35% prevalence of cardiac manifestations in patients with SSc, the majority of which remains subclinical. Patients with SSc often demonstrate angiographically normal epicardial coronary arteries despite underlying dysregulation in the coronary microvasculature. Coronary flow reserve (CFR) is a noninvasive marker of coronary microvascular circulation.

Purpose
This meta-analysis aimed to compare CFR between patients with SSc and healthy controls.

Methods
A comprehensive literature search of the major bibliographic databases, including PubMed/MEDLINE, Embase, and the Cochrane Library was conducted. The aim was to identify studies comparing CFR between patients with SSc and healthy controls. The standardized mean differences (SMDs) with 95% confidence intervals (CIs) were pooled using an inverse-variance random-effects model. Statistical significance was set at p &lt; 0.05. Heterogeneity was assessed using the Higgins I2 metric.

Results
Four studies were included in this meta-analysis, with a total of 210 participants (129 patients with SSc; 81 healthy controls). In the SSc and control groups, 88.3% and 70.3% of the patients, respectively, were female. The mean ages of the SSc and control group were 52.2 ± 13.2 and 47.77 ± 9.8, respectively. The pooled analysis demonstrated a statistically significant reduction in CFR associated with SSc [SMD: -1.44; 95% CI: -1.76, -1.13; p&lt;0.00001] compared to healthy controls. No heterogeneity was observed in the effect estimates [I2 = 0%].

Conclusion
SSc is associated with a higher risk of coronary microvascular dysfunction, as indicated by the reduced CFR. The results of this meta-analysis demonstrate the importance of a comprehensive cardiac evaluation in patients with SSc. Early aggressive targeted interventions for impaired CFR in SSc patients may lead to improved clinical outcomes. Further prospective studies are required to elucidate the prognostic impact of a blunted CFR.
Figure 1