bluuebunny/crossref_metadata_2025_split huggingface dataset:
Left ventricular morphology in patients with aortic coarctation and bicuspid aortic valve: novel insights from a statistical shape modelling framework
Authors: Sophocleous F , Standen L , Doolub G , Laymouna R , Bucciarelli-Ducci C , Caputo M , Manghat N , Hamilton M , Curtis S , Biglino G 
Published: October 2022

Abstract

Background
The functional implications of left ventricular (LV) morphological characterization in congenital heart disease (CHD) are not widely explored.

Purpose
This study qualitatively and quantitatively assessed LV shape associations with a) LV function and b) thoracic aortic morphology in patients with aortic coarctation (CoA) with/without bicuspid aortic valve (BAV).

Methods
A statistical shape modelling (SSM) framework was employed to analyse three-dimensional (3D) LV shapes from cardiac magnetic resonance (CMR) imaging data in n=110 cases including: isolated CoA (n=25), CoA+BAV (n=30), isolated BAV (n=30), and age-matched healthy controls (n=25). Average 3D templates (Picture 1) and deformations were computed. Correlations between shape data and CMR-derived morphometric parameters (i.e. sphericity, conicity) as well as CMR-derived global and apical strain values were assessed to elucidate possible functional implications. The relationship between LV shape features and arch architecture (i.e. gothicity, tortuosity) was also explored by means of regression analysis.

Results
The LV template was shorter and more spherical in CoA patient (Picture 1), as also confirmed by statistical analysis of the SSM-derived shape modes. LV sphericity, which was higher in CoA, was associated (p≤0.04) with lower global longitudinal, radial and circumferential strain, irrespective of the presence of aortic stenosis and/or regurgitation. Conversely, neither LV morphology nor LV strain was not associated with arch architecture.

Conclusions
Differences in LV morphology were observed between CoA and BAV patients. Increasing LV sphericity was associated with reduced strain, independent of aortic arch architecture and functional aortic valve disease.

Funding Acknowledgement
Type of funding sources: Foundation. Main funding source(s): British Heart Foundation and NIHR BRC
Impact of lifetime concentration of mannose on renal function: insights from Mendelian randomization
Authors: Mazidi M , Shekoohi N , Katsiki N , Banach M 
Published: October 2022

Abstract

Background
Mannose is a sugar monomer of the aldohexose series of carbohydrates, important in human metabolism, especially in the glycosylation of certain proteins. There is a handful of controversial data from observational studies on the serum levels of mannose and risks of renal disease.

Purpose
We performed a Mendelian Randomization (MR) analysis to obtain unconfounded estimates of the casual associations between genetically instrumented serum mannose, estimated glomerular filtration rate (eGFR) and the risk for chronic kidney disease (CKD defined as eGFR &lt;60 ml/min/1.73 m2).

Methods
MR was implemented by using summary-level data from the largest ever genome-wide association studies (GWAS) conducted on serum mannose and renal function. Inverse variance weighted method (IVW), weighted median (WM)-based method, MR-Egger, MR-Robust Adjusted Profile Score (RAPS), MR-Pleiotropy RESidual Sum and Outlier (PRESSO) were also applied. Sensitivity analysis was conducted using the leave-one-out method. The analyses were performed in the total population, in non-diabetics and in patients with type 2 diabetes mellitus (T2DM).

Results
Serum mannose concentrations were not significantly associated with CKD risk (IVW: beta=1.018, p=0.273), but they were negatively related to eGFR in the total population (IVW: beta=−0.137, p=0.003), the non-diabetics (IVW: beta=−0.126, p=0.018) and the T2DM patients (IVW: beta=−0.344, p=0.004). None of the MR-Egger estimates showed heterogeneity, and the MR-PRESSO analysis did not find any possibility of outliers for all of the estimates. The pleiotropy test also indicated a low chance of pleiotropy for all estimations (p&gt;0.242), as did the MR-RAPS analysis. Leave-one-out method demonstrated that the observed associations were not driven by single-nucleotide polymorphisms.

Conclusions
Our results highlighted that individuals with genetically higher serum mannose levels have a significantly lower eGFR, regardless of the presence or absence of T2DM. However, no association between serum mannose concentrations and the risk of CKD was observed.

Funding Acknowledgement
Type of funding sources: None.
Impact of sodium-glucose co-transporter 2 inhibitors on cardiovascular outcomes in patients with chronic kidney disease: Hong Kong-wide, observational, propensity score matched analysis
Authors: Sun W , Yan B 
Published: October 2022

Abstract

Purpose
The impact of SGLT2i on patients with advanced chronic kidney disease (CKD) is limited. We aimed to compare hospitalization for heart failure (HHF) and cardiovascular (CV) death between new users of SGLT2i versus non-users across the spectrum of CKD stages.

Methods
We retrospectively analyzed 22,657 patients with CKD who were prescribed SGLT2i between August 2015 and August 2020 in 16 public hospitals in Hong Kong. Propensity-matched cohorts of SGLT2i users and non-users (n=3,704 per group) were generated on the basis of age, gender, baseline eGFR, co-morbidities and medications. Time to HHF and CV death was analyzed using COX proportional hazards model. Subgroup analysis was performed to detect heterogeneity of effect across stages of CKD.

Results
Of the whole cohort (N=22,657), the percentage of SGLT2i users in CKD stage G1 to G5 were 82.1%, 49.0%, 19.8%, 10.3%, 4.3%, and 1.6%, respectively. SGLT2i users and non-users groups were well balanced at baseline (mean age 64.7±12.7, female 37.1%), with a median follow-up of 2.8 (IQR: 1.1–5.1) years (22876.5 person-years). Overall, SGLT2i was associated with reduced risk of HHF (Hazards Ratio (HR) 0.12 (95% CI (0.10–0.16) and CV death (HR 0.17 (95% CI (0.12–0.25), compared with non-users. Subgroup analysis demonstrated benefit of SGLT2i on CV death in G3 to G5 groups but not in patients in earlier CKD stages (P for interaction &lt;0.001) (Table). Reduction in risk of HHF was comparable across all CKD stages (P for interaction = 0.1).

Conclusion
Utilization of SGLT2i was associated with significant reduction in HHF and CV death in patients with moderate to severe CKD in a real-world setting. Our results suggest significant heterogeneity in CV death reduction with the largest benefit in patients with stage G3a and more advanced CKD.

Funding Acknowledgement
Type of funding sources: None.
CAD in kidney transplant recipients: a real-world assessment pre-ISCHEMIA-CKD
Authors: Rocha B , Amador R , Maltes S , Cunha G , Mateus C , Aguiar C , Weigert A , Mendes M 
Published: October 2022

Abstract

Background
The ISCHEMIA-CKD trial has shown that an initial invasive strategy, as compared to conservative treatment, did not reduce the risk of death and non-fatal myocardial infarction, nor did it improve quality-of-life in patients with advanced chronic kidney disease (CKD) and coronary artery disease (CAD) with moderate-to-severe ischemia. Similar findings were reported in patients with CKD enlisted for kidney transplantation (KT). We aimed to evaluate screening and treatment CAD strategies in patients who ultimately underwent KT at our center.

Methods
This is a single-center study of consecutive patients who received a KT from 2015 to 2020. Obstructive CAD was defined whenever one of the following criteria was met: lesion with a stenosis &gt;70% (or &gt;50%, if left main disease) or CAD requiring revascularization, as per the Heart Team discussion. CAD evaluation refers to non-invasive or invasive coronary angiography and/or stress testing, irrespective of clinical scenario.

Results
A total of 324 patients underwent KT [mean age 55±12 years; 65.1% male; CKD most often due to hypertensive or diabetic nephropathy and polycystic kidney disease – 41.8%; median time from renal replacement therapy (RRT) to KT – 60 (40–88) months]. A flow-chart summarizing CAD diagnosis over time is depicted in Figure 1. Overall, 119 (36.7%) patients had CAD evaluation prior to KT, of whom 21 underwent myocardial revascularization – 8, 12 and 1 patients with acute coronary syndrome (ACS), chronic coronary syndrome (CCS) and silent ischaemia, respectively. At a median time of 46 (25–66) months after KT, 36 (11.1%) more patients had CAD evaluation, of whom 8 underwent percutaneous myocardial revascularization – 6 and 2 for ACS and CCS, respectively. Those with obstructive CAD were older (64 vs 54 years-old; p&lt;0.001), with a higher burden of cardiovascular (CV) risk factors (p&lt;0.001) and more likely to have had a CV death (9.5 vs. 1.0%; p=0.025) or CV hospitalization (38.1 vs. 13.4%; p=0.007). CAD status (revascularized vs. non-revascularized) was not associated with improved major outcomes at follow-up. We found no strong predictors of CAD requiring revascularization post-KT, including time from RRT to KT. There were no patients with refractory angina, left main disease or reduced left ventricular ejection fraction (&lt;40%) in need of myocardial revascularization over follow-up.

Conclusions
Obstructive CAD was uncommon in our cohort of patients who received a KT, most of whom with asymptomatic or mildly (monthly angina) symptomatic CCS or non-fatal ACS. These findings, together with the most recent evidence, may argue against routine CAD screening in all patients being enlisted for KT. Notwithstanding, randomized evidence is eagerly awaited to further guide treatment decisions in the post-ISCHEMIA-CKD era.

Funding Acknowledgement
Type of funding sources: None.
The difference in prognostic value between high-sensitive cardiac troponin T and I for long-term major adverse cardiovascular events in hemodialysis patients
Authors: Wongcharoen W , Ratnachina K , Noppakun K , Phrommintikul A 
Published: October 2022

Abstract

Background
Previous studies using conventional cardiac troponin (cTn) assays have shown conflicting results in the predictability of major adverse cardiovascular events (MACEs) in hemodialysis patients.

Objective
We aimed to evaluate the prognostic values of high-sensitivity cTnT (hs-cTnT) and hs-cTnI assays for long-term MACEs in asymptomatic chronic hemodialysis patients.

Methods
A total of 198 asymptomatic patients undergoing regular hemodialysis (mean age 62.4±14.8 years) were enrolled in this study. Pre-dialysis hs-cTnT and hs-cTnI levels were measured at the time of study entry. The primary outcome was the prognostic value of hs-cTnT and hs-cTnI for all-cause mortality.

Results
At baseline, the median values of hs-cTnT and hs-cTnI were 61.1 ng/L (IQR 36.6–102.0 ng/L) and 18.4 ng/L (IQR 9.5–36.6 ng/L), respectively. During a median follow-up period of 408 days (IQR 343–415 days), 35 (17.7%) patients developed MACEs, and 20 (10.1%) patients died. The patients with hs-cTnT level above the highest quartile (&gt;102 ng/L) had an increased risk of all-cause mortality (HR 3.34; 95% CI 1.39–8.04, P=0.007) and MACEs (HR 1.99; 95% CI 1.00–3.96, P=0.049), compared to those with lower hs-cTnT level. The association between hs-cTnT and all-cause mortality remained significant after adjustment for age, gender, and comorbidities. On the contrary, hs-cTnI level was not associated with long-term all-cause mortality and MACEs.

Conclusions
We demonstrated that level of hs-cTnT, but not hs-cTnI, was associated with higher risk of long-term mortality and MACEs. As a result, hs-cTnT may be a better prognostic factor than hs-cTnI in this population.

Funding Acknowledgement
Type of funding sources: Public Institution(s). Main funding source(s): Faculty of Medicine Endowment Fund for medical research
Cardiac involvement in creatine deficiency syndrome
Authors: Del Franco A , Battini R , Kusmic C , Forini F S , L'Abbate S , Masotti S , Musetti V , Borrelli C , Barison A , Emdin M , Vergaro G 
Published: October 2022

Abstract

Background
Previous reports have demonstrated electrocardiographic and echocardiographic abnormalities consistent with early-stage cardiomyopathy in patients with creatine transporter (CrT) deficiency, but cardiac involvement has never been accurately characterized.

Purpose
To investigate the cardiac phenotype associated with creatine deficiency in a murine transgenic model and in patients with creatine deficiency syndrome (CDS).

Methods
Wild type and transgenic CrT−/y mice (n=20) were serially evaluated in vivo by electrocardiogram (EKG) and echocardiography for six months, and ex vivo by histological and biochemical analyses. Nine patients with CDS (n=4 with L-arginine:glycine amidinotransferase - AGAT- deficiency, n=5 with CrT deficiency) underwent blood samples, including cardiac biomarkers, EKG, Holter monitoring, echocardiography and cardiac magnetic resonance (CMR).

Results
Compared to wild type, CRT−/y mice showed a prolongation of QT interval (p=0.008) (Fig. 1), as well as significant reduction in cardiac ATP production from mitochondria (p&lt;0.001) (Fig. 2). No differences were detected in the left ventricular systolic function, in terms of ejection fraction and global longitudinal strain, along the whole follow-up. Similarly, 3 patients with CrT deficiency also showed a prolonged QTc interval (median QTc 515 ms), while other 2 had a borderline QTc at Holter monitoring, while no tachyarrhythmias could be observed. No subject had abnormal systolic and diastolic function. At CMR, an increase of native T1 value was reported in the 4 subjects (median 1076 ms) with AGAT deficiency, 1 with an increase of extracellular volume matching with the detection of late gadolinium enhancement. Finally, subjects with AGAT deficiency showed an increase level of plasma norepinephrine. Familiar carriers (3 for AGAT and 1 for CrT) showed no notable cardiac functional alterations, except for QTc prolongation in 2 subjects.

Conclusion
Prolonged QT interval is observed in the murine model and in subjects with CrT deficiency. Biohumoral signs of neurohormonal activation and an initial replacement fibrosis – the latter suggested by the increase of native T1 – are identified in subjects with AGAT deficiency, but their clinical significance remains to be determined.

Funding Acknowledgement
Type of funding sources: None.
Distribution and cardiac outcomes of neuromuscular disorders referred to an inherited cardiac disease unit
Authors: Garcia Perez-Carlos M , Martinez-Garcia F , San Roman-Monserrat I , Sabater-Molina M , Navarro-Penalver M , Gil-Ortuno C , Munoz-Esparza C , Gimeno J R 
Published: October 2022

Abstract

Backgroud
Neuromuscular disorders may present with varied cardiac involvement, including myocardial and conduction tissue disease. Sudden death is a common adverse event of cardiomyopathy

Purpose
The objective was to present clinical characteristics of neuromuscular disorders referred to a dedicated inherited cardiac disease unit with special interest in the mode of presentation, clinical course and cardiac complications.

Methods
Cardiological anamnesis, 12-lead electrocardiogram and bidimensional echocardiogram were performed to every individual. Gadolinium cardiac MRI/24 hour-Holter/coronariography were performed in particular cases where results of previous tests made it mandatory.

Results
199 patients (aged 43.1±18.1 years, 45.2% females, 54.8% males) with neurological disorders evaluated in an inherited cardiac disease clinic from 2003–2021 were included. There were 20 (10.1%) dystrophynopathies, 20 (10.1%) limb girdle muscular dystrophy, 14 (7.0%) other muscular dystrophies (Emery-Dreifuss, facio-scapulo-humeral, oculopharyngeal), 70 (35.2%) myotonic myopathies (Steinert myotonic dystrophy, Becker myotonia congenita, Thomsen myotonia congenita), 7 (3.5%) myofibrillar myopathies, 14 (7.0%) congenital myopathies, 18 (9.0%) metabolic myopathies, 12 (6.0%) unknown origin inherited myopathies, 24 (12.1%) non-myopathic neurological diseases. There were 44 (22.11%) patients affected with a cardiomyopathy. 51/199 (25.6%) had conduction disturbances. 33/51 had pathological cardiac findings without clinical cardiomyopathy.
Age of diagnosis of neurological and cardiomyopathy conditions were 28.4±20.4 and 40.6±18.4 years old respectively. Reasons for diagnosis were symptoms (164, 82.4%), family screening (27, 13.6%), incidental finding (7, 3.5%), sudden death (1, 0.5%). 31 (15.6%) had atrial fibrillation, 17 (8.5%) required pacemaker and 15 (7.5%) ICD implantation. 32 (16.1%) patients died or had severe cardiac outcome. 7 (3.5%) had sudden death or equivalent, 3 (1.5%) heart-failure-death, 1 (0.5%) received cardiac transplantation, 18 (9.1%) had other-disease-related-death and 3 (1.5%) other disease non-cadiac-related-death).

Conclusion
Neuromuscular diseases require periodic cardiac evaluation. Despite onset of neurological symptoms usually precede cardiac involvement, the burden of cardiac involvement and complications is highly significant. Cause of death in neurological conditions with cardiac involvement is mostly driven by the severity of the cardiomyopathy.

Funding Acknowledgement
Type of funding sources: None.
A systematic review and meta-analysis on the effect of selective serotonin reuptake inhibitors on endothelial function
Authors: Delialis D , Mavraganis G , Dimoula A , Ajdini E , Bampatsias D , Dimopoulou A M , Sianis A , Maneta E , Neofytou O , Petropoulos I , Konstantinou G , Misegiannidis A , Kokras N , Stamatelopoulos K , Georgiopoulos G 
Published: October 2022

Abstract

Background
Depression and atherosclerotic cardiovascular disease (ASCVD) are commonly clustered in affected patients. Endothelial dysfunction is an early marker of ASCVD while also reported in patients with depression. Emerging evidence suggests that selective serotonin receptor inhibitors (SSRIs) may improve endothelial function. However, clinical studies assessing flow-mediated dilation (FMD), the gold-standard method to evaluate conduit artery endothelial function, in response to SSRIs treatment included limited number of patients and did not provide consistent results.

Purpose
In the present study we aim to evaluate the effect of SSRIs treatment on endothelial function assessed by longitudinal changes in FMD.

Methods
We performed a systematic review to retrieve and subsequently meta-analyze eligible studies in patients with depression who received SSRIs and had available measurements of FMD change before and after treatment.

Results
In 5 studies and 323 individuals in total, SSRIs were associated with increased FMD at the end of follow-up compared to baseline measurement (pooled mean change 1.97%, 95% CI 0.17, 3.77, P=0.032, I2=87.4%). These results did not substantially change when analysis was restricted to patients with history of atherosclerotic cardiovascular disease (ASCVD). Similarly, FMD changes were higher in individuals receiving SSRIs compared to not-treated subjects (pooled mean difference 2.5%. 95% CI 0.7, 4.2, P&lt;0.001, I2=82.7%). Substantial heterogeneity regarding with respect to follow-up duration, demographics, and SSRIs agents.

Conclusion
SSRIs significantly improve FMD, the gold-standard marker of endothelial function. Further investigation is warranted for the role of FMD as a possible therapeutic biomarker in patients with depression and established or subclinical ASCVD.
Prospero registration: CRD42021252241

Funding Acknowledgement
Type of funding sources: None.
Role of global longitudinal strain in the assessment of left ventricular systolic function in patients with systemic lupus erythematosus: a systemic review and meta-analysis
Authors: Gegenava M , Gegenava T 
Published: October 2022

Abstract

Background
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized with high cardiovascular morbidity and mortality. However, cardiac involvement, especially at an early stages of the disease is largely underdiagnosed due to non-specific nature of the symptoms and low sensitivity of current diagnostic tools such as 2D conventional echocardiography derived left ventricular ejection fraction (LVEF), on the other hand, speckle tracking echocardiography (STE) derived left ventricular global longitudinal strain (LV GLS) has shown to be a reliable and sensitive tool for the diagnosis of subtle myocardial changes in various entities.

Purpose
The present study aimed to perform an extensive systemic review and meta-analysis of the current case-control studies based on the assessment of the left ventricular systolic function with standard and advanced echocardiographic methods.

Methods
The objectives, literature search strategies, inclusion and exclusion criteria, outcome measurements, and methods of statistical analysis were analyzed according to an established protocol of the cochrane collaboration steps and meta-analysis of observational studies in epidemiology recommendations (MOOSE).

Results
A total of 825 papers were collected according to our searching criteria, of those 20 studies including 1121 SLE patients and 1010 controls with evaluated LVEF and 8 studies including 387 patients and 283 controls with evaluated LV GLS were selected. We found, that overall patients with SLE exhibited lower levels of LVEF [weighted mean difference -WMD (95%CI) 0.336 (−0.423 to −0.248); p&lt;0.001] (Fig. 1), although separately some included studies showed that the difference in terms of LVEF between SLE and the control group is not always significant. LV GLS was significantly lower in SLE patients as compared to controls [WMD (95%CI) −1.341 (−1.517 to −1.166); p&lt;0.001] (Fig. 1), LV GLS was unequivocally lower in SLE patients (Fig. 2) in every reported study, moreover some studies showed significant association between deteriorated LV GLS and cardiovascular events.

Conclusions
LV systolic function as measured by LVEF and LV GLS is significantly affected in SLE patients. Data from meta-analysis suggest that STE derived LV GLS assessment potentially represents a new tool to improve precise and early assessment of LV function and may improve risk-stratification in patients with SLE.

Funding Acknowledgement
Type of funding sources: None.