bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Triglycerides - Glucose Index: An independent predictor of late subclinical cardiotoxicity in adult survivors of childhood, adolescent and young adult cancer
Authors: Ouabdesselam S , Ait Mokhtar O , Benkhedda S 
Published: October 2024

Abstract

Introduction
The Triglycerides - Glucose index (TyG index) has been identified as a reliable alternative for estimating insulin resistance (IR). Numerous recent studies have provided strong statistical evidence suggesting that this index is associated with the development and prognosis of cardiovascular pathologies.

Objectives
The aim of this study was to investigate the predictive role of the TyG index on the decrease in left ventricular longitudinal global strain (GLS) assessed on two-dimensional echocardiography in asymptomatic adult survivors of childhood, adolescent and young adult cancer.

Methods
The study included patients aged 18 years and older, asymptomatic cardiovascular survivors of childhood, adolescent and young adult cancer treated with anthracyclines with or without mediastinal radiotherapy. Anthropometric characteristics, cardiovascular risk factors and cancer treatment-related characteristics were collected. The TyG index was calculated using the formula: ln [fasting triglycerides (mg/dl) × fasting glucose (mg/dl)/2]. GLS was assessed and expressed as an absolute value. A GLS equal to 17.3% was retained as the threshold value after calculation in a referent group matched to patients according to age and gender. Cardiac biomarkers GDF 15, ultra-sensitive troponin I and NT-proBNP levels were measured in addition to fasting blood glucose and lipid profiles. Multivariate analysis using linear regression was performed to identify associations between these different parameters.

Results
A total of 105 cancer survivors from childhood, adolescence and young adulthood were included. The sex ratio was 1.3. The mean age of the patients was 25 years, the mean time since completion of cancer treatment was 10.6 years, the mean cumulative doses of anthracyclines and mediastinal radiotherapy were successively 245.75 ± 75.14 mg/m2 and 34.6 ± 6.19 Gy. Mean GLS was 18.5 ± 2.83%, mean LVEF 60.6 ± 5.69%. None of the patients had any known diabetes or treatment to lower blood glucose or triglyceride levels. No patient had a history of cardiovascular disease. In the univariate study, the factors associated with lower GLS were patient age at recruitment (p = 0.03), mean time since completion of cancer treatment when this was greater than ten years (p = 0.005), dyslipidemia (p = 0.012), obesity (p = 0.037) and TyG (p = 0.037). In multivariate analysis, lower GLS was related to mean time since completion of cancer treatment (p = 0.015) and TyG index (p = 0.002).

Conclusion
Our results suggest that the TyG index, as a simple and inexpensive marker of insulin resistance, could help identify cancer survivors from childhood, adolescence and young adulthood who would be at risk of subclinical cardiac dysfunction. Prospective studies with larger numbers are needed to confirm these findings.
Chronotropic incompetence as a critical predictor for cardiovascular outcomes in heart failure with preserved ejection function
Authors: Lin T , Chen T Y C , Wu C K W , Lin L Y L 
Published: October 2024

Abstract

Background
Chronotropic incompetence (CI), linked with exercise intolerance, is a prevalent feature of heart failure with preserved ejection fraction (HFpEF). Our study aimed to explore the impact of CI on cardiovascular outcomes in HFpEF patients.

Methods
From November 2019 to December 2022, we enrolled 359 subjects who underwent invasive cardiopulmonary exercise testing (iCPET) due to heart failure symptoms. After excluding individuals without HFpEF (those with resting pulmonary capillary wedge pressure [PCWP] &lt; 15mmHg or exercise PCWP &lt; 25mmHg), we identified 113 patients for long-term follow-up. Our assessment of cardiovascular outcomes encompassed hospitalization for heart failure (HHF) and cardiovascular death. We employed Cox regression analysis to evaluate the associations between exercise hemodynamic parameters and outcomes.

Results
Among the cohort, 85 (75.2%) subjects with CI were older (71 vs. 66 years) and more frequently women (61 vs. 28%) compared to those without CI. At peak exercise, patients with CI exhibited significantly reduced left atrial booster strain, impaired right ventricle-arterial coupling, decreased systemic vascular resistance, cardiac output (CO), stroke volume, VO2, respiratory exchange ratio, and minute ventilation/carbon dioxide production (VE/VCO2) slope. A significant increase in PCWP (36 ± 10 vs. 26 ± 11mmHg, p=0.012) was noted in patients with CI. Over a median follow-up of 22.6 months, 20 (17.7%) subjects experienced cardiovascular events. Multivariate Cox proportional analyses revealed that CI (Hazard ratio [HR] 1.725, 95% confidence intervals [CI] 1.212-2.413) and an elevated PCWP/CO slope (HR 1.829, 95% CI 1.331-2.382) were predictive of outcomes.

Conclusions
Patients with CI demonstrated heightened filling pressure, a steeper VE-VCO2 slope, and reduced VO2 compared to those without CI. These factors likely contribute to adverse cardiovascular outcomes in HFpEF patients with CI.
Novel method in mice to evaluate left atrial (LA) systolic contribution to left ventricular volume (LV) using pressure-volume (PV) loops
Authors: Baker H , Christie R M , Sam F 
Published: October 2024

Abstract

Background
LA myopathy is a critically important non-LV contributor to the progression of HFpEF (heart failure with preserved ejection fraction) in patients and is associated with a severe phenotype, leading to impaired cardiac output reserve and reduced exercise capacity. In normal humans LA systole contributes ~20% of total LV filling, but with HFpEF, this contribution decreases to &lt;16% with a greater reliance on this contribution to LV filling.

Purpose
We sought to investigate LA function as a critical component of cardiac function analysis by utilizing the LV pressure signal to identify and quantify the contribution of volume during LA systole to the total LV volume in mice with HFpEF.

Methods
Hypertension (HTN)-associated HFpEF C57BL/6J mice were subjected to chronic aldosterone infusion and 1% NaCl for 4 weeks (SAUNA model). Obesity after a high fat diet (HFD: 60% fat diet) for 16 weeks followed by the SAUNA protocol, induced HTN and obesity associated HFpEF. Blood pressure was monitored weekly. Mice were anesthetized with isoflurane, intubated, chest opened to expose the heart and allow placement of a PV catheter (Transonic) which was introduced into the LV via apical stab with a 27G needle. Calibration of the PV catheter was performed according to the manufacturer’s instructions. Atrial systole was identified using 2nd order derivative of the LV pressure signal. Contribution of LA systole was calculated using volume at the beginning of LA systole identified by the 2nd order derivative of the LV pressure signal and subtracting from the LV end diastolic volume. The % of LA systole contribution was calculated as a % of the total LV stroke volume. Data was analyzed with LabChart pro software (AD Instruments).

Results
SAUNA mice had normal LVEF, moderate HTN and lung congestion. PV relationships demonstrated Tau was impaired in HFpEF vs. control mice (14±1 vs. 10±0.5 ms) with a shift of the PV loop to the left (Fig. A.) In control mice, the atrial systole contributed 39± 4% to LV volume and was impaired in HFpEF mice 20± 3% a 1.95-fold reduction (P&lt;0.01). Importantly atrial systole contribution was increased in obese mice 53±5 %. However, the combination of obesity and HTN, both common comorbidities in HFpEF, resulted in a reduced LA systole contribution by 1.43-fold to 37± 9%, (P&lt;0.005; Fig B).

Conclusion
A novel method of % atrial systole from LV PV loop using 2nd order derivative to quantify the volume contribution of atrial systole to total LV stroke volume was identified in mice. LA dysfunction was present in murine HTN-associated HFpEF with/without obesity.
Transpulmonary proteome gradients identify inflammatory pathways involved in the development of pulmonary vasculopathy in heart failure
Authors: Melenovsky V , Jarolim P , Kutilkova E , Jenca D , Binova J , Benes J , Al-Hiti H , Miklovic M , Borlaug B A 
Published: October 2024

Abstract

Background
Some, but not all, patients with heart failure (HF) develop pulmonary vascular disease (PVD), which contributes to poor prognosis. Mechanisms leading to PVD in HF are poorly understood. Unbiased analysis of transpulmonary gradients may identify not only markers but also mediators of PVD by identifying proteins that may be consumed or elaborated across the lungs.

Purpose
Examine hemodynamics and transpulmonary proteome gradients in HFrEF and controls.

Methods
21 non-HF controls and 160 patients with advanced HFrEF underwent pulmonary artery (PA) catheterization with blood sampling from the PA catheter in the wedged position (02sat &gt; 90%, indicating pulmonary venous blood) and the un-wedged position to obtain transpulmonary proteome gradients. Samples from controls and HF from the highest quartile (Q4, n=40) and lowest quartile (Q1, n=40) of pulmonary vascular resistance (PVR) were analyzed using proteomic PEA assay of 275 proteins (Olink Target 96, panels CVII, CVIII, Inflammation). Pulmonary artery concentrations ("markers") or transpulmonary fold-change gradients (i.e. putative "mediators") of normalized protein expression (NPX) were plotted against significance; Benjamini–Hochberg FDR&lt;0.05 considered as significant.

Results
Patients displayed typical characteristics of HFrEF (age 56±8y, NYHA 3.0 ±0.6, 87% males, LVEF 24±9.6%), Controls had similar anthropometrics, gender and age. Comparing all HF to Con, 38 markers of HF were identified (NPX fold-change&gt;2), including 33 up (top 5: NTproBNP, BNP, GDF15, FGF23, IL8) and 5 down. HF patients in Q1 had median PVR 1.5 (IQR: 0.3-1.7) WU and those in Q4 had PVR 5.4 (4.3-6.6) WU. Comparison of Q1 and Q4 identified 3 protein markers of high PVR in PA blood from HF: chemokine CCL3, TNFRSF13B and surfactant protein-D (PSP-D). Examination of protein gradients from HF lungs (Figure) showed significant uptake of 14 protein mediators, most of which were associated with inflammatory responses (top 5: OSM, MMP9, CCL19, BNP, TR), and release of 8 mediators (top 4: IL-6, IL33, CCL4, CXCL10). In contrast, protein gradients were negligible in controls. Patients in Q4 PVR group were characterized by the highest pulmonary uptake of OSM (Oncostatin-M), lymphatic chemokine CCL19, BNP, MMP9, and had more significant transpulmonary release of IL6 and IL33. Across all patients, OSM lung uptake was the strongest correlate of transpulmonary pressure gradient (r=-0.3, p&lt;0.001).

Conclusions
Lungs of patients with HF, and particularly those with high PVR, display abnormal uptake and release of proinflammatory CC and CXC chemokines and cytokines from IL1 and IL6 family, along with increased pulmonary uptake of IL6-type cytokine Oncostatin-M, a known mediator of lung inflammation and fibrosis, that acts via gp130/JAK/STAT, suggesting a novel role in PVD due to HF.Transpulmonary proteome in HF patients
Telomere shortening and cardiac alterations in asymptomatic type 2 diabetes patients: impact of sex
Authors: Balfanz P , Riccardi B , El Mernissi K , Zhang Y , Alassaad L , Thibault H , Moulin P , Bergerot C , Audureau E , Derumeaux G 
Published: October 2024

Abstract

Background
Telomere shortening is associated with the occurrence of deleterious events in the context of cardiometabolic disorders, including type 2 diabetes mellitus (T2DM). However, no evidence is available on the link between leukocyte telomere length (LTL) and subclinical cardiac alterations in T2DM patients.

Purpose
Our aim is to evaluate the relation between LTL and cardiovascular function in asymptomatic T2DM patients, taking into consideration the impact of the sex.

Methods
We analyzed a cohort of asymptomatic T2DM patients free from any overt cardiovascular disease (including coronary artery disease) and other T2DM comorbidities. A detailed metabolic and echocardiographic evaluation was performed together with LTL measurements at inclusion and after 2 years of follow-up. Univariate analyses in regard of the comparison of three graded LTL tertiles and different gender were used to test individual relationships betweenbioclinical and echocardiographic parameters and LTL measures. Subsequently, an unsupervised clustering method (self-organizing maps [SOM]) was used to identify cluster at risk of cardiomyopathy.

Results
We studied 89 T2DM patients aged 50±4 years (43% female) with a mean T2DM duration of 10±5.8 years and an average follow-up of 2.1±0.2 years. Leukocyte TL analysis demonstrated a slight but significant attrition after 2 years. The analysis of echocardiographic variables (transmitral flow velocities, velocity of mitral annular motion, left ventricular ejection fraction) did not show any evidence for ouvert cardiomyopathy. However, in the lower LTL tertile a higher proportion of patients with global longitudinal strain [GLS]&lt;18% was found [41.6% vs. 22.8% vs. 21.6%]. Interestingly, leukocyte TL was associated with T2DM duration, FIB-4, a noninvasive indice used to assess fibrosis associated with non-alcoholic fatty liver disease (NAFLD), and usage of GLP-1 agonists. Comparison of men and women by univariate analysis did not show any differences in both LTL and echocardiographic parameters. However, unsupervised cluster method (SOM) unmasked a subgroup of female T2DM patients with diastolic alterations (e’ mean) and systolic alteration (GLS) both linked with lower LTL, whereas no specific subgroup in male T2DM patients could be distinguished.

Conclusion
Our study identifies subclinical diastolic and systolic dysfunction together with shorter LTL in a subgroup of female T2DM patients. These findings raise the importance of considering sex effect in the understanding of diabetic cardiomyopathy.
Comparing the anti-remodeling effect of sacubitril/valsartan and angiotensin-converting enzyme inhibition on myocardial samples of advanced heart failure patients undergoing heart transplantation
Authors: Nagy D , Balint T , Kocsis-Balogh P , Horvath Z , Olah A , Sayour A A , Barta B A , Merkely B , Radovits T , Ruppert M 
Published: October 2024

Abstract

Background
In decreasing heart failure (HF) hospitalization and cardiovascular death in HF patients with reduced ejection fraction, Sacubitril/Valsartan (SAC/VAL) treatment was proved to be superior to angiotensin-converting enzyme inhibition (ACEi). According to recent experimental results and clinical data based on echocardiography and circulating biomarkers, this benefit might be at least partially attributed to a greater anti-remodeling effect. However, there is a lack of direct evidence from human myocardial samples for this assumption.

Purpose
Therefore, we aimed to compare the anti-remodeling effect of SAC/VAL treatment to ACEi on myocardial samples of HF patients undergoing heart transplantation (HTX).

Methods
We studied left ventricular (LV) samples of seventy advanced HF patients who underwent HTX and received either SAC/VAL (SAC/VAL group, N=32) or ACEi treatment (ACEi group, N=38) for at least three months prior to HTX. Furthermore, all patients received beta-blockers and mineralocorticoid receptor antagonists titrated to maximally tolerated or target dose. Our groups were matched for age, sex, ejection fraction and other clinical parameters. Patients with liver or kidney failure, mechanical circulatory support, systemic inflammatory/fibrotic diseases or positive inotrope treatment were excluded. Myocardial mRNA expression of fibrotic markers and B-type natriuretic peptide (BNP) were measured with qRT-PCR and normalized to glyceraldehyde 3-phosphate dehydrogenase expression. Interstitial fibrosis area was assessed histologically.

Results
Preoperative plasma N-terminal pro-BNP levels were similar in the two groups (SAC/VAL: 4363±752 pg/mL vs. ACEi: 4616±1020 pg/mL; p=0.911). In contrast, the mRNA level of BNP in the myocardium was lower in patients treated with SAC/VAL (SAC/VAL: 2.2±1.05 vs. ACEi: 5.2±1.74; p=0.006). TIMP metallopeptidase inhibitor 1 (SAC/VAL: 0.07±0.01 vs. ACEi: 0.13±0.02; p=0.011), TIMP metallopeptidase inhibitor 2 (SAC/VAL: 0.06±0.01 vs. ACEi: 0.11±0.01; p&lt;0.001), collagen type I alpha 1 chain (SAC/VAL: 0.02±0.00 vs. ACEi: 0.08±0.02; p&lt;0.001) and collagen type III alpha 1 chain (SAC/VAL: 0.12±0.02 vs. ACEi: 0.27±0.04; p&lt;0.001) relative gene expressions were also decreased in the LV of SAC/VAL-treated patients. Histology analysis confirmed reduced interstitial myocardial fibrosis area in the SAC/VAL group as well (SAC/VAL: 7.2±0.4% vs. ACEi: 8.6±0.5%; p=0.031).

Conclusions
SAC/VAL treatment decreased the myocardial expression of BNP and fibrosis-related genes to a greater extent compared with ACEi in LV samples of patients undergoing HTX. Histological analysis also verified the differences in fibrosis. Thus, the anti-remodeling effect of SAC/VAL might be superior to ACEi even in advanced HF.
Clinical characteristics of patients with raised BNP referred from primary care to an outpatient heart failure with potential heart failure using NICE guidelines
Authors: Bain R , Walters M , Whickham K , Jones R 
Published: October 2024

Abstract

Introduction
UK NICE guidelines (1) mandate the referral of patients with potential heart failure (signs, symptoms and raised BNP) for specialist opinion including diagnostic echocardiography. We have analysed the demographic and clinical characteristics of 233 consecutive referrals over a nine month period of such patients from primary care to our outpatient cardiology service.

Purpose
To identify any differences between those who are subsequently identified as having reduced LV systolic function (HFrEF) and those with preserved LV systolic function. We have further explored any potential differences between those with moderately raised (&gt;440 &lt;2000ng/L) and those with grossly raised levels (&gt;2000ng/L) of BNP as NICE guidance proposes a difference in urgency of assessment for these two patient cohorts.

Methods
All patients had diagnostic echocardiography following the British Society of Echocardiography guidelines (2) and were clinically assessed by a consultant cardiologist and specialist heart failure nurse.

Results
Of the 233 patients, 64 (27%) were identified as having HFrEF with the remaining 169 having preserved LV systolic function. In patients with HFrEF the majority had grossly raised BNP (62.5%) whereas with preserved LV systolic function the majority had moderately raised BNP (70.5%); Table 1.
Within the referred population, demographics and clinical characteristics were broadly similar for patients with HFrEF and those with preserved LV systolic function for age and cardiovascular comorbidities (IHD, diabetes mellitus, hypertension) but were different for gender and heart rhythm. Patients with HFrEF and moderately raised BNP were twice as likely to be in sinus rhythm (75%) than those with grossly raised BNP (37.5%). In patients with moderately raised BNP those with preserved LV systolic function were more likely to be in AF than those with HFrEF (41% v. 25%). No gender difference was seen in patients with preserved LV systolic function whereas patients with HFrEF were twice as likely to be male; Table 2.

Conclusions
1. The majority of patients with raised BNP and potential heart failure referred from primary care do not have HFrEF (72.5%)
2. Regardless of their LV systolic function those patients with the highest BNP levels are more likely to be in AF
3. Of patients with a raised BNP and HFrEF twice as many are male whereas no gender difference is seen in those with a raised BNP and preserved LV systolic
4. Whilst the mean age of both groups (preserved and reduced LV systolic function) is the same, in both groups those with grossly raised BNP are on average 5 years older than those with moderately raised BNP.
A new heart transplant resource: DBD donor with out-of-hospital cardiac arrest
Authors: Fischetti G , Giovannico L , Parigino D , Ramirez A D , Santeramo V , Savino L , Mazzone F , Silva A M , Di Bari N , Bottio T , Milano A D 
Published: October 2024

Abstract

The aim of the present study is to analyze the differences in terms of cardiac transplant survival in organ recipients from a DBD (donor with brain death) donor characterized by out-of-hospital cardiac arrest (OHCA) and from a DBD donor not characterized by OHCA, in order to find new strategies to expand the donor pool. We analyzed the differences in mortality 30 days and 120 days after transplantation between the two groups of recipients, the length of stay in the ICU, the length of post-operative stay in the hospital, mechanical ventilation, the use of ECMO, the use of CVVH and the possible occurrence of ischemic and/or haemorrhagic stroke. 78 patients were compared: 13 recipients from a donor with OHCA with an average age of 55.18 (44.35 - 63.1) and 65 recipients from a donor without OHCA with an average age of 57.74 (50.9 - 66). The populations under study presented almost the same characteristics in terms of initial diagnosis, risk factors, comorbidities and list status. Comparing the results, no statistically significant differences were found between the two groups for ICU stay (p=1.000), for in-hospital stay (p=0.920) and for mechanical ventilation (p=0.95 ). No statistically significant difference was detected between the two groups even in terms of ECMO support (p=0.90), ischemic stroke (p=0.70), hemorrhagic stroke (p=0.781). From the analysis of the survival curves it can be seen that there is no statistically significant difference between the two groups either with regard to 30-day mortality (p=0.905) or 120-day mortality (p=0.957). The use of a DBD donor with OHCA represents a valid resource in the field of heart transplantation. In the present study it does not affect the recipient's survival rate. 30 days after heart transplantation mortality is conditioned by the intrinsic characteristics of the recipients.Kaplan-Meier 30 day survivalKaplan-Meier 30 day survival