bluuebunny/crossref_metadata_2025_split huggingface dataset:
LV-GLS is a predictor of all-cause death and cardiovascular MACE events in patients with neuro-immunological disorders
Authors: Khanna S , Wen I , Gupta A , Thakur A , Bhat A , Chen H H L , Gan G C H , Tan T C 
Published: October 2021

Abstract

Background
Neuro-immunological disorders encompass several disease states, including multiple sclerosis (MS), autoimmune encephalitis (AE) and myasthenia gravis (MG). These autoimmune conditions are mediated via pro-inflammatory cytokines, and there is growing evidence to suggest cardiovascular involvement within these inflammatory states. Left ventricular global longitudinal strain (LV-GLS) is proposed to be a more sensitive measure of LV systolic function when compared to standard two-dimensional measures such as LV ejection fraction (LVEF).

Purpose
The purpose of this study was to assess for subclinical cardiac dysfunction in a cohort of patients with neuro-immunological disorders and correlate this with the development of outcomes on follow-up.

Methods
Consecutive patients with MS, AE and MG admitted to our institution during 2013–2020 were assessed (n=102). Patients without pre-existing cardiovascular disease, LVEF &lt;50% or lack of comprehensive transthoracic echocardiography during their index admission were included (n=55). This group was compared to age- and gender-matched controls (n=55) LV-GLS was measured offline using vendor-independent software (TomTec Arena, Germany v4.6) by two cardiologists blinded to the patient group or outcomes. These patients were followed for up for the composite outcome of all-cause death and major adverse cardiovascular events (MACE).

Results
A total of 55 patients (31 MS, 14 AE and 10 MG) were age- and gender- matched to 55 controls. There was no significant difference in baseline demographic characteristics or cardiovascular risk factors between groups. Patients with neuro-immunological disorders demonstrated impaired LV-GLS (−17.6±3.5 vs −20.8±1.9; p&lt;0.01) when compared to healthy controls, despite an LVEF within the normal range (60.9±7.7 vs 64.1±5.7; p=0.02) in both groups. There were a total of 9 (16.4%) outcomes during a mean follow-up of 41.0±33.0 months. LV-GLS was the only significant echocardiographic predictor of all-cause death and MACE events (p=0.013) on multi-variate analysis.

Conclusions
Our results suggest that patients with neuro-immunological disorders have subclinical LV dysfunction as assessed by LV-GLS which has prognostic capacity in this population. Further larger studies are required to further characterize this phenomenon.

Funding Acknowledgement
Type of funding sources: None.
Diagnostic value of simultaneous 99mTc-sestamibi/123I-BMIPP imaging parameters for predicting the improvement of left ventricular wall motion after acute myocardial infarction using CZT SPECT system
Authors: Hida S , Fujita Y , Hatano T , Morishima T , Yamashita J , Murata N , Ito R , Chikamori T 
Published: October 2021

Abstract

Background
Although the presence of 99mTc-sestamibi/123I-BMIPP-mismatch, the reverse redistribution (RR) of 99mTc-sestamibi and RR of 123I-BMIPP in patients with acute myocardial infarction (AMI) are known to significant markers for predicting the improvement of LV wall motion in the infarcted territory in chronic phase, few studies were performed to analyze them by simultaneous dual-isotope imaging using cadmium-zinc-telluride (CZT) SPECT system.

Purpose
The purpose of this study was to evaluate whether the presence of 99mTc-sestamibi/123I-BMIPP-mismatch or RR of 99mTc-sestamibi, RR of 123I-BMIPP make better prediction of the improvement of LV wall motion in the infarcted territory.

Methods
We evaluated 42 consecutive patients with AMI who had undergone both dual-isotope SPECT in acute phase and stress myocardial SPECT using 99mTc-tracers in chronic phase by Discovery NM530c. The presence of 99mTc-sestamibi/123I-BMIPP-mismatch, RR of 99mTc-sestamibi and RR of 123I-BMIPP were determined using traditional definition. The improvement of LV wall motion in the infarcted territory from acute phase to chronic phase was assessed using QGS.

Results
Of 42 patients, the improvement of LV wall motion in the infarcted territory from acute phase to chronic phase was found in 29 patients. The presence of 99mTc-sestamibi/123I-BMIPP-mismatch and RR of 99mTc-sestamibi and RR of 123I-BMIPP were significantly linked to predict the improvement of LV wall motion (p=0.0001, p=0.0001 and p=0.002, respectively). To predict the improvement of LV wall motion in the infarcted territory in chronic phase, the presence of 99mTc-sestamibi/123I-BMIPP-mismatch showed sensitivity of 93%, specificity of 85% and accuracy of 91%, while RR of 99mTc-sestamibi and RR of 123I-BMIPP had sensitivities of 72%, 48%, specificities of 85%, 100% and accuracies of 76%, 64%, respectively. The multivariate discriminant analysis revealed that the combination of 99mTc-sestamibi/123I-BMIPP-mismatch, RR of 99mTc-sestamibi and RR of 123I-BMIPP best predicted the improvement of LV wall motion in the infarcted territory in chronic phase with sensitivity of 93%, specificity of 85% and accuracy of 91% (chi-square=40.6), compared with RR of 99mTc-sestamibi and RR of 123I-BMIPP only (sensitivity 79%, specificity 85% and accuracy of 81%, chi-square=16.9).

Conclusions
The addition of 99mTc-sestamibi/123I-BMIPP-mismatch on RR of 99mTc-sestamibi and RR of 123I-BMIPP in patients with AMI, help better predict the improvement of LV wall motion in the infarcted territory in chronic phase.

Funding Acknowledgement
Type of funding sources: None.
Normal ranges of global left ventricular myocardial work indices in adults: a meta-analysis
Authors: Ngo T , Truong V , Phan T , Pham T , Nguyen T , Le T , Palmer C , Chung E , Mazur W 
Published: October 2021

Abstract

Background
Non-invasive global myocardial work recently emerged as new parameter to characterize left ventricle function with potential advantages over both ejection fraction and global longitudinal strain.

Purpose
We aimed to perform a meta-analysis of normal ranges of non-invasive left ventricular myocardial work (MW) indices including global constructive work (GCW), global work index (GWI), global wasted work (GWW), and global work efficiency (GWE) and to identify confounding factors that may contribute to variance in reported measures.

Methods
The authors searched four databases, Pubmed, Scopus, Embase, and Cochrane Library through January 2021 using the key terms “myocardial work”,“global constructive work”, “global wasted work”, “global work index”, “global work efficiency”. Studies were included if the articles reported LV myocardial work using 2D transthoracic echocardiography in healthy normal subjects, either in the control group or comprising the entire study cohort. The weighted mean was estimated by using the random effect model with a 95% confidence interval. Heterogeneity across studies was assessed using the I2 test. Publication bias was examined by funnel plot and Egger's regression test.

Results
The search yielded 476 articles. After abstract and full text screening we included 13 datasets with 1665 patients for meta-analysis. The reported normal mean values of GCW and GWI among the studies were 2278 (95% CI, 2167 to 23878; I2=95%), and 2.010 (95% CI, 1922 to 2098, I2=97%), respectively. The mean GWE was 96.0 (95% CI, 95.6% to 96.5; I2=92%), and the mean GWW was 79.7% (95% CI, 68.8% to 90.7%; I2=90%) (Figure). Furthermore, age and gender did not significantly contribute to variations in normal values. No evidence of significant publication bias was observed in the funnel plots and the Egger test.

Conclusion
In this meta-analysis, we provide echocardiographic reference ranges for non-invasive indices of MW. These normal values should serve as a template for clinical and research use for this promising technology.

Funding Acknowledgement
Type of funding sources: None.
SPECT-guided myocardial perfusion and metabolic fatty acid planar imaging to assess the severity of the pulmonary hypertension in patients with chronic thromboembolic pulmonary hypertension
Authors: Ono R , Miyauchi H , Iimori T , Sawada K , Kuwabara Y , Kobayashi Y 
Published: October 2021

Abstract

Background
Patients with chronic thromboembolic pulmonary hypertension (CTEPH) represent right ventricular (RV) enlargement and hypertrophy, which consequently increase the RV myocardial perfusion. Although the main energy source of myocardium is fatty acid, it remains unknown whether myocardial fatty acid metabolism is altered in loaded RV. Herein, we report a novel approach to assess the RV perfusion and fatty acid metabolism, which is called SPECT-guided planar imaging.

Purpose
To evaluate if SPECT-guided myocardial perfusion and metabolic fatty acid planar imaging reflects the severity of the pulmonary hypertension in patients with chronic thromboembolic pulmonary hypertension.

Methods
The study groups included 30 patients with CTEPH and 20 healthy controls. In these patients with CTEPH, 15 patients underwent pulmonary thromboendarterectomy (PEA). Mean pulmonary artery pressure (mPAP) by right heart catheterization was obtained in all CTEPH patients. 201Thallium (201Tl) and iodine-123-beta-methyl iodophenyl pentadecanoic acid (123I-BMIPP) planar myocardial imaging was performed in all participants. For the patients undergoing PEA, repetitive SPECT-guided 201Tl and 123I-BMIPP planar imaging was performed one year after the procedure. To assess the RV overload, the planar images were performed in left anterior oblique position, optimized to separate the RV from the left ventricular (LV) using SPECT-guided transverse imaging. We measured the total counts of 201Tl and 123I-BMIPP in both the RV and LV. Moreover, we calculated their relative counts of the RV to LV (abbreviated as HR/HL (Tl) and HR/HL (BMIPP), respectively) to determine the indices of myocardial perfusion and fatty acid metabolism, respectively.

Results
Both HR/HL (Tl) and HR/HL (BMIPP) were elevated in the CTEPH patients compared with control (0.62±0.14 vs. 0.36±0.07, p&lt;0.01 and 0.57±0.14 vs. 0.34±0.06, p&lt;0.01, respectively). In the CTEPH patients, average mPAP was 44.0±9.52 mmHg, which was correlated with HR/HL (Tl) (r=0.675, p&lt;0.001) and HR/HL (BMIPP) (r=0.685, p&lt;0.01). Furthermore, the decrease of average mPAP 1 year after PEA was positively associated with the decrease of HR/HL (Tl) (r=0.646, p&lt;0.01) and HR/HL (BMIPP) (r=0.504, p&lt;0.05) 1 year after PEA.

Conclusions
In patients with CTEPH, RV myocardial perfusion and fatty acid metabolism was upregulated and moderately correlated with mPAP. SPECT-guided 201Tl and 123I-BMIPP planar imaging is a novel and noninvasive imaging modality to assess the severity of PH.

Funding Acknowledgement
Type of funding sources: None.
Low endothelial shear stress, microcalcification activity and high-risk plaque features: merging computational flow modelling, OCT and 18F-NaF PET/CT
Authors: Doyle B J , Kelsey L J , Majeed K , Bellinge J , Parker L P , Richards S , Schultz C J 
Published: October 2021

Abstract

Background
Endothelial shear stress (ESS) has a critical role in endothelial function. Abnormal shear stress leads to endothelial dysfunction, which contributes to arterial plaque initiation and development. Four dimensional magnetic resonance can determine shear stress in the larger arteries but cannot resolve the detail needed to calculate shear stress in the coronary arteries and thus methods such as computational fluid dynamics (CFD) are required. Additionally, a key feature of biologically active plaques is microcalcification activity, and this can be detected using 18F-sodium fluoride (18F-NaF) positron emission tomography (PET). Furthermore, using high resolution optical coherence tomography (OCT), the high-risk features plaques can be visualized and quantified. We aimed to merge these three techniques to investigate if low ESS is associated with high-risk plaque features and active microcalcifications in acute coronary syndrome.

Methods
We began by merging OCT images with CTCA images to obtain detailed 3D reconstructions of the target vessel. We then simulated blood flow and calculated the ESS, from which we extracted the area of low ESS (&lt;0.4 Pa). We quantified plaque features using OCT and measured the maximum 18F-NaF uptake, and compared data at both the coronary segment and whole artery level (Figure 1).

Results
We investigated 20 arteries from 18 patients which we obtained 38 coronary segments according to the SCCT guidelines. We found that areas of low ESS were were significantly and positively associated with high-risk plaque features: macrophage infiltration (segment, rs=0.33, p=0.043; artery, rs=0.46, p=0.041) and presence of cholesterol crystals (segment, rs=0.45, p=0.005; artery, rs=0.58, p=0.007). Vessel segments with thin-capped fibroatheroma had greater area of low ESS (20 vs 4%). The uptake of 18F-NaF was positively associated with the area of low ESS (segment, rs=0.52, p=0.001; artery, rs=0.64, p=0.002). We found that there were typically more plaque features found in regions of low ESS (Table 1).

Conclusion
Here we provide the first data associating low ESS with both high-risk plaque features and active microcalcifications in patients with acute coronary syndrome. Although our sample size is small, these data are encouraging and could lead to better understanding of how best to deem a plaque “high risk”.

Funding Acknowledgement
Type of funding sources: Public hospital(s). Main funding source(s): Royal Perth Hospital Medical Research Foundation Figure 1Table 1
Added prognostic value of plaque burden to computed tomography angiography anatomic assessment and myocardial perfusion imaging in patients with diabetes Mellitus
Authors: Alnabelsi T , Ahmed A I , Han Y , Al Rifai M , Nabi F , Cainzos-Achirica M , Al-Mallah M H 
Published: October 2021

Abstract

Introduction
Cardiac computed tomographic angiography (CCTA)-derived measures of coronary artery disease (CAD) burden such as segment involvement score (SIS), which quantifies the number of segments with plaque, have been shown to independently predict incident cardiovascular events.

Purpose
We aimed to compare the added prognostic value of plaque burden to CCTA anatomic assessment and single photon emission computed tomography (SPECT) physiologic assessment in patients with diabetes undergoing both tests.

Methods
Consecutive patients with diabetes who underwent clinically indicated CCTA and SPECT myocardial imaging for suspected coronary artery disease at a tertiary care center were retrospectively identified from medical records. Stenosis severity and segment involvement score (SIS) were determined from CCTA, and presence of ischemia was determined from SPECT. Patients were followed from date of imaging for major adverse cardiovascular events (MACE; inclusive of all-cause death, non-fatal myocardial infarction, and percutaneous coronary intervention or coronary artery bypass grafting 90-days after imaging test.)

Results
A total of 778 patients were included (mean age 60.6±14.4 years, 55% males). Obstructive stenosis (left main ≥50%, all other coronary segments ≥70%) and ischemia were found in 15% and 16% of patients respectively. After a median follow-up of 31 months, 87 (11%) patients experienced a MACE. In multivariable Cox regression models, SIS significantly predicted outcomes in models including obstructive stenosis and ischemia (HR 1.17, 95% CI 1.10 - 1.24, p&lt;0.001; 1.16, 95% CI 1.10 - 1.23, p&lt;0.001). The addition of SIS also significantly improved discrimination (Harrel's C 0.75, p=0.006; 0.76, p=0.006 in models with CCTA obstructive stenosis and SPECT ischemia respectively). Results were consistent using subgroups of summed scores by composition of plaque (calcified vs non-calcified) and alternate definitions of obstructive stenosis.

Conclusion
Our results suggest that in high-risk patients with diabetes and suspected coronary disease, SIS has incremental prognostic value over ischemia by SPECT or stenosis by CCTA in predicting incident cardiovascular outcomes.

Funding Acknowledgement
Type of funding sources: None.
Circadian disruption on the susceptibility to sepsis-induced cardiac dysfunction: a prospective multi-modal imaging study
Authors: Pu J , Yan F , Yang Y , Xiu J , Shan P 
Published: October 2021

Abstract

Background
Sepsis is a significant cause of mortality, and cardiac dysfunction is one of the vital predictors for mortality of sepsis. However, the factors associated with the susceptibility to sepsis-induced cardiac dysfunction remain unclear. Disruption of circadian rhythms can profoundly influence cardiac health; however, to the knowledge of the authors, the relationship of circadian disruption to cardiac involvement in patients with sepsis is unknown.

Purpose
We aim to investigate the impact of circadian disruption on the susceptibility to sepsis-induced cardiac dysfunction.

Methods
Study patient data were obtained from the image database of EARLY-MYO-SEPSIS (EARLY assessment of MYOcardial tissue characteristics by multi-modal imaging in SEPSIS) registry, which was a prospective, multi-center registry of sepsis patients who have undergone cardiac magnetic resonance imaging (MRI) and echocardiography from 8 sites (clinical trial number NCT04513795). Cardiac involvement was evaluated using a comprehensive assessment comprising of echocardiography (with global longitudinal strain calculation), cardiac MRI and cardiac biomarker evaluation. Logistic regression was performed to identify independent predictors of left ventricular systolic dysfunction in sepsis.

Results
A total of 216 intensive care unit patients with sepsis was enrolled in the present analysis. Septic patients with a history of circadian disruption (i.e., sleep insufficiency &lt;6 hours) presented more cardiac involvements (as indicated by edema on the cardiac MRI along with cardiac deformation and increased cardiac biomarkers) compared with those without circadian disruption history. Moreover, septic patients with a history of circadian disruption had increased mortality and incidence of heart failure. A history of circadian disruption was identified as an independent predictor of left ventricular systolic dysfunction in sepsis.

Conclusions
Our data from EARLY-MYO-SEPSIS registry demonstrated a previously unappreciated circadian sensitivity to sepsis-induced cardiac dysfunction.

Funding Acknowledgement
Type of funding sources: Public grant(s) – National budget only. Main funding source(s): This work was supported by grants from the National Science Fund for Distinguished Young Scholars (81625002) and National Natural Science Foundation of China (81930007)
The microvascular endothelial redoxome established through tandem mass tag mass spectrometry
Authors: Cottrill S B , Lermant A , Cantley J , Murdoch C E , Sneddon C ,   Systems Medicine, School of Medicine, University of Dundee, UK
Published: October 2021

Abstract

Redox signalling plays an important role in endothelial cell (EC) physiology and pathophysiology. Proteins sense redox signals via cysteine thiol groups. A common oxidative post-translational modification (oxPTM) on cysteine thiols is S-glutathionylation which is reversed to a free thiol state by glutaredoxin (Glrx). OxPTMs alter protein function, location and stability. Identifying which proteins undergo modification will help determine the role of redox signalling in EC function. A proteome-wide screen of human cardiac microvascular endothelial cells identified redox-sensitive proteins involved in vascular signalling mechanisms.

Methods
Human microvascular endothelial cells (HCMVEC, Lonza) were exposed to VEGF (50ng/ml, 24h) or hypoxia (0.5% O2, 24h) with adenoviral (ad) Glrx (Vectorlabs) overexpression or adLacZ (control). A tandem mass tag mass spectrometry system (TMT) coupled with a thiol-switch technique was used to quantify changes in redox sensitive thiol modifications. Protein lysates were treated with MMTS to alkylate unmodified thiols. Iodo-TMT six-plex probes were tagged to redox-sensitive sites after reversal of oxPTMs by DTT. Samples were pooled and processed by nLC-MS/MS. The abundance of each peptide in different conditions was compared with either adGlrx or adLacZ (control) expression to provide a ratio of changes in redox modifications.

Results
Iodo-TMT analysis revealed 113 unique thiol modifications identified on 78 different proteins using a ±1.5-fold threshold in a given treatment. Additionally, 44 modifications in 33 proteins were present in at least 2 different conditions, namely Glrx under VEGF and hypoxic conditions. A STRING interaction network identified clusters of 10 proteins involved in organonitrogen synthesis and 6 proteins in angiogenesis. Jagged-1 involved in the regulation of angiogenic sprouting through the Notch pathway was established as a target of redox signalling. Identified redox sensitive cysteines were found in extracellular EFG1 and the calcium binding EGF12 domains. Seven different In Silico programs (including MutationTaster, PolyPhen-2 and PANTHER) predicting the impact of substitution mutations indicated a functional affect for these redox sensitive sites, demonstrating the importance of these residues.

Conclusion
A non-biased proteomics approach identified novel thiol modifications on proteins involved in microvascular function. Future work will demonstrate the impact of these redox-sensitive thiol modifications on microvascular function to provide a better understanding of redox signalling in protein function and disease.

Funding Acknowledgement
Type of funding sources: Public Institution(s). Main funding source(s): MRC-DTP,European Union's Horizon 2020 research and innovation programme.