bluuebunny/crossref_metadata_2025 huggingface dataset:
Lymphatic Vessel–Mediated Attenuation of Persistent Macrophage Infiltration Improves Fat Grafting Outcomes in Mice Models
Authors: Zhou Cheng , Sun TianYi , Zhao Jing , Xu YiDan , Dong ZiQing , Lu Feng , Li Bin
Published: June 2024

Background

Persistent macrophage infiltration may lead to adverse consequences, such as calcifications and nodules in fat grafts. Lymphatic vessels, which transport inflammatory cells, are involved in regulating inflammatory responses. Less is known, however, about lymphatic vessels after fat grafting.

Objectives

The aim of this study was to explore the regulation of fat graft survival by lymphatic vessels.

Methods

A common adipose graft model was constructed to assess the processes responsible for changes in the number of lymphatic vessels in grafts. Adipose tissue samples from C57/BL6 mice and green fluorescent protein–expressing mice were cross-grafted to determine the source of lymphatic vessels. The number of lymphatic vessels in the grafts was increased by treatment with vascular endothelial growth factor C, and the effects of this increase on fat grafting were evaluated.

Results

The number of lymphatic vessels was greater in postgrafted fat than in inguinal fat before transplantation, with lymphatic vessels in these grafts gradually transitioning from donor to recipient sources. Lymphatic vessels grew more slowly than blood vessels during early stages of grafting; during later stages, however, the number of blood vessels declined markedly, with more lymphatic vessels than blood vessels being observed 60 days after grafting. Vascular endothelial growth factor C treatment increased graft lymphatics and distant volume retention, while reducing fibrosis and oil sacs. Lymphatic vessels acted as drainage channels for macrophages, with the degree of sustained macrophage infiltration decreasing with increases in the number of lymphatic vessels.

Conclusions

Increasing the number of lymphatic vessels is beneficial for fat graft survival, which may be related to a reduction in prolonged macrophage infiltration.

Level of Evidence: 4
Decoding the Implications of Glucagon-like Peptide-1 Receptor Agonists on Accelerated Facial and Skin Aging
Authors: Ridha Zainab , Fabi Sabrina Guillen , Zubar Raheel , Dayan Steven H
Published: June 2024

Following the advent of glucagon-like peptide-1 receptor agonists (GLP-1RAs), subsequent unintended effects such as accelerated facial aging and altered skin health have been noted. This review delves deeper into the causative underlying mechanisms and provides insights into the intricate relationship between GLP-1RAs, adipose tissue, and premature facial aging, thereby highlighting the need for a nuanced understanding of their effects on facial alterations and skin health. Studies exploring the potential effects of GLP-1RAs on facial alterations and offering insights into the possible underlying mechanisms, causes, and clinical implications were included. The accelerated facial aging and altered skin health observed in GLP-1RA patients appears to be multifactorial, involving loss of dermal and subcutaneous white adipose tissue, and altered proliferation and differentiation of adipose-derived stem cells (ADSCs), and impacts on the production and secretion of hormonal and metabolic factors. These changes compromise the structural integrity and barrier function of the skin and may lead to diminished facial muscle mass, further exacerbating the appearance of aging. The insights presented call for a paradigm shift in the clinical management of facial changes induced by GLP-1RAs, with a focus on treatment strategies aimed at targeting ADSC stimulation. These include autologous fat transfers to reintroduce cells rich in ADSCs for rejuvenation, composite fat grafting combining autologous fat with/without stromal vascular fraction, and the strategic use of soft tissue fillers for volume restoration and biostimulation. This review highlights the potential role of GLP-1RAs in modulating adipose tissue dynamics, thereby contributing to accelerated aging through metabolic, structural, and hormonal pathways.

Level of Evidence: 5
RCSB protein Data Bank: exploring protein 3D similarities via comprehensive structural alignments
Authors: Bittrich Sebastian , Segura Joan , Duarte Jose M , Burley Stephen K , Rose Yana
Published: June 2024

Motivation

Tools for pairwise alignments between 3D structures of proteins are of fundamental importance for structural biology and bioinformatics, enabling visual exploration of evolutionary and functional relationships. However, the absence of a user-friendly, browser-based tool for creating alignments and visualizing them at both 1D sequence and 3D structural levels makes this process unnecessarily cumbersome.

Results

We introduce a novel pairwise structure alignment tool (rcsb.org/alignment) that seamlessly integrates into the RCSB Protein Data Bank (RCSB PDB) research-focused RCSB.org web portal. Our tool and its underlying application programming interface (alignment.rcsb.org) empowers users to align several protein chains with a reference structure by providing access to established alignment algorithms (FATCAT, CE, TM-align, or Smith–Waterman 3D). The user-friendly interface simplifies parameter setup and input selection. Within seconds, our tool enables visualization of results in both sequence (1D) and structural (3D) perspectives through the RCSB PDB RCSB.org Sequence Annotations viewer and Mol* 3D viewer, respectively. Users can effortlessly compare structures deposited in the PDB archive alongside more than a million incorporated Computed Structure Models coming from the ModelArchive and AlphaFold DB. Moreover, this tool can be used to align custom structure data by providing a link/URL or uploading atomic coordinate files directly. Importantly, alignment results can be bookmarked and shared with collaborators. By bridging the gap between 1D sequence and 3D structures of proteins, our tool facilitates deeper understanding of complex evolutionary relationships among proteins through comprehensive sequence and structural analyses.

Availability and implementation

The alignment tool is part of the RCSB PDB research-focused RCSB.org web portal and available at rcsb.org/alignment. Programmatic access is available via alignment.rcsb.org. Frontend code has been published at github.com/rcsb/rcsb-pecos-app. Visualization is powered by the open-source Mol* viewer (github.com/molstar/molstar and github.com/molstar/rcsb-molstar) plus the Sequence Annotations in 3D Viewer (github.com/rcsb/rcsb-saguaro-3d).
Dual-energy computed tomography iodine quantification combined with laboratory data for predicting microvascular invasion in hepatocellular carcinoma: a two-centre study
Authors: Li Huan , Zhang Dai , Pei Jinxia , Hu Jingmei , Li Xiaohu , Liu Bin , Wang Longsheng
Published: June 2024

Objectives

Microvascular invasion (MVI) is a recognized biomarker associated with poorer prognosis in patients with hepatocellular carcinoma. Dual-energy computed tomography (DECT) is a highly sensitive technique that can determine the iodine concentration (IC) in tumour and provide an indirect evaluation of internal microcirculatory perfusion. This study aimed to assess whether the combination of DECT with laboratory data can improve preoperative MVI prediction.

Methods

This retrospective study enrolled 119 patients who underwent DECT liver angiography at 2 medical centres preoperatively. To compare DECT parameters and laboratory findings between MVI-negative and MVI-positive groups, Mann-Whitney U test was used. Additionally, principal component analysis (PCA) was conducted to determine fundamental components. Mann-Whitney U test was applied to determine whether the principal component (PC) scores varied across MVI groups. Finally, a general linear classifier was used to assess the classification ability of each PC score.

Results

Significant differences were noted (P < .05) in alpha-fetoprotein (AFP) level, normalized arterial phase IC, and normalized portal phase IC between the MVI groups in the primary and validation datasets. The PC1-PC4 accounted for 67.9% of the variance in the primary dataset, with loadings of 24.1%, 16%, 15.4%, and 12.4%, respectively. In both primary and validation datasets, PC3 and PC4 were significantly different across MVI groups, with area under the curve values of 0.8410 and 0.8373, respectively.

Conclusions

The recombination of DECT IC and laboratory features based on varying factor loadings can well predict MVI preoperatively.

Advances in knowledge

Utilizing PCA, the amalgamation of DECT IC and laboratory features, considering diverse factor loadings, showed substantial promise in accurately classifying MVI. There have been limited endeavours to establish such a combination, offering a novel paradigm for comprehending data in related research endeavours.
Universal Targeted Haplotyping by Droplet Digital PCR Sequencing and Its Applications in Noninvasive Prenatal Testing and Pharmacogenetics Analysis
Authors: Gai Wanxia , Wang Guangya , Lam W K Jacky , Yuen Liz Y P , Jiang Peiyong , Yu Stephanie C Y , Leung Tak Y , Lau So Ling , Lo Y M Dennis , Chan K C Allen
Published: June 2024

Background

The analysis of haplotypes of variants is important for pharmacogenomics analysis and noninvasive prenatal testing for monogenic diseases. However, there is a lack of robust methods for targeted haplotyping.

Methods

We developed digital PCR haplotype sequencing (dHapSeq) for targeted haplotyping of variants, which is a method that compartmentalizes long DNA molecules into droplets. Within one droplet, 2 target regions are PCR amplified from one template molecule, and their amplicons are fused together. The fused products are then sequenced to determine the phase relationship of the single nucleotide polymorphism (SNP) alleles. The entire haplotype of 10s of SNPs can be deduced after the phase relationship of individual SNPs are determined in a pairwise manner. We applied dHapSeq to noninvasive prenatal testing in 4 families at risk for thalassemia and utilized it to detect NUDT15 diplotypes for predicting drug tolerance in pediatric acute lymphoblastic leukemia (72 cases and 506 controls).

Results

For SNPs within 40 kb, phase relation can be determined with 100% accuracy. In 7 trio families, the haplotyping results for 97 SNPs spanning 185 kb determined by dHapSeq were concordant with the results deduced from the genotypes of both parents and the fetus. In 4 thalassemia families, a 19.3-kb Southeast Asian deletion was successfully phased with 97 downstream SNPs, enabling noninvasive determination of fetal inheritance using relative haplotype dosage analysis. In the NUDT15 analysis, the variant status and phase of the variants were successfully determined in all cases and controls.

Conclusions

The dHapSeq represents a robust and scalable haplotyping approach with numerous clinical and research applications.
Genetic variants associated with cardiorespiratory symptoms of long COVID. The GINA-COVID study
Authors: Polo-Alonso S , Camps-Vilaro A , Degano I R , Marti-Lluch R , Pinsach-Abuin M , Selga E , Puigdecanet E , Pedrerol-Alvarez M , Puigmule M , Perez A , Subirana I , Elosua R , Brugada R , Ramos R , Marrugat J
Published: June 2024

Introduction

SARS-CoV-2 infection can cause persistent symptoms, which are known as long COVID (LC). The WHO defines this condition as the presence of any symptom after the viral infection that persist for at least 3 months. Its incidence is estimated to be between 10% and 70% of all COVID cases, and include a wide range of symptoms. Some of them are related with the cardiorespiratory (CR) systems. The identification of the genetic variants related to the CR symptoms of LC could enhance the prevention of these symptoms after the viral infection.

Purpose

To evaluate the association between genetic variants and CR symptoms of LC.

Methods

We conducted a case-control study that involved 2,422 patients infected with SARS-CoV-2 from Catalan primary care and hospitals. Follow-up for a minimum of 1 year was performed, spontaneously declared symptoms and duration were recorded. Then, we considered LC CR cases the occurrence at least one of the following CR symptoms (dyspnea, polypnea, fatigue, chest pain, heart palpitations or cough) 3 months or more after infection (WHO definition). Controls were COVID-19 participants without any CR symptom in that period. Individuals were genotyped by the Axiom Spanish Biobank Array, with 757,836 markers that include rare and low-frequency Spanish variants. Genome-wide association study was performed by fitting a logistic regression adjusting for age, sex and the first 10 principal components. P-value significance threshold was established at 5x10-8.

Results

Following the quality control process for genotyping, a total of 2,147 participants were considered, with cases comprising 41.43% of the sample. Cases and controls characteristics are shown in Table 1. Cases were younger, predominantly female, and of American descent compared to controls. The prevalence of smoking, hypertension and history of coronary artery disease was lower in cases than in controls, as well as the risk of coronary artery disease. Upon genotyping, no significant associations between LC CR symptoms and genetic variants were obtained in the association study (Figure 1).

Conclusions

LC cases with CR symptoms exhibit a more favourable cardiovascular risk profile compared to controls. Nevertheless, there is no significant association observed between genetic variants and the CR symptoms of LC.
Screening for arrhythmogenic heart disease in school age children-a pilot study
Authors: Bagkaki A , Parthenakis F , Chlouverakis G , Anastasakis A , Papagiannis I , Germanakis I
Published: June 2024

Introduction

There is a relative lack of data regarding efficacy of cardiovascular (CV) screening programs including ECG when applied in young children, for early detection of unrecognized genetic conditions associated with high risk for sudden cardiac death (SCD).

Purpose

We evaluated the performance of a CV screening program, including 12-lead ECG recording, when applied in selected populations of Mediterranean children.

Methods

A CV screening program for primary schools, approved by Ministry of Health, was applied in a sample of primary schools of a Mediterranean island, in geographical isolated areas with reported increased SCD incidence. Participation was voluntary following parental consent. After completion of a standardized history questionnaire by parents, children underwent clinical evaluation and 12-lead ECG recording, at local health stations. A stepwise referral pattern was established, including pediatric cardiology evaluation and molecular DNA confirmatory testing, whenever the possibility of inherited arrhythmogenic CV disease was increased.

Results

929 primary school children, (462 male, 467 female), median age 8,5 (range 5,5 -11,5 yrs) have been evaluated during eight years (2014-22). 52 children (5,6%) had an indication for further diagnostic or lifestyle modification for CV risk factors, including ECG abnormalities (n=16, 1.7%), abnormal heart auscultation (n=21, 2.2%), hypertension (n=10, 1%) and positive 1st degree family history of SCD (n= 5, 0.5%).

ECG abnormalities included WPW (n=1, 0.1%), VES (n=4, 0.4%), probable LVH (n=2), abnormal QRS axis (n=7 ) and QTc prolongation (n=2, 0.2%) both boys, with QTc 475 and QTc 490. Children with ECG abnormalities underwent further evaluation including ambulatory ECG monitoring and regular follow up. Family ECG screening was positive in one child with prolonged QTc (490ms, wide T wave), regarding his father (QTc=460) and one sister (QTc=490). Further molecular DNA testing was negative in the first child, while it revealed a novel KCNH2 heterozygous mutation (NP_000229.1:p.Ser606Tyr) in child and affected family members in the second case. In silico analysis using Polyphen-2 and SIFT suggested that the Ser606Tyr mutation might be harmful, and the family was advised to receive b-blocker prophylactic treatment.

Conclusions

A stepwise approach from ECG population screening to molecular diagnostics can detect and genetically characterize subclinical cases of inherited CV disease, associated with arrhythmogenic SCD also in pediatrics. Larger scale studies are needed to define the cost-effectiveness of a structured CV disease screening including ECG in school age children.
Comparison of peripheral muscle strength, functional capacity and activities of daily living in frail and non-frail adult individuals with congenital heart disease
Authors: Topcuoglu C , Vardar Yagli N , Ertugrul I , Aykan H , Karagoz T , Saglam M
Published: June 2024

Background/Introduction

Frailty is associated with a higher incidence of cardiovascular disease and risks of all-cause mortality, leading to a reduction in life expectancy. Cardiorespiratory fitness and peripheral muscle strength are shown to be the strongest predictors of the level of frailty and the potential for frailty to decrease over time.

Purpose

The aim of this study was to compare peripheral muscle strength, functional capacity and activities of daily living in frail and non-frail adult individuals with congenital heart disease (ACHD).

Methods

A cross-sectional study design was used. A total of 36 individuals with ACHD, 14 frail (24.50±10.14 years) and 22 non-frail (24.68±6.24 years) were included in the study. Frailty; according to the Fried criteria, which consist of parameters as muscle strength weakness, involuntary weight loss, decreased physical activity, decreased mobility, and fatigue. Peripheral muscle strength was assessed using a digital dynamometer, functional capacity using the Six Minute Walk Test (6MWT) and activities of daily living using the Glittre Activities of Daily Living Test.

Results

Knee extensor muscle strength (p=0.011), shoulder abduction muscle strength (p=0.012) and 6MWT distance (p=0.007) in frail individuals with ACHD was lower than non-frail individuals. Glittre Activities of Daily Living Test duration was higher in frail individuals with ACHD than in non-frail individuals (p=0.023).

Conclusion(s)

Upper and lower peripheral muscle strength, functional capacity and activities of daily living were impaired in individuals with frail ACHD. Early assessment of frailty in individuals with ACHD and implementation of individualized exercise training programs in frail individuals may be useful in reducing the impact associated with frailty.
Cognitive impairment is associated with lower physical function in patients with heart failure
Authors: Klompstra L , Papageorgiou J M , Jaarsma T , Stromberg A
Published: June 2024

Introduction

Cognitive impairment is a common and serious comorbidity in patients with heart failure (HF) and its prevalence follows the severity of the condition. Preventing deterioration in patients with heart failure is key to improve outcomes. Cognitive impairment might be correlated to physical function.

Purpose

To assess cognitive impairment in patients with HF and exploring its potential association with physical function.

Methods

Data was collected in 246 patients with HF (mean age 68±10, 28% female). Cognition was measured with the Montreal Cognitive Assessment (MoCA). Physical function was measured with an activity monitor – Actigraph (minutes/day spent in sedentary time, light physical activity and moderate to vigorous physical activity (MVPA) as well as steps daily), exercise capacity (6-minute walk test), self-selected walking speed (gait speed for 10 meters in seconds) and the dynamic balance/mobility (Sit-to-stand test: number in 30 seconds). Difference in physical function between patients who have mild to moderate cognitive impairment (MoCA cut off value 26) were compared to patients who had no to light cognitive impairment (MoCA Cut off value ³27) with Mann-Whitney U tests.

Results

A total of 246 patients with HF were evaluated, 171 patients (70%) had mild cognitive impairment and 3 patients (1%) had moderate cognitive impairment. Patients with mild or moderate cognitive impairment, were older (mean 69 vs. 63 years old, p-value<.001) and with diverse comorbidities, as they suffered more often from COPD (18% vs 7%, p-value=0.015) and stroke (15% vs. 6%, p-value 0.028) compared to patients with no to light cognitive impairment. Patients with mild or moderate cognitive impairment spent more time sedentary (median 562 vs. 530 min/day, p-value=0.029), less time in MVPA (median 10 vs. 21 min/day, p-value=0.003) compared to patients with no to light cognitive impairment and walked less steps a day (median 3884 vs. 5206, p-value=0.002). No differences were found in spent time in light physical activity (206 vs 226 min/day p-value=0.65). Patients with mild or moderate cognitive impairment walked a lower number of meters on the 6MWT (median 438 vs. 528 meters, p-value=<.001), were slower on gait speed (median 6 vs. 5 seconds, p-value<.001) and on the sit-to-stand test (median 11 vs. 9 times, p-value<.001) compared to patients with no to light cognitive impairment.

Conclusion

71% of patients with heart failure had mild or moderate cognitive impairment, which was negative associated with physical function. Screening for cognitive impairment together with physical function may decrease adverse events by identifying those who need tailored care.
Is GRACE 2.0 a better predictor of post-MI mortality than GRACE in patients with known diabetes compared to those without?
Authors: Soman B , Chrysostomou P , Chatterjee T , De Silva R , Sathyapalan T , Chattopadhyay S
Published: June 2024

Purpose

To explore whether there is any difference in the predictive ability of GRACE 2.0 in determining post-MI mortality at 6 months after discharge in patients with and without diabetes.

Methods

A large dataset of patients admitted to a medium sized district general hospital in UK collected over 6 years for submission to the Myocardial Infarction National Audit Project (MINAP) was analysed. This is a validated dataset with high case ascertainment. GRACE and GRACE 2.0 scores and probabilities for death at 6 months were computed using web-based calculators. Diabetes status was recorded from the patient’s history, drug chart and individual case note review. The mortality data was obtained from hospital and general practice records. The patients were censored at the last recorded contact with a health professional after discharge. GRACE 2.0 model discrimination was assessed by comparing the area under the receiver operating curve (AUC) in patients with and without diabetes using the DeLong method. GRACE 2.0 model calibration was assessed graphically by comparing the observed % and the mean predicted % of mortality in each decile of the GRACE score.

Results

2838 patients were entered into the database over the 6-year period. Complete data was available for 2784 patients. 783 patients had known diabetes. Death within 6 months of admission occurred in 242 patients (89(11.4%) with and 153(7.6%) without diabetes). GRACE was worse at predicting mortality in patients with (AUC 0.746, 95% CI 0.714 to 0.776) than without (AUC 0.814 95% CI 0.796 to 0.831) diabetes (δAUC 0.0679, p=0.0323). GRACE 2.0 had similar results (AUC 0.753 95% CI 0.721 to 0.783 with diabetes and AUC 0.817 95% CI 0.799 to 0.833 without diabetes; δAUC 0.0634, p=0.0450) (Fig 1 Upper panel). Predictive efficacy of GRACE 2.0 for mortality was similar to GRACE in both patients with and without diabetes. Calibration curves show that the mortality predicted by GRACE 2.0 was consistently higher than the observed mortality especially in diabetic patients suggesting that the it overestimated risk in this group (Fig 1 Lower panel).

Conclusion

GRACE 2.0 is worse in predicting mortality in patients with diabetes than in those without. There is no difference in the predictive ability of GRACE 2.0 versus GRACE in patients with diabetes. GRACE 2.0 seems it overestimates risk in both groups.
Myocardial micro-alternation index (MMI) does not associate with the ischemic response in coronary artery disease patients
Authors: Tiksnadi B B , Putra A P , Ikhsani R , Tarsidin N F
Published: June 2024

Background

ECG dispersion mapping (ECG-DM) was one of non-invasive parameters to observe micro-electrical changes in the ECG signal. This was assessed using the Myocardial Micro-alternation Index (MMI), whose reflect abnormalities in the myocardium at a metabolic level, indicating ischemia, based on small-invasive test. Until now there has been no study that specifically examines the ischemic response to MMI in the coronary artery disease (CAD) population. Finding ischemic with treadmill test still frequently performed in our daily practice due to lack availability and feasibility of imaging test, and somehow the specificity of the test is moderately-high and similar with imaging test.

Purpose

Aim to determine the association between Myocardial Micro-alternation Index (MMI) and the ischemic response in CAD patients.

Methods

This was a cross-sectional observational study done in Tertiary General Hospital. Subjects included were 18-79 years old patients who were hospitalized with CAD in 6 months to 2 years prior, either because of acute coronary syndrome or underwent elective revascularization procedures (primary coronary intervention/PCI or coronary artery bypass graft/CABG). All patients were assessed for ECG dispersion mapping with 3-minute recordings. The ECG dispersion mapping was analyzed by the system and reported as MMI. Ischemic response was obtained for treadmill test results with maximal test or symptom limited protocol. Positive or suggestive ischemic response was defined by ST-depression more than 0.05 mv if downslope or horizontal, or 0.1mv if upsloping, in minimal two leads and in three consecutive beats.

Results

Among 68 patients included in this study, two was excluded due to inability to perform exercise test. Form 66 patients, 58 (87.9%) were men and the mean age was 57 ± 10.2 years. The median of MMI was 18 (1-61)%. Twenty-four patients (36.4%) had a positive or suggestive ischemic response, while the rest was negative. The median of MMI in positive ischemic was 18 (1-52)% and in the negative ischemic response was 18 (14-61)%. The Mann-Whitney analysis showed that there were no associations between MMI and ischemic response (p 0.707).

Conclusion(s)

There are no associations between Myocardial micro-alternans index with ischemic response in patients with chronic stable coronary artery disease patients. The utility of MMI to predict ischemia might need imaging test to confirm. ECG Positive Ischemic Response  MMI Picture
The role of intracoronary physiology measurements and acetylcholine provocation testing in patients with INOCA. First data from Latvia
Authors: Vitola B , Trusinskis K , Mintale I , Erglis A
Published: June 2024

Introduction

For diagnosis of exact INOCA endotype the invasive measurements of coronary flow reserve (CFR), index of microvascular resistance (IMR), which both represents the microvascular function, and acetylcholine (ACH) provocation test to diagnose vasospasm is mandatory.

Purpose

To perform the intracoronary physiological testing, including measurements of CFR, IMR and ACH provocation test for defining the INOCA endotypes – microvascular angina (MVA), vasospastic angina (VSA), microvascular spasm (MVS), or combination of them.

Methods

The invasive examination was performed in a single University Hospital from March 2023 till December 2023 in patients presented with cardiac symptoms, significant ischemic signs at exercise ECG test and non-obstructed epicardial coronary arteries during invasive or computed tomography coronary angiography (epicardial stenosis less than 50% and/or fractional flow reserve (FFR) >0.80). The criteria for MVA were CFR ≤ 2.5 and IMR ≥ 25. The VSA was assessed if significant (>90%) vasospasm occurred during ACH provocation test with subsequent ischemic signs in ECG and chest pain during the test. In patients presented with the ischemic signs in ECG and chest pain during the ACH provocation test, without vasospasm – the MVS was defined.

Results

Invasive functional testing was performed for 20 patients. 15 patients (75.0%) were women. The mean age of the patients was 59.9 ± 9.4 years. The most common cardiac symptoms were chest pain (18, 90.0%), dyspnea (15, 75.0%), fatigue (14, 70.0%), headache (8, 40.0%) and excessive sweating (6, 30.0%). 3 (15.0%) patients were current or ex-smokers. Dyslipidemia was present in 20 (100.0%), arterial hypertension in 17 (85.0%) and type 2 Diabetes mellitus (T2DM) in 3 (15.0%) patients. In 8 (40.0%) patients the somatoform autonomic dysfunction was suggested as a primary diagnosis after the first tests.

3 patients (15.0%) showed normal values of all measurements. 8 (40.0%) patients were diagnosed with MVA, 6 (30.0%) with VSA, MVS was assessed in 1 (5.0%) patient and the combination of MVA and VSA was observed in 2 (10.0%) cases.

Conclusion

The first clinical data of INOCA diagnostics of patients in Latvia are very promising since the amount of INOCA patients is high. The patients are underdiagnosed and remains symptomatic without tailored medical treatment, emphasizing that every INOCA endotype requires different treatment. More clinical evidence will be needed to routinely adapt coronary function testing during invasive management.
Colchicine additional effect on atrial fibrillation onset prevention in patients with chronic coronary diseases, depending on the level of non-high-density lipoprotein cholesterol
Authors: Malidze D , Jojua N , Gognadze T , Noniashvili M , Hamza M
Published: June 2024

Introduction

Colchicine may be beneficial for decreasing the incidence of AF in post-cardiac surgery and post-pulmonary vein ablation patients but may not decrease the incidence of AF in patients with coronary artery disease.

The purpose was to learn, whether colchicine is effective in maintaining sinus rhythm in patients with high risk on atrial fibrillation incidence, with coronary artery disease, considering patients Non-HDL cholesterol level.

Materials and methods

A total 114 patients with a high risk of developing AF by the FIND-AF algorithm underwent randomization by 2 groups. The group A, 62 patients with high non HDL cholesterol ≥160 mg/dl and the group B, 52 patients with low level non HDL cholesterol <160 mg/dl. The group A patients were divided into 2 subgroups, group 1A, 32 patients were assigned to the colchicine in a low dose (0.5 mg per day), and 30 patients - Group 1B, non-colchicine group, also group 2 was divided by two group, group 2A, 28 patient assigned to the low dose colchicine and group 2B, 24 patient not receiving colchicine. The groups did not differ significantly in terms of baseline significant comorbidities, treatment and age. The primary endpoint was incidence of AF episode > 30 second during a 6-month period. Data were analyzed using IBM SPSS version 20. P < 0.05 was considered statistically significant.

Results

in Group 1A there were significantly low rate of AF onset, then in Group 1B, 4 (12.52%) versus 9 (33.33%), without colchicine, respectively; p = 0.016), As in group 2 A, and 2B, the rates of AF onset were not significantly differentiated from each other’s, 5(17.85 %) with colchicine group versus 5 (20.83 %) without colchicine, respectively; p=0.181.

Conclusion

The effect of colchicine on reducing AF in patients with chronic coronary artery disease is not neutral on all patients. In patients category with high non-HDL level ≥160 mg/dl - colchicine treatment was associated with significantly lower AF incidence. colchicine 1A1B  2a2b colchicine
Usefulness of cognitive assessment in the prediction of documented atrial fibrillation and ischaemic stroke: a cross-sectional study
Authors: Pal T , Baba D F , Preg Z , Nemes-Nagy E , German-Sallo M
Published: June 2024

Background/Introduction

Atrial fibrillation (AF) is sometimes detected when thromboembolic events occur, commonly ischaemic stroke (IS). In patients with AF, the prevalence of cognitive dysfunction (CD) is higher, independently from IS.

Purpose

Evaluating the usefulness of cognitive evaluation and the CHA2DS2-VASc score for the prediction of documented AF and IS.

Methods

In this cross-sectional retrospective study, we included 469 patients with cardiovascular diseases. Between December 2016 and November 2019, all patients completed two cognitive tests during hospitalization. The Montreal Cognitive Assessment (MoCA) and the Mini Mental State Examination (MMSE) were used. The associations between cognitive test scores (standard and optimal cut-off values) and AF/IS were analyzed by logistic regression. We determined the area under the curve (AUC) of CD tests and optimal cut-off values using the receiver operating characteristic curves and the maximum Youden index.

Results

We found a significant association between the standard MoCA cut-off value for CD (<26 points) and the presence of documented AF (OR: 1.83, 95% CI: 1.11-3.01, p= 0.0174) and IS (OR: 2.09, 95% CI: 1.04-4.22, p= 0.0379). The standard MMSE score of <24 points was a risk factor for the presence of a previous IS (OR: 2.43, 95% CI: 1.3-4.53, p= 0.0051). For the prediction of documented AF, the optimal cut-off score was <26 for MoCA and <28 points for MMSE. For MoCA, the optimal cut-off was <23 points in the prediction of IS and <28 points for MMSE. The determined CHA2DS2-VASc cut-off score for AF was >3 points and for IS >5 points. The receiver operating characteristic curve analyses showed non-inferiority between CD tests and CHA2DS2-VASc score in anticipating documented episodes of AF and were superior to CHA2DS2-VASc score in the prediction of a previous IS (MoCA: AUC dif: 0.128; p= 0.0110, MMSE: AUC dif: 0.130, p= 0.0084).

Conclusions

In this study, we demonstrated that the MoCA and MMSE tests can detect the presence of documented AF and IS. Risk factors for AF were MoCA <26 points and MMSE <28 points while for IS MoCA <23 points and MMSE <28 points. In patients who present cognitive impairment AF screening may be appropriate.
Impact of a mobile health-based disease management program on coronary risk factors among chronic ischemic heart disease holders
Authors: Miki T , Yamada J , Ishida S , Sakui D , Kanai M , Hagiwara Y
Published: June 2024

Background

Ischemic Heart Disease (IHD) is a leading global cause of death. Management often involves controlling factors such as low-density lipoprotein (LDL) cholesterol.[1] In recent years, mobile health (mHealth) technologies have significantly impacted chronic disease management, offering novel, personalized healthcare approaches.[2] These technologies enable continuous monitoring and real-time interventions, making them particularly suitable for managing conditions like IHD. mHealth has become integral to modern healthcare, especially for long-term conditions, due to its ability to provide personalized care and enhance patient engagement. While there is growing evidence of mHealth's efficacy in cardiac failure and other aspects of cardiovascular health, studies focusing specifically on LDL cholesterol as a primary outcome in the context of IHD are limited. Previous studies have focused primarily on the acute phase.[3] Furthermore, it's recognized that mHealth's success often hinges on the inclusion of professional guidance and feedback, which enhances its effectiveness.[2]

Purpose

This study investigates the effectiveness of a Mobile Health-Based Disease Management Program in reducing LDL cholesterol in individuals with chronic IHD.

Methods

In this retrospective study, IHD patients participated in a Mobile Health-Based Disease Management Program from December 2018 to October 2022. The program involved bi-weekly phone consultations, app-based monitoring, and regular physician updates over 6 months. The primary measure was the change in LDL cholesterol levels, with secondary outcomes including body weight, HDL cholesterol, triglycerides, HbA1c, uric acid, blood pressure, salt intake, and sleep duration. Effectiveness was evaluated using paired t-tests, with analyses conducted in R software.

Results

Of the 266 participants, results included a significant reduction in LDL cholesterol levels from an average of 98.82 (SD 40.92) to 86.62 (SD 39.86) mg/dL. Other health indicators also improved: average body weight dropped from 77.51 (SD 17.53) to 72.39 (SD 19.84) kg, and triglyceride levels decreased from 145.83 (SD 98.52) to 115.89 (SD 77.12) mg/dL. These results indicate a positive effect on overall metabolic health. Stratified analysis showed that participants with higher initial LDL levels experienced more substantial improvements in various health metrics.

Conclusion

This study demonstrates that the Mobile Health-Based Disease Management Program effectively lowered LDL cholesterol, particularly in individuals with higher initial levels, showcasing its potential in managing cardiovascular risk in chronic IHD. Future research should focus on the broader application and long-term sustainability of such programs.
Branched chain amino acids and physical activity in a sample of healthy, non-obese people
Authors: Liu K , Borreggine R , Gallart-Ayala H , Ivanisevic J , Marques-Vidal P
Published: June 2024

Background

Physical activity (PA) has been demonstrated to improve insulin sensitivity and reduce the risk of cardiovascular diseases. BCAA (branched chain amido acid) metabolism play a role in maintaining system energy homeostasis at rest and during activity, high BCAA levels being associated with an increased risk of cardiovascular disease (CVD) and diabetes. However, there is still limited research on the relationship between PA intensity and human plasma BCAA.

Aims

To assess the associations between BCAA (Valine, Leucine and Isoleucine) and PA in a somple of healthy, non-obese, middle-aged people.

Methods

Cross-sectional study using data from the CoLaus|PsyCoLaus study conducted in our city. BCAA concentrations were measured by stable isotope dilution liquid chromatography – mass spectrometry (LC-MS) assay. Time spent in PA was assessed by questionnaire and categorized into sedentary, light, moderate and vigorous intensity.

Results

On bivariate analysis, BCAA levels were significantly and positively associated with total energy expenditure and negatively with light PA and sleep time. Those findings were confirmed after multivariable analysis, a negative association between BCAA levels and duration of sleep, light and moderate PA, and a positive association between BCAA levels and total energy expenditure, sedentary behaviour and vigorous PA being observed (table).

Conclusion

sleep time, light and moderate intensity PA are negatively associated with BCAA, suggesting that the beneficial effects of PA on CVD could partly be mediated by decreases in BCAA levels. The unexpected positive association between total energy expenditure and vigorous PA with BCAA levels should be further explored.
Characteristics of Japanese patients with heart failure with sarcopenia - a study using cardiopulmonary exercise testing
Authors: Takeda S , Harada K , Mamiya K , Terashima S , Matsunaga S , Kataoka T , Harada K , Nagao T , Shinoda T , Yamada S , Murohara T
Published: June 2024

Background

Sarcopenia has been frequently associated with comorbidities among patients with heart failure; it probably contributes to their poor prognosis despite the pathophysiology of the relationship between these two conditions being unclear. Furthermore, there are insufficient data to evaluate sarcopenia in patients with heart failure using cardiopulmonary exercise testing (CPX).

Purpose

This study aimed to elucidate the clinical characteristics of patients with heart failure with sarcopenia using CPX.

Methods

We examined 635 Japanese patients (mean age 65 ± 13 years, 77% men) who were hospitalised for heart failure and could undergo cardiac rehabilitation between November 2014 and November 2021. Patients with severe heart failure for whom CPX testing was not feasible were excluded.

Blood testing, echocardiogram, physical performance measurement and CPX were performed during hospitalisation. Sarcopenia was diagnosed based on the Asian Working Group for Sarcopenia 2019 criteria using handgrip strength, skeletal muscle mass and walking speed.

Oxygen uptake (VO2), carbon dioxide output (VCO2) and minute volume of ventilation (VE) were measured during CPX. The oxygen pulse at peak exercise (peak oxygen pulse) was calculated as peak VO2 divided by peak heart rate. The dead space to tidal volume ratio (minimum VD/VT), minimum ventilator equivalent for carbon dioxide (minimum VE/VCO2) and respiratory exchange ratio were measured using the single-breath analysis of carbon dioxide.

Results

Of the 635 patients, 54 (8.5%; 44 men) had sarcopenia complications; they were older, had a lower ejection fraction and higher B-type natriuretic peptide (BNP) levels than patients without sarcopenia (Table 1).

Multivariate analysis revealed that age (r = −0.062, p < 0.01), BNP level (r = 0.110, p < 0.01), peak VO2 (r = −0.016, p < 0.01) and minimum VE/VCO2 (r = 0.011, p < 0.01) were significantly associated with sarcopenia in patients with heart failure.

Logistic regression analysis indicated that peak VO2, peak oxygen pulse, minimum VD/VT and minimum VE/VCO2 were independently associated with sarcopenia complications (Table 2).

Conclusions

The CPX results demonstrated that patients with heart failure with sarcopenia had lower cardiac output and worse ventilation efficiency than those without sarcopenia, suggesting that sarcopenia complications further reduce cardiopulmonary function in patients with heart failure, which in turn contributes to the poor prognosis of the disease.
Acute effects of inspiratory muscle training on microcirculation in chronic heart failure patients
Authors: Katsoula C , Karatzanos E , Vasileiou I , Briasoulis A , Papadopoulou E , Kalampakos N , Dimopoulos S , Routsi C , Nanas S , Vasileiadis I
Published: June 2024

Introduction

Patients with chronic heart failure (CHF) have been presented with microcirculation alterations and vascular endothelial dysfunction. Exercise training programs, including inspiratory muscle training (IMT) as an alternative/additional means of exercise, have been shown to improve the functional status of these patients. However, there has not been much data on the acute effect of IMT on systemic microcirculation.

Purpose

The aim of this study was to investigate the acute effect of an IMT session on the microcirculation of non-exercising muscles (systemic effect) in CHF patients.

Method

Thirty-four (30♂/4♀) stable CHF patients [age: 61±9 years, EF: 34±8%, VO2peak: 17.5±4.0 ml/kg/min, NYHA class ≥II) participated in a single IMT session (5 sets/10 repetitions at 60% of maximum inspiratory pressure). Systemic microcirculation was assessed with near-infrared spectroscopy (NIRS) and the 3-min vascular occlusion technique at the thenar muscle, before and after the session. Variables evaluated were the basal tissue oxygen saturation (StO2), the oxygen consumption rate and the reperfusion rate. Values are in mean and standard deviation.

Results

After the IMT session, the reperfusion rate was increased (from 3.4±1.6 to 3.9±1.7 %/min, p=0.007). The oxygen consumption rate was also increased (from 12.7±3.8 to 13.2±3.9 %/min, p=0.021). Finally, the basal tissue oxygen saturation values tended to increase (from 85.5±6.4. to 84.7±6.2%, p=0.065), an alteration of not any clinical significance.

Conclusions

An IMT session had a beneficial effect on the systemic microcirculation of CHF patients, particularly on the reperfusion rate which reflects endothelial function.
Diagnostic performance of single-lead electrocardiograms for arterial hypertension diagnosis: a machine learning approach
Authors: Angelaki E , Barmparis G , Fragkiadakis K , Maragkoudakis S , Zacharis E , Plevritaki A , Malikides O , Kalomoirakis P , Lasithiotaki G , Vardas P , Kochiadakis G , Tsironis G , Marketou M
Published: June 2024

Background

Awareness and early identification of hypertension is among the most crucial components in reducing the burden of cardiovascular disease (CVD). Artificial intelligence-based analysis of electrocardiograms (ECGs) can improve diagnosis and patients’ management. ECG technology is now ubiquitous in smartwatches and other wearables and can record a single-lead ECG which is equivalent to lead I on a standard 12-lead ECG. Our aim was to develop machine learning (ML) algorithms to diagnose hypertension from single-lead ECGs.

Methods

We enrolled 1254 subjects (539 male, aged 60.22±12.46 years),with and without essential hypertension, and no indications of CVD. A 12-lead ECG of 10 seconds duration in resting position was performed on each subject using a digital electrocardiograph. A Random Forest (RF) was then trained on features derived only from lead I tracings.

Results

The RF model was able to distinguish hypertensive from normotensive subjects on a hold-out test set, with 81% accuracy, AUC/ROC 0.82, sensitivity 88%, and specificity 70% (both using a threshold of 0.5) using only features from lead I. Age, body mass index, the area under the T wave divided by the QRS complex area, the area under QRS segment adjusted for BMI, the QT corrected interval, and the PQ interval, were the most important anthropometric and ECG-derived features in terms of the success of our model (Figure 1).

Conclusions

This study demonstrates the promising potential of detecting an undiagnosed hypertension opportunistically, using a single-lead ECG. Our findings offer the opportunity to evolve innovative technologies to improve hypertension awareness at the community level.
The relationship of puberty onset and blood pressure in children: a cross-lagged panel analysis
Authors: Quispe-Haro C , Pikhart H , Bobak M , Ksinan A J
Published: June 2024

Background

The difficulties to assess the blood pressure (BP) during young ages have led to the underdiagnose of hypertension. As the long-term consequences of children hypertension seem detrimental for the cardiovascular health, the study of risk factors of hypertension in children and adolescents is urgently needed. Evidence suggests that characteristics of puberty onset—measured as menarche, puberal growth, or voice break—are associated with the increase in BP, however, a full evaluation of the puberal maturation measured with Tanner stages remain underexplored. Onset of puberty at early ages could be associated with increased risk of hypertension, however, body mass index (BMI) seems to have a confounding effect.

Aim

We aim to estimate the longitudinal effect of Tanner stages and BMI on BP.

Methods

We used a cohort of 1,504 children (52% males) assessed at ages 11, 13 and 15. Puberty development was rated using the Tanner scale, as pediatricians rated from one to five the presence of pubic hair for both genders, the size of the breasts among girls, and the size of genitals among boys, with the resulting scale a sum of scores for both genders. The systolic and diastolic BP were measured at each visit and standardized for age, sex, and height and transformed into percentiles. The z-scores of BMI were estimated using individuals’ weight, height, age, and sex. A cross-lagged panel model and maximum likelihood with missing values were used to estimate the causal effect of Tanner stages and BMI on BP.

Results

After controlling for BMI, we found that higher Tanner stage at ages 11 and 13 was not statistically significantly associated with an increase in systolic BP at ages 13 and 15, respectively. However, one standard deviation (SD) increase in BMI at age 11 predicted a subsequent increase of 0.09 SD (95%CI: 0.02 to 0.17) in systolic BP at age 13, and one SD increase in BMI at age 13 predicted a 0.09 SD (0.01 to 0.16) increase in systolic BP at age 15. We had similar findings when we used diastolic BP as outcome: only BMI at age 11 was significantly associated with increased diastolic BP at age 13 (0.13, 0.05 to 0.20).

Conclusion

Our findings suggest that the increase in the Tanner stage was not causally associated with an increase in BP. Like adults, BMI is a potential target for the prevention of hypertension in children. More evidence is needed to explore common causes of children's hypertension and early puberty.