bluuebunny/crossref_metadata_2025 huggingface dataset:
Aminopeptidases trim Xaa-Pro proteins, initiating their degradation by the Pro/N-degron pathway
Authors: Chen Shun-Jia , Kim Leehyeon , Song Hyun Kyu , Varshavsky Alexander
Published: October 2021

Significance

The Gid4 protein of the yeast proline (Pro)/N-degron pathway targets proteins for degradation by recognizing their N-terminal (Nt) Pro residue. This proteolytic pathway can also target proteins that bear Nt-Pro at position 2 instead of position 1. In the present study, we used genetic and biochemical approaches to discover that Fra1 and Icp55 are specific aminopeptidases that trim the Nt-Ala (A) and Nt-Ser (S) residues fromAP-Aro10 andSP-Pck1 proteins, respectively, thereby yielding Nt-Pro and initiating degradation of these proteins by the Pro/N-degron pathway. In addition to discovering the mechanism of targeting ofXPproteins, these insights have also expanded the diversity of substrates of the Pro/N-degron pathway.
Enhancing the photo-luminescence stability of CH3NH3PbI3 film with ionic liquids
Authors: Ma Weifeng , Ding Chunjie , Wazir Nasrullah , Wang Xianshuang , Kong Denan , Li An , Zou Bingsuo , Liu Ruibin
Published: October 2021

The methylammonium lead triiodide (CH3NH3PbI3)-based perovskite shows a great alluring prospect in areas of solar cells, lasers, photodetectors, and light emitting diodes owing to their excellent optical and electrical advantages. However, it is very sensitive to the surrounding oxygen and moisture, which limits its development seriously. It is urgent to spare no effort to enhance its optical and electrical stability for further application. In this paper, we synthesize the MAPbI3 perovskite film on the glass substrate with/without the ionic liquid (IL) of 1-Butyl-3-methylimidazolium tetrafluoroborate (BMIMBF4) by a simple two-step sequential solution method. The additive of BMIMBF4 can improve the quality of crystal structure. Moreover, the photo-luminescence (PL) intensity of MAPbI3 film with BMIMBF4 is much stronger than the pure MAPbI3 film after a week in the air, which is almost ten-fold of the pure one. Meanwhile, under the illumination of 405-nm continuous wave (CW) laser, the fluorescent duration of the MAPbI3 film with BMIMBF4 is approximately 2.75 min, while the pure MAPbI3 film is only about 6 s. In fact, ionic liquid of BMIMBF4 in the perovskite film plays a role of passivation, which prevents the dissolution of MAPbI3 into CH3NH3 and PbI2 and thus enhances the stability of environment. In addition, the ionic liquid of BMIMBF4 possesses high ionic conductivity, which accelerates the electron transport, so it is beneficial for the perovskite film in the areas of solar cells, photodetectors, and lasers. This interesting experiment provides a promising way to develop the perovskite’s further application.
Growth, characterization, and Raman spectra of the 1T phases of TiTe2, TiSe2, and TiS2
Authors: Tang Xiao-Fang , Zhu Shuang-Xing , Liu Hao , Zhang Chen , Wu Qi-Yi , Liu Zi-Teng , Song Jiao-Jiao , Guo Xiao , Wang Yong-Song , Ma He , Zhao Yin-Zou , Wu Fan-Ying , Liu Shu-Yu , Liu Kai-Hui , Yuan Ya-Hua , Huang Han , He Jun , Xu Wen , Liu Hai-Yun , Duan Yu-Xia , Meng Jian-Qiao
Published: October 2021

High-quality large 1T phase of TiX
2 (X = Te, Se, and S) single crystals have been grown by chemical vapor transport using iodine as a transport agent. The samples are characterized by compositional and structural analyses, and their properties are investigated by Raman spectroscopy. Several phonon modes have been observed, including the widely reported A
1g
and Eg
modes, the rarely reported Eu
mode (∼183 cm−1 for TiTe2, and ∼185 cm−1 for TiS2), and even the unexpected K mode (∼85 cm−1) of TiTe2. Most phonons harden with the decrease of temperature, except that the K mode of TiTe2 and the Eu
and “A
2u
/Sh” modes of TiS2 soften with the decrease of temperature. In addition, we also found phonon changes in TiSe2 that may be related to charge density wave phase transition. Our results on TiX
2 phonons will help to understand their charge density wave and superconductivity.
The pathophysiology of sepsis — 2021 update: Part 2, organ dysfunction and assessment
Authors: Jacobi Judith
Published: October 2021

Purpose

This is the second article in a 2-part series discussing the pathophysiology of sepsis. Part 1 of the series reviewed the immunologic response and overlapping pathways of inflammation and coagulation that contribute to the widespread organ dysfunction. In this article (part 2), major organ systems and their dysfunction in sepsis are reviewed, with discussion of scoring systems used to identify patterns and abnormal vital signs and laboratory values associated with sepsis.

Sepsis is a dysregulated host response to infection that produces significant morbidity, and patients with shock due to sepsis have circulatory and cellular and metabolic abnormalities that lead to a higher mortality. Cardiovascular dysfunction produces vasodilation, reduced cardiac output and hypotension/shock requiring fluids, vasopressors, and advanced hemodynamic monitoring. Respiratory dysfunction may require mechanical ventilation and attention to volume status. Renal dysfunction is a frequent manifestation of sepsis. Hematologic dysfunction produces low platelets and either elevation or reduction of leukocytes, so consideration of the neutrophil:lymphocyte ratio may be useful. Procoagulant and antifibrinolytic activity leads to coagulation that is stimulated by inflammation. Hepatic dysfunction manifest as elevated bilirubin is often a late finding in sepsis and may cause reductions in production of essential proteins. Neurologic dysfunction may result from local endothelial injury and systemic inflammation through activity of the vagus nerve.

Conclusion

Timely recognition and team response with efficient use of therapies can improve patient outcome, and pharmacists with a complete understanding of the pathophysiologic mechanisms and treatments are valuable members of that team.
Managing the life cycle of a portfolio of open data resources at the SIB Swiss Institute of Bioinformatics
Authors: Gabella Chiara , Duvaud Severine , Durinx Christine
Published: October 2021

Data resources are essential for the long-term preservation of scientific data and the reproducibility of science. The SIB Swiss Institute of Bioinformatics provides the life science community with a portfolio of openly accessible, high-quality databases and software platforms, which vary from expert-curated knowledgebases, such as UniProtKB/Swiss-Prot (part of the UniProt consortium) and STRING, to online platforms such as SWISS-MODEL and SwissDrugDesign. SIB’s mission is to ensure that these resources are available in the long term, as long as their return on investment and their scientific impact are high. To this end, SIB provides its resources, in addition to stable financial support, with a range of high-quality, innovative services that are, to our knowledge, unique in the field. Through this first-class management framework with central services, such as user-centric consulting activities, legal support, open-science guidance, knowledge sharing and training efforts, SIB supports the promotion of excellence in resource development and operation. This review presents the ecosystem of data resources at SIB; the process used for the identification, evaluation and development of resources; and the support activities that SIB provides. A set of indicators has been put in place to select the resources and establish quality standards, reflecting their multifaceted nature and complexity. Through this paper, the reader will discover how SIB’s leading tools and databases are fostered by the institute, leading them to be best-in-class resources able to tackle the burning matters that society faces from disease outbreaks and cancer to biodiversity and open science.
Conversation with the Twenty-First Century Social Work: Some ‘Post(s)’ Perspectives
Authors: Yadav Raj
Published: October 2021

This article explores ‘post(s)’ perspective understandings for the 21st century social work. Drawing mainly on post-debates, this article argues that human beings and their societies will evolve in unimagined ways in the future than these have been in all of their previous historical periods. Social work therefore must re-invent and re-adjust itself in the rest of the 21st century. Such re-invention and re-adjustment, however, will pivot around some complex theoretical narratives concerning to the ‘post(s)’ contexts and conditions of the 21st century.
Onset pattern of nigrostriatal denervation in early Parkinson’s disease
Authors: Pineda-Pardo José A , Sánchez-Ferro Álvaro , Monje Mariana H G , Pavese Nicola , Obeso José A
Published: October 2021

The striatal dopaminergic deficit in Parkinson’s disease exhibits a typical pattern, extending from the caudal and dorsal putamen at onset to its more rostral region as the disease progresses. Clinically, upper-limb onset of cardinal motor features is the rule. Thus, according to current understanding of striatal somatotopy (i.e. the lower limb is dorsal to the upper limb) the assumed pattern of early dorsal striatal dopaminergic denervation in Parkinson’s disease does not fit with an upper-limb onset. We have examined the topography of putaminal denervation in a cohort of 23 recently diagnosed de novo Parkinson’s disease patients and 19 age-/gender-matched healthy subjects assessed clinically and by 18F-DOPA PET; 15 patients were re-assessed after 2 years. There was a net upper-limb predominance of motor features at onset. Caudal denervation of the putamen was confirmed in both the more- and less-affected hemispheres and corresponding hemibodies. Spatial covariance analysis of the most affected hemisphere revealed a pattern of 18F-DOPA uptake rate deficit that suggested focal dopamine loss starting in the posterolateral and intermediate putamen. Functional MRI group-activation maps during a self-paced motor task were used to represent the somatotopy of the putamen and were then used to characterize the decline in 18F-DOPA uptake rate in the upper- and lower-limb territories. This showed a predominant decrement in both hemispheres, which correlated significantly with severity of bradykinesia. A more detailed spatial analysis revealed a dorsoventral linear gradient of 18F-DOPA uptake rate in Parkinson’s disease patients, with the highest putamen denervation in the caudal intermediate subregion (dorsoventral plane) compared to healthy subjects. The latter area coincides with the functional representation of the upper limb. Clinical motor assessment at 2-year follow-up showed modest worsening of parkinsonism in the primarily affected side and more noticeable increases in the upper limb in the less-affected side. Concomitantly, 18F-DOPA uptake rate in the less-affected putamen mimicked that recognized on the most-affected side. Our findings suggest that early dopaminergic denervation in Parkinson’s disease follows a somatotopically related pattern, starting with the upper-limb representation in the putamen and progressing over a 2-year period in the less-affected hemisphere. These changes correlate well with the clinical presentation and evolution of motor features. Recognition of a precise somatotopic onset of nigrostriatal denervation may help to better understand the onset and progression of dopaminergic neurodegeneration in Parkinson’s disease and eventually monitor the impact of putative therapies.
Aphasia localization: was Pierre Marie right?
Authors: Coutinho Léo , Caramelli Paulo , Teive Hélio A Ghizoni
Published: October 2021

Language and its associated disorders have puzzled humanity since the dawn of civilization. The first descriptions of aphasia go back to classical antiquity. The Egyptians and Babylonians believed speech was a divine gift to mortals, and their descriptions of aphasia attributed these events to their Gods’ anger and disfavour. The Edwin Smith Surgical Papyrus and the Hippocratic Corpus report several aphasia cases, relating this phenomenology to apoplexy, epilepsy, and other illnesses.
Hepatocellular carcinoma risk variant modulates lncRNA HLA-DQB1-AS1 expression via a long-range enhancer–promoter interaction
Authors: Wang Haoxue , Yang Beifang , Cai Xiaomin , Cheng Xiang , Shen Na , Liu Li , Li Jiaoyuan , Wang Ying , He Heng , Ying Pingting , Li Bin , Lu Zequn , Yang Nan , Wang Xiaoyang , Zhang Fuwei , Li Yanmin , Wang Wenzhuo , Ning Caibo , Zhu Ying , Chang Jiang , Miao Xiaoping , Tian Jianbo , Zhong Rong
Published: October 2021

Substantial evidence highlighted the critical role of long non-coding RNAs (lncRNA) in driving hepatocarcinogenesis. We hypothesized that functional variants in genome-wide association studies (GWASs) associated loci might alter the expression levels of lncRNAs and contribute to the development of hepatocellular carcinoma (HCC). Here, we prioritized potentially cis-expression quantitative trait loci-based single nucleotide polymorphism (SNP)-lncRNA association together with the physical interaction by the analyses from Hi-C data in GWAS loci of chronic hepatitis B and HCC. Subsequently, by leveraging two-stage case-control study (1738 hepatitis B [HBV]) related HCC cases and 1988 HBV persistent carriers) and biological assays, we identified that rs2647046 was significantly associated with HCC risk (odds ratio = 1.26, 95% CI = 1.11 to 1.43, P = 4.14 × 10−4). Luciferase reporter assays and electrophoretic mobility shift assays showed that rs2647046 A allele significantly increased transcriptional activity via influencing transcript factor binding affinity. Allele-specific chromosome conformation capture assays revealed that enhancer with rs2647046 interacted with the HLA-DQB1-AS1 promoter to allele-specifically influence its expression by CTCF-mediated long-range loop. Cell proliferation assays indicated that HLA-DQB1-AS1 is a potential oncogene in HCC. Our study showed HLA-DQB1-AS1 regulated by a causal SNP in a long-range interaction manner conferred the susceptibility to HCC, suggesting an important mechanism of modulating lncRNA expression for risk-associated SNPs in the etiology of HCC.
Utility and Applicability of Rapid Diagnostic Testing in Antimicrobial Stewardship in the Asia-Pacific Region: A Delphi Consensus
Authors: Apisarnthanarak Anucha , Bin Kim Hong , Moore Luke S P , Xiao Yonghong , Singh Sanjeev , Doi Yohei , Kwa Andrea Lay-Hoon , Ponnampalavanar Sasheela Sri La Sri , Cao Qing , Kim Shin-Woo , Lee Hyukmin , Santanirand Pitak
Published: October 2021

Rapid diagnostic tests (RDTs) facilitate fast and accurate identification of infectious disease microorganisms and are a valuable component of multimodal antimicrobial stewardship (AMS) programs but are currently underutilized in the Asia-Pacific region. An experienced group of infectious diseases clinicians, clinical microbiologists, and a clinical pharmacist used a modified Delphi consensus approach to construct 10 statements, aiming to optimize the utility and applicability of infection-related RDTs for AMS in the Asia-Pacific region. They provide guidance on definition, types, optimal deployment, measuring effectiveness, and overcoming key challenges. The Grading of Recommendations Assessment, Development, and Evaluation system was applied to indicate the strength of the recommendation and the quality of the underlying evidence. Given the diversity of the Asia-Pacific region, the trajectory of RDT development will vary widely; the collection of local data should be prioritized to allow realization and optimization of the full benefits of RDTs in AMS.
Mitigating Institutional Attitudes toward Sign Languages: A Model for Language Vitality Surveys
Authors: Webster Jenny
Published: October 2021

This paper is about attitudes toward sign languages. The paper presents an idea to help make sign language surveys better in the future. In 2018, UNESCO (the United Nations Educational, Scientific and Cultural Organization) published a sign language survey and a spoken language survey together for the first time. This was very important to show that spoken languages and signed languages are equal. But the sign language survey has some weaknesses. The idea presented in this paper says that: when people make sign language surveys, they should be aware of discrimination and negative attitudes; they should give signers access to the survey in sign language; and they should help signers decide what actions they can do to protect their sign language.
Intravascular ultrasound for peri-procedural geometric orifice area measurement during transcatheter pulmonary valve replacement
Authors: Kalinczuk L , Wozniak O , Mintz G S , Rynkiewicz K , Skotarczka W , Zielinski K , Michalowska I , Biernacka K , Ruzyllo W , Demkow M
Published: October 2021

Introduction

Large imaging filed intravascular ultrasound (IVUS) offering superior online tomographic perspective and visual accuracy could guide transcatheter pulmonary valve replacement (TPVR) for right ventricular outflow tract (RVOT) insufficiency. It is unknown whether geometric orifice area (GOA) measured by IVUS corresponds with effective orifice area (EOA) measure by transthoracic echocardiography (TTE) after successful TPVR.

Purpose

To compare minimal inner-leaflets cross-sectional area delineated in systole (min GOA) measured by IVUS versus EOA calculated = right ventricle stroke volume (measured in baseline cardiac magnetic resonance) / pulmonary valve velocity time integral (measured early post-procedure by Vivid e95).

Methods

After successful TPVR a 10MHz Vision PV 0.035" (60mm imaging field) IVUS catheter was slowly pulled from the distal pulmonary artery to the right ventricle with continuous imaging of RVOT. IVUS measurements included inner-valve dimension for several evenly spaced cross-sections along the entire length and perpendicular to RVOT long axis. Measured were outer-frame diameters (minimal and maximal) and its cross-sectional area, and cross-sectional area of the visual orifice (min GOA) identified exclusively at the coaptation site (Fig 1).

Results

There were 11 pts (median age 30 [25–36] yrs, 4 ♀, all but one with Tetralogy of Fallot) who had undergone prior corrective surgery (5 transannular patch, 2 bioprosthetic valve or 4 pulmonary homograft). Overall, 176 cross-sections were analyzed. Overall, min GOA measured 3.7±1.0cm2, and was 68%±9% of the valve-outer area (5.5±1.5cm2). It was substantially larger than calculated EOA (3.7±1.0cm2 vs 2.0±0.5cm2; p<0.001). The ratio of max/min GOA diameter was 1.11±0.11 signifying low eccentricity and was not related to EAO.

Conclusions

After successful balloon-expandable valve implantation to treat RVOT insufficiency, geometric orifice dimension was significantly smaller then outer valve frame dimension. Visual measure of geometric orifice area during the procedure using IVUS documented its circularity and indicated that it was larger than EOA calculated upon functional measure.

Funding Acknowledgement

Type of funding sources: Public hospital(s). Main funding source(s): This work was supported by the research grant (2.4/VI/18) founded by the National Institute of Cardiology in Warsaw (Poland). IVUS visualization of ES3.
Three-dimensional echocardiography in transcatheter edge-to-edge tricuspid valve repair
Authors: Orban M , Wolff S , Stolz L , Braun D , Stark K , Mehr M , Stocker T , Orban M , Hagl C , Massberg S , Nabauer M , Hausleiter J
Published: October 2021

Background

Transcatheter tricuspid valve repair (TTVR) is a new treatment option for severe tricuspid regurgitation (TR). First reports have reported conflicting results on development of right ventricular (RV) function after TTVR and questioned the role of conventional echocardiographic parameters to predict outcome.

Purpose

The aim of this study was to evaluate 3D echocardiography for the comprehensive assessment of RV function and its prognostic value for TTVR-treated patients.

Methods

We included patients undergoing TTVR from February 2017 to July 2019 who had preprocedural 3D assessment of RV volumes and ejection fraction. At follow-up (FU), 3D echo was performed to evaluate right ventricular reverse remodeling. All-cause mortality was assessed as clinical endpoint.

Results

75 patients treated with TTVR for isolated, severe TR had 3D echo assessment. TTVR reduced TR from grade ≥3+ to ≤2+ in 83.1% of patients at discharge. 3D-RV end-diastolic volume (−46.3 ml, p<0.001), end-systolic volume (−22.0 ml, p=0.027) and 3D-RV ejection fraction (−4.7%, p<0.001) decreased at short-term FU at 1-month and remained stable at 6-month FU. An impaired preprocedural 3D-RVEF <44% conferred higher mortality risk (Figure), and was an independent predictor for 1-year mortality (hazard ratio 5.32, p=0.033) in multivariable analysis. Tricuspid annular systolic excursion (TAPSE) and RV fractional area change were not predictive for this endpoint. Importantly, the observed decrease of 3D-RVEF function after TTVR was not associated with outcome (p=0.22 for decrease of 3D-RVEF vs. no decrease of 3D-RVEF in Kaplan-Meier analysis). Instead, left ventricular stroke volume index increased by 9.2% from 26.0 to 28.4 ml/m2 (p<0.01)

Conclusion

TTVR leads to right ventricular reverse remodeling and decrease of RV systolic function after TTVR. Impaired preprocedural RV systolic function is associated with worse clinical outcome. In contrast, the observed decrease of RV systolic function after TTVR was not associated with outcome.

Funding Acknowledgement

Type of funding sources: Public hospital(s). Main funding source(s): Klinikum der Universtität München Figure 1
Genetic polymorphisms of interleukin-6 and interleukin-10 are not associated with new onset atrial fibrillation after coronary artery bypass graft surgery
Authors: Rubanenko O , Shchukin Y , Rubanenko A
Published: October 2021

Purpose

To estimate the association of the genetic polymorphisms of Interleukin-6 (IL-6) and Interleukin-10 (IL-10) with new onset atrial fibrillation (AF) in postoperative period of coronary artery bypass graft (CABG) surgery in patients with coronary artery disease (CAD).

Methods

Studied were 158 patients who underwent CABG. In all the patients routine laboratory and instrumental tests were performed. Patients also underwent genetic polymorphisms of IL-6 C174G, IL-10 C592A and IL-10 G1082A estimation. All the patients were divided into two groups: 1 group comprised 111 patients without AF (82.0% men, median age 62.0 (56.0; 66.0) years, 2 group - 47 patients with AF development after CABG (84.4% men, median age 65.0 (61.0; 70.0) years).

Results

During the observation period AF occurred in 29.7% patients, on average 5.2 (2.0; 7.0) days after surgery. Patients of group 2 had longer history of CAD (60.0 (13.5; 138.0) vs. 15.5 (8.0; 72.0) months, p=0.01), had more often NYHA III class (27.7% vs. 9.0%, p=0.002) and larger left atrial (LA) diameter (44.0 (40.5; 46.0) mm vs. 38.0 (36.0; 40.0) mm, p<0.0001) comparing with group 1.

Genotype CC IL-6 C174G was found in 19.8% patients of the 1 group and in 25.5% patients of the 2 group (p=0.42), genotype CG - in 56.8% and 53.2% (p=0.68), genotype GG - in 23.4% and 21.3% (p=0.77) respectively. Genotype CC IL-10 C592A was found in 62.2% patients of the 1 group and 46.8% patients of the 2 group (p=0.29), genotype CA - in 37.8% patients of the 1 group and in 53.2% patients of the 2 group (p=0.07) respectively. Genotype GG IL-10 G1082A was found in 25.2% patients of the 1 group and 23.4% patients of the 2 group (p=0.8), genotype GA - in 48.6% patients of the 1 group and in 59.6% patients of the 2 group (p=0.2), genotype AA - in 26.2% patients of the 1 group and in 17.0% patients of the 2 group (p=0.3) respectively.

All estimated genotypes fulfilled expectations of Hardy-Weinberg equilibrium.

According to the result of multivariate regression analysis the odds ratio for AF development in postoperative period of CABG for history of CAD more than 20 months - 1.1 (95% CI, 1.03–1.2, p=0.04), for LA dimension more than 41 mm - 1.5 (95% CI, 1.28–1.79, p<0.0001).

Conclusion

Our investigation showed that increased left atrial dimension and the history of coronary artery disease were associated with postoperative atrial fibrillation development in patients who underwent coronary artery bypass graft surgery. However, genetic polymorphisms of IL-6 C174G, IL-10 C592A and IL-10 G1082A were not significantly associated with postoperative atrial fibrillation development.

Funding Acknowledgement

Type of funding sources: None.
Low voltage in limb leads in arrhythmogenic cardiomyopathy
Authors: Peters S
Published: October 2021

Low voltage in limb leads characterizes left ventricular involvement in arrhythmogenic cardiomyopathy. A large collective of patients with arrhythmogenic cardiomyopathy including 438 patients (268 males, mean age 46.8±11.6 years) were analyzed.

Method

Low voltage in limb leads were analyzed in typical patients with arrhythmogenic cardiomyopathy. Several other ECG features such a slow voltage in precordial leads, epsilon waves, right precordial T wave inversions, QRS fragmentation, typical appearance in lead aVR, amplitude of T wave inversion in special right ventricular leads, and developing complete right bundle branch block.

Results

Low voltage in limb leads was found in 60 patients (15%). Two patients represented with low voltage in limb leads and T wave inversions in inferolateral leads charactizing arrhythmogenic left ventricular leads with moderate reduction of left ventricular function with a large aneurysm of the apex. The other patients presented with sustained RBBB-VT. In 38 patients low voltage in limb leads and typical ECG findings of arrhythmogenic cardiomyopathy were found. These patients had arrhythmogenic biventricular cardiomyopathy of moderate reduction of left ventricular function and typical arrhythmias. Low voltage in limb and precordial leads was found in 14 patients with two cardiac deaths due to therapy-resistant heart failure. In 6 cases low voltage in limb and precordial leads and developing complete right bundle branch block were found. Four patients were tranplanted, two cases died due to heart failure. These 20 patients characterize advances, end-stage disease arrhythmogenic cardiomyopathy.

Conclusion

Standard ECG can differentiate between arrhythogenic left ventricular, arrhythmogenic biventricular, and arrhythmogenic advanced end-stage cardiomyopathy

Funding Acknowledgement

Type of funding sources: None.
Microvolt t-wave alternans its clinical significance in the assessment of the risk of sudden cardiac death among patients with hypertrophic cardiomyopathy
Authors: Pawlak M , Trzos E , Kurpesa M
Published: October 2021

Some patients with hypertrophic cardiomyopathy (HCM) are at significant risk of premature sudden death. Identification of the risk factors may enable effective prevention of adverse cardiac events in these patients. Assessment of the microvolt T-wave alternans (MTWA) is a recognized non-invasive diagnostic test used in risk stratification of sudden cardiac death (SCD). However, the number of reports on the frequency of occurrence of MTWA in HCM is small. Aim: Evaluation of the prognostic value of MTWA in predicting the risk of arrhythmic events (sudden cardiac death, documented VT/VF, appropriate ICD discharge) in patients with HCM.

Material and methods

122 patients with HCM underwent detailed clinical assessment and ECG- and echocardiographic examination. They underwent 24-hour ambulatory ECG monitoring, and the following elements were analysed: 1) arrhythmias, 2) heart rate variability (HRV) and the QT segment, 3) the presence of ventricular late potentials (LP), 4) heart rate turbulence (HRT). MTWA assessment was made during a test on a treadmill (Cambridge Heart). In accordance with the adopted criteria, the test was interpreted as negative, positive or indeterminate. Subsequently, positive and indeterminate results were described collectively as MTWA(+) and negative results as MTWA(−). Then the patients were divided into two groups: Group 1 – 57 patients (46,7%) with MTWA(−), and Group 2 – 65 patients (53,2%) with MTWA(+). In order to stratify the risk, the following were adopted as composite primary endpoints: sudden cardiac death or hospitalization for life-threatening arrhythmias (VT/VF), and appropriate ICD discharge.

Results

The mean follow-up period of the patients was 57±8 months; during that time, events that met the criteria for the endpoint occurred in 16 patients. On the basis of univariate analysis, 10 variables with a significant influence on the occurrence of an event were selected (unexplained syncope, NT-proBNP values elevated above 411 pg/ml, size of the left atrium over 44mm, diastolic thickness of the interventricular septum over 25 mm, the presence of MTWA(+), the QRS width >90 msec, QTc >467 msec, QTd >70 msec, SDNN <110 msec, and sinus rhythm turbulence parameters TS <2,9 ms/2RR). These variables were then included in a multivariate analysis. The model from a Cox regression analysis showed that the presence of unexplained syncope (HR=1,4), MTWA(+) (HR=1,5), size of the left atrium over 44mm (HR=5), and the thickness of the interventricular septum over 25 mm (HR=1,5) increased the risk of sudden events.

Conclusions

1) Patients with hypertrophic cardiomyopathy had a significant percentage of positive results of the microvolt T-wave alternans test (MTWA+), 2) Positive MTWA test result in patients with hypertrophic cardiomyopathy can help to identify patients at risk of sudden cardiac death.

Funding Acknowledgement

Type of funding sources: None.
Atrial fibrillation in unexplained syncope: observations from the Reveal LINQ registry
Authors: Del Greco M , Natale A , Kusano K , Verma A , Beinart S , Diener H.-C , Amin A , Kasner S , Pouliot E , Noreli F , Mittal A ,   Reveal LINQ Registry Investigators
Published: October 2021

Background

Implantable loop recorders (ILRs) have come to play an important role in the workup of patients with recurrent syncope of uncertain origin. In addition to detecting bradyarrhythmias related to syncope, which is the main diagnostic focus in these patients, ILRs are also capable of uncovering subclinical atrial fibrillation (AF).

Purpose

We sought to determine the percentage of patients monitored with an ILR for unexplained syncope who have AF detected and to describe clinical actions taken in these patients.

Methods

Patients enrolled in the Reveal LINQ Registry who received an ILR for unexplained syncope and had at least one follow-up form were included. The device automatically detects AF episodes lasting ≥2 minutes. Patients were considered to have AF based on an AF diagnosis made by the treating physician during follow-up or if device-detected AF was adjudicated as true AF by an external reviewer. AF detection rates were calculated using Kaplan-Meier methods.

Results

In total, 498 patients (aged 61.8±20.0 years, 49.6% female, CHA2DS2VASc score 2.2±1.7) were included and followed for 22±12 months. A history of AF was present in 97 (20%) patients, while 401 patients had no history. By 18 months, the incidence of AF was 70.9% (95% CI, 60.8%, 80.3%) in patients with a history of AF and 21.4% (95% CI, 17.4%, 26.1%) in patients without (Figure). AF detection in those with (30.4%) and without (30.1%) syncope during follow-up was similar. By the end of follow-up, and among patients with newly detected AF, 29/86 (33.7%) were on oral anticoagulation, 7 (8.1%) underwent AF ablation, 6 (7.0%) underwent other type of ablation, and 2 (2.3%) received cardioversion. Other actions among the whole cohort included implant of an IPG, ICD, or CRT in 98/498 (19.7%).

Conclusion

Among patients monitored with ILRs to determine the cause of recurrent syncope episodes, approximately 1 in 5 patients had new AF detected. In addition to improving the management of patients with syncope, ILR data served to support AF-related clinical decisions.

Funding Acknowledgement

Type of funding sources: Private company. Main funding source(s): Medtronic Inc Incidence of AF according to baseline AF
Left atrial reservoir strain is reduced in patients with myocardial infarction with non-obstructive coronary arteries
Authors: Malaty M , Chen H H L , Gan G
Published: October 2021

Background

Myocardial infarction with non-obstructive coronary arteries (MINOCA) represents a management conundrum given the poorly understood pathogenic mechanisms. In recent years, novel echocardiographic measures such as deformation/strain analysis have enabled early identification of left atrial (LA) remodelling and dysfunction which take place prior to structural alterations. LA dysfunction is an important biomarker of cardiovascular disease and an independent predictor of atrial arrhythmias which may play a fundamental role in the pathogenesis of MINOCA.

Purpose

The goal of our study was to evaluate and characterise LA function by speckle tracking strain echocardiography in patients with MINOCA.

Methods

Patients admitted to our institution with acute myocardial infarction were assessed and those diagnosed with MINOCA who underwent transthoracic echocardiogram (TTE) within 48-hours of their coronary angiogram were included. Diagnosis of MINOCA was based on the 2017 ESC working group position paper on myocardial infarction with non-obstructive coronary arteries. Two-dimensional speckle tracking strain analysis of the LA and left ventricle (LV) was performed offline using vendor independent software (TomTec Arena). Clinical and echocardiographic measures were compared to healthy controls identified from our echocardiography database. We excluded patients with history of atrial fibrillation, heart failure and LV dysfunction (LVEF <50%).

Results

The cohort consisted of 82 patients; 41 patients with MINOCA were compared to 41 age and sex matched controls (61% male, mean age 51±12.8 years). At baseline, patients with MINOCA had a higher prevalence of modifiable vascular risk factors including smoking, hypertension and diabetes (p<0.001 for all). Of the echocardiographic parameters, no differences in left ventricular (LV) parameters including LV global longitudinal strain (p=0.463), indexed LV mass (p=0.084) and the E/e' (p=0.391) was appreciated. Though there was no difference in LA volumes or volumetric parameters of LA function (LAEF; p=0.328), patients with MINOCA had a lower LA reservoir strain (29.7±8.5% vs 33.2±6.5%; p=0.04; 95% CI 0.32–5.33).

Conclusion

Patients with MINOCA demonstrated lower LASr despite normal LV and LA volumes. This suggests that LA dysfunction may play a role in the pathogenesis of MINOCA. Further studies are required to evaluate the significance of our findings.

Funding Acknowledgement

Type of funding sources: None.
The photoplethysmography dictionary: practical guidance on signal interpretation and clinical scenarios from TeleCheck-AF
Authors: Van Der Velden R M J , Verhaert D V M , Hermans A N L , Gawalko M , Duncker D , Manninger M , Hemels M , Pisters R , Lodzinski P , Steven D , Sultan A , Crijns H J G M , Pluymaekers N A H A , Hendriks J M , Linz D ,   The TeleCheck-AF investigators
Published: October 2021

Introduction

During the coronavirus disease 2019 (COVID-19) pandemic, numerous centres in Europe used on-demand photoplethysmography (PPG) technology to remotely assess heart rate and rhythm in conjunction with teleconsultations within the TeleCheck-AF project.

Purpose

To develop an educational structured stepwise practical guide on how to interpret PPG signals and to study typical clinical scenarios how on-demand PPG was used in the TeleCheck-AF project.

Methods

During an online conference, the structured stepwise practical guide on how to interpret PPG signals was discussed and further refined during an internal review process. We provide the number of respective PPG recordings and number of patients managed within a clinical scenario during the TeleCheck-AF project.

Results

To interpret PPG recordings, we introduce a structured stepwise practical guide and provide representative PPG recordings. In the TeleCheck-AF project, 2522 subjects collected 90.616 recordings. The majority of these recordings was classified by the PPG algorithm as sinus rhythm (57.6%), followed by atrial fibrillation (AF) (23.6%). In 9.7% of recordings the quality was too low to interpret. Other observed rhythms were tachycardia (1.4%), extra systoles (4.7%), bigeminy episodes (1.8%), trigeminy episodes (0.6%) and atrial flutter (0.2%). The most frequent clinical scenario where PPG technology was used in the TeleCheck-AF project was follow-up after AF ablation (1110 patients) followed by heart rate and rhythm assessment around (tele)consultation (966 patients), sometimes including remote PPG-guided adaption of rate or rhythm control. 275 patients were followed around cardioversion, either (semi-)acute or elective. Other possible scenarios are assessment of palpitations, assessment of symptom-rhythm correlation and monitoring during up-titration of heart failure medication.

Conclusion

We introduce a newly developed structured stepwise practical guide on PPG signal interpretation developed based on presented experiences from TeleCheck-AF. The present clinical scenarios for the use of on-demand PPG technology derived from the TeleCheck-AF project will help to implement PPG technology in the management of arrhythmia patients.

Funding Acknowledgement

Type of funding sources: None. TeleCheck-AF clinical scenariosClassification of PPG recordings
Utility of miR-155, miR-21 and miR-16 in plasma as biomarkers of atrial fibrillation
Authors: Ortega-Hernandez J A , Escobar-Alvarado J , Sanchez-Munoz F , Amezcua-Guerra L M , Sanchez-Gloria J L , Toledo-Lugo A , Gonzalez-Pacheco H , Marquez-Murillo M , Springall R
Published: October 2021

Background

Atrial fibrillation (AF) is associated with increased morbidity and mortality. MicroRNAs (miRs) are post-transcriptional regulators that could be useful in the study of AF.

Purpose

To investigate whether miR-16, miR-21 and miR-155 may differentiate between AF and sinus rhythm.

Methods

29 controls and 42 AF (June 2019-May 2020). Lipid profile, hsCRP were measured. Serum RNA extraction was performed. Hsa-miR-21, hsa-miR-16, hsa-miR-155, and cel-miR-39 were amplified RT-PCR. Quantitative results for miR levels were generated according to the 2-ΔCt method using cel-miR-39 for normalization. Correlations were assessed by Spearman rank test. Logistic regression analysis was adjusted by age, sex, and BMI vs miR's. A p<0.05 was set for significance.

Results

(controls vs AF): age (56 [52–63] vs 60 [64–67] years, p=0.122), BMI (30.52 [27.69–32.67] vs 29.65 [26.3–32.9] kg/m2 p=0.779), female 17 (58.6%) vs 19 (45.2%), p=0.268; total cholesterol (198.4 [17.2–215] vs 171.3 [150.3–216.8] mg/dL, p=0.066), LDL (126.6 [114.7–141.6] vs 99.2 [80.7–124] mg/dL, p=0.005) HDL (40.4 [36.8–45.8] vs 43.8 [36.9–48.5] p=0.326) and CRP (2.69 [1.22–4.72] vs 2.92 [1.4–4.76] mg/L p=0.835). The CHA2DS2VASC score in AF was <2=11 (45.2%) and ≥2= 26 (54.8%).

MicroRNA levels (controls vs AF): miR-21 0.0195 (0.0095–0.0275) vs 0.042 (0.028–0.098) p<0.001; miR-155 0.0178 (0.0108–0.0309) vs 0.01 (0.0056–0.0169) p<0.001, and miR-16 0.5238 (0.2618–1.992) vs 0.1652 (0.0765–0.3816) p<0.001.

In the logistic regression miR-21 had a positive correlation with AF, c=0.851 p=0.002, Wald=9.89. miR-16 and miR-155 a negative relation (c=0.76,0.72; p=0.036, 0.043, Wald=4.39, 4.085; respectively) (Fig. 1A, B, C).

For multivariable analysis we used miR-16, miR-21, and miR-155 as previous analysis demonstrated significance with an overall model c=0.90 p=0.028 (Wald=14.2) and significance was seen in the miR-21 Wald= 9.33 (p=0.002); and miR-155 Wald=4.7 (p=0.03); miR-16 was not significant (Wald=2.7, p=0.1). A ternary plot was performed using the predicted outputs of the model. (Fig. 2)

Conclusion

miR-16, miR-21 and miR-155 are useful for the discrimination of AF vs sinus rhythm and may be part of important physiopathological pathways in AF.

Funding Acknowledgement

Type of funding sources: Public hospital(s). Main funding source(s): Instituto Nacional de Cardiología Ignacio Chávez Figure 1. Logistic regression curvesFigure 2. Multivariate ternary plot of miRs
Increased FDG uptake in AF individuals suggesting atrial inflammation visualized by FDG PET/CT with glucose uptake suppression protocols
Authors: Kupusovic J , Weber M , Kessler L , Pesch E , Riesinger L , Wakili R , Dobrev D , Rischpler C , Rassaf T , Siebermair J
Published: October 2021

Background

Pathophysiology of atrial fibrillation (AF) is multifactorial. Attention has been drawn towards atrial inflammation underlying arrhythmogenic remodeling. The aim of our study was to evaluate if a specific preparation protocol for positron emission tomography/computed tomography (PET/CT) with 18Fluor-labelled fluorodeoxyglucose (18F-FDG) was capable of detecting atrial hypermetabolism as surrogate for inflammation in AF, with the specific hypothesis that protocols specifically aiming to suppress physiologic glucose metabolism (fasting protocols: inflammation and malignancy preparation) were superior to non-fasting protocols.

Methods

We conducted a single-center study including n=75 patients with a history of AF and n=75 controls without AF (matched for age, sex and left ventricular systolic function) undergoing three different preparation protocols (each n=25 per group): i.) inflammation, ii.) malignancy and iii.) viability protocol before 18F-FDG-PET/CT. We performed visual analysis of local detectable atrial uptake (figure 1A) and assessed quantitative uptake in predetermined loci of the atria and endocrine adipose tissue (EAT), using maximum standardized uptake values (SUVmax) and target to background ratios (TBR).

Results

Our analysis of visual atrial 18F-FDG uptake revealed that atrial uptake was exclusively observed in AF patients using the malignancy (13/25 patients) and inflammation (10/25 patients) protocol, while the viability preparation revealed atrial uptake both in AF (n=6 patients) and non-AF patients (n=5 patients).

With respect to quantitative measures between AF and non-AF individuals using the inflammation protocol, patients with AF showed significantly higher uptake values in the right atrium (SUVmax: 2.54±0.75 vs. 2.03±0.66, p=0.01); TBR 1.51±0.44 vs. 1.18±0.20, p<0.01), right atrial appendage (SUVmax: 2.44±0.71 vs. 2.02±0.64, p=0.03; TBR: 1.47±0.47 vs. 1.20±0.26, p=0.02) and also in EAT (SUVmax: 1.39±0.46 vs. 1.13±0.40, p=0.04), figure 1B. Despite a trend of higher tracer uptake related to the presence of AF in left atrial structures, no statistical significances could be observed between AF and non-AF individuals.

Conclusion

This retrospective study demonstrates that protocols specifically designed to suppress physiologic glucose uptake seem to be superior in detecting atrial FDG uptake, which could be indicative of atrial inflammation in AF patients. Based on our results the right atrium seems to be more affected from these changes. These results point towards a potential role of right atrial inflammatory processes in AF pathophysiology besides the established left atrial ectopic triggers.

Funding Acknowledgement

Type of funding sources: None.
Direct oral anticoagulants vs warfarin in non-valvular atrial fibrillation. Meta-analysis, includes all published trials
Authors: Arreaga-Perez C , Evangelista-Barragan D , Zarate-Zapata A , Penaherrera E , Zuniga-Bohorquez J J , Garcia-Matamoros F , Flores-Delgado M , Barrera-Rivera M , Bravo-Sanchez P , Tejada-Franco A , Gilbert-Orus M D , Morejon-Barragan P A
Published: October 2021

Introduction

Warfarin, despite its limitations, is still used as standard treatment in patients with Atrial Fibrillation, but it has been demonstrated that Direct Oral Anticoagulants (DOAC) offer many advantages over warfarin in the prevention of strokes.

Purpose

The goal was to determinate the safety and effectiveness in reducing systemic thromboembolism, ischemic stroke, hemorrhagic stroke, cerebral hemorrhage and cardiovascular mortalityof the direct oral anticoagulants (DOACs) over warfarin in patients with non-valvular atrial fibrillation, conducting an analysis of the studies of DOACs, including the ENGAGE study on the use of edoxaban, affirming its safety including the pivotal essays available.

Method

A systematic search of PubMed's bibliographic database was made for the selection of the articles.Clinical essays from less than 10 years, in phase III and multicentric studies were selected.

Results

The main objective was the significant reduction in the incidence of stroke/systemic thromboembolism with the use of DOACs vs. Warfarin (2,73% vs. 3,24%), the reduction of hemorrhagic stroke was (0.41% vs. 0.94%), ischemic stroke (3.12% vs. 3.5%), cardiovascular death with DOACs was 6.02% vs. Warfarin 6.84%, (compared with previous studies that demonstrated effectiveness with max doses affirming safety and effectiveness).

Conclusion

Our meta-analysis is the first to date to evaluate all the pivotal trials published,we include the ENGAGE trial. In non-valvular atrial fibrillation, the use of DOACs, in comparison with Warfarin, significantly reduced the risk of stroke/systemic thromboembolism by 16.3%, ischemic stroke by 11.1%, hemorrhagic stroke by 54.6%, cardiovascular mortality by 12.9%.

Funding Acknowledgement

Type of funding sources: None.
The effect of patient weight and amiodarone use on the energy of a successful shock in cardioversion of atrial arrhythmias – single-center experience study
Authors: Jiravsky O , Rucki L , Chovancik J , Spacek R , Svobodnik A , Stepanova R , Kubat T , Fiala M
Published: October 2021

Background

Electrical cardioversion (DCCV) is an effective method of sinus rhythm restitution. Recently published data suggest higher efficiencies of higher discharge energies. The influence of individual parameters on the success of cardioversion is still studying.

Purpose

To evaluate the influence of individual patient parameters on the energy of a successful external defibrillator shock during cardioversion of atrial arrhythmias

Methods

The retrospective analysis cohort of all patients treated by DCCV due to atrial arrhythmias between 10/2015 and 1/2020. To evaluate potential predictors for the choice of a higher initial discharge using one-dimensional logistic regression and to include parameters significant at the 10% level of significance (p<0.1) in the multidimensional logistic regression model.

Results

1986 electrical cardioversions of 984 patients (382 repeated procedures of the same patients in a cohort). 1292 (65.1%) men and 694 (34.9%) women aged 67.0 (±10.2) years.

Mean energy of the first shock 118.9 (±19.2) J with a success rate of 77.8%, energy of the second shock 154.0 (±26.3) J, which increased the overall success to 80.0%, and mean high of the third shock 173.9 (±25.6) J, when the total efficacy of DCCV in sinus rhytm restitution reached 89.8%.

From the univariate binary regression, parameters significant at the 10% level of significance (p<0.1) were selected and included in a multidimensional logistic regression model. Only the patient's weight and the use of amiodarone proved to be statistically significant. Weight with OR 1.21 and use of amiodarone with OR 1.43.

Conclusion

Patient weight and amiodarone use are predictors of the need to use higher energy electric cardioversion.

Discussion

Amiodarone medication does not appear to increase the defibrillation threshold, but rather is a feature that represents the group of patients treated with more aggressive antiarrhythmic therapy for advanced atrial arrhythmias with more significant structural impairment, but this attitude requires further study.

Funding Acknowledgement

Type of funding sources: Private hospital(s). Main funding source(s): VAVIA: IGS202009 - Racionální algoritmus při elektivní elektrické kardioverzi fibrilace síní.