bluuebunny/crossref_metadata_2025 huggingface dataset:
Microfabricated porous SU-8 membranes as innervation interfaces for hiPSC-neurons in microfluidic devices
Authors: Salpavaara T , Joki T , Skogberg A , Calejo M T , Lekkala J , Narkilahti S , Kallio P
Published: October 2021

In this study, we developed microfabricated porous membranes aimed at facilitating innervation in 3D cell culture models. The aim of the paper is to introduce a fabrication method for porous membranes with adjustable size, shape and location of the pores without obstructing imaging or the connectivity of the cells. The method is based on making a patterned SU-8 layer on a sacrificial aluminium layer by UV lithography and releasing it with etching. With the proposed method, we were able to produce single-layer self-supporting membranes that were used as interfaces in compartmentalized microfluidic devices. The functionality of the membranes and their cytocompatibility were tested by culturing human pluripotent stem cell (hPSC)-derived neurons on their surfaces. In vitro experiments demonstrated that a dense neural network develops on top of the proposed membranes within a week. Neurites were able to migrate through the pores to the bottom side of the membranes. We achieved partial, but still significant, axonal isolation. The results of this study will pave the way for the development of optimized innervated tissue models by using the combination of porous SU-8 membrane substrates, microelectrode arrays and hPSC-derived neurons in compartmentalized cell cultivation devices.
Evaluation of medication administration timing variance using information from a large health system’s clinical data warehouse
Authors: Loput Charity M , Saltsman Connie L , Rahm Risa C , Roberts Wm Dan , Sharma Sanya , Borum Cindy , Casey Jennifer A
Published: October 2021

Purpose

An analysis to determine the frequency of medication administration timing variances for specific therapeutic classes of high-risk medications using data extracted from a health-system clinical data warehouse (CDW) is presented.

Methods

This multicenter retrospective, observational analysis of medication administration data from 14 hospitals over 1 year was conducted using a large enterprise health-system CDW. The primary objective was to assess medication administration timing variance for focused therapeutic classes using medication orders and electronic medication administration records data extracted from the electronic health record (EHR). Administration timing variance patterns between standard hospital staffing shifts, within therapeutic drug classes, and for as-needed (PRN) medications were also studied. To assess medication administration timing variance, calculated variables were created for time intervals of 30-59, 60-120, and greater than 120 minutes. Scheduled medications were assessed for delayed administration and PRN medications for early administration.

Results

A total of 5,690,770 medication administrations (3,418,275 scheduled and 2,272,495 PRN) were included in the normalized data set. Scheduled medications were frequently subject to delays of ≥60 minutes (15% of administrations, n = 275,257) when scheduled for administration between 9-10 AM and between 9-10 PM. By therapeutic drug class, scheduled administrations of insulins, heparin products, and platelet aggregation inhibitors were the most commonly delayed. For PRN medications, medications in the anticoagulant and antiplatelet agent class (most commonly heparin flushes and line-management preparations) were most likely to be administered early, defined as more than 60 minutes from the scheduled time of first administration.

Conclusion

The findings of this study assist in understanding patterns of delayed medication administration. Medication class, time of day of scheduled administration, and frequency were factors that influenced medication administration timing variance.
DeepTrio: a ternary prediction system for protein–protein interaction using mask multiple parallel convolutional neural networks
Authors: Hu Xiaotian , Feng Cong , Zhou Yincong , Harrison Andrew , Chen Ming
Published: October 2021

Motivation

Protein–protein interaction (PPI), as a relative property, is determined by two binding proteins, which brings a great challenge to design an expert model with an unbiased learning architecture and a superior generalization performance. Additionally, few efforts have been made to allow PPI predictors to discriminate between relative properties and intrinsic properties.

Results

We present a sequence-based approach, DeepTrio, for PPI prediction using mask multiple parallel convolutional neural networks. Experimental evaluations show that DeepTrio achieves a better performance over several state-of-the-art methods in terms of various quality metrics. Besides, DeepTrio is extended to provide additional insights into the contribution of each input neuron to the prediction results.

Availability and implementation

We provide an online application at http://bis.zju.edu.cn/deeptrio. The DeepTrio models and training data are deposited at https://github.com/huxiaoti/deeptrio.git.

Supplementary information

Supplementary data are available at Bioinformatics online.
Molecular diversity and historical phylogeography of the widespread genus Mastiglanis (Siluriformes: Heptapteridae) based on palaeogeographical events in South America
Authors: Gales Suellen M , Ready Jonathan Stuart , Sabaj Mark H , Bernt Maxwell J , Silva Derlan José Ferreira , Oliveira Claudio , Oliveira Guilherme , Sales João Bráullio L
Published: October 2021

The catfish family Heptapteridae, endemic in the Neotropical region, is composed of small- to medium-sized species. The genus Mastiglanis was monotypic until very recently and is often misidentified as Imparfinis because of similarities in diagnostic characters, including the length of maxillary barbels and limited pigmentation. We provide the first molecular inference of diversity for samples identified as Mastiglanis. Partial 16S and COI sequences were produced for 84 samples identified morphologically as Mastiglanis from the Amazon, Orinoco and Essequibo river basins. Species delimitation and phylogenetic methods recovered the genus as monophyletic, but samples assigned to the species Mastiglanis asopos yielded 21 distinct operational taxonomic units, often in sympatry. The first cladogenesis event, at ~12 Mya, was associated with marine incursions and/or vicariance events between the northward-flowing systems in the west and the rivers that drain to the east. Subsequent diversification during the Miocene and Pliocene was inferred to have resulted from environmental changes associated with Andean orogeny, whereas recent diversification in the late Pliocene and Pleistocene was inferred to result from environmental changes during glacial cycles. Despite the many probable cryptic species found across the large geographical distribution of the genus, further sampling is expected to increase taxonomic richness in this genus.
Genetically engineered birds; pre-CRISPR and CRISPR era
Authors: Dehdilani Nima , Yousefi Taemeh Sara , Goshayeshi Lena , Dehghani Hesam
Published: October 2021

Generating biopharmaceuticals in genetically engineered bioreactors continues to reign supreme. Hence, genetically engineered birds have attracted considerable attention from the biopharmaceutical industry. Fairly recent genome engineering methods have made genome manipulation an easy and affordable task. In this review, we first provide a broad overview of the approaches and main impediments ahead of generating efficient and reliable genetically engineered birds, and various factors that affect the fate of a transgene. This section provides an essential background for the rest of the review, in which we discuss and compare different genome manipulation methods in the pre-clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR era in the field of avian genome engineering.
Primary lung cancer in women after previous breast cancer
Authors: Nobel Tamar B , Carr Rebecca A , Caso Raul , Livschitz Jennifer , Nussenzweig Samuel , Hsu Meier , Tan Kay See , Sihag Smita , Adusumilli Prasad S , Bott Matthew J , Downey Robert J , Huang James , Isbell James M , Park Bernard J , Rocco Gaetano , Rusch Valerie W , Jones David R , Molena Daniela
Published: October 2021

Background

Breast cancer is the most common malignancy among women in the USA. Improved survival has resulted in increasing incidence of second primary malignancies, of which lung cancer is the most common. The United States Preventive Services Task Force (USPSTF) guidelines for lung-cancer screening do not include previous malignancy as a high-risk feature requiring evaluation. The aim of this study was to compare women undergoing resection for lung cancer with and without a history of breast cancer and to assess whether there were differences in stage at diagnosis, survival and eligibility for lung-cancer screening between the two groups.

Methods

Women who underwent lung-cancer resection between 2000 and 2017 were identified. Demographic, clinicopathological, treatment and outcomes data were compared between patients with a history of breast cancer (BC-Lung) and patients without a history of breast cancer (P-Lung) before lung cancer.

Results

Of 2192 patients included, 331 (15.1 per cent) were in the BC-Lung group. The most common method of lung-cancer diagnosis in the BC-Lung group was breast-cancer surveillance or work-up imaging. Patients in the BC-Lung group had an earlier stage of lung cancer at the time of diagnosis. Five-year overall survival was not statistically significantly different between groups (73.3 per cent for both). Overall, 58.4 per cent of patients (1281 patients) had a history of smoking, and 33.3 per cent (731 patients) met the current criteria for lung-cancer screening.

Conclusion

Differences in stage at diagnosis of lung cancer and treatment selection were observed between patients with and without a history of breast cancer. Overall, there were no statistically significant differences in genomic or oncogenic pathway alterations between the two groups, which suggests that lung cancer in patients who previously had breast cancer may not be affected at the genomic level by the previous breast cancer. The most important finding of the study was that a high percentage of women with lung cancer, regardless of breast-cancer history, did not meet the current USPSTF criteria for lung-cancer screening.
Clinical trials in amyotrophic lateral sclerosis: a systematic review and perspective
Authors: Wong Charis , Stavrou Maria , Elliott Elizabeth , Gregory Jenna M , Leigh Nigel , Pinto Ashwin A , Williams Timothy L , Chataway Jeremy , Swingler Robert , Parmar Mahesh K B , Stallard Nigel , Weir Christopher J , Parker Richard A , Chaouch Amina , Hamdalla Hisham , Ealing John , Gorrie George , Morrison Ian , Duncan Callum , Connelly Peter , Carod-Artal Francisco Javier , Davenport Richard , Reitboeck Pablo Garcia , Radunovic Aleksandar , Srinivasan Venkataramanan , Preston Jenny , Mehta Arpan R , Leighton Danielle , Glasmacher Stella , Beswick Emily , Williamson Jill , Stenson Amy , Weaver Christine , Newton Judith , Lyle Dawn , Dakin Rachel , Macleod Malcolm , Pal Suvankar , Chandran Siddharthan
Published: October 2021

Amyotrophic lateral sclerosis is a progressive and devastating neurodegenerative disease. Despite decades of clinical trials, effective disease-modifying drugs remain scarce. To understand the challenges of trial design and delivery, we performed a systematic review of Phase II, Phase II/III and Phase III amyotrophic lateral sclerosis clinical drug trials on trial registries and PubMed between 2008 and 2019. We identified 125 trials, investigating 76 drugs and recruiting more than 15 000 people with amyotrophic lateral sclerosis. About 90% of trials used traditional fixed designs. The limitations in understanding of disease biology, outcome measures, resources and barriers to trial participation in a rapidly progressive, disabling and heterogenous disease hindered timely and definitive evaluation of drugs in two-arm trials. Innovative trial designs, especially adaptive platform trials may offer significant efficiency gains to this end. We propose a flexible and scalable multi-arm, multi-stage trial platform where opportunities to participate in a clinical trial can become the default for people with amyotrophic lateral sclerosis.
Tofacitinib Adherence and Outcomes in Refractory Inflammatory Bowel Disease
Authors: Wiles C Alex , Shah Nisha B , Bell Jake , Pabla Baldeep S , Scoville Elizabeth A , Dalal Robin L , Beaulieu Dawn B , Schwartz David A , Horst Sara N
Published: October 2021

Background

Tofacitinib has been approved for moderate-to-severe ulcerative colitis and studied in Crohn’s disease. Understanding medication adherence to oral medications in severe disease is essential.

Methods

We retrospectively reviewed adherence and real-world outcomes of inflammatory bowel disease patients who initiated tofacitinib at a single care center. Adherence was measured by proportion of days covered.

Results

Sixty-three patients were identified. All patients failed at least one prior biologic therapy. Mean proportion of days covered was 95.7% for ulcerative colitis and 93.1% for Crohn’s disease. Significant clinical and endoscopic response was seen.

Conclusion

Adherence was high in a cohort with highly refractory disease.
Impact of gamification on glycaemic control among patients with type 2 diabetes mellitus: a systematic review and meta-analysis of randomized controlled trials
Authors: Kaihara Toshiki , Intan-Goey Valent , Scherrenberg Martijn , Falter Maarten , Frederix Ines , Akashi Yoshihiro , Dendale Paul
Published: October 2021

Aims 

The prevalence of type 2 diabetes mellitus (T2DM) is very high and still rising. Optimal medical therapy and lifestyle management are essential in reducing the long-term complications of T2DM. Gamification, which is the use of design elements, and characteristics of games in a non-gaming context, is an innovative approach to improve healthy behaviour. It thereby could be able to improve glycaemic control in T2DM. The aim of this systematic review and meta-analysis is to evaluate the effect of gamification on glycaemic control expressed by haemoglobin A1c (HbA1c) levels in T2DM patients.

Methods and results 

All articles from 2000 to 2021 were searched in electronic databases (PubMed, Cochrane Library, Embase). The total number of patients was 704. The rate of male participants and their mean ages ranged, respectively, from 46% to 94% and 60 to 63 years. Inclusion criteria were randomized controlled trials of T2DM management using gamification which included HbA1c as an outcome measure. A meta-analysis was performed. After removing duplicates, 129 articles were screened and a total of 3 articles corresponding to the inclusion criteria were identified. Haemoglobin A1c was significantly reduced [mean difference −0.21; 95% confidence interval (−0.37 to −0.05); P = 0.01; I2 = 0%] in the intervention group using gamification as compared to the control group.

Conclusion 

Gamification has a positive effect on glycaemic control expressed by HbA1c changes in patients with T2DM. However, only three studies were included in this review. More research is needed to confirm the effectiveness of gamification in T2DM.
Long-term durability after surgical aortic valve replacement with the Trifecta and the Intuity valve—a comparative analysis
Authors: Werner Paul , Coti Iuliana , Kaider Alexandra , Gritsch Jasmin , Mach Markus , Kocher Alfred , Laufer Guenther , Andreas Martin
Published: October 2021

OBJECTIVES

Long-term durability of surgical bio-prostheses is a key factor, especially in the era of transcatheter aortic valve replacement. We compared the incidence of structural valve deterioration (SVD) between patients undergoing surgical aortic valve replacement (SAVR) with the Trifecta (Abbott Laboratories, Abbott Park, IL, USA) or the Intuity valve (Edwards Lifesciences, Irvine, CA, USA).

METHODS

Between April 2010 and May 2020, 1118 patients underwent SAVR with the Trifecta (n = 346) and the Intuity (n = 772) valve at a single centre. A total of 1070 patients (Trifecta n = 298, Intuity n = 772) were analysed after the exclusion of patients with pure regurgitation and endocarditis. Retro- and prospective echocardiographic and clinical follow-up was performed. Cox proportional hazards regression models were performed to identify prognostic factors for SVD, aortic re-interventions and mortality.

RESULTS

With 27 cases (Trifecta n = 23, Intuity n = 4) of SVD observed, cumulative incidence of SVD was significantly higher in the Trifecta cohort (P < 0.001). Implantation of a Trifecta valve [hazard ratio (HR) 11.20; 95% confidence interval 3.79–33.09], log-transformed preoperative creatinine (HR 2.47; 1.37–4.44) and sex (male HR 0.42; 0.19–0.92) emerged as prognostic factors of SVD. A significantly higher cumulative incidence of re-interventions was observed in the Trifecta cohort (P = 0.004) and valve type was an independent time-varying risk factor (HR at 12 months 2.78; 95% confidence interval 1.42–5.45). Overall, no significant differences in all-cause mortality were observed between the groups (log-rank test: P = 0.052).

CONCLUSIONS

SVD was significantly more frequent in patients receiving a Trifecta valve and its implantation was an independent risk factor for the occurrence of SVD and aortic valve re-interventions. This comparative analysis of 2 low-gradient bioprosthesis put the long-term durability of the Trifecta valve in question and need to be taken into consideration when performing bioprosthetic SAVR.
Third-generation laser balloon ablation for atrial fibrillation treatment: a multicenter experience
Authors: Rovaris G , Martignani C , Miracapillo G , Colella A , Giaccardi M , Forleo G.B , Giomi A , Giacopelli D , Grassini D , Pozzi M , Montemerlo E , Ziacchi M , Schiavone M , Biffi M
Published: October 2021

Background

Laser balloon ablation is a promising option for performing pulmonary vein isolation (PVI) which is the cornerstone of invasive atrial fibrillation (AF) treatment.

Purpose

We aimed to investigate the acute efficacy and safety of the novel third-generation of the laser balloon system in an initial multicenter experience.

Methods

First and consecutive patients who underwent PVI with LB3 for drug-resistant paroxysmal or persistent AF at 7 Italian sites were included in this analysis. Study endpoints were acute procedural efficacy, defined as successful isolation of all identified PVs without radiofrequency touch-up, total and fluoroscopy times, and periprocedural complications.

Results

Our population included 86 patients (81% males, mean age 60.6±9.5 years) who underwent a procedure of PVI using LB3 between June 2020 and March 2021.

Most patients had paroxysmal AF (74%) and were in sinus rhythm at the beginning of the procedure. The mean procedure time was 138±60 min; fluoroscopy time was 22±17 min and the mean ablation time was 44±40 min. Of the 313 targeted PVs, 311 (99.4%) could be isolated with first-pass LB3 application, while 2 (0.6%) required radiofrequency touchup. At the end of the procedure, all patients were in sinus rhythm and 26 (32%) received electrical cardioversion to achieve stable sinus rhythm.

The total rate of major compilations was 1.2% (1/82 patients): one pericardial tamponade requiring epicardial puncture. No surgical intervention was necessary, and the patient recovered without any sequalae. There were no vascular access complications or phrenic nervy palsy. Three pinhole balloon raptures (3.5%) were observed during energy applications that required replacement of the whole system but had no effect on patient safety.

Conclusions

In a first multicenter experience, the LB3 system for PVI was safe with excellent acute efficacy.

Funding Acknowledgement

Type of funding sources: None.
Pulmonary veins reconnection pattern differences after failed radiofrequency ablation and cryoballoon ablation for atrial fibrillation
Authors: Antoun I , Sihdu B , Mavilakandy A , Merzaka L , Stafford P , Sandilands A , Somani R , Ng G.A
Published: October 2021

Point-by-point radiofrequency ablation (RF) and one-shot cryoballoon ablation (CRYO) electrically isolate pulmonary veins (PVs) in atrial fibrillation (AF) using different techniques and energies. This study aimed to examine differences in PVs reconnection pattern and ablation lesions required to re-isolate PVs after failed RF and failed CRYO.

Methods

Twenty-four patients who had their repeat ablation between January 2017-December 2020 were studied with six months of learning curve for CRYO. Fourteen patients had paroxysmal atrial fibrillation (PAF). Failed first ablations were defined by electrocardiogram (ECG) documented AF within twelve months following three months blanking period. Repeat ablations were performed using CARTO3® mapping system, which was utilized to locate ablation lesions and impedance drop details.

Results

2,260 lesions were collected from 63 reconnected PVs (31 isolated after RF vs 32 isolated veins after CRYO). 849 lesions were targeted towards triggers. Repeat ablation procedure time was similar between both cohorts. However, repeat ablation after failed CRYO had longer fluoroscopy time (19.8±2 vs 12.4±2.1 minutes, P=0.019). The right lower pulmonary vein (RLPV) was reconnected after failed CRYO for AF in 92% of patients and 100% in PAF patients.

Although PV reconnection pattern was similar between both cohorts, RLPV and left upper pulmonary vein (LUPV) required more ablation lesions after failed CRYO. Left lower pulmonary vein (LLPV) and right upper pulmonary vein (RUPV) required more ablation lesions after failed RF. Impedance drop was similar in both cohorts.

Conclusion

After failed CRYO for PAF, RLPV was reconnected in all patients. RUPV and LLPV required more ablation lesions after failed RF, while RLPV and LLPV required more ablation lesions after failed CRYO.

Funding Acknowledgement

Type of funding sources: None. PVs reconnection patternLesions number and percentage comparison
Socioeconomic status and trends in utilization of catheter ablation in patients hospitalized with atrial fibrillation in united states
Authors: Rojulpote C , Patil S , Gonuguntla K , Kharbanda P , Karambelkar P , Kela K , Singh V , Nadadur S , Kumar M , Buch T
Published: October 2021

Introduction

Atrial fibrillation (AF) is the most common arrhythmia encountered in a hospital setting. However, there is little data on the relationship of socioeconomic status (SES) and the utilization of catheter ablation amongst patients admitted with AF.

Methods

The National Inpatient Sample database was queried from 2003 to 2014 using ICD 9 revised diagnosis codes to identify patients who were hospitalized with a primary diagnosis of AF. SES was determined by median household income (MHI) and divided into quartiles (0–25th, 26–50th, 51–75th, and 76–100th). Trends were analyzed using Cochran Armitage test.

Results

We analyzed 3,618,133 patients with AF that were admitted from 2003 to 2014 (median age: 72 [IQR 61 – 81], female 52.6%). Trends stratified by MHI to compare catheter ablation rates of all 12 years revealed significant differences (Figure 1). A multivariable logistic regression accounting for sociodemographic factors revealed an increasing trend of catheter ablation utilization with higher MHI (Figure 1).

Conclusion

Over a 12-year period, patients admitted to the hospital with AF with higher MHI were found to have increasing rates of catheter ablation utilization due to AF. Conversely, a decline in catheter ablation rates were noted in patients with lower MHI.

Funding Acknowledgement

Type of funding sources: None.
Effectiveness and safety of edoxaban in atrial fibrillation patients from the ETNA-AF global registry
Authors: De Caterina R , Wang R , Shi L , Pecen L , Ye X , Reimitz P.-E , Chen C , Unverdorben M , Giugliano R.P
Published: October 2021

Background/Introduction

ETNA-AF (ETNA) is a multinational, prospective, observational study evaluating the experience with edoxaban in the clinical practice of patients with atrial fibrillation (AF). ENGAGE AF-TIMI 48 was a randomized double-blind trial that tested the clinical benefits of edoxaban versus warfarin. The recommended dose is 60 mg, dose-reduced to 30 mg daily in patients with at least 1 of 3 label-indicated criteria (renal impairment [creatinine clearance: 15–≤50 mL/min], weight ≤60 kg, or concomitant use of potent P-glycoprotein inhibitors).

Purpose

We assessed whether the effectiveness and safety of edoxaban in clinical practice were consistent with findings from the pivotal randomized clinical trial.

Methods

We obtained patient-level data from ETNA and ENGAGE AF-TIMI 48. We initially extracted patients from similar geographic regions, and then used propensity-score matching (PSM) to adjust key baseline characteristic differences between studies. The primary effectiveness endpoint was all stroke or systemic embolism (SSE) and mortality; the safety endpoint was major bleeding (MB). We used Cox proportional hazards models to compare event rates for the clinical outcomes between ETNA and ENGAGE AF-TIMI 48.

Results

8,615 AF patients with CHADS2 score ≥2 received the 60 mg edoxaban recommended dose (5,462 ETNA; 3,153 ENGAGE AF-TIMI 48). After PSM, key baseline characteristics were well-balanced between the studies: mean age 71.0 years (SD: 9.07); for both ETNA and ENGAGE AF-TIMI 48 median CHA2DS2-VASc score and median HAS-BLED score were 4 and 2. The annualized incidence rate of SSE was 1.65% in ETNA vs 1.53% in ENGAGE AF-TIMI 48 (HR 0.98; 95% CI 0.49, 1.93; p=0.94). ETNA had similar annualized mortality, 2.81%, compared with ENGAGE AF-TIMI 48, 2.34%, (HR 1.49; 95% CI 0.84, 2.63; p=0.17). MB was less frequent in ETNA vs ENGAGE AF-TIMI 48 (1.10% vs 3.56%; HR 0.25; 95% CI 0.14, 0.44; p<0.05). Findings were similar for the recommended 30 mg edoxaban reduced dose.

Conclusions

The effectiveness of edoxaban in clinical practice from a large registry was consistent with efficacy findings from the randomized controlled trial. We observed a lower rate of bleeding events in the ETNA observational study compared with the ENGAGE AF-TIMI 48 trial.

Funding Acknowledgement

Type of funding sources: Private company. Main funding source(s): This study was sponsored by Daiichi Sankyo Inc.
Reversed apico-basal myocardial relaxation sequence during exercise in related to impaired diastolic function and attenuated stroke volume response in LQTS mutations carriers
Authors: Charisopoulou D , Koulaouzidis G , Rydberg A , Henein M.Y
Published: October 2021

Background

Speckle-tracking echocardiography studies in inherited long QT syndrome (LQTS) have recently shown myocardial relaxation disturbances at rest in the form of delayed onset of relaxation as a result of prolonged and dispersed mechanical contraction.

The aim of this study was to assess disturbances in left ventricular regional myocardial relaxation sequence during exercise.

Methods

Forty seven (age 45±15 years, 25 female, LVEF: 65±6%, 36 LQT1 and 11 LQT2 whereof 20 symptomatic) patients underwent cardiac exercise test using Bruce protocol. ECG and echo parameters were recorded at rest, during peak exercise (p.e.) and at were compared with 35 healthy individuals. All time intervals were calculated from onset of R wave on superimposed ECG and were corrected to R-R interval.

Results

LQTS patients had longer QTc interval than controls at all the three exercise phases. LV longitudinal tESR, a reflector of relaxation delay was examined separately in the LV basal, mid and apical segments. At rest, no significant differences were noted between the two groups at the basal (490±59 vs. 486±36, p=0.6) and mid LV cavity regions (488±45 vs. 498±39, p=0.3); whereas in patients were seen more prolonged tESR in the apical regions (467±52 vs. 512±44, p<0.0001).

At peak exercise, patients had longer tESR at all three LV segments; basal (394±67 vs. 316±30, p<0.0001), mid cavity (363±64 vs. 340±32, p=0.03) and apical (348±60 vs. 368±28, p=0.03). The apico-basal relaxation dispersion (Δt ESRbase-apex) was significantly more pronounced in patients than in controls both at rest (49±43 vs. −29±19, p<0.0001) and at p.e. (46±38 vs. −40±22, p<0.0001). Moreover, the longitudinal relaxation sequence was reversed in patients (positive values for Δt ESRbase-apex); the early relaxation phase at the base was more delayed than at the apex, opposite to controls in whom the early relaxation onset occurred earlier in LV base than at apex. The magnitude of this apico-basal relaxation dispersion (Δt ESRbase-apex) correlated with longer QTc interval (r=0.9, p<0.0001), lower ESR (r=−0.8, p<0.0001) and attenuated LV stroke volume (r=−0.9, p<0.0001). This difference in Δt ESRbase-apex was more pronounced in symptomatic patients at p.e. than in asymptomatic (69±44 vs. 32±26, p<0.0007).

Conclusion

Our results showed reversed longitudinal relaxation sequence with more delayed early relaxation contraction phase at LV base than at LV apex in LQTS mutation carriers opposite to controls. These disturbances worsened at peak exercise and were related to longer QTc intervals and symptomatic patients.

Funding Acknowledgement

Type of funding sources: None.
Out-of-hospital cardiac arrest in COVID-19 era. A single center experience
Authors: Aschieri D , Villani M , Lanati M , Didio M.T , Pellizzoni V , Villani G.Q
Published: October 2021

Introduction

In the COVID-19 pandemic several adverse cardiovascular sequelae (myocarditis, AMI and heart failure) has been reported but it is unclear whether there is an influence of COVID-19 on incidence of out-of-hospital sudden death (OHCA) and its management by emergency medical services (EMS)

Aim

The aim of the study was to evaluate these items comparing OHCA during COVID-19 pandemic to that of pre-COVID era using the Progetto Vita Registry.

Method

We compared (OHCA) that occurred in Piacenza province during the first three months of COVID-19 outbreak (from February to April 2020, Period A) with those that occurred during the same period in 2019 (from February to April 2019, Period B) We collected data from the electronic database of the emergency medical system to identify patients affected by COVID-19, including both patient with symptoms suggestive of infection (history of fever before out-of-hospital cardiac arrest, with cough, dyspnea, or both) and patients with positive results of pharyngeal swabs test to detect SARS-CoV-2 obtained before the event or after death.

Results

1. Demographic characteristics of patients were similar in both periods (Period A 70/156 Female, mean age 79.2±5 yrs, Period B 39 Female, mean age 81.5±4 years,)

2. An higher number of OHCA were observed in the Period A vs Period B (A 156 cases vs B 78 cases, p 0.005). 68 cases (43%) of OHCA were associated with a COVID-19 disease

3. The EMS response time was longer in Period A vs B (A 16.4±4 min, vs B 11.1±3 min, p 0.05)

4. Initial cardiac rhythm was shockable in 10 subjects in the Period A (6,4%) and in 15 subjects in Period B (19.2%, p 005), possibly related to longer EMS response time

5. The global survival rate was higher in Period B vs A (B 5 patients, 6.4% vs 0 patients 0% p 0.05)

6. No one received cardiopulmonary resuscitation from bystanders in Period B.

Conclusion

During COVID-19 pandemic in Piacenza there was an increase in OCHA compared to the pre-COVID era. The COVID 19 Pandemic influences the bystanders attitude to practice an early cardiopulmonary resuscitation intervention and the performance of EMS, worsening the outcome of patients.

Funding Acknowledgement

Type of funding sources: None.
Performance of the multisensory cardiac implantable electronic device algorithm HeartLogic in a real-world ambulant chronic heart failure population
Authors: Feijen M , Egorova A.D , Treskes R.W , Schalij M.J , Beeres S.L.M.A
Published: October 2021

Background

Early detection of an upcoming episode of decompensated heart failure (HF) and timely adjustment of medical therapy may prevent a HF hospitalization. The novel multisensory cardiac implantable electronic device (CIED) based algorithm entitled HeartLogic™ (HL) aims to alert in case of upcoming fluid retention. This study investigates the performance of an HL alert in chronic HF patients in an ambulant HF care-path.

Methods

All chronic HF patients with a CIED and an activated HL algorithm implanted in our centre since 2018 were included. Patients were followed from 01–01–2018 until 01–02–2021 according to the HL-based care-path (Figure 1). The HL index was automatically generated from sensors assessing S3, S3/S1, thoracic impedance, respiratory- and night heartrate. Indexes were monitored continuously and an alert was issued when the pre-set threshold of 16 was surpassed. An alert was classified as true positive when the patient had at least two symptoms and/or signs of congestion during the alert episode. An alert was considered false positive when the patient had not more than one symptom or sign of congestion during the alert episode. If a patient had at least two symptoms and/or signs of congestion without an HL alert, the episode was classified as false negative.

Results

In total, 100 patients (median age 69 years [IQR 60–77], 78% male) were included. The etiology of HF was ischemic in 45% and 71% had a CRT-D device. Median follow-up was 13 months [IQR 6–23] and in total the follow-up comprised 126 patient-years. In 56 patients, there were 132 alerts, mean alert rate was 1.05 per patient-year. As it was unfeasible to strictly follow the specific HL care-path in 13 alert episodes, these alerts were excluded from further analyses. Based on the remaining 119 alert episodes, the positive predictive value for early detection of congestion was 77% and the negative predictive value was 97%. Sensitivity was 79% and specificity 97%.

Conclusion

In a real-world HF population, the HL algorithm can accurately predict an upcoming episode of decompensated heart failure.

Funding Acknowledgement

Type of funding sources: None. Overview of the HL based care-path
Walking in a straight line–the early detection of cardiomyopathy by the general physician
Authors: Ker J
Published: October 2021

Introduction

The orientation of muscle fibers in the left ventricle is sophisticated. This peculiar orientation causes the left ventricle to contract in three directions–longitudinal, radial and circumferential. Normal myocardial mechanics is essential for systolic and diastolic function. For the clinician an impairment in longitudinal function is of utmost importance, as it has been shown to be an early marker of left ventricular dysfunction, be that systolic or diastolic. Longitudinal function of the left ventricle can be quantified with tissue velocity imaging (TVI), mitral annular plane systolic excursion (MAPSE) and global longitudinal strain (GLS), as measured by speckle-tracking.

GLS measured by speckle-tracking is more technically challenging than measuring MAPSE and furthermore, in a setting with limited resources, not always widely available. Surprisingly, there is a paucity of data on the correlation of GLS to MAPSE. As GLS is the latest modality used to quantify longitudinal function of the LV and TVI is also more technically challenging than MAPSE, MAPSE was the chosen modality to compare to GLS. Furthermore, not all echocardiography systems are equipped for TVI and GLS, whereas that is not the case for MAPSE. MAPSE is therefore an easily acquired skill and widely available.

Purpose of this study

To determine whether MAPSE, when compared to GLS, is an accurate way to quantify longitudinal function of the left ventricle. If this is shown to be the case, then MAPSE will be a proven, readlily available and easily acquired skill to detect cardiomyopathy, whether primary or secondary to a wide variety of systemic diseases.

Methods

175 patients who presented with a variety of primary cardiac diseases and/or systemic diseases with the potential for cardiac involvement were included into the study.

175 patients with normal cardiac function were also included into the study.

Left ventricular longitudinal function of the left ventricle was quantified in each patient by means of MAPSE, as well as GLS measured by speckle-tracking. In order to correct MAPSE to body size, MAPSE:LV length was measured.

The correlation of MAPSE with GLS was assessed by means of a two-by-two table.

Results

In this group of 350 patients, split into 2 equal groups-175 with cardiomyopathy, either primary or secondary due to systemic disease, and 175 with no cardiomyopathy, the distinction is clear. The exposore, a GLS <−20% and a MAPSE:LV-lenghth <20% versus no exposure – a GLS <−20% and a MAPSE: LV-length >20% leads to a likelihood ratio of 485 (p=0) and a Pearson correlation of 525 (p=0) that impaired LV-longitudinal function is present.

Conclusion

A MAPSE: LV-length <20% correlates reliably with an impaired GLS. This is a reliable substitute for GLS and for the general physician who screens for early cardiomyopathy this is a skill that will be cheaper and more easily learned than GLS.

Funding Acknowledgement

Type of funding sources: None. GLSMAPSE
Left atrial conduit flow rate at baseline and during exercise: an index of impaired relaxation in patients with heart failure and preserved ejection fraction
Authors: Marino P , Zanaboni J , Degiovanni A , Patti G , Fraser A
Published: October 2021

Introduction

In healthy subjects, adrenergic stimulation augments left ventricular (LV) long-axis shortening/lengthening, and increases left atrial (LA) to LV intracavitary pressure gradients in early diastole. Lower increments are observed in patients with heart failure with preserved ejection fraction (HFpEF).

Purpose

We hypothesized that exercise in HFpEF would similarly impair passive LV filling in early-mid diastole, during conduit flow from pulmonary veins.

Methods

Twenty HFpEF patients (67.8±9.8 years; 11 women), diagnosed according to 2007 ESC recommendations, underwent ramped semi-supine bicycle exercise to submaximal target heart rate (∼100) or symptoms. Seventeen asymptomatic subjects (64.3±8.9 years; 7 women) served as controls. Simultaneous LA and LV volumes were measured from pyramidal 3D echocardiographic full-volume datasets acquired from apical window at baseline and during stress, together with brachial arterial pressure. LA conduit function was computed, from minimum LV volume to ECG P wave, as [LV volume (time) – LV minimum volume] – [LA maximum volume – LA volume (time)] and expressed as average flow rate. The slope of the single-beat preload recruitable stroke work (PRSW) quantified LV inotropic state.

Results

There were divergent responses in conduit flow rate, which increased by 40% during exercise in control subjects (+17.8±37.3 ml/s) but decreased by 18% in patients with HFpEF (−9.6±42.3 ml/s) (p=0.046); increments during stress correlated with PRSW slope changes (p=0.003).

Conclusion

In HFpEF conduit flow rate decreases when diastolic dysfunction develops during exercise, in parallel with LV inotropic state changes, thereby contributing to impaired stroke volume reserve. Conduit flow can be measured as a marker of LV relaxation.

Funding Acknowledgement

Type of funding sources: None.
Diagnostic performance of conventional right ventricular function echocardiography parameters in acute pulmonary embolism. Comparison with 3D ejection fraction and longitudinal strain
Authors: Ramos Lopez N , Islas Ramirez F.I.R , Mahia Casado P.M.C , Enriquez Vazquez D.E.V , Ferrera C.F.D , Viana Tejedor A.V.T , Galvan Herraez L.G.H , Pedrajas J.M.P , Bustamante Mandrion J.B.M , Perez Serrano M.P.S , Higueras Nafria J.H.N , Manas Hernandez A.M.H , Fernandez Ortiz A.F.O , Salinas Sanguino P.S.S , Macaya C.M.M
Published: October 2021

Background

Assessment of right ventricular (RV) function by transthoracic echocardiography (TTE) in acute pulmonary embolism (PE) has an essential role to stratify the severity. However, there is no individual TTE parameter that seems to provide reliable information on RV function.

Purpose

The objective is to compare the usefulness of advanced echocardiographic parameters, 3D RV ejection fraction (3DEF) and free wall 2D TTE speckle-tracking (2D-ST), in comparison to conventional ones in the RV dysfunction evaluation in patients with acute PE.

Methods

We prospectively recruited 86 patients with intermediate-high and high-risk bilateral PE from 2018 to 2020 in our centre. TTE during admission included 3DRVEF and 2D-ST and conventional parameters

(pulsed tissue Doppler S wave (S'), TAPSE, and fractional area change (FAC)). Normal values were stablished according to European guidelines.

Results

Mean age was 63.7±16.5 years, 58% males. Reperfusion treatment was performed in a 26.8%. Characteristics at admission and ETT parameters are shown on Table1. The proportion of patients with RV dysfunction evaluated by conventional parameters (42.9% by CAF, 20.8% by TAPSE and 17.7% by S') was lower than using 3DEF and ST (74.5% and 66,7% respectively).

Correlation amongst parameters is depicted in table2. FAC had the best correlation with 3DEF and FWLS (p<0.001). If considering 3DEF as “gold standard” in this cohort, FAC had the best performance to detect RV systolic dysfunction with a sensitivity and specificity of 45.9% and 93.2%, respectively, and a positive predictive value of 94.4%. TAPSE and S' had sensitivity of 21.6% and 17.1% respectively and 100% specificity. FWLS had 84.2% and 84.6% of sensitivity and specificity with a positive and negative predictive value of 94.1% and 64.7% respectively.

Conclusion

Advanced RV function assessmentby 3DEF and 2D-ST can help to identify a greater number of patients with RV dysfunction in high and intermediate-high risk acute PE compared with conventional parameters. FAC seems to be the best option to asses RV systolic function if 3D echo is not available.

Funding Acknowledgement

Type of funding sources: None. Table 1Table 2
Heart failure as a complication of COVID-19 infection: systematic review and meta-analysis
Authors: Zuin M , Zuliani G , Roncon L , Rigatelli G
Published: October 2021

Background

The prevalence and prognostic implications of heart failure (HF), as a complication of COVID-19 infection remains unclear.

Aims

We performed a systematic review and metanalysis aimed to evaluate the pooled incidence of acute HF as a cardiac complication of COVID-19 disease and to estimate the related mortality risk in these patients.

Methods

Data were obtained searching MEDLINE, Scopus and Web of Science for all investigations published any time to December 26, 2020. If statistical heterogeneity was 50%, the results were derived from the fixed-effects model otherwise the random-effects model.

Results

Overall, 1064 patients [mean age 66 years, 618 males] were included in the final analysis reviewing six investigations. The cumulative in-hospital rate of COVID-19 patients complicated by acute HF ranged between 6.9 to 63.4% among the studies reviewed. A random effect model revealed a pooled incidence of COVID-19 patients complicated by acute HF in 20.2% of cases (95% CI: 11.1–33.9%, p<0.0001 I2=94.4%) (Figure 1, Panel A). A second pooled analysis, based on a random-effect model, confirmed a significant increased risk of death in COVID-19 patients complicated by acute HF during the infection (OR 9.36, 95% CI 4.76–18.4, p<0.0001, I2=56.6%) (Figure 1, Panel B). The Egger's tests revealed no evidence of publication bias in estimating both the primary and secondary outcome (t=0.058, p=0.956 and t=1.402, p=0.233, respectively). Meta-regression analysis, using age as moderator variable, failed in founding a statistically significant relationship with the incidence of acute HF onset as a complication of COVID-19 disease (p=0.062) or the mortality risk among the same subjects (p=0.053).

Conclusions

Acute HF represents a frequent complication of COVID-19 infection associated with a higher risk of mortality in the short-term period.

Funding Acknowledgement

Type of funding sources: None. Figure 1. (A) Forest plot investigating the pooled incidence of acute heart failure as a complication of COVID-19 disease. (B) Forest plot investigating the mortality risk in COVID-19 patients complicated by acute heart failure.
Incremental value of hyponatremia to the ADHERE risk tree to predict in-hospital mortality in patients with acute heart failure
Authors: Chirino D , Vitale F , Iglesias J , Leonardi M , Matias N , Calderon G , Dizeo C
Published: October 2021

Background

Of the numerous risk scores developed to predict in-hospital events, the Adhere risk tree (ADHERE) is one of the easiest to calculate and uses systolic pressure and renal function on admission. However, it does not consider other important predictors, equally readily available, such as natraemia. The prognostic value of adding hyponatraemia to ADHERE in patients with AHF has been little studied.

Purpose

The aim of this study is to evaluate if the presence of hyponatraemia on admission improves the predictive capacity of the Adhere risk tree (ADHERE) score in patients with acute heart failure (AHF).

Materials and methods

A retrospective study was performed in two coronary units in Argentina. Patients with diagnostic of AHF were included and in-hospital mortality was considerate as primary end point. With the admission data, the patients were classified according to the risk levels of ADHERE into 5 groups: Low risk, Intermediate 3, intermediate 2, intermediate 1 and high risk. In addition, the natraemia on admission was recorded. A model was built integrating ADHERE and natraemia (ADH-Na) by logistic regression. Receiver operating characteristic (ROC) curves were drawn up and the area under the curve (AUC) was calculated to assess the discrimination capacity of both variables and to establish the cut-off point for natraemia. Net reclassification improvement (NRI) index was calculated.

Results

1200 patients were included with an age 66±15 years old, 35% woman. In hospital mortality was 4% (n=48). ADHERE and hyponatremia (defined with a cut-off point of Na <134 mE/L) were independent predictors of mortality (OR 1.69 (95% CI 1.37–2.09), p<0.001 and OR 2.03 (95% CI 1.19 - 3.47), p=0.009, respectively). The discrimination capacity of ADHERE improved significantly when hyponatraemia was introduced into the risk model: the AUC for ADHERE was 0.65 (95% CI 0.535–0.72) and for ADH-Na was 0.74 (CI05% 0.66–0.82), p=0.04. The NRI was 16.5% (CI95% 0.92 – 32.33%). The table shows mortality in the different risk categories with both models.

Conclusion

Adding hyponatremia to the ADHERE risk model contributes to improving the predictive capacity of in-hospital mortality in patients with AHF.

Funding Acknowledgement

Type of funding sources: None. Mortality in two modelsROC Curve Caparations