bluuebunny/crossref_metadata_2025 huggingface dataset:
The empty code cart: Drug shortages over time
Authors: Gentile Tyler , Snee Isabel , Heinrichs Dorothy , Hockstein Max A , Mazer-Amirshahi Maryann , Fox Erin R
Published: May 2024

Purpose

In high-acuity situations such as cardiac arrest, clinicians rely on prepared medications stocked in code carts to provide timely and accurate pharmacotherapy. We examined shortage trends for medications commonly used in code carts.

Methods

Drug shortage data from 2001 to 2022 were retrieved from the University of Utah Drug Information Service (UUDIS) to characterize shortages reported for commonly used code cart medications. Data extracted included the number of shortages, shortage duration, drug characteristics, and reason for the shortage.

Results

From 2001 to 2022, 71 drug shortages for code cart medications were reported. The number of new shortages peaked in 2010, and the number of total shortages peaked in 2010. At the end of the study period, 61 (84.7%) shortages had been resolved. For resolved shortages, the mean shortage duration was 18.2 months. The drug with the greatest number of reported shortages was dextrose (10 total), the drug with the longest resolved shortage was calcium chloride injection (116 months), and the drug with the longest active shortage was atropine injection (165 months at the end of the study period). Throughout the entire study period, only 2 suppliers provided commercially available prefilled syringes of dextrose for stocking on code carts. The most common reason for shortages, when reported, was manufacturing delays.

Conclusion

Medications commonly used in code carts were frequently impacted by drug shortages, which have the potential to impact patient care. Institutional protocols for mitigation and larger efforts to promote a more resilient drug supply chain are critical to ensure patient safety and quality care.
Prospective associations of occupational and leisure-time physical activity with risk of diabetes: a cohort study from the United States
Authors: Matthews Timothy A , Liu Xinyue , Chen Liwei , Li Jian
Published: May 2024

Objectives

Leisure-time physical activity (LTPA) can reduce the risk of incident diabetes, whereas the role of occupational physical activity (OPA) in developing diabetes is still unclear due to conflicting evidence. Moreover, the joint associations of OPA and LTPA with incident diabetes among US workers have not yet been systematically examined. The objective of this study was to assess the independent and joint associations of OPA and LTPA with incident diabetes.

Methods

This prospective cohort study included 1406 workers free from diabetes at baseline (2004–2006) from the national, population-based Mid-life in the United States (MIDUS) study. Associations of OPA and LTPA at baseline with incident diabetes during 9 years of follow-up were examined using Poisson regression models. High OPA was defined based on engagement in physical demands at work, and high LTPA was defined as participation in moderate or vigorous LTPA at least once per week.

Results

High OPA was associated with an increased risk of diabetes compared to low OPA (adjusted risk ratios and 95% confidence interval = 1.52 [1.04, 2.22]), while high LTPA was associated with a decreased risk of diabetes compared to low LTPA (0.66 [0.44, 0.97]). Diabetes risk was the highest among workers with high OPA and low LTPA (2.30 [1.30, 4.07]).

Conclusions

In a national, population-based prospective cohort study of US workers, high OPA was associated with an elevated risk of diabetes, while high LTPA was associated with a decreased diabetes risk. The combination of high OPA and low LTPA exhibited the greatest risk of diabetes.
A SARS-CoV-2 outbreak in a public order and safety training facility in England, June 2021
Authors: Gilham Ellie L , Raja Amber I , van Veldhoven Karin , Nicholls Gillian , Sandys Vince , Atkinson Barry , Spencer Antony , Nicholls Ian , Cooke Joan , Bennett Allan , Morgan Derek , Keen Chris , Fletcher Tony , Pearce Neil , Manley Petra , Brickley Elizabeth B , Chen Yiqun
Published: May 2024

Background

The public order and safety (POS) sector remains susceptible to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreaks, as workplace attendance is typically compulsory and close physical contact is often needed. Here, we report on a SARS-CoV-2 outbreak with an attack rate of 39% (9/23), which occurred between 19 and 29 June 2021 among a cohort of new POS recruits participating in a mandatory 18-week training programme in England.

Methods

The COVID-OUT (COVID-19 Outbreak investigation to Understand Transmission) study team undertook a multidisciplinary outbreak investigation, including viral surface sampling, workplace environmental assessment, participant viral and antibody testing, and questionnaires, at the two associated training facilities between 5 July and 24 August 2021.

Results

Environmental factors, such as ventilation, were deemed inadequate in some areas of the workplace, with carbon dioxide (CO2) levels exceeding 1,500 ppm on multiple occasions within naturally ventilated classrooms. Activities during safety training required close contact, with some necessitating physical contact, physical exertion, and shouting. Furthermore, most participants reported having physical contact with colleagues (67%) and more than one close work contact daily (97%).

Conclusions

Our investigation suggests that site- and activity-specific factors likely contributed to the transmission risks within the POS trainee cohort. Potential interventions for mitigating SARS-CoV-2 transmission in this POS training context could include implementing regular rapid lateral flow testing, optimizing natural ventilation, using portable air cleaning devices in classrooms, and expanding use of well-fitted FFP2/FFP3 respirators during activities where prolonged close physical contact is required.
Predmoter—cross-species prediction of plant promoter and enhancer regions
Authors: Kindel Felicitas , Triesch Sebastian , Schlüter Urte , Randarevitch Laura Alexandra , Reichel-Deland Vanessa , Weber Andreas P M , Denton Alisandra K
Published: May 2024

Motivation

Identifying cis-regulatory elements (CREs) is crucial for analyzing gene regulatory networks. Next generation sequencing methods were developed to identify CREs but represent a considerable expenditure for targeted analysis of few genomic loci. Thus, predicting the outputs of these methods would significantly cut costs and time investment.

Results

We present Predmoter, a deep neural network that predicts base-wise Assay for Transposase Accessible Chromatin using sequencing (ATAC-seq) and histone Chromatin immunoprecipitation DNA-sequencing (ChIP-seq) read coverage for plant genomes. Predmoter uses only the DNA sequence as input. We trained our final model on 21 species for 13 of which ATAC-seq data and for 17 of which ChIP-seq data was publicly available. We evaluated our models on Arabidopsis thaliana and Oryza sativa. Our best models showed accurate predictions in peak position and pattern for ATAC- and histone ChIP-seq. Annotating putatively accessible chromatin regions provides valuable input for the identification of CREs. In conjunction with other in silico data, this can significantly reduce the search space for experimentally verifiable DNA–protein interaction pairs.

Availability and implementation

The source code for Predmoter is available at: https://github.com/weberlab-hhu/Predmoter. Predmoter takes a fasta file as input and outputs h5, and optionally bigWig and bedGraph files.
Total mesorectal excision in MRI-defined low rectal cancer: multicentre study comparing oncological outcomes of robotic, laparoscopic and transanal total mesorectal excision in high-volume centres
Authors: Rutgers Marieke L , Burghgraef Thijs A , Hol Jeroen C , Crolla Rogier M , van Geloven Nanette A , Leijtens Jeroen W , Polat Fatih , Pronk Apollo , Smits Anke B , Tuyman Jurriaan B , Verdaasdonk Emiel G , Sietses Colin , Consten Esther C , Hompes Roel
Published: May 2024

Background

The routine use of MRI in rectal cancer treatment allows the use of a strict definition for low rectal cancer. This study aimed to compare minimally invasive total mesorectal excision in MRI-defined low rectal cancer in expert laparoscopic, transanal and robotic high-volume centres.

Methods

All MRI-defined low rectal cancer operated on between 2015 and 2017 in 11 Dutch centres were included. Primary outcomes were: R1 rate, total mesorectal excision quality and 3-year local recurrence and survivals (overall and disease free). Secondary outcomes included conversion rate, complications and whether there was a perioperative change in the preoperative treatment plan.

Results

Of 1071 eligible rectal cancers, 633 patients with low rectal cancer were identified. Quality of the total mesorectal excision specimen (P = 0.337), R1 rate (P = 0.107), conversion (P = 0.344), anastomotic leakage rate (P = 0.942), local recurrence (P = 0.809), overall survival (P = 0.436) and disease-free survival (P = 0.347) were comparable among the centres. The laparoscopic centre group had the highest rate of perioperative change in the preoperative treatment plan (10.4%), compared with robotic expert centres (5.2%) and transanal centres (2.1%), P = 0.004. The main reason for this change was stapling difficulty (43%), followed by low tumour location (29%). Multivariable analysis showed that laparoscopic surgery was the only independent risk factor for a change in the preoperative planned procedure, P = 0.024.

Conclusion

Centres with expertise in all three minimally invasive total mesorectal excision techniques can achieve good oncological resection in the treatment of MRI-defined low rectal cancer. However, compared with robotic expert centres and transanal centres, patients treated in laparoscopic centres have an increased risk of a change in the preoperative intended procedure due to technical limitations.
Impact of clinical frailty on surgical and non-surgical complications after major emergency abdominal surgery
Authors: Snitkjær Christian , Rehné Jensen Lasse , í Soylu Liv , Hauge Camilla , Kvist Madeline , Jensen Thomas K , Kokotovic Dunja , Burcharth Jakob
Published: May 2024

Background

Major emergency abdominal surgery is associated with a high risk of morbidity and mortality. Given the ageing and increasingly frail population, understanding the impact of frailty on complication patterns after surgery is crucial. The aim of this study was to evaluate the association between clinical frailty and organ-specific postoperative complications after major emergency abdominal surgery.

Methods

A prospective cohort study including all patients undergoing major emergency abdominal surgery at Copenhagen University Hospital Herlev, Denmark, from 1 October 2020 to 1 August 2022, was performed. Clinical frailty scale scores were determined for all patients upon admission and patients were then analysed according to clinical frailty scale groups (scores of 1–3, 4–6, or 7–9). Postoperative complications were registered until discharge.

Results

A total of 520 patients were identified. Patients with a low clinical frailty scale score (1–3) experienced fewer total complications (120 complications per 100 patients) compared with patients with clinical frailty scale scores of 4–6 (250 complications per 100 patients) and 7–9 (277 complications per 100 patients) (P < 0.001). A high clinical frailty scale score was associated with a high risk of pneumonia (P = 0.009), delirium (P < 0.001), atrial fibrillation (P = 0.020), and infectious complications in general (P < 0.001). Patients with severe frailty (clinical frailty scale score of 7–9) suffered from more surgical complications (P = 0.001) compared with the rest of the cohort. Severe frailty was associated with a high risk of 30-day mortality (33% for patients with a clinical frailty scale score of 7–9 versus 3.6% for patients with a clinical frailty scale score of 1–3, P < 0.001). In a multivariate analysis, an increasing degree of clinical frailty was found to be significantly associated with developing at least one complication.

Conclusion

Patients with frailty have a significantly increased risk of postoperative complications after major emergency abdominal surgery, especially atrial fibrillation, delirium, and pneumonia. Likewise, patients with frailty have an increased risk of mortality within 90 days. Thus, frailty is a significant predictor for adverse events after major emergency abdominal surgery and should be considered in all patients undergoing major emergency abdominal surgery.
Intervention Pathways following a Social Work Assessment: An Analysis of National Administrative Data for Children’s Social Care in England
Authors: Hood Rick , Goldacre Allie , Jones Ed , Martin Emma , Clements Keith , Webb Calum
Published: May 2024

The majority of children referred to social care services in England go on to receive a statutory assessment by a social worker. Research has identified consistent categories of demand based on the needs identified in assessments. However, little is known about the relationship between children’s assessed needs and their subsequent intervention pathways. To explore this relationship, secondary analysis was undertaken of a national administrative data-set including all children who received a social work assessment in England from 2015 to 2020 (n = 3.6 m). Children’s characteristics, assessed needs and intervention pathways were compared for each episode of CSC involvement. Regression analysis then explored how the proportion of children receiving different types of provision varied according to their needs as well as intersections of gender, age and ethnicity. The findings showed significant differences across twelve categories of demand, pointing to variation in the assessment and response to similar types of presenting needs. Implications are discussed for the planning and design of services.
Personality and quality-of-life improvement after apomorphine infusion in Parkinson’s disease
Authors: Boussac Mathilde , Harroch Estelle , Barthelemy Christel , Ory-Magne Fabienne , Leung Clémence , Fabbri Margherita , Arbus Christophe , Brefel-Courbon Christine
Published: May 2024

People with Parkinson’s disease with motor fluctuations can be treated by continuous subcutaneous apomorphine infusion (CSAI) to reduce their symptoms. Nonetheless, factors are lacking to predict patients’ quality-of-life amelioration after CSAI. This pilot study aimed to evaluate associations between personality dimensions and quality-of-life improvement after 6 months of CSAI.

Thirty-nine people with Parkinson’s disease awaiting CSAI were included. Linear regression models between ‘Temperament and Character Inventory’ personality dimensions at baseline and percentage of change in Parkinson’s Disease Questionnaire-39 scores after 6 months of CSAI were realized (n = 35). The Temperament and Character Inventory was also compared between patients awaiting CSAI and patients awaiting deep brain stimulation of the sub-thalamic nucleus (n = 39 from the PREDI-STIM study).

Higher reward dependence scores were associated with a better quality-of-life outcome after 6 months of CSAI, while self-directedness scores were associated with a better quality of life before CSAI (as opposed to harm avoidance, reward dependence and self-transcendence scores associated with a worse quality of life). Moreover, people with Parkinson’s disease awaiting deep brain stimulation of the sub-thalamic nucleus had similar Temperament and Character Inventory dimensions compared to patients awaiting CSAI.

People with Parkinson’s disease with higher reward dependence scores at baseline had the best quality-of-life improvement after 6 months of CSAI. This finding could be used to better prepare and accompany people with Parkinson’s disease during CSAI establishment. Moreover, this result could serve as an orientation factor to second-line treatments.
Does Adjunctive Clindamycin Have a Role in Staphylococcus aureus Bacteremia? A Protocol for the Adjunctive Treatment Domain of the Staphylococcus aureus Network Adaptive Platform (SNAP) Randomized Controlled Trial
Authors: Anpalagan Keerthi , Dotel Ravindra , MacFadden Derek R , Smith Simon , Voss Lesley , Petersiel Neta , Marks Michael , Marsh Julie , Mahar Robert K , McGlothlin Anna , Lee Todd C , Goodman Anna , Morpeth Susan , Davis Joshua S , Tong Steven Y C , Bowen Asha C ,   the Adjunctive Clindamycin Domain-Specific Working Group for the Staphylococcus aureus Network Adaptive Platform (SNAP) Trial Group, Anpalagan Keerthi , Dotel Ravindra , MacFadden Derek R , Smith Simon , Voss Lesley , Petersiel Neta , Marks Michael , Davis Joshua S , Bowen Asha C , Bonten Marc , Bowen Asha C , Daneman Nick , van Hal Sebastiaan J , Heriot George S , Lewis Roger J , Lye David C , McQuilten Zoe , Paterson David L , Robinson J Owen , Roberts Jason A , Scarborough Matthew , Webb Steve A , Whiteway Lynda , Walls Genevieve , Lee Todd C , Yahav Dafna , Hensgens Marjolein , Cheng Matthew P , Morpeth Susan , Tong Steven Y C , Davis Joshua S
Published: May 2024

Background

The use of adjunctive antibiotics directed against exotoxin production in Staphylococcus aureus bacteremia (SAB) is widespread, and it is recommended in many guidelines, but this is based on limited evidence. Existing guidelines are based on the theoretical premise of toxin suppression, as many strains of S. aureus produce toxins such as leukocidins (eg, Panton-Valentine leukocidin, toxic shock syndrome toxin 1, exfoliative toxins, and various enterotoxins). Many clinicians therefore believe that limiting exotoxin production release by S. aureus could reduce its virulence and improve clinical outcomes. Clindamycin, a protein synthesis inhibitor antibiotic, is commonly used for this purpose. We report the domain-specific protocol, embedded in a large adaptive, platform trial, seeking to definitively answer this question.

Methods and Analysis

The Staphylococcus aureus Network Adaptive Platform (SNAP) trial is a pragmatic, randomized, multicenter adaptive platform trial that aims to compare different SAB therapies, simultaneously, for 90-day mortality rates. The adjunctive treatment domain aims to test the effectiveness of adjunctive antibiotics, initially comparing clindamycin to no adjunctive antibiotic, but future adaptations may include other agents. Individuals will be randomized to receive either 5 days of adjunctive clindamycin (or lincomycin) or no adjunctive antibiotic therapy alongside standard-of-care antibiotics. Most participants with SAB (within 72 hours of index blood culture and with no contraindications) will be eligible to participate in this domain. Prespecified analyses are defined in the statistical appendix to the core protocol, and domain-specific secondary analyses will be adjusted for resistance to clindamycin, disease phenotype (complicated or uncomplicated SAB) and Panton-Valentine leukocidin–positive isolate.
Serial cardiopulmonary exercise testing in young patients after one-and-half ventricle repair and Fontan procedure: a comparative study
Authors: Vecchiato Marco , Mazzucato Barbara , Battista Francesca , Neunhaeuserer Daniel , Quinto Giulia , Aghi Andrea , Varnier Maurizio , Gasperetti Andrea , Di Salvo Giovanni , Vida Vladimiro , Padalino Massimo Antonio , Ermolao Andrea
Published: May 2024

Aim

The Fontan procedure is a palliative surgical treatment for different congenital heart diseases with a univentricular heart, but it has been associated with decreased exercise capacity, cardiovascular morbidity, and premature mortality. The one-and-half ventricle repair (1.5VR) was introduced as an alternative to the Fontan procedure, specifically for selected patients with borderline hypoplastic right ventricle (HRV), aiming for a more physiological circulation. Despite these efforts, the benefit of 1.5VR over Fontan circulation comparison on clinical and functional outcomes remains unclear. The aim of this study was to investigate and compare young patients with HRV after 1.5VR with those with functional single right or left ventricles (FSRV or FSLV) after Fontan palliation over a 10-year follow-up period.

Methods and results

In this retrospective observational study, serial cardiopulmonary exercise tests (CPETs) performed in patients with 1.5VR and Fontan circulation between September 2002 and March 2024 have been analysed. Only patients with at least 10 years of follow-up were considered. A total of 43 patients were included (age at baseline 8.6 ± 2.6 years): 21 with FSLV, 12 with FSRV, and 10 with 1.5VR. No differences in cardiorespiratory fitness and efficiency were shown at the first CPET assessment among the three groups. At 10-year follow-up, 1.5VR had higher cardiorespiratory fitness and efficiency compared to FSLV and FSRV patients.

Conclusion

These findings suggest that the 1.5VR may provide superior long-term functional outcomes than the Fontan procedure in patients with borderline HRV. Further studies are needed to evaluate the impact on hard clinical endpoints.
Genetic profiles of oligometastatic non-small-cell lung cancer and corresponding brain metastases
Authors: Werner Raphael S , Rechsteiner Markus , Moch Holger , Curioni-Fontecedro Alessandra , Weller Michael , Weiss Tobias , Regli Luca , Le Rhun Emilie , Mairinger Fabian , Opitz Isabelle , Soltermann Alex
Published: May 2024

OBJECTIVES

In patients with oligometastatic non-small-cell lung cancer (NSCLC), systemic therapy in combination with local ablative treatment of the primary tumour and all metastatic sites is associated with improved prognosis. For patient selection and treatment allocation, further knowledge about the molecular characteristics of the oligometastatic state is necessary. Here, we performed a genetic characterization of primary NSCLC and corresponding brain metastases (BM).

METHODS

We retrospectively identified patients with oligometastatic NSCLC and synchronous (<3 months) or metachronous (>3 months) BM who underwent surgical resection of both primary tumour and BM. Mutation profiling of formalin-fixed paraffin-embedded tumour cell blocks was performed by targeted next-generation sequencing using the Oncomine Focus Assay panel.

RESULTS

Sequencing was successful in 46 paired samples. An oncogenic alteration was present in 31 primary tumours (67.4%) and 40 BM (86.9%). The alteration of the primary tumours was preserved in the corresponding BM in 29 out of 31 cases (93.5%). The most prevalent oncogenic driver in both primary tumours and BM was a KRAS (Kirsten rat sarcoma viral oncogene) mutation (s = 21). In 16 patients (34.8%), the BM harboured additional oncogenic alterations. The presence of a private genetic alteration in the BM was an independent predictor of shorter overall survival.

CONCLUSIONS

In oligometastatic NSCLC, BM retain the main genetic alterations of the primary tumours. Patients may profit from targeted inhibition of mutated KRAS. Additional private genetic alterations in the BM are dismal.
Renal artery stenosis increases the risk of incident atrial fibrillation and cardiovascular events incorporating death
Authors: Chan Y , Lau N , Yiu K H , Tse H F
Published: May 2024

Background

Renal artery stenosis (RAS) remains an under-recognized clinical risk factor for cardiovascular complications. Its long-term impact on AF arrhythmogenesis is unclear.

Objective

To investigate the role of RAS on incident AF and related adverse cardiovascular events

Methods

We performed a retrospective cohort study that comprised 100 patients with ultrasonographically-confirmed atherosclerotic RAS, and 50 age- and sex-matched controls who were healthy renal transplant donors (age 52.6 ±5.6 vs 50.1 ±10.7years, women 59% vs 70%). Incident AF was ascertained from clinical records. Primary endpoint was defined as the composite of incident AF, myocardial infarction, unstable angina, heart failure, ischemic stroke, peripheral arterial disease, end-stage renal failure, and cardiovascular death.

Results

Over a follow-up duration of 4818 ± 2751 days, RAS was significantly associated with incident AF (9.4% versus 0%, P=0.025). Kaplan-Meier analyses showed that RAS was associated with reduced incident AF event-free survival (Log-rank Mantel-Cox=4.6 P=0.032, Figure). Multivariable logistic regression showed that after adjustment for potential confounders (including age, sex, smoking, alcohol use, history of hypertension, diabetes mellitus, myocardial infarction, heart failure, ischemic stroke, renal function and serum low-density lipoprotein level), RAS was independently associated with substantially increased risk of the primary endpoint (OR=27.8, 95%CI [2.3 – 333.9], P=0.009),

Conclusions

RAS is an important and under-recognized independent risk factor for AF and cardiovascular events incorporating death. Its pathophysiological implications with a view to potential interventions need to be further explored.
Clinical characteristics and genetic substrate of lone atrial fibrillation: a single center experience
Authors: Berruquier P , Dusi V , Saglietto A , Vallarino C , Bertello E , Tallone L , Solano A , Brach Del Prever G M , Giustetto C , Matta M , Castagno D , Ferraris F , Deaglio S , De Ferrari G M , Anselmino M
Published: May 2024

Background

Juvenile-onset lone atrial fibrillation (LAF) may be the initial manifestation of a concealed channelopathy or cardiomyopathy (CMP) or it may be due to an atrial specific genetic susceptibility. Clinical characteristics, genetic background and proper management are still largely unknown.

Purpose

Aim of the present study is to describe the clinical and genetic characteristics of patients with juvenile-onset LAF.

Methods

We enrolled patients referred to our center for ablation between 1/2018 and 11/2023 with a first diagnosis of LAF before the age of 60, a structurally normal heart (absence of known CMP, ischemic, valvular, congenital heart disease) and no overt channelopathy. A concealed Brugada syndrome was systematically excluded. Genetic testing was performed using Next Genome Sequencing and a dedicated gene panel.

Results

89 patients were included (84% male, LAF onset 43 ± 8 years, BMI 25 ± 7 kg/m2): 32% had a first-degree family history of AF (including 15% below 60 years), 18% of sudden death, 8% of cardiac conduction disorders and 2% of CMP. Cardiovascular risk factors included arterial hypertension in 24%, smoking in 47% and obstructive sleep apnea syndrome in 4%; 20% were competitive athletes. Most patients (89%) presented with paroxysmal AF and 92% were symptomatic (mainly palpitations). At presentation LVEF was 61±5% and LAVI 35±14 ml/m2. Median follow-up time after the first AF episode was 6 years (IQR 4-10). Most patients (81, 91%) underwent at least one transcatheter ablation procedure after failed anti-arrhythmic drug (AAD) therapy (mostly IC). The first procedure (73% radiofrequency, 27% cryoablation) included pulmonary veins isolation (PVI) in all and additional lesions in 5%; the second procedure (n=18, 22% of the ablation group) included PV re-isolation in all (mostly due to multiple vein reconnections) and additional lesions in 17%; the third procedure (n=8, 10% of the ablation group) included PV re-isolation in 25% and additional lesions in 75%. The remaining 8 patients were treated with AAD only (mostly IC). By the last follow-up, 7% of patients in the ablation group and 25% in the AAD group had documented recurrences (even though 50% of those who received ablation were still on AAD). Among the 35 patients subjected to genetic investigation, 10 have available results: 30% tested positive for C4-C5 variants (2 for KCNQ1, 1 for TTN), 50% for C3 variants (RYR2, ABCC9, LMNA, KCNH2 and RMB20) and 20% were negative.

Conclusions

In the present single center cohort of patients with juvenile-onset LAF, a positive family history was found in almost one third of patients. Despite prompt diagnosis and treatment (including >1 ablation in 20% of patients), recurrences rate is not trivial. The yield of genetic test so far is high, supporting its use in this population.
Atrial functional mitral regurgitation as a marker of atrial remodeling and ablation outcomes in atrial fibrillation patients
Authors: Mohsen Y , Horlitz M , Stoeckigt F , Rottlaender D
Published: May 2024

Background

Atrial fibrillation (AF) triggers a cascade of atrial remodeling processes, significantly impacting atrial function and the efficacy of ablation therapies. This remodeling fosters the development of atrial cardiomyopathy and atrial dilation, which is linked to the emergence of mitral regurgitation, paving the way for the concept of atrial functional mitral regurgitation (aFMR).

Our study delves into the intricate relationship between aFMR and the electrical architecture of the atrium, specifically focusing on left atrial bipolar voltage and the prevalence and extent of low-voltage areas (LVAs) in AF patients. By exploring these associations, this research aims to deepen our understanding of the interplay between the atrial substrate alterations and the development of aFMR.

Methods

A total of 282 patients were enrolled, who had presented for a redo PVI procedure after experiencing AF recurrence following a previous PVI. All patients received echocardiography prior to the electrophysiological procedure. All procedures were performed using 3D mapping and radiofrequency ablation. Reconnected pulmonary veins were detected in all patients and were re-isolated. The voltage of the electroanatomical points was documented on each of the atrial walls. LVAs were calculated in selected HD maps. Patients were followed-up for one year after the blanking period.

Results

Our cohort comprised 282 patients, predominantly male (69.4%), with a mean age of 64 years. 56% of the patients presented with persistent AF. LA area was larger in patients with aFMR ≥ 1+ as compared to aFMR < 1+ (17.0 [14.6-19.7] vs 20.6 [16.6-24.7] cm2, p<0.001). We observed significant differences in left atrial voltage and LVA extent between patients with varying degrees of aFMR (Table 1). Upon further investigation Patients with aFMR = 1+ showed significantly lower atrial voltage compared with aFMR < 1+ yet no significant increase in LVAs area. Patients with aFMR = 2 exhibited lower average voltage amplitudes in all atrial regions and larger LVA in the posterior wall, atrial roof, and septum compared to their aFMR < 1+ counterparts. Notably, the recurrence of AF was significantly higher in the AFMR ≥ 1+ (59% vs 46% p=0.027) group within one year of follow-up. aFMR was associated with AF recurrence even after adjusting for sex, age and AF types (HR:1.517, 95% CI: 1.057-2.184, p=0.025).

Conclusion

The presence of aFMR in AF patients may serve as a marker of progressive atrial remodeling and the onset of left atrial cardiomyopathy, characterized by reduced atrial voltage and increased LVAs. Additionally, aFMR is linked to the outcomes of PVI, suggesting that aFMR should be considered in the decision-making process for AF therapy. Further research is needed to explore the potential reversibility of these changes.Left atrial voltage and low voltage area
Plasmatic NT-proBNP is strongly associated with atrial fibrillation in patients without severely reduced left ventricular ejection fraction in an ICD collective
Authors: Allgaier R , Strack C , Wallner S , Hubauer U , Lehn P , Luchner A , Maier L , Jungbauer C
Published: May 2024

Background and objectives

Atrial fibrillation is common in patients with chronic heart failure and associated with poor outcome in these patients. Plasmatic NT-proBNP represents the gold standard biomarker for chronic heart failure. Further, a recent analysis showed a strong association of plasmatic NT-proBNP and atrial fibrillation (AFib). Aim of the study was to assess the association of plasmatic NT-proBNP depending on left ventricular ejection fraction (LVEF) in a cohort of patients with implantable cardioverter defibrillator (ICD).

Methods

412 patients were included in the study. Blood samples were used to assess plasmatic NT-proBNP. Follow-up was performed after 45 months. LVEF was estimated by echocardiography according to Simpsons’ method. At enrollment, a 12-lead electrocardiogram was performed (sinus rhythm (SR, n = 306), atrial fibrillation (AFib, n = 79)). Patients were divided into two subgroups by LVEF of 40%.

Results

Patients suffering from severely reduced LVEF ≤ 40% showed significant higher age, higher rates of chronic kidney disease, diabetes, coronary artery disease, primary prevention ICD indication, coronary artery disease, dilatative cardiomyopathy and plasmatic NT-proBNP compared to patients with LVEF > 40% (each p < 0.05). There were no differences regarding hypertension and occurrence of AFib between patients with LVEF ≤ 40% compared to patients with LVEF < 40% (each p = n.s.).

In ROC analysis there was a significantly higher AUC in patients with LVEF > 40% (AUC: 0.87, IQR 0.82-0.92) compared to patients with severely reduced LVEF ≤ 40% (AUC: 0.72, IQR 0.64-0.80) regarding plasmatic NT-proBNP and prediction of AFib (p < 0.002).

In patients with LVEF > 40% plasmatic NT-proBNP was shown as significant predictor regarding existence of atrial fibrillation in binary logistic regression analysis, beside age (p < 0.05). Diabetes, hypertension, serum creatinine, coronary artery disease and primary prevention ICD indication were no significant predictors (p = n.s.). In patients with LVEF ≤ 40% plasmatic NT-proBNP was not shown as significant predictor regarding existence of atrial fibrillation in binary logistic regression analysis.

Conclusion

Elevated levels of plasmatic NT-proBNP are strongly associated with the prevalence of atrial fibrillation in patients without severely reduced LVEF in a cohort of ICD patients.
Stroke after implantable cardioverter-defibrillator shocks in patients with heart failure
Authors: Dyrbus M , Pyka Ł T , Kurek A K , Niedziela J T , Adamowicz-Czoch E , Ostrega M A , Sokola K , Pres D W , Tajstra M P , Gasior M
Published: May 2024

Introduction

In patients with atrial fibrillation (AF), an elevated risk of stroke has been demonstrated in the first days after successful electrical cardioversion of AF. Shock therapies delivered by implantable cardioverter-defibrillators (ICD) often result in termination of AF, potentially increasing the risk of stroke in those patients. However, the association between ICD shocks and the risk of stroke in patients with AF is unknown.

Purpose

To define whether there is any temporal association between ICD shocks and strokes in remotely monitored patients with heart failure (HF) and AF.

Methods

The clinical data of patients enrolled in the remote monitoring (RM) programme after implantation of an ICD were obtained from the single-centre COMMIT-HF registry. The data regarding the occurrence of the first stroke after inclusion to the registry were obtained (based on the International Classification of Diseases codes I63-I64) from the healthcare provider. The RM data of all patients were obtained from the investigator-initiated and -maintained registry of RM, which summarizes all major findings in remotely monitored patients in our department. Each patient with a stroke had the RM history evaluated for the period of the prior 30 days, with emphasis on the last 10 days preceding stroke.

Results

During the period between 2011 and 2020, 1,299 patients with detailed clinical characteristics were enrolled in the RM programme, and their clinical data are summarized in Table 1.There were 33.4% patients with AF at baseline, and AF de novo was identified during follow-up in further 14.0% of patients. Among patients without and with AF at baseline, respectively 30.9% and 34.1% received any ICD shocks during follow-up (p=NS). In 38.2% of patients without AF at baseline, who developed de novo AF, at least one shock occurred.

The median follow-up was 4.4 years, and the incidence of stroke was 45 (3.5%) in the studied population, with a rate of stroke of 2.8% (25/865) in patients without AF at baseline and 4.6% (20/434) in patients with AF (p=NS), as presented in Figure 1. The median (Q1-Q3) time from ICD implantation to stroke was 1.5 (0.8-2.5) years. Strokes occurring less than 10 days from ICD shock were noted in only two patients (0.5% of patients with any ICD shock) and both occurred within 24 hours from the shock. In the first case, the device appropriately terminated ventricular tachycardia which degenerated to ventricular fibrillation after antitachycardia pacing, and in the second case, a shock therapy was delivered due to VF in a 59-year-old male with HF and concomitant paroxysmal AF, who was on chronic treatment with warfarin.

Conclusions

Our findings indicate an overall low risk of stroke associated with ICD shocks, both in patients with and without AF.Baseline population characteristicsAnalysed population flowchart
Incidence and predictors of heart failure events following cardiac surgery in patients with atrial fibrillation - insights from the LAAOS-III trial
Authors: Xing L Y , Whitlock R , Belley-Cote E , Mcintyre W F , Paparella D , Svendsen J H , Diederichsen S Z , Brady K , Connolly S , Wong J , Conen D , Johnson L , Healey J S
Published: May 2024

Background

Atrial fibrillation (AF) is a common comorbidity in patients undergoing cardiac surgery and further increases the risk of incident heart failure (HF). However, only limited data exist on HF events following surgery in patients with AF.

Methods

The Left Atrial Appendage Occlusion Study (LAAOS) III was a randomized trial evaluating concomitant left atrial appendage occlusion in patients with AF undergoing cardiac surgery. In this secondary analysis, we aimed to identify independent predictors of the composite outcome of HF hospitalization or HF-related death following discharge, using a multivariable Cox model – incorporating sex, age (≥65 vs <65 years), systolic blood pressure (≤140 vs >140 mmHg), body mass index (BMI; <25 vs 25-29.9 vs ≥30 kg/m2), diabetes mellitus (DM), prior HF diagnosis, prior stroke, ischemic heart disease (IHD), heart valve surgery, AF history duration, rhythm on discharge electrocardiogram, and trial allocation. Supplementary analyses were undertaken to further assess the continuous variables using cubic spline regression.

Results

Of 4770 patients enrolled, in-hospital death occurred in 201 (4.2%) and complete discharge data were available for 4564 (95.7%). During a median follow up of 3.9 years, 533 (11.7%) of 4564 patients were hospitalized for HF. In total, 873 (19.1%) died after discharge, including 95 HF-related deaths. The composite outcome of HF hospitalization or HF-related death occurred at an annualized event rate of 3.31%/year [95% confidence interval: 3.04-3.60]. The independent risk factors included age (event rate of 3.64%/year vs 2.03%/year for ≥65 vs <65 years; hazard ratio (HR) 1.71 [1.32-2.21]), DM (4.71%/year vs 2.71%/year for with vs without DM; HR 1.59 [1.34-1.90]), prior HF diagnosis (4.27%/year vs 2.17%/year for with vs without HF; HR 2.00 [1.66-2.41]), IHD (3.63%/year vs 2.85%/year for with vs without IHD; HR 1.26 [1.03-1.54]), AF history duration (3.81%/year vs 2.89%/year for >2 vs <0.5 years; HR 1.23 [1.01-1.50]), and AF rhythm at discharge (3.87%/year vs 2.68%/year for AF vs non-AF rhythm; HR 1.31 [1.09-1.58]). The supplementary spline analyses further revealed a positive correlation between BMI and the risk of the composite outcome (p-value 0.042).

Conclusions

In patients with AF undergoing cardiac surgery, post-discharge HF hospitalization and HF-related death occurred at a rate of 3.31% per year. Our study identified several significant risk factors including advanced age, higher BMI, DM, prior HF diagnosis, IHD, AF history >2 years, and AF rhythm at discharge.The associations of HF with age and BMI
A novel score predictor for atrial fibrillation in cardiac implantable electronic device patients
Authors: Jaroonpipatkul S , Sathapanasiri T , Pokawattana A , Navaravong L
Published: May 2024

Background

Atrial fibrillation (AF) in individuals with cardiac implantable electronic devices is associated with heightened risks of adverse outcomes. Despite this, risk stratification for AF development in this patient cohort remains unexplored. Consequently, we present the development and validation of a simplified multi-parameter risk-based scoring system for predicting AF in patients with cardiac implantable electronic devices.

Methods and Results

A cohort of 226 consecutive patients with cardiac implantable electronic devices at Rajavithi Hospital underwent comprehensive follow-up to observe AF development, defined by 12-lead EKG evidence of AF. Analysis encompassed risk factors and AF incidence. The resulting V-DASH score integrated a History of vascular disease, including coronary artery disease (CAD) and peripheral arterial disease (PAD) (1.5 points), Diabetes (1 point), Apical lead position (1 point), Sex (female gender (1.5 points)), and Hypertension (1 point). Predictive value assessment revealed that Diabetes, Female gender, and a history of vascular disease were significantly associated with AF incidence. Apical lead position and Hypertension emerged as robust risk factors for AF development.

Over a median follow-up duration of 13 months, 8 (3.53%) patients developed AF. The incidence of AF exhibited a noteworthy escalation in correlation with the V-DASH score (4.68 times higher risk per point increase). Among patients with a V-DASH score ≥4, the probability of AF occurrence was 97.34%. The V-DASH score demonstrated exceptional predictive capability (area under the curve, 0.90; 95% CI, 0.79–1.00), calibration ability (Hosmer-Lemeshow goodness-of-fit P=0.552), and accuracy (sensitivity 87.50% and specificity 83.94%), surpassing other clinical scores such as the C2HEST score.

Conclusions

The V-DASH score emerged as a robust predictor of AF incidence in patients with cardiac implantable electronic devices, with the highest risk observed in those with a V-DASH score ≥4. The potential clinical utility of the V-DASH score in this patient population warrants further investigation.ROC curve for predicting AFPerformance calibration plot
The correlation between left atrium voltage mapping and 3D late gadolinium enhancement cardiac magnetic resonance imaging findings in patients with known atrial fibrillation
Authors: Dadon Z , Saadon Weinshtock M , Michowitz Y , Tovia-Brodie O , Tam D , Ilan M , Zabern M , Glikson M , Rav Acha M , Wolak A
Published: May 2024

Introduction

The non-invasive cardiac magnetic resonance imaging-based late gadolinium enhancement (LGE-CMR) of the left atrium (LA) fibrosis distribution and degree can be utilized for preprocedural planning and real-time guidance of AF ablation. There is an ongoing discussion with somewhat conflicting results regarding the accuracy of LGE-CMR of the LA as compared with the invasive electroanatomical mapping (EAM). Earlier data mainly encompassed post-ablation patients with an EAM involving a relatively small number of acquired points.

Aim

To evaluate the accuracy of LGE-CMR-based LA fibrosis using the ADAS 3D LA software among ablation-naive AF patients as compared with EAM using the CARTO-3 navigation system.

Methods

Patients with non-permanent AF, naive to previous ablation/cardiac surgery, who underwent CARTO-based AF ablation with preceding LGE-CMR scan were selected for the study. The 3D substrate atrial maps were generated based on the LGE-CMR (CMR-fib) using the ADAS 3D LA software and the CARTO EAM (EAM-fib). A fibrosis threshold of 1.2-1.32 was established for the CMR-fib using the Image Intensity Ratio whereas a threshold of 0.2-0.5mV was applied for the EAM-fib. The two 3D-maps were assessed for fibrosis using anatomically synchronized quantitative point by point comparison. The EAM was set as the gold standard.

Results

The study included 26,777 points acquired from 17 patients (aged 65.8±7.92 yrs with 6 females and 10 paroxysmal AF cases). CMR-fib showed 22.0% of LGE, while the EAM-fib demonstrated 48.8% of low voltage areas. The CMR-fib vs. EAM-fib point by point comparison concluded with an agreement of 73.1% and interrater reliability of 0.45 (p<0.001). The sensitivity and specificity were 45.0% and 99.9%, respectively, while the PPV and NPV were 99.8% and 65.6%, respectively. The Area Under the Curve (AUC) was calculated as 72.4.

Increase of the EAM-fib threshold for scar (to 0.5-1.5mV) led to a further decrease in the assessment diagnostic performance and the interrater reliability. The lowest agreement was tested in the LA roof segments and the higher in the inferoseptal and posterior walls.

Conclusion

The LGE-CMR underestimates the presence of scar as presented by the EAM, however, those detected are mostly accurate. The low sensitivity that was demonstrated between the two methods may be attributed to the lower spatial resolution of the CMR as well as the superficial subendocardial layer mapped by EAM as compared with the averaged transmural mapping of the CMR-fib. A follow-up larger-scale study is required to assess the accuracy of LGE-CMR-based assessment of fibrosis, considering various wall thicknesses and establishing the scar threshold on the ADAS software, particularly for ablation-naive patients.
Improvement in atrial functional and ventricular functional tricuspid regurgitation following catheter ablation or cardioversion of atrial fibrillation
Authors: Kuru B , Gerede Uludag D M , Baskowski E , Akyurek O , Altin T , Candemir B , Dumlupinar E
Published: May 2024

Background

The majority of cases of significant tricuspid regurgitation (TR) are secondary to tricuspid annular dilation and leaflet tethering in the context of RV remodeling due to pressure or volume overload, as seen in patients with pulmonary hypertension (primary or secondary to left-sided heart disease) or dilated cardiomyopathies. Secondary TR induced by tricuspid valve annular dilatation secondary to right atrial dilatation is referred to as atrial functional TR, while secondary TR caused by RV remodeling is referred to as ventricular functional TR. In current guidelines, GDMT (Guideline-Directed Medical Therapy) is effective for secondary TR attributable to HF with reduced LVEF. Normal sinus rhythm should be restored for secondary TR caused by AF-related annular dilatation. In patients with ventricular functional TR, however, AF may also accompany the clinical condition. It is unknown whether restoring sinus rhythm will reduce tricuspid regurgitation in these patients.

Purpose

The objective of this study was to investigate the degree of tricuspid regurgitation change in patients with atrial and ventricular functional tricuspid regurgitation after sinus rhythm restoration.

Methods

A retrospective cohort study of patients undergoing AF ablation and cardioversion at a single center between 2019 and 2023 was performed. Patients with at least grade 1 TR on echocardiography and a baseline echocardiogram and a follow-up echocardiogram after ablation were included. A-FTR and V-FTR were defined according to the latest ACC/AHA guidelines. According to the latest guidelines, patients with mild to severe FTR were classified as A-FTR if they had atrial fibrillation, left ventricular ejection fraction >60%, pulmonary artery systolic pressure (PASP) <50 mm Hg, no left-sided valve disease, and normal-appearing tricuspid leaflets. FTR patients who did not meet at least one of these three criteria were defined as ventricular FTR (V-FTR).

Results

A total of 88 patients were enrolled. The prevalence of A-FTR in our cohort was 62% (53 patients), and 38% of the patients were in the V-FTR group. There was no significant difference between the A-FTR and V-FTR groups regarding age, gender, and NYHA class. 21 of the patients underwent DCCV, and 67 underwent catheter ablation. The prevalence of severe FTR was similar (%17 in A-FTR vs. %8,6 in V-FTR, p= 0.205). There was no difference in preintervention TR grade between the two groups. TR severity improved significantly from baseline to follow-up in both V-FTR and A-FTR patients. These outcomes were observed in patients who underwent both DCCV and catheter ablation.

Conclusion

The degree of tricuspid regurgitation is reduced with sinus rhythm restoration in patients with both ventricular functional and atrial functional TR.Changes in TR severity with interventionGraph of changes in severity of TR