Imaging and atrial fibrillation: A new paradigm for precision targeting of AF?
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ABSTRACT:
SUBMITTER: Chung MK
PROVIDER: S-EPMC8417787 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BACKGROUND:Atrial fibrillation represents the most common arrhythmia leading to increased morbidity and mortality, yet, current treatment strategies have proven inadequate. Conventional treatment with antiarrhythmic drugs carries a high risk for proarrhythmias. The soluble epoxide hydrolase enzyme catalyzes the hydrolysis of anti-inflammatory epoxy fatty acids, including epoxyeicosatrienoic acids from arachidonic acid to the corresponding proinflammatory diols. Therefore, the goal of the study is to directly test the hypotheses that inhibition of the soluble epoxide hydrolase enzyme can result in an increase in the levels of epoxyeicosatrienoic acids, leading to the attenuation of atrial structural and electric remodeling and the prevention of atrial fibrillation. METHODS AND RESULTS:For the first time, we report findings that inhibition of soluble epoxide hydrolase reduces inflammation, oxidative stress, atrial structural, and electric remodeling. Treatment with soluble epoxide hydrolase inhibitor significantly reduces the activation of key inflammatory signaling molecules, including the transcription factor nuclear factor ?-light-chain-enhancer, mitogen-activated protein kinase, and transforming growth factor-?. CONCLUSIONS:This study provides insights into the underlying molecular mechanisms leading to atrial fibrillation by inflammation and represents a paradigm shift from conventional antiarrhythmic drugs, which block downstream events to a novel upstream therapeutic target by counteracting the inflammatory processes in atrial fibrillation.
| S-EPMC4869994 | biostudies-literature
Project description:IntroductionA multidisciplinary approach is needed for the management of atrial fibrillation (AF) in which the patient has a central role. Smart devices create opportunities to improve AF management. This paper aimed to evaluate the in-house developed AF-EduApp application on its usability, satisfaction, and communication effectiveness with the care team.MethodsDuring a multicenter, prospective randomized controlled trial, 153 AF patients were included in the AF-EduApp study, with a minimum follow-up of 12 months and a maximum follow-up of 15 months if taking oral anticoagulation (OAC). The AF-EduApp contains six main modules: Questionnaires, Education, Measurement data entry, Medication overview with reminders, Appointments, and Communication with the care team. The App focuses on four main goals: (1) to improve AF knowledge, (2) to increase self-care capabilities, (3) electronic monitoring to improve therapy adherence to OAC, and (4) communication with the care team. Patients unable to use the AF-EduApp were assigned to a no-App control group (n = 41) without intervention comparable to the standard care group (SC, n = 346) of the AF-EduCare study.ResultsA total of 152 patients effectively used the App during a mean follow-up of 386.8 ± 108. 1 days (one included patient could not install the application due to an iPhone from the United States). They opened the application on average on 130.1 ± 144.7 days. Of the 109 patients still in follow-up after 12 months (i.e. patients who did not withdraw and on OAC), 90 patients (82.6%) actively used the application at least one day in the next 41 days. The Measurement module was the most used, with a median of used days over the total available days of 6.4%. A total of 75 App patients (49.3%) asked questions, mostly clinical-related questions (e.g. medication use, or actionability on clinical entered parameters). A mean score of 8.1 ± 1.7 about the "perceived quality of follow-up in the past year" was given by the App ITT patients, compared to a score of 7.7 ± 2.0 by the SC group (P = .072). Patients who used the App were more attracted to future follow-up with an application compared to patients who would be capable of using the application of the SC group (31.6% vs. 12.5%; P < .001).ConclusionThis study showed a positive attitude towards using a mobile application, with AF patients using the application one-third of the available days. Patients used the App most for entering measured parameters, and to contact the care team.
| S-EPMC10562600 | biostudies-literature
Project description:Our study aims to illustrate the potential use of atrial iPSC-CMs for modeling AF in a dish, elucidating the underlying cellular mechanisms, and identifying novel mechanism-based therapies custom-tailored for individual patients
2021-06-16 | GSE154084 | GEO
Project description:Atrial fibrillation (AF), the most common cardiac arrhythmia, is a major contributor to population mortality and morbidity. The goal of this study is to explore molecular mechanisms of the AF-induced profibrotic remodelling in human atrial fibroblasts (ACFs). Specifically, we assessed single-cell transcriptome of cultured human ACFs treated with calcitonin(CT) or vehicle (from 6 individual patients) and of freshly-isolated ACFs from patients with AF (4 individual patients) vs controls (4 individual patients) (SR). We found that ACF transcriptome was unaltered by CT in cultured ACFs, and identified 5 transcriptional clusters with 23 differentially expressed transcripts in AF in freshly-ioslated ACFs.
2020-07-10 | GSE148506 | GEO
Project description:Atrial fibrillation (AF), the most common cardiac arrhythmia, is a major contributor to population mortality and morbidity. The goal of this study is to explore molecular mechanisms of the AF-induced profibrotic remodelling in human atrial fibroblasts (ACFs). Specifically, we assessed single-cell transcriptome of cultured human ACFs treated with calcitonin(CT) or vehicle (from 6 individual patients) and of freshly-isolated ACFs from patients with AF (4 individual patients) vs controls (4 individual patients). We found that ACF transcriptome was unaltered by CT in cultured ACFs, and identified 5 transcriptional clusters with 23 differentially expressed transcripts in AF in freshly-ioslated ACFs.
2020-07-10 | GSE148504 | GEO
Project description:AimsThe complex relationship between left atrial (LA) structure and function, electrical burden of atrial fibrillation (AF) and stroke risk is not well understood. We aimed to describe LA structure and function in AF.Methods and resultsLeft atrial structure and function was assessed in 971 subjects enrolled in the echocardiographic substudy of ENGAGE AF-TIMI 48. Left atrial size, emptying fraction (LAEF), and contractile function were compared across AF types (paroxysmal, persistent, or permanent) and CHADS2 scores as an estimate of stroke risk. The majority of AF patients (55%) had both LA enlargement and reduced LAEF, with an inverse relationship between LA size and LAEF (R = -0.57, P < 0.001). With an increasing electrical burden of AF and higher CHADS2 scores, LA size increased and LAEF declined. Moreover, 19% of AF subjects had impaired LAEF despite normal LA size, and LA contractile dysfunction was present even among the subset of AF subjects in sinus rhythm at the time of echocardiography.ConclusionsIn a contemporary AF population, LA structure and function were increasingly abnormal with a greater electrical burden of AF and higher stroke risk estimated by the CHADS2 score. Moreover, LA dysfunction was present despite normal LA size and sinus rhythm, suggesting that the assessment of LA function may add important incremental information in the evaluation of AF patients.Clinical trial registrationhttp://www.clinicaltrials.gov; ID = NCT00781391.
| S-EPMC4048534 | biostudies-literature
Project description:BackgroundGenomewide association studies have identified several loci associated with atrial fibrillation (AF) and have been reportedly associated with response to catheter ablation for AF in patients of European ancestry; however, associations between top susceptibility loci and AF recurrence after ablation have not been examined in Asian populations. We examined whether the top single nucleotide polymorphisms (SNPs) at chromosomes 4q25 (PITX2), 16q22 (ZFHX3), and 1q21 (KCNN3) were associated with AF in a Korean population and whether these SNPs were associated with clinical outcomes after catheter ablation for AF.Methods and resultsWe determined the association between 4 SNPs and AF in 1068 AF patients who underwent catheter ablation (74.6% male, aged 57.5±10.9 years, 67.9% paroxysmal AF) and 1068 age- and sex-matched controls. The SNPs at the PITX2 and ZFHX3 loci, but not the KCNN3 locus, were significantly associated with AF (PITX2/rs6843082_G: odds ratio 3.41, 95% CI 2.55 to 4.55, P=1.32×10(-16); PITX2/rs2200733_T: odds ratio 2.05, 95% CI 1.66 to 2.53, P=2.20×10(-11); ZFHX3/rs2106261_A: odds ratio 2.33, 95% CI 1.87 to 2.91, P=3.75×10(-14); KCNN3/rs13376333_T: odds ratio 1.74, 95% CI 0.93 to 3.25, P=0.085). Among those patients who underwent catheter ablation for AF, none of the top AF-associated SNPs were associated with long-term clinical recurrence of AF after catheter ablation.ConclusionsSNPs at the PITX2 and ZFHX3 loci were strongly associated with AF in Korean patients. In contrast to prior reports, none of the 4 top AF-susceptibility SNPs predicted clinical recurrence after catheter ablation.
| S-EPMC4599462 | biostudies-literature
Project description:IntroductionDigital technology creates the opportunity to develop and evaluate new tools, such as smartphone applications, to support integrated atrial fibrillation management. This study aimed to develop, evaluate, and validate a new, integrated care application (AF-EduApp) mainly focusing on targeted atrial fibrillation education to improve patient self-care capabilities and therapy adherence.MethodsThe newly developed AF-EduApp, available for Android and iOS, consists of six different modules. The prototype was validated and optimized for its usability and functionality at Jessa Hospital Hasselt and Antwerp University Hospital in two phases: (1) validity evaluation with interviews of an expert panel with 15 healthcare professionals and 10 atrial fibrillation patients, and (2) a pilot study of 1 month with 20 atrial fibrillation patients.ResultsBoth experts and patients found that the application aids atrial fibrillation management. Based on the input of patients and experts, the main optimizations concerned the medication module (patient choice on setting reminder; interactivity of reminders with a "taken" or "snooze" function) and development of a clinical dashboard for the caregivers allowing telemonitoring of measurements and feedback to the patients. After the pilot study (n = 20), 16 patients indicated they wanted to use the app for a longer period. The measurement (27%) and education (17%) modules were the two most used modules with a significant improvement in knowledge (71.9% to 87.5%; P = 0.013).DiscussionThe AF-EduApp received a positive evaluation from health professionals and atrial fibrillation patients. Further development should be focused on the medication module and improvement of the clinical dashboard.
| S-EPMC8725214 | biostudies-literature
Project description:IntroductionAtrial fibrillation (AF) is a major cardiovascular health problem: it is common, chronic and incurs substantial healthcare expenditure because of stroke. Oral anticoagulation reduces the risk of thromboembolic stroke in those at higher risk; but for a number of patients, stroke is the first manifestation of undetected AF. There is a rationale for the early diagnosis of AF, before the first complication occurs, but population-based screening is not recommended. Previous prediction models have been limited by their data sources and methodologies. An accurate model that uses existing routinely collected data is needed to inform clinicians of patient-level risk of AF, inform national screening policy and highlight predictors that may be amenable to primary prevention.Methods and analysisWe will investigate the application of a range of deep learning techniques, including an adapted convolutional neural network, recurrent neural network and Transformer, on routinely collected primary care data to create a personalised model predicting the risk of new-onset AF over a range of time periods. The Clinical Practice Research Datalink (CPRD)-GOLD dataset will be used for derivation, and the CPRD-AURUM dataset will be used for external geographical validation. Both comprise a sizeable representative population and are linked at patient-level to secondary care databases. The performance of the deep learning models will be compared against classic machine learning and traditional statistical predictive modelling methods. We will only use risk factors accessible in primary care and endow the model with the ability to update risk prediction as it is presented with new data, to make the model more useful in clinical practice.Ethics and disseminationPermissions for CPRD-GOLD and CPRD-AURUM datasets were obtained from CPRD (ref no: 19_076). The CPRD ethical approval committee approved the study. The results will be submitted as a research paper for publication to a peer-reviewed journal and presented at peer-reviewed conferences.Trial registration detailsA systematic review to incorporate within the overall project was registered on PROSPERO (registration number CRD42021245093). The study was registered on ClinicalTrials.gov (NCT04657900).
| S-EPMC8565546 | biostudies-literature
Project description:ObjectivesThe CArdioSurgEry Atrial Fibrillation (CASE-AF) registry is a prospective, multicentre study for collecting and analysing real-world data of surgical atrial fibrillation (AF) treatment. This study aimed to evaluate outcomes of surgery for long-standing persistent AF at 1 year.MethodsIn total, 17 centres consecutively include all eligible patients with continuous AF lasting for ≥1 year. Exclusion criteria are missing informed consent or age <18 years. For patient-reported outcomes measures, the European Heart Rhythm Association score was used. No presence of AF (based on ECG findings including Holter ECG and/or implanted devices), no re-ablation, no further cardioversion and no rehospitalization due to AF after a 3-month blanking period defined no AF recurrence at 1 year.ResultsFrom January 2017 to January 2020, a total of 1115 patients were enrolled in CASE-AF. Of them, 202 patients (mean age 69.7 ± 7.8 years, 27.2% female) underwent surgical ablation of long-standing persistent AF (study cohort), mostly accompanied by left atrial appendage closure (n = 180 [89%], resection n = 75 [42%]) and predominantly performed as concomitant (n = 174 [86%]) and left atrial only procedure (n = 144 [71%]). Early mortality (30 days) was 2.0% and morbidity was low. At follow-up (median 14.4 months, interquartile range, 12.7-17.6 months, 100% complete), 106 patients (56%) had no AF recurrence and 93% of them were asymptomatic. AF recurrence was accompanied by AF-related rehospitalization (n = 12, P = 0.003), direct current shock cardioversion (n = 23, P < 0.001), AF ablation (n = 7, P = 0.003) and stroke (n = 3, P = 0.059). Multivariable analysis identified cryoablation, predominantly performed endocardially including additional left atrial (74%) and biatrial (42%) lesions, as a significant factor for freedom from AF recurrence (odds ratio 2.7, 95% confidence interval 1.07-6.79, P = 0.035).ConclusionsAccording to CASE-AF, surgical ablation of long-standing persistent AF is most effective when concomitantly performed using endocardial cryoablation. Ongoing follow-up allows further elucidation of efficacious treatment strategies.
| S-EPMC10749739 | biostudies-literature