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Chronic kidney disease (CKD) represents a significant global health challenge, characterized by kidney damage and decreased function. Its prevalence has steadily increased, necessitating a comprehensive understanding of its epidemiology, risk factors, and management strategies. While traditional prognostic markers such as estimated glomerular filtration rate (eGFR) and albuminuria provide valuable insights, they may not fully capture the complexity of CKD progression and associated cardiovascular (CV) risks.This paper reviews the current state of renal and CV risk prediction in CKD, highlighting the limitations of traditional models and the potential for integrating artificial intelligence (AI) techniques. AI, particularly machine learning (ML) and deep learning (DL), offers a promising avenue for enhancing risk prediction by analyzing vast and diverse patient data, including genetic markers, biomarkers, and imaging. By identifying intricate patterns and relationships within datasets, AI algorithms can generate more comprehensive risk profiles, enabling personalized and nuanced risk assessments.Despite its potential, the integration of AI into clinical practice faces challenges such as the opacity of some algorithms and concerns regarding data quality, privacy, and bias. Efforts towards explainable AI (XAI) and rigorous data governance are essential to ensure transparency, interpretability, and trustworthiness in AI-driven predictions.
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BACKGROUND: The subcutaneous implantable cardioverter-defibrillator (S-ICD) has emerged as an alternative to transvenous systems for prevention of sudden cardiac death. However, concerns have been raised regarding its efficacy and safety in obese individuals. OBJECTIVE: The purpose of this study was to perform a meta-analysis to evaluate the efficacy and safety of the S-ICD in patients with obesity by assessing the relationship between body mass index (BMI) and clinical outcomes. METHODS: A comprehensive search of multiple databases was conducted for English-language peer-reviewed studies reporting clinical outcomes in S-ICD recipients with (BMI ≥30 kg/m2) and without obesity (BMI <30 kg/m2). Data on preimplantation screening failure, defibrillation testing, complications, appropriate and inappropriate shocks, and survival were analyzed using standard, random-effects, meta-analytical techniques. RESULTS: Twenty-nine studies involving 20,486 patients were included. There was no statistically significant difference in mean BMI values of patients with failed or successful preimplantation screening (mean difference -0.60 kg/m2; 95% confidence interval [CI] -2.06 to 0.86). Obesity was associated with higher rates of failed defibrillation testing at ≤65 J (odds ratio [OR] 2.16; 95% CI 1.39-3.35), and malpositioning/suboptimal positioning occurred more frequently in obese compared to nonobese patients (OR 3.37; 95% CI 1.76-6.44). Increased BMI as a continuous variable (per increase in 1 kg/m2 BMI) was associated with elevated defibrillation thresholds (OR 1.05; 95% CI 1.03-1.08); higher risk of complications (hazard ratio [HR] 1.04; 95% CI 1.02-1.05); a trend toward an increased number of appropriate shocks (HR 1.02; 95% CI 1.00-1.04); and no significant increase in the risk of inappropriate shocks (HR 1.01; 95% CI 0.99-1.03). CONCLUSION: This meta-analysis underscores the importance of considering obesity in S-ICD implantation decisions. Although S-ICD remains effective in obese patients, attention to potential technical challenges and higher complication rates is warranted.
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BACKGROUND: To preserve the benefit of atrial sensing without the implantation of an additional lead, a single-lead ICD system with a floating atrial dipole (DX ICD) has been developed. The purpose of this nationwide survey was to provide an overview of the current key influences of device selection focusing on DX ICD and to test the applicability of a previously published decision-making flowchart of ICD-type selection. METHODS: An online questionnaire was sent to all implanting centers in Hungary. Eleven centers reported data from 361 DX ICD and 10 CRT-DX systems implantations between February 2021 and May 2023. RESULTS: The most important influencing clinical factors indicated by the participating doctors were elevated risk of atrial fibrillation (AF)/stroke (56%), risk of sinus/supraventricular tachycardias (SVT) (42%), and a potential need for CRT upgrade in the future (36%). The DX ICD was considered in the majority of cases instead of the VVI system (87%), and only in a small proportion instead of a DDD ICD (13%). 60% of the patients with DX ICDs were also included into remote monitoring-based follow-up. In 83% of the cases, good (>2 mV) or excellent (>5) atrial signal amplitude was recorded within 6 weeks after the implantation. CONCLUSION: In the current national survey, the most important influencing factors indicated by the implanters for selecting a DX ICD were the elevated risk of stroke or sinus/SVT and a potential need for CRT upgrade in the future. These findings support the use of a previously published decision-making flowchart.
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Desfibriladores Implantables , Humanos , Estudios Prospectivos , Encuestas y Cuestionarios , Masculino , Femenino , Hungría , Fibrilación Atrial , Anciano , Persona de Mediana EdadRESUMEN
BACKGROUND: Electrographic flow (EGF) mapping enables full spatiotemporal reconstruction of organized wavefront propagation to identify extrapulmonary vein sources of atrial fibrillation (AF). OBJECTIVES: FLOW-AF (A Randomized Controlled Study to Evaluate the Reliability of the Ablacon Electrographic FLOW [EGF] Algorithm Technology [Ablamap Software] to Identify AF Sources and Guide Ablation Therapy in Patients With Persistent Atrial Fibrillation) was multicenter, randomized controlled study of EGF mapping to: 1) stratify a nonparoxysmal AF population undergoing redo ablation; 2) guide ablation of these extrapulmonary vein AF sources; and 3) improve AF recurrence outcomes. METHODS: FLOW-AF enrolled persistent atrial fibrillation (PerAF)/long-standing PerAF patients undergoing redo ablation at 4 centers. One-minute EGF maps were recorded from standardized biatrial basket positions. Patients with source activity ≥26.5% were randomized 1:1 to PVI + EGF-guided ablation vs PVI only; patients without sources ≥26.5% threshold were not randomized. Follow-up and electrocardiographic monitoring occurred at 3, 6, and 12 months. RESULTS: We enrolled 85 patients (age 65.6 ± 9.3 years, 37% female, 24% long-standing PerAF). Thirty-four (40%) patients had no sources greater than threshold; at least 1 source greater than threshold was present in 46 (60%) (EGF-guided ablation, n = 22; control group, n = 26). Patients with sources were older (68.2 vs 62.6 years; P = 0.005) with higher CHA2DS2-VASc scores (2.8 vs 1.9; P = 0.001). The freedom from safety events was 97.2%, and 95% of EGF-identified sources were successfully ablated. In randomized patients, AF-free survival at 12 months was 68% for EGF-guided ablation vs 17% for the control group (P = 0.042); freedom from AF/atrial tachycardia/atrial flutter at 12 months was 51% vs 14% (P = 0.103), respectively. CONCLUSIONS: In nonparoxysmal AF patients undergoing redo ablation, EGF mapping identified AF sources in 60% of patients, and could be successfully ablated in 95%. Compared with PVI alone, PVI + source ablation improved AF-free survival by 51% on an absolute basis. (FLOW-AF: A Study to Evaluate the Ablacon Electrographic FLOW EGF Technology [A Randomized Controlled Study to Evaluate the Reliability of the Ablacon Electrographic FLOW (EGF) Algorithm Technology (Ablamap Software) to Identify AF Sources and Guide Ablation Therapy in Patients With Persistent Atrial Fibrillation]; NCT04473963).
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Members of the family Trichomeriaceae, belonging to the Chaetothyriales order and the Ascomycota phylum, are known for their capability to inhabit hostile environments characterized by extreme temperatures, oligotrophic conditions, drought, or presence of toxic compounds. The genus Knufia encompasses many polyextremophilic species. In this report, the genomic and morphological features of the strain FJI-L2-BK-P2 presented, which was isolated from the Mars 2020 mission spacecraft assembly facility located at the Jet Propulsion Laboratory in Pasadena, California. The identification is based on sequence alignment for marker genes, multi-locus sequence analysis, and whole genome sequence phylogeny. The morphological features were studied using a diverse range of microscopic techniques (bright field, phase contrast, differential interference contrast and scanning electron microscopy). The phylogenetic marker genes of the strain FJI-L2-BK-P2 exhibited highest similarities with type strain of Knufia obscura (CBS 148926T) that was isolated from the gas tank of a car in Italy. To validate the species identity, whole genomes of both strains (FJI-L2-BK-P2 and CBS 148926T) were sequenced, annotated, and strain FJI-L2-BK-P2 was confirmed as K. obscura. The morphological analysis and description of the genomic characteristics of K. obscura FJI-L2-BK-P2 may contribute to refining the taxonomy of Knufia species. Key morphological features are reported in this K. obscura strain, resembling microsclerotia and chlamydospore-like propagules. These features known to be characteristic features in black fungi which could potentially facilitate their adaptation to harsh environments.
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Ascomicetos , Marte , Filogenia , Nave Espacial , Ascomicetos/genética , Ascomicetos/clasificación , Ascomicetos/aislamiento & purificación , Genoma Fúngico/genética , Genómica/métodosRESUMEN
(1) Background: Early reintervention increases the risk of infection of cardiac implantable electronic devices (CIEDs). Some operators therefore delay lead repositioning in the case of dislocation by weeks; however, there is no evidence to support this practice. The aim of our study was to evaluate the impact of the timing of reoperation on infection risk. (2) Methods: The data from consecutive patients undergoing lead repositioning in two European referral centers were retrospectively analyzed. The odds ratio (OR) of CIED infection in the first year was compared among patients undergoing early (≤1 week) vs. delayed (>1 week to 1 year) reoperation. (3) Results: Out of 249 patients requiring CIED reintervention, 85 patients (34%) underwent an early (median 2 days) and 164 (66%) underwent a delayed lead revision (median 53 days). A total of nine (3.6%) wound/device infections were identified. The risk of infection was numerically lower in the early (1.2%) vs. delayed (4.9%) intervention group yielding no statistically significant difference, even after adjustment for typical risk factors for CIED infection (adjusted OR = 0.264, 95% CI 0.032-2.179, p = 0.216). System explantation/extraction was necessary in seven cases, all being revised in the delayed group. (4) Conclusions: In this bicentric, international study, delayed lead repositioning did not reduce the risk of CIED infection.
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Introduction: Despite numerous investigations into the impact of drugs/probiotics on the gut microbiota composition in Familial Mediterranean Fever (FMF) patients, the question as to whether there exists a significant bacterial diversity(ies) independent of the placebo effect that can be reliably considered in clinical and nutritional trials remains unresolved. Methods: This study represents the in augural analysis of the placebo's influence on the gut microbiota of both healthy individuals and FMF afflicted men, utilizing previously collected data from PhyloChip™ DNA microarray experiments. A total of 15 healthy and 15 FMF male volunteers, aged 18 to 50, participated in this partially randomized placebo trial, which is accessible through the GEO Series accession number GSE111835. Results and Discussion: Key findings from current investigations include i. the anticipated divergence in gut bacteria resistance to placebo between healthy and FMF individuals, ii. the minor impact of placebo on gut bacterial diversities in healthy individuals, with Enterobacteriaceae diversities identified as placebo-resistant among "healthy" gut bacteria, and iii. the comprehensive influence of placebo on all bacterial phyla in the gut microbiome of FMF patients, extending to nearly all bacterial genera, except for the resilience of gut Akkermansia muciniphila spp. to placebo in FMF patients. This study underscores the susceptibility of Faecalibacterium, Blautia, and Clostridium genera to placebo. Consequently, this investigation holds significance for the proper design of placebo-controlled trials and establishes a foundation for further exploration of the gut-brain axis. Furthermore, it contributes valuable insights to discussions regarding proposals for probiotic therapies, particularly focusing on Faecalibacterium spp., Blautia spp., and Clostridium spp.
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Fiebre Mediterránea Familiar , Microbioma Gastrointestinal , Probióticos , Humanos , Masculino , Akkermansia , Bacterias , Fiebre Mediterránea Familiar/tratamiento farmacológico , Fiebre Mediterránea Familiar/microbiología , Probióticos/farmacología , Adolescente , Adulto Joven , Adulto , Persona de Mediana EdadRESUMEN
BACKGROUND: The use of an antibacterial envelope is cost-effective for patients at high risk of developing cardiac implantable electronic device (CIED) infection. The identification of these high-risk patients may be facilitated using a clinical risk score. The aim of the current study is to evaluate the PADIT score for identifying high-risk patients in patients undergoing a CIED procedure in a tertiary academic center. METHODS: This was a retrospective single-center study of consecutive patients undergoing a CIED procedure between January 2016 and November 2021. Patients who received an antibacterial envelope were excluded from this study. The primary endpoint was hospitalization for a CIED infection in the first year after the procedure. RESULTS: A total of 2333 CIED procedures were performed in the study period (mean age 61.6 ± 16.3 years, male sex 64.5%, previous CIED infection 1.7%, immunocompromised 5.4%). The median PADIT score was 4 (interquartile range, 2-6). CIED infection occurred in 10 patients (0.43%). The PADIT score had good discrimination in predicting major CIED infection (C-statistic 0.70; 95% confidence interval [CI] 0.54 to 0.86, P = 0.03). Using an optimal PADIT score cut-off value of 7, the risk of CIED infection was higher in the patients with a PADIT score of ≥ 7 in comparison to those with a lower PADIT score (1.23% vs. 0.26%, P = 0.02; odds ratio 4.8, 95% CI 1.4 to 16.6, P = 0.01). CONCLUSIONS: The PADIT score is a clinically useful score for identifying patients at high risk of developing CIED infection. The use of an antibacterial envelope in these high-risk patients may be cost-effective.
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BACKGROUND: Insulin resistance plays an important role in the development of post-transplantation diabetes mellitus (PTDM) in kidney transplant recipients (KTRs). Current methods for the direct determination of insulin resistance are complicated and invasive. Therefore, this study aimed to investigate the relevance of indirect insulin resistance indices in relation to the development of PTDM in KTRs. METHODS: We included 472 stable outpatient KTRs without diabetes at baseline from a prospective cohort study. Four indirect insulin resistance indices, namely homeostasis model assessment-insulin resistance (HOMA-IR), visceral adiposity index (VAI), lipid accumulation product (LAP), and triglycerides-glucose (TyG) index, were assessed. We analyzed each measure using the receiver operating characteristic (ROC) curve for PTDM development. The optimal cut-off value for each parameter was determined using the Youden index. RESULTS: After a median of 9.6 years (interquartile range (IQR) 6.6-10.2) of follow-up, 68 (14%) KTRs developed PTDM. In Cox regression analyses, all indirect insulin resistance indices associated with incident PTDM were independent of potential confounders. ROC curve was 0.764 (95% CI, 0.703-0.826) for HOMA-IR, 0.685 (95% CI, 0.615-0.757) for VAI, 0.743 (95% CI, 0.678-0.808) for LAP, and 0.698 (95% CI, 0.629-0.766) for TyG index, with respective optimal cut-off values of 2.47, 4.01, 87.0, and 4.94. CONCLUSIONS: Indirect insulin resistance indices can be used to predict incident PTDM in KTRs. In addition to HOMA-IR, insulin-free surrogates of insulin resistance might serve as useful methods to identify KTRs at risk of PTDM, thus obviating the necessity to measure insulin.
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BACKGROUND: Chronic limb-threatening ischemia (CLTI) is associated with high rates of long-term cardiovascular mortality. Exercise stress testing to detect obstructive coronary artery disease (CAD) can be difficult in this subset of patients due to inability to undergo exercise testing, presence of balanced ischemia and severe coronary artery calcification (CAC). AIM: To test the feasibility of regadenoson stress dynamic perfusion computed tomography (DPCT) in CLTI patients. METHODS: Between 2018 and 2023, coronary computed tomography angiography (CTA) and, in the case of a calcium score higher than 400, DPCT, were performed in 25 CLTI patients with a history of endovascular revascularization. RESULTS: Of the 25 patients, 19 had a calcium score higher than 400, requiring DPCT image acquisition. Obstructive CAD could be ruled out in 10 of the 25 patients. Of the 15 CTA/DPCT+ patients, 13 proceeded to coronary angiography (CAG). Revascularization was necessary in all 13 patients. In these 13 patients, vessel-based sensitivity and specificity of coronary CTA/DPCT as compared to invasive evaluation was 75%, respectively. At follow-up (27 ± 21 months) there was no statistically significant difference in all-cause mortality between CTA/DPCT- positive and -negative patients (p = 0.065). CONCLUSIONS: Despite a high prevalence of severe CAC, coronary CTA complemented by DPCT may be a feasible method to detect obstructive and functionally significant CAD in CLTI patients.
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Background: Accessory pathways (APs) with multiple atrial insertions are often unrecognized and associated with initial catheter ablation (CA) failure. Recently, a novel dipole charge density mapping (DCDM) system was developed that allows mapping of complex arrhythmias based on a single beat. We aim to present the first-in-human report of 3D visualization of a single AP with two atrial insertion sites using high-resolution DCDM. Case summary: A 43-year-old man with recurrent symptomatic atrioventricular re-entrant tachycardia and previously failed CA attempts underwent repeated CA using DCDM. Dipole charge density mapping identified two quasi-simultaneous early atrial activation sites at the left lateral and left anterolateral atrial aspects of the mitral annulus, suggesting the presence of a single AP with dual atrial insertion sites. Successful radiofrequency CA was performed at the mid-body of the AP. Discussion: The true prevalence of APs with multiple atrial insertion sites may be higher than currently reported. This is the first-in-human report of 3D visualization of a single AP with two atrial insertion sites using high-resolution DCDM. Dipole charge density mapping allows the accurate localization of APs with multiple insertion sites based on a single beat.
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INTRODUCTION: Pulmonary vein isolation (PVI) is a pivotal part of ablative therapy for atrial fibrillation (AF). Currently, there are multiple techniques available to realize PVI, including: manual-guided cryoballoon (MAN-CB), manual-guided radiofrequency (MAN-RF), and robotic magnetic navigation-guided radiofrequency ablation (RMN-RF). There is a lack of large prospective trials comparing contemporary RMN-RF with the more conventional ablation techniques. This study prospectively compared three catheter ablation techniques as treatment of paroxysmal AF. METHODS: This multicenter, prospective study included patients with paroxysmal AF who underwent their first ablation procedure. Procedural parameters (including procedural efficiency), complication rates, and freedom of AF during 12-month follow-up, were compared between three study groups which were defined by the utilized ablation technique. RESULTS: A total of 221 patients were included in this study. Total procedure time was significantly shorter in MAN-CB (78 ± 21 min) compared to MAN-RF (115 ± 41 min; p < .001) and compared to RMN-RF (129 ± 32 min; p < .001), whereas it was comparable between the two radiofrequency (RF) groups (p = .062). A 3% complication rate was observed, which was comparable between all groups. At 12-month follow-up, AF recurrence was observed in 40 patients (19%) and was significantly lower in the robotic group (MAN-CB 19 [24%], MAN-RF 16 [23%], RMN-RF 5 [8%] AF recurrences, p = .045) (multivariate hazard ratio of RMN-RF on AF recurrence 0.32, 95% confidence interval: 0.12-0.87, p = .026). CONCLUSION: RMN-guided PVI results in high freedom of AF in patients with paroxysmal AF, when compared to cryoablation and manual RF ablation. Cryoablation remains the most time-efficient ablation technique, whereas RMN nowadays has comparable efficiency with manual RF ablation.
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Fibrilación Atrial , Ablación por Catéter , Criocirugía , Venas Pulmonares , Procedimientos Quirúrgicos Robotizados , Humanos , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/cirugía , Ablación por Catéter/métodos , Criocirugía/métodos , Fenómenos Magnéticos , Estudios Prospectivos , Venas Pulmonares/cirugía , Recurrencia , Resultado del TratamientoRESUMEN
BACKGROUND: The presence of an untreated chronic total coronary occlusion (CTO) is associated with a higher risk of ventricular arrhythmias (VAs). This increased risk may be modulated by the presence of an existing scar. OBJECTIVES: To evaluate whether scar size is associated with VA in patients with an implantable cardioverter-defibrillator (ICD) and a CTO. METHODS: In this retrospective study we included patients with a CTO that received an ICD between 2005 and 2015. Scar size was estimated using the Selvester QRS score on a baseline 12lead ECG. The primary endpoint was any appropriate ICD therapy. RESULTS: Our study population comprised 148 CTO patients with a median scar size at baseline of 18% (IQR, 9-27%). Patients with a scar size ≥18% more often had a CTO located in the left anterior descending artery and a higher proportion of poor left ventricular function (<35%) and infarct-related CTO compared to patients with a smaller scar size (<18%). During a median follow-up of 35 months (interquartile range [IQR], 8-60 months), 42 patients (28%) received appropriate ICD therapy. The cumulative 5-year event rate was higher in the patients with a large scar in comparison to those with a smaller or no scar (36% versus 19%, P = 0.04). Multivariable Cox regression analysis demonstrated that large scar and diabetes mellitus were independent factors associated with appropriate ICD therapy. CONCLUSION: In ICD recipients with an untreated CTO, a larger scar is an independent factor associated with an increased risk of VA.
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Oclusión Coronaria , Desfibriladores Implantables , Humanos , Oclusión Coronaria/diagnóstico , Oclusión Coronaria/diagnóstico por imagen , Estudios Retrospectivos , Arritmias Cardíacas/diagnóstico , Arritmias Cardíacas/epidemiología , Arritmias Cardíacas/etiología , Desfibriladores Implantables/efectos adversos , Factores de Riesgo , Resultado del TratamientoRESUMEN
With rising incidence and prevalence of type 2 diabetes, prevention including identification of prospective biomarkers becomes increasingly relevant. Although ketone bodies recently received a renewed interest as potential biomarkers, data linking these metabolites to diabetes risk are scarce. Therefore, the present prospective study investigated a potential association between fasting ketone bodies and incident type 2 diabetes in the general population. This study from the PREVEND cohort included 3,307 participants from the general population initially free of diabetes or impaired fasting glucose. Baseline fasting ketone body concentrations were measured by nuclear magnetic resonance spectroscopy. One hundred twenty-six participants (3.8%) developed type 2 diabetes during a median (interquartile range) follow-up of 7.3 (6.3-7.6) years. In Kaplan-Meier analysis, sex-stratified ketone body levels strongly positively associated with incident type 2 diabetes, which was confirmed in Cox regression analyses adjusted for several potential confounders. There was no significant interaction by sex. Both 3-ß-hydroxybutyrate and acetoacetate+acetone individually associated with incident type 2 diabetes. In conclusion, fasting plasma ketone body levels are strongly positively associated with incident type 2 diabetes in the general population independent of several other recognized risk factors. These results may have important implications for diabetes prevention including dietary strategies. ARTICLE HIGHLIGHTS: The identification of biomarkers that predict type 2 diabetes is increasingly relevant for personalized medicine strategies. Data regarding ketone bodies and incident type 2 diabetes are scarce. This study shows that ketone bodies, either combined or as individual subspecies, are strongly associated with incident type 2 diabetes in the general population, independent of potential confounders. These results may have important implications for diabetes prevention including dietary strategies.
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Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/epidemiología , Cuerpos Cetónicos , Glucemia/metabolismo , Estudios Prospectivos , Ácido 3-Hidroxibutírico , Ayuno , BiomarcadoresRESUMEN
Background: Electrographic flow (EGF) mapping enables the dynamic detection of functional or active atrial fibrillation (AF) sources outside the pulmonary veins (PVs), and the presence or absence of these sources offers a novel framework for classifying and treating persistent AF patients based on the underlying pathophysiology of their AF disease. Objective: The primary objective of the FLOW-AF trial is to evaluate the reliability of the EGF algorithm technology (Ablamap software) to identify AF sources and guide ablation therapy in patients with persistent AF. Methods: The FLOW-AF trial (NCT04473963) is a prospective, multicenter, randomized clinical study in which patients with persistent or long-standing persistent AF who have failed prior PV isolation (PVI) undergo EGF mapping after confirmation of intact PVI. In total, 85 patients will be enrolled and stratified based on the presence or absence of EGF-identified sources. Patients with an EGF-identified source above the predetermined activity threshold of ≥26.5% will be randomized in a 1:1 fashion to PVI only vs PVI + ablation of EGF-identified extra-PV sources of AF. Results: The primary safety endpoint is freedom from serious adverse events related to the procedure through 7 days following the randomization procedure; and the primary effectiveness endpoint is the successful elimination of significant sources of excitation with the target parameter the activity of the leading source. Conclusions: The FLOW-AF trial is a randomized study designed to evaluate the ability of the EGF mapping algorithm to identify patients with active extra-PV AF sources.
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BACKGROUND: Catheter ablation (CA) remains challenging due to suboptimal success rates in persistent atrial fibrillation (AF). Existing mapping technologies cannot reliably distinguish sources in this patient population. Recently, the novel electrographic flow (EGF) mapping system was developed using a modified Horn-Schunk optical flow algorithm to detect and quantify patterns of electrical wavefront propagation in the atria. OBJECTIVES: To test the hypothesis that targeted source ablation based on EGF mapping is superior to empiric AF ablation. METHODS: We included all consecutive patients undergoing EGF guided ablation for persistent AF. All patients underwent pulmonary vein isolation (PVI) and were treated with the same EAM system (CARTO). The outcome of PVI+EGF guided CA was compared with data of PVI-only procedures (PVI-only group) and PVI plus additional empiric adjunctive linear and substrate ablations (PVI+LINES group). 12-months outcome as freedom from AF and atrial tachycardia/flutter (AT/AFL), procedural safety and efficiency characterized by procedure duration, fluoroscopy use, radiofrequency applications and duration, were analyzed. Both intention-to-treat and per protocol analysis were conducted. RESULTS: A total number of 70 patients (39 in PVI+EGF, 16 in PVI-only and 15 patients in PVI+LINES group) were enrolled. Intention-to-treat analysis showed fewer AF recurrences in PVI+EGF as compared with the PVI-only or PVI+LINES groups at 12 months (25.6% vs. 62.5% vs. 53.3%, p = .02). There were no differences in AT/AFL recurrence (17.9% vs. 37.5% vs. 20.0%, p = .37). Procedure times were longer in PVI+EGF group (p < .01), and there were no differences in fluoroscopy use (p = .67). CONCLUSION: Our data suggest that patients treated with EGF-guided CA developed fewer AF recurrences. Although the procedure times are longer, it seems to be safe and offers a more targeted, patient-specific ablation strategy beyond PVI than adjunctive empiric lines and substrate ablation in this complex group of patients.
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Fibrilación Atrial , Ablación por Catéter , Venas Pulmonares , Taquicardia Supraventricular , Humanos , Factor de Crecimiento Epidérmico , Resultado del Tratamiento , Venas Pulmonares/cirugía , Ablación por Catéter/métodos , RecurrenciaRESUMEN
Filamentous fungi are an essential source of bioactive mycotoxins. Recent efforts have focused on developing antifungal agents that are effective against invasive yeasts, such as Candida spp. By screening fungal strains isolated from regions surrounding the Chernobyl nuclear power plant disaster for antifungal activity against Candida albicans, we found that Aspergillus melleus IMV 01140 produced compounds that inhibited the growth of the yeast. The active compound produced by A. melleus was isolated and found to be neoaspergillic acid, a compound that is closely related to aspergillic acid. While aspergillic acid and its derivatives have been characterized and were found to have antibacterial and antifungal properties, neoaspergillic acid has been much less studied. Even though neoaspergillic acid and related compounds were found to have antibacterial and antitumoral effects, further investigation into this group of compounds is limited by challenges associated with large-scale production, isolation, and purification. The production of neoaspergillic acid has been shown to require co-cultivation methods or special growth conditions. In this work, neoaspergillic acid and related compounds were found to be produced by A. melleus under laboratory growth conditions. The biosynthetic gene cluster of neoaspergillic acid was predicted using the aspergillic acid gene cluster as a model. The biosynthetic pathway for neoaspergillic acid was then confirmed by establishing an in vitro CRISPR-ribonucleoprotein system to individually delete genes within the cluster. A negative transcriptional factor, mcrA, was also eliminated to further improve the production of neoaspergillic acid and the related compounds for future studies.
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BACKGROUND: Implantable cardioverter-defibrillators (ICDs) are frequently used for primary and secondary prevention in patients with cardiomyopathies due to different etiologies. However, long-term outcome studies in patients with noncompaction cardiomyopathy (NCCM) are scarce. OBJECTIVES: This study summarizes the long-term outcome of ICD therapy in patients with NCCM compared with those with dilated cardiomyopathy (DCM) or hypertrophic cardiomyopathy (HCM). METHODS: Prospective data from our single-center ICD registry were used to analyze the ICD interventions and survival in patients with NCCM (n = 68) compared with patients with DCM (n = 458) and patients with HCM (n = 158) from January 2005 to January 2018. RESULTS: This NCCM population with an ICD for primary prevention comprised 56 (82%) patients with a median age of 43 years and 52% males, compared with 85% in patients with DCM and 79% in patients with HCM (P = 0.20). During a median follow-up of 5 years (IQR: 2.0-6.9 years), appropriate and inappropriate ICD interventions were not significantly different. Nonsustained ventricular tachycardia during Holter monitoring in patients with NCCM was the only significant risk factor for appropriate ICD therapy in patients with NCCM, with a HR of 5.29 (95% CI: 1.12-24.96). The long-term survival was significantly better in the univariable analysis in the NCCM group. However, there was no difference in multivariable Cox regression analyses between the cardiomyopathy groups. CONCLUSIONS: At 5 years of follow-up, the rate of appropriate and inappropriate ICD interventions in NCCM was comparable to that in DCM or HCM. In multivariable analysis, no differences in survival were found between the cardiomyopathy groups.