Citations

Abstract Background Heart failure (HF) and atrial fibrillation (AF) are intertwined, sharing common risk factors and influencing each other in a reciprocal manner. While left ventricular diastolic dysfunction (LVDD) stands as a hallmark of HF's hemodynamic profile, its direct correlation with heightened AF risk remains uncertain. Our recent validation of an artificial intelligence-enabled electrocardiogram (AI-ECG) algorithm for LVDD detection has opened new avenues. Yet, whether AI-ECG-detected LVDD correlates with long-term AF risk remains unexplored. Methods We performed a retrospective study among all patients with a comprehensive LVDD assessment from the test population of the AI-ECG LVDD study between September 2001 and June 2022. Patients with prior documented AF according to health records or previous ECG were excluded. Patients were classified by AI-ECG as normal diastolic function (DF), grade 1 (G1), grade 2 (G2), or grade 3 (G3) LVDD. We assessed the risk of AF across AI-ECG LVDD grade, with normal DF as reference, with competing risk models. Results Of 97,023 patients free of AF at baseline, 63,533 (65.4%), 10,776 (11.1%), 18,940 (19.5%), and 3,774 (3.9%) were classified as normal DF, G1-LVDD, G2-LVDD, and G3-LVDD, respectively. Worse AI-ECG LVDD was associated with older age, lower left ventricular ejection fraction (LVEF), and higher rates of HF, diabetes, hypertension, chronic pulmonary disease, renal failure, and cardiovascular disease (p-of-trend<0.001 for all). Over a median follow-up of 4.8 years (interquartile range 1.8-9.2 years), new-onset AF occurred in 6,795 (7.0%) patients. In multivariable survival analysis, adjusted to multiple risk factors including LVEF and clinical HF, G2 and G3 LVDD, representing patients with high filling pressures, were independently associated with a higher AF-risk [G2-LVDD: adjusted hazard ratio (aHR) 1.64 (95% confidence interval (95%CI) 1.52-1.73), G3-LVDD: aHR 2.24 (95%CI 2.02-2.48)]. Conclusion The AI-ECG LVDD algorithm independently predicts long-term AF risk, regardless of LVEF and clinical HF status, highlighting its potential for identifying high-risk populations and guiding proactive monitoring and management.

Abstract Background The determination of left ventricular diastolic dysfunction (LVDD) and filling pressure in patients with significant (>moderate) mitral regurgitation (MR) poses a complex challenge. We recently validated an artificial intelligence-enabled electrocardiogram (AI-ECG) algorithm to detect LVDD and estimate LV filling pressures. Methods This retrospective study sought to examine the risk of all-cause mortality across AI-ECG LVDD grades. Patients from the AI-ECG LVDD study test cohort who underwent transthoracic echocardiography confirming significant MR and an ECG within fourteen days of each other at Mayo Clinic between 09/2001 and 06/2022 were included. LVDD status was determined based on the index ECG, and patients were categorized into groups representing normal diastolic function (NDF) or LVDD grades 1 (G1), 2 (G2), or 3 (G3). Results Of 4,019 patients with significant MR (mean age 69.8, 49.0% women), 1,175 (29.2%), 1,881 (46.8%), and 963 (24.0%) were classified by AI-ECG as NDF/G1-LVDD, G2-LVDD, and G3-LVDD, respectively. The median mitral effective regurgitant orifice area was 26 mm² (interquartile range 20-36 mm²). Over a median follow-up of 3.5 years, 1,636 (40.7%) patients died. In multivariable survival analysis adjusted for multiple risk factors, a worse AI-ECG LVDD grade was independently associated with an increased death risk [G2DD: adjusted hazard ratio (aHR) 1.98 (95% confidence interval (95% CI) 1.63-2.40), G3DD: aHR 2.59 (95% CI 2.09-3.20)]. These findings were consistent when accounting for mitral valve intervention and among patients with >moderate MR or after mitral valve intervention. Conclusion In patients with significant MR, the grading of LVDD by AI-ECG is independently associated with all-cause mortality.

Vascular access is an indispensable component of haemodialysis therapy for end-stage kidney disease patients. The arteriovenous fistula (AVF) is most common, but importantly, two-year failure rates are greater than fifty percent. AVF failure can occur due to a lack of suitable vascular remodelling, and inappropriate inflammation preventing maturation, or alternatively neointimal hyperplasia and vascular stenosis preventing long-term use. A comprehensive mechanistic understanding of these processes is still lacking, but recent studies highlight an essential role for inflammation from uraemia and the AVF itself. Inflammation affects each cell in the cascade of AVF failure, the endothelium, the infiltrating immune cells, and the vascular smooth muscle cells. This review examines the role of inflammation in each cell step by step and the influence on AVF failure. Inflammation resulting in AVF failure occurs initially via changes in endothelial cell activation, permeability, and vasoprotective chemokine secretion. Resultingly, immune cells can extravasate into the subendothelial space to release inflammatory cytokines and cause other deleterious changes to the microenvironment. Finally, all these changes modify vascular smooth muscle cell function, resulting in excessive and unchecked hyperplasia and proliferation, eventually leading to stenosis and the failure of the AVF. Finally, the emerging therapeutic options based off these findings are discussed, including mesenchymal stem cells, small-molecule inhibitors, and far-infrared therapies. Recent years have clearly demonstrated a vital role for inflammation in deciding the fate of the AVF, and future works must be centred on this to develop therapies for a hitherto unacceptably underserved patient population.

The objective of this project was to develop a standardized list of renally eliminated and potentially nephrotoxic drugs that will help inform initiatives to improve medication safety. Several available lists of medications from the published literature including original research articles and reviews, and from regulatory agencies, tertiary references, and clinical decision support systems were compiled, consolidated, and compared. Only systemically administered medications were included. Medication combinations were included if at least 1 active ingredient was considered renally dosed or potentially nephrotoxic. The medication list was reviewed for completeness and clinical appropriateness by a multidisciplinary team of individuals with expertise in critical care, nephrology, and pharmacy. An initial list of renally dosed and nephrotoxic drugs was created. After reconciliation and consensus from clinical experts, a standardized list of 681 drugs is proposed. The proposed evidence-based standardized list of renally dosed and potentially nephrotoxic drugs will be useful to harmonize epidemiologic and medication quality improvement studies. In addition, the list can be used for clinical purposes with surveillance in nephrotoxin stewardship programs. We suggest an iterative re-evaluation of the list with emerging literature and new medications on an approximately annual basis.

Cardiac sonographers are frequently exposed to ergonomic risks such as postural stress and high levels of physical exertion while performing scanning tasks, contributing to work-related pain, and discomfort among cardiac sonographers. Passive exoskeletons are a potential ergonomic intervention with the potential to mitigate some of the risks associated with scanning. This study examined the effectiveness of a passive upper body exoskeleton in reducing the levels of work-related pain, discomfort, and workload in cardiac sonographers while performing transthoracic echocardiograms (TTE). Twelve cardiac sonographers were asked to use the HAPO FRONT exoskeleton while performing TTEs during a full workday. Participants were asked to rate their body part discomfort and workload throughout the day, both with and without the exoskeleton. The exoskeleton did not significantly decrease discomfort or workload associated with performing TTEs, except for a slight reduction in the discomfort at the left hand/wrist. This result indicates that the HAPO FRONT was not effective or appropriate for use by cardiac sonographers. Future development and study of purpose-designed exoskeletons for healthcare applications may provide greater benefits to cardiac sonographers.

Abstract Objectives To describe mismatch repair (MMR) and microsatellite instability (MSI) testing practices in laboratories using the College of American Pathologists (CAP) MSI/MMR proficiency testing programs prior to the 2022 publication of the MSI/MMR practice guidelines copublished by CAP and the Association of Molecular Pathology (AMP). Methods Data from supplemental questionnaires provided with the 2020-B MSI/MMR programs to 542 laboratories across different practice settings were reviewed. Questionnaires contained 21 questions regarding the type of testing performed, specimen/tumor types used for testing, and clinical practices for checkpoint blockade therapy. Results Domestic laboratories test for MSI/MMR more often than international laboratories (P = .04) and academic hospitals/medical centers test more frequently than nonhospital sites/clinics (P = .03). The most commonly used testing modality is immunohistochemistry, followed by polymerase chain reaction, then next-generation sequencing. Most laboratories (72.6%; 347/478) reported awareness of the use of immune checkpoint inhibitor therapy for patients with high MSI or MMR-deficient results. Conclusions The results demonstrate the state of MMR and MSI testing in laboratories prior to the publication of the CAP/AMP best practice guidelines, highlighting differences between various laboratory types. The findings indicate the importance of consensus guidelines and provide a baseline for comparison after their implementation.

Background Atherosclerosis is highly prevalent in people with chronic kidney disease (CKD), including those receiving peritoneal dialysis (PD). Although it is lifesaving, PD induces profound systemic inflammation, which may aggravate atherosclerosis. Therefore, the hypothesis is that this PD‐induced inflammation aggravates atherosclerosis via immune cell activation. Methods and Results ApoE −/− mice were subjected to a 5/6 nephrectomy to induce CKD. Three weeks later, mice were fed a high‐cholesterol diet. Half of the nephrectomized mice then received daily peritoneal infusions of 3.86% Physioneal for 67 further days (CKD+PD) until the end of the experiment, and were compared with mice without CKD. Sham operated and PD‐only mice were additional controls. CKD+PD mice displayed more severe atherosclerotic disease than control mice. Plaque area increased, and plaques were more advanced with a vulnerable phenotype typified by decreased collagen content and decreased fibrous cap thickness. Increased CD3 + T‐cell numbers were present in plaques and perivascular adipose tissue of CKD and CKD+PD mice. Plaques of CKD+PD mice contained more iNOS + immune cells. Spleens of CKD+PD mice showed more CD4 + central memory, terminally differentiated type 1 T‐helper (Th1), Th17, and CX3C motif chemokine receptor 1 + (CX3CR1) CD4 + T‐cells with less regulatory and effector T‐cells. Conclusions PD‐fluid exposure in uremic mice potentiates systemic and vascular T‐cell‐driven inflammation and aggravates atherosclerosis. PD polarized CD4 + T‐cells toward an inflammatory Th1/Th17 phenotype, and increased CX3CR1 + CD4 + T‐cells, which are associated with vascular homing in CKD‐associated atherosclerosis. Targeting CD4 + T‐cell activation and CX3CR1 + polarization has the potential to attenuate atherosclerosis in PD patients.