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In patients with diabetes, peripheral arterial disease, particularly below the knee, is associated with medial arterial calcification. This is a frequent and potentially serious complication, affecting all types of diabetes. In recent years, our understanding of the pathophysiology and clinical significance of medial arterial calcification has improved considerably. Here, we offer a short narrative review of the epidemiology, clinical consequences, and pathophysiology of this complication. Now that medial arterial calcification of the lower limbs is better understood, we also focus on the prospect of treatments targeting arterial calcification., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:, (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Cardiometabolic disorders contribute to the global burden of cardiovascular diseases. Emerging sphingolipid metabolites like sphingosine-1-phosphate (S1P) and its receptors, S1PRs, present a dynamic signalling axis significantly impacting cardiac homeostasis. S1P's intricate mechanisms extend to its transportation in the bloodstream by two specific carriers: high-density lipoprotein particles and albumin. This intricate transport system ensures the accessibility of S1P to distant target tissues, influencing several physiological processes critical for cardiovascular health. This review delves into the diverse functions of S1P and S1PRs in both physiological and pathophysiological conditions of the heart. Emphasis is placed on their diverse roles in modulating cardiac health, spanning from cardiac contractility, angiogenesis, inflammation, atherosclerosis and myocardial infarction. The intricate interplays involving S1P and its receptors are analysed concerning different cardiac cell types, shedding light on their respective roles in different heart diseases. We also review the therapeutic applications of targeting S1P/S1PRs in cardiac diseases, considering existing drugs like Fingolimod, as well as the prospects and challenges in developing novel therapies that selectively modulate S1PRs., (© 2024 The Author(s). FEBS Letters published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

Background: Paroxysmal atrial fibrillation (pAF) may progress through cardiac remodeling to persistent atrial fibrillation (psAF). However, some may present in psAF without a preceding history of pAF. A preceding history of pAF may affect recurrence after direct current cardioversion (DCCV)., Objective: The aim of this study was to determine whether a preceding history of pAF is associated with a difference in recurrence rates after DCCV compared with patients without a preceding history of pAF., Methods: A prospective procedural database at a Veterans Affairs center identified 565 patients who underwent their first DCCV for psAF. Initial rhythm history was separated by prior pAF, and those with none were considered primary psAF. Electrocardiography follow-up was standardized at 1 month and 3 months after cardioversion., Results: Patients who underwent their first DCCV for psAF were more likely to have presented with primary psAF (81.6%). Those with pAF had a similar left atrial size but were more likely to have chronic kidney disease, sleep apnea, previous stroke, and use of antiarrhythmic drugs at the time of cardioversion. Patients with pAF had earlier recurrence and shorter median AF survival time, 1.6 months compared with 5 months (Kaplan-Meier plot, P = .0101). This difference persisted in controlling for antiarrhythmic drug use. Recurrence type was mostly persistent AF, similar in both groups., Conclusion: Patients with primary psAF may have a more sustained response to DCCV compared with those with a preceding history of pAF. Thus, those patients with pAF may benefit from a more aggressive, early rhythm control strategy because of higher likelihood of recurrence with DCCV., Competing Interests: Disclosures The authors have no conflicts of interest to disclose., (Published by Elsevier Inc.)

Background: Lead dwell time is the single strongest predictor of failure and complications in transvenous lead extraction., Objectives: To report the success rate and complications of transvenous lead extractions with implant dwell time of at least 15 years., Methods: Procedural and patient data were prospectively collected into a database. The excimer laser was the primary method for lead extraction with the use of mechanical rotational sheaths and femoral snares at operator discretion., Results: A total of 442 patients between 2011 and 2020 underwent lead extraction (705 leads) primarily for infection or device failure at our high-volume center. Forty-one patients with 71 leads > 15 years old were included in this cohort. Mean patient age was 53.5 ± 18.5 years, 67.5% were male. Mean lead dwell time was 19.6 ± 4.4 years. Thirty-six of 41 (88%) patients had successful extraction of all leads compared to 96% in the remaining 401 patients, p value.004. Of the five patients without fully successful extractions two of these patients had abandoned leads (three total) that were clinically significant. There were two (4.9%) major complications in the very old lead group and six (1.5%) in the other group. In the very old lead group, one patient experienced right atrial appendage perforation requiring surgical repair and recovered well. One patient experienced new complete heart block requiring 2 min of CPR but did well thereafter. There was no procedure-related mortality., Conclusions: Despite challenges posed by older leads, very old leads can be safely and effectively extracted with low complication rates., (© 2024 Wiley Periodicals LLC.)

Background: Safe and effective management of venous vascular access is a key component of electrophysiology (EP) procedures. Recently, the Z-stitch method has been developed for effective venous hemostasis. However, the standard postprocedure protocol often includes prolonged bed rest, which may affect patient satisfaction. The ZEBRA (Z stitch Early Bed Rest Assessment) study aims to systematically investigate and quantify patient satisfaction metrics and safety parameters associated with the early mobilization after Z-stitch placement., Objective: This study primarily investigates whether early mobilization following Z-stitch placement in venous vascular access management during EP procedures enhances patient satisfaction without compromising safety., Methods: In this prospective, multicenter, randomized clinical trial, approximately 200 patients undergoing various EP procedures at Oregon Health and Science University and Veterans Affairs Portland Health Care System will be randomly assigned to either a 1- or 4-hour bed rest regimen post-Z stitch. Patient satisfaction will be assessed through survey, alongside monitoring for hematomas, bleeding complications, and other safety endpoints. The study includes stratification based on heparin administration and sheath size to ensure robust and nuanced data analysis., Results: We anticipate that early mobilization will lead to higher patient satisfaction scores. We also expect to closely monitor and report the incidence of hematomas, pain medication use, healthcare costs, patient outcomes at 30 days, time to ambulation, and hospital readmissions or emergency visits related to groin complications., Conclusion: The ZEBRA study is poised to fill a critical knowledge gap in postprocedure care in EP labs. By rigorously evaluating the impact of early mobilization on patient satisfaction and safety, this study could significantly influence future guidelines and improve patient experiences in EP procedures., (© 2024 Heart Rhythm Society. Published by Elsevier Inc.)

Background: Studies have demonstrated that coronary artery calcification on one hand and non-alcoholic fatty liver disease (NAFLD) on the other hand are strongly associated with cardiovascular events. However, it remains unclear whether NAFLD biomarkers could help estimate cardiovascular risk in individuals with type 2 diabetes (T2D). The primary objective of the present study was to investigate whether the biomarkers of NAFLD included in the FibroMax® panels are associated with the degree of coronary artery calcification in patients with T2D., Methods: A total of 157 and 460 patients with T2D were included from the DIACART and ACCoDiab cohorts, respectively. The coronary artery calcium score (CACS) was measured in both cohorts using computed tomography. FibroMax® panels (i.e., SteatoTest®, FibroTest®, NashTest®, and ActiTest®) were determined from blood samples as scores and stages in the DIACART cohort and as stages in the ACCoDiab cohort., Results: CACS significantly increased with the FibroTest® stages in both the DIACART and ACCoDiab cohorts (p-value for trend = 0.0009 and 0.0001, respectively). In DIACART, the FibroTest® score was positively correlated with CACS in univariate analysis (r = 0.293, p = 0.0002) and remained associated with CACS independently of the traditional cardiovascular risk factors included in the SCORE2-Diabetes model [β = 941 ± 425 (estimate ± standard error), p = 0.028]. In the ACCoDiab cohort, the FibroTest® F3-F4 stage was positively correlated with CACS in point-biserial analysis (r pbi  = 0.104, p = 0.024) and remained associated with CACS after adjustment for the traditional cardiovascular risk factors included in the SCORE2-Diabetes model (β = 234 ± 97, p = 0.016). Finally, the prediction of CACS was improved by adding FibroTest® to the traditional cardiovascular risk factors included in the SCORE2-Diabetes model (goodness-of-fit of prediction models multiplied by 4.1 and 6.7 in the DIACART and ACCoDiab cohorts, respectively). In contrast, no significant relationship was found between FibroMax® panels other than FibroTest® and CACS in either cohort., Conclusions: FibroTest® is independently and positively associated with the degree of coronary artery calcification in patients with T2D, suggesting that FibroTest® could be a relevant biomarker of coronary calcification and cardiovascular risk., Trial Registration: ClinicalTrials.gov identifiers NCT02431234 and NCT03920683., (© 2024. The Author(s).)

Background: The impact of lead fixation mechanism on extractability is poorly characterized., Objective: We aimed to compare the technical difficulty of transvenous lead extraction (TLE) of active vs passive fixation right ventricular (RV) leads., Methods: A total of 408 patients who underwent RV TLE by a single expert electrophysiologist at Oregon Health & Science University between October 2011 and June 2022 were identified and retrospectively analyzed; 331 (81%) had active fixation RV leads and 77 (19%) had passive fixation RV leads. The active fixation cohort was further stratified into those with successfully retracted helices (n = 181) and failed helix retraction (n = 109). A numerical system (0-9) devised using 6 procedural criteria quantified a technical extraction score (TES) for each RV TLE. The TES was compared between groups., Results: Helix retraction was successful in ≥55% of active fixation TLEs. The mean TES for active-helix retracted, active-helix non-retracted, and passive fixation groups was 1.8, 3.5, and 3.7, respectively. The TES of the active-helix retracted group was significantly lower than those of the active-helix non-retracted group (adjusted P < .01) and the passive fixation group (adjusted P < .01). There was no significant difference in TES between the passive fixation and active-helix non-retracted groups in multivariate analysis ( P = .18). The TLE success rate of the entire cohort was >97%, with a major complication rate of 0.5%., Conclusion: TLE of active fixation leads where helical retraction is achieved presents fewer technical challenges than does passive fixation RV lead extraction; however, if the helix cannot be retracted, active and passive TLE procedures present similar technical challenges., (© 2023 Heart Rhythm Society. Published by Elsevier Inc.)

Background: Patients with type 2-diabetes mellitus (T2D), are characterized by visceral and ectopic adipose tissue expansion, leading to systemic chronic low-grade inflammation. As visceral adiposity is associated with severe COVID-19 irrespective of obesity, we aimed to evaluate and compare the predictive value for early intensive care or death of three fat depots (cardiac, visceral and subcutaneous) using computed tomography (CT) at admission for COVID-19 in consecutive patients with and without T2D., Methods: Two hundred and two patients admitted for COVID-19 were retrospectively included between February and June 2020 and distributed in two groups: T2D or non-diabetic controls. Chest CT with cardiac (CATi), visceral (VATi) and subcutaneous adipose tissue (SATi) volume measurements were performed at admission. The primary endpoint was a composite outcome criteria including death or ICU admission at day 21 after admission. Threshold values of adipose tissue components predicting adverse outcome were determined., Results: One hundred and eight controls [median age: 76(IQR:59-83), 61% male, median BMI: 24(22-27)] and ninety-four T2D patients [median age: 70(IQR:61-77), 70% male, median BMI: 27(24-31)], were enrolled in this study. At day 21 after admission, 42 patients (21%) had died from COVID-19, 48 (24%) required intensive care and 112 (55%) were admitted to a conventional care unit (CMU). In T2D, CATi was associated with early death or ICU independently from age, sex, BMI, dyslipidemia, CRP and coronary calcium (CAC). (p = 0.005). Concerning T2D patients, the cut-point for CATi was  > 100 mL/m 2 with a sensitivity of 0.83 and a specificity of 0.50 (AUC = 0.67, p = 0.004) and an OR of 4.71 for early ICU admission or mortality (p = 0.002) in the fully adjusted model. Other adipose tissues SATi or VATi were not significantly associated with early adverse outcomes. In control patients, age and male sex (OR = 1.03, p = 0.04) were the only predictors of ICU or death., Conclusions: Cardiac adipose tissue volume measured in CT at admission was independently predictive of early intensive care or death in T2D patients with COVID-19 but not in non-diabetics. Such automated CT measurement could be used in routine in diabetic patients presenting with moderate to severe COVID-19 illness to optimize individual management and prevent critical evolution., (© 2022. The Author(s).)