Search

Aims: Transvenous lead extraction (TLE) is performed using non-laser and laser techniques with overall high efficacy and safety. Variation in outcomes between the two approaches does exist with limited comparative evidence in the literature. We sought to compare non-laser and laser TLE in a meta-analysis., Methods and Results: We searched Medline, Embase, Scopus, ClinicalTrials.gov, and CENTRAL databases for TLE studies published between 1991 and 2021. From the included 68 studies, safety and efficacy data were carefully evaluated and extracted. Aggregated cases of outcomes were used to calculate odds ratio (OR), and pooled rates were synthesized from eligible studies to compare non-laser and laser techniques. Subgroup comparison of rotational tool and laser extraction was also performed. Non-laser in comparison with laser had lower procedural mortality (pooled rate 0% vs. 0.1%, P < 0.01), major complications (pooled rate 0.7% vs. 1.7%, P < 0.01), and superior vena cava (SVC) injury (pooled rate 0% vs. 0.5%, P < 0.001), with higher complete success (pooled rate 96.5% vs. 93.8%, P < 0.01). Non-laser comparatively to laser was more likely to achieve clinical [OR 2.16 (1.77-2.63), P < 0.01] and complete [OR 1.87 (1.69-2.08), P < 0.01] success, with a lower procedural mortality risk [OR 1.6 (1.02-2.5), P < 0.05]. In the subgroup analysis, rotational tool compared with laser achieved greater complete success (pooled rate 97.4% vs. 95%, P < 0.01) with lower SVC injury (pooled rate 0% vs. 0.7%, P < 0.01)., Conclusion: Non-laser TLE is associated with a better safety and efficacy profile when compared with laser methods. There is a greater risk of SVC injury associated with laser sheath extraction., Competing Interests: Conflict of interest: M.G. has received research funding from Attune Medical and workshop fee from Cook Medical and has acted as a consultant and a paid speaker for Biosense Webster, Cook Medical, and Adagio. C.T.S. has received consulting fees and travel expenses from Medtronic; consulting fees and research support from Biotronik; research support from Abbott; workshop fees, consulting fees, educational grants, and research support from Cook Medical; consulting fees from Spectranetics/Philipps; and consulting fees from AngioDynamics. M.S. has received research funding from Abbott and workshop fee from Cook Medical. Z.A. has received a workshop fee from Cook Medical. All remainder authors have declared no conflicts of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Familial hypercholesterolemia (FH) is common, but underdiagnosed, and few systematic early screening programs exist., Objective: To assess health outcomes among those with a recorded diagnosis of FH and potential cases of FH with no recorded diagnosis., Methods: Retrospective cohort study using the UK Clinical Practice Research Datalink. Records of adults were classified as diagnosed FH (FH Coded ), or via accepted algorithms using LDL-C and clinical characteristics as potential FH (FH Potential ) or unlikely FH (FH Unlikely ) using the DLCN or EUROASPIRE criteria (but no record of FH). Outcomes assessed were premature cardiovascular (CV) events, premature deaths and life expectancy., Results: Among 1,729,046 individuals free from CV events, a record of FH Coded before the age of 40 was 0.3/1000 (IQR 0.3-0.4) and increased with age. Where LDL-C levels were available, 1.8/1000 (IQR 1.6-2.0) could be classified as FH Potential . LDL-C was higher for both FH Coded and FH Potential vs FH Unlikely (185.6 and 216.6 vs 116 mg/dL, respectively, p <0.001). Compared to FH Unlikely both FH Coded and FH Potential cohorts had a higher risk of premature cardiovascular events (both p <0.001) with highest rates among FH Coded . Risk of premature deaths did not differ between FH Coded and FH Unlikely, but was 1.88 (95% CI 1.27-2.78, p  = 0.002) for FH Potential vs FH Coded and 2.40 (95% CI 1.57-3.67, p <0.001) for FH Potential vs FH Unlikely . At age 18, the FH Potential cohort had a life expectancy 16 years lower than the FH Coded cohort ( p <0.001)., Conclusions: Potential cases of FH had a doubling in risk of premature death and a large reduction in life expectancy compared to individuals with a recorded diagnosis of FH. These findings strengthen the critical importance of identifying potential cases of FH early and early treatment., Competing Interests: Professor Kausik K. Ray reports the following; Unrestricted research grants to Imperial College London from Amgen, Daiichi Sankyo, Regeneron, Sanofi, SC, EC or advisory boards honoraria from Novartis, Esperion, Daiichi Sankyo, Abbott, Bayer, Eli Lilly, Silence Therapeutics, CSL Behring, New Amsterdam Pharma, Sanofi, Amgen, Novo Nordisk, BI, Scribe, Vaxxinity, CRISPR, AZ, Kowa, Cargene, Honoria for CME and non CME from Novartis, Novo Nordisk, BI, AZ, Viatris, Daiichi Sankyo, Amgen, Sanofi and stock options PEMI-31. Dr. Demetris Pillas provided consultancy services to Amgen Ltd. Dr. Savvas Hadjiphilippou has no disclosures. Professor Kamlesh Khunti has received research grants from Lilly, Sanofi-Aventis, Boehringer Ingelheim, Merck, Sharpe & Dohme, and Novo Nordisk, has provided consultancy services to Amgen, Novartis, Novo Nordisk, Sanofi-Aventis, Lilly, Servier, and Merck, Sharpe & Dohme, has served in non-remunerative positions of influence at Lilly, Sanofi-Aventis, Merck, Sharpe & Dohme, and Novo Nordisk and has participated in Speakers Bureau for Lilly, Sanofi-Aventis, Merck, Sharpe & Dohme, and Novo Nordisk. Dr. Sreenivasa Rao Kondapally Seshasai has provided consultancy services to Amgen. Dr. Antonio J. Vallejo-Vaz reports current or past participation in research grants to Imperial College London from Pfizer, Amgen, MSD, Sanofi-Aventis, Daiichi Sankyo, and Regeneron; personal fees for consulting from Bayer and Regeneron; and honoraria for lectures from Amgen, Mylan, Akcea, and Ferrer; all outside the submitted work. Dr David Neasham is employed at Amgen Ltd. Ms. Janet Addison was previously employed at Amgen Ltd., (© 2023 The Authors. Published by Elsevier B.V.)

Objective: To evaluate the clinical efficacy and safety of leflunomide (L) added to the standard-of-care (SOC) treatment in COVID-19 patients hospitalised with moderate/critical clinical symptoms., Design: Prospective, open-label, multicentre, stratified, randomised clinical trial., Setting: Five hospitals in UK and India, from September 2020 to May 2021., Participants: Adults with PCR confirmed COVID-19 infection with moderate/critical symptoms within 15 days of onset., Intervention: Leflunomide 100 mg/day (3 days) followed by 10-20 mg/day (7 days) added to standard care., Primary Outcomes: The time to clinical improvement (TTCI) defined as two-point reduction on a clinical status scale or live discharge prior to 28 days; safety profile measured by the incidence of adverse events (AEs) within 28 days., Results: Eligible patients (n=214; age 56.3±14.9 years; 33% female) were randomised to SOC+L (n=104) and SOC group (n=110), stratified according to their clinical risk profile. TTCI was 7 vs 8 days in SOC+L vs SOC group (HR 1.317; 95% CI 0.980 to 1.768; p=0.070). Incidence of serious AEs was similar between the groups and none was attributed to leflunomide. In sensitivity analyses, excluding 10 patients not fulfilling the inclusion criteria and 3 who withdrew consent before leflunomide treatment, TTCI was 7 vs 8 days (HR 1.416, 95% CI 1.041 to 1.935; p=0.028), indicating a trend in favour of the intervention group. All-cause mortality rate was similar between groups, 9/104 vs 10/110. Duration of oxygen dependence was shorter in the SOC+L group being a median 6 days (IQR 4-8) compared with 7 days (IQR 5-10) in SOC group (p=0.047)., Conclusion: Leflunomide, added to the SOC treatment for COVID-19, was safe and well tolerated but had no major impact on clinical outcomes. It may shorten the time of oxygen dependence by 1 day and thereby improve TTCI/hospital discharge in moderately affected COVID-19 patients., Trial Registration Numbers: EudraCT Number: 2020-002952-18, NCT05007678., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Global trends in cardiovascular disease (CVD) exhibit considerable interregional and interethnic differences, which in turn affect long-term CVD risk across diverse populations. An in-depth understanding of the interplay between ethnicity, socioeconomic status, and CVD risk factors and mortality in a contemporaneous population is crucial to informing health policy and resource allocation aimed at mitigating long-term CVD risk. Generating bespoke large-scale and reliable data with sufficient numbers of events is expensive and time-consuming but can be circumvented through utilization and linkage of data routinely collected in electronic health records (EHR)., Objective: We aimed to characterize the burden of CVD risk factors across different ethnicities, age groups, and socioeconomic groups, and study CVD incidence and mortality by EHR linkage in London., Methods: The proposed study will initially be a cross-sectional observational study unfolding into prospective CVD ascertainment through longitudinal follow-up involving linked data. The government-funded National Health System (NHS) Health Check program provides an opportunity for the systematic collation of CVD risk factors on a large scale. NHS Health Check data on approximately 200,000 individuals will be extracted from consenting general practices across London that use the Egton Medical Information Systems (EMIS) EHR software. Data will be analyzed using appropriate statistical techniques to (1) determine the cross-sectional burden of CVD risk factors and their prospective association with CVD outcomes, (2) validate existing prediction tools in diverse populations, and (3) develop bespoke risk prediction tools across diverse ethnic groups., Results: Enrollment began in January 2019 and is ongoing with initial results to be published mid-2021., Conclusions: There is an urgent need for more real-life population health studies based on analyses of routine health data available in EHRs. Findings from our study will help quantify, on a large scale, the contemporaneous burden of CVD risk factors by geography and ethnicity in a large multiethnic urban population. Such detailed understanding (especially interethnic and sociodemographic variations) of the burden of CVD risk and its determinants, including heredity, environment, diet, lifestyle, and socioeconomic factors, in a large population sample, will enable the development of tailored and dynamic (continuously learning from new data) risk prediction tools for diverse ethnic groups, and thereby enable the personalized provision of prevention strategies and care. We anticipate that this systematic approach of linking routinely collected data from EHRs to study CVD can be conducted in other settings as EHRs are being implemented worldwide., International Registered Report Identifier (irrid): PRR1-10.2196/17548., (©Kanika Dharmayat, Maria Woringer, Nikolaos Mastellos, Della Cole, Josip Car, Sumantra Ray, Kamlesh Khunti, Azeem Majeed, Kausik K Ray, Sreenivasa Rao Kondapally Seshasai. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 02.10.2020.)

Aims: Systematic review of literature to evaluate safety of intracoronary (i.c.) pharmacologic testing with acetylcholine (ACh), or ergonovine (ERGO), to induce coronary artery spasm., Methods and Results: Review of all relevant publications using MEDLINE and EMBASE databases yielded 10 publications, totalling 9,444 patients. Prevalence of provoked spasm varied from 2.3% to 54.7% of patients tested in the selected studies. The wide variability in prevalence was due to heterogeneity of study populations and provocation protocols. No deaths were reported. Overall occurrence of major (0.8%) and minor (4.7%) complications for i.c. pharmacologic testing was low. Compared to ERGO, ACh showed significantly higher rate of major (1.09% vs 0.15%; p<0.001) and minor complications (5.87% vs 2.36%; p<0.001)., Conclusion: Provocative testing with i.c. ACh or ERGO are safe and can facilitate the diagnosis of inducible coronary artery spasm during diagnostic coronary angiography. These tests should be part of the routine armamentarium of interventional cardiologists., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objectives: To describe low-density lipoprotein (LDL) cholesterol management and lipid-lowering treatment patterns in patients with a cardiovascular (CV) event., Design: Retrospective cohort study using Clinical Practice Research Datalink records linked with Hospital Episode Statistics data., Setting: Routine clinical practice in the UK from 2006 to 2012., Participants: Individuals ≥18 years were selected at their first CV-related hospitalisation (first event cohort) if they had received ≥2 lipid-lowering therapy prescriptions within 180 days beforehand. Patients were stratified into four mutually exclusive subgroups based on the presence or absence of vascular disease and of diabetes. Those with a second CV hospitalisation within 36 months were included in a separate cohort (second event cohort)., Primary and Secondary Outcome Measures: LDL levels in the year prior to the CV event and 12 months later as well as measures of adherence to lipid-lowering therapy during the 12 months after the CV hospitalisation., Results: There were 24 093 patients in the first event cohort, of whom 5274 were included in the second event cohort. Most received moderate intensity statins at baseline and 12 months. Among the four first event cohort subgroups at baseline, the proportions with an LDL of <1.8 mmol/L was similar between the two diabetic cohorts (36% to 38%) and were higher than those in the two non-diabetic cohorts (17% to 22%) and in the second event cohort (31%). An incremental 5% to 9% had an LDL below 1.8 mmol/L at 12 months, suggesting intensification of therapy. The proportion of adherent patients (medication possession ratio of≥0.8) was highest for statins, ranging from 68% to 72%. For ezetimibe, the range was 65% to 70%, and for fibrates, it was 48% to 62%., Conclusions: Despite the existence of effective therapies for lowering cholesterol, patients do not reach achievable LDL targets., Competing Interests: Competing interests: MD, MG, and RG work with Outcomes Insights, Inc., which was funded to conduct this study. LK is an employee of Amgen, Inc. KK has acted as a consultant and speaker for Novartis, Novo Nordisk, Sanofi-Aventis, Lilly, Merck Sharp & Dohme, Janssen, Astra Zeneca and Boehringer Ingelheim. He has received grants in support of investigator and investigator-initiated trials from Novartis, Novo Nordisk, Sanofi-Aventis, Lilly, Pfizer, Boehringer Ingelheim, Merck Sharp & Dohme, Janssen and Roche and has served on advisory boards for Lilly, Sanofi-Aventis, Merck Sharp & Dohme, Novo Nordisk, Boehringer Ingelheim, Janssen and Astra Zeneca. SRKS has provided consulting to Amgen and received grants from Kowa and Sanofi. KKR has provided consultancy to Amgen, Sanofi, Pfizer, Regeneron, Astra Zeneca, Kowa, Aegerion, Merck Sharp & Dohme, Lilly and ISIS, and received grants from Sanofi, Regeneron, Amgen, Pfizer and Merck Sharp & Dohme through his institution., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)