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1. A systematic review and meta-analysis of upgrade to biventricular or conduction system pacing approaches

Author

N Kaza, V Htun, A Miyazawa, F Simader, B Porter, J P Howard, A Arnold, D P Francis, Z I Whinnett, M J Shun-Shin, and D Keene

Subjects
Cardiology and Cardiovascular Medicine
Abstract

Introduction Chronic RV pacing has been recognised as being harmful to cardiac function. Patients undergoing a de novo pacemaker implant with even mild LV impairment are recommended to instead receive a physiological pacing strategy (biventricular or conduction system pacing [CSP]). No corresponding guideline recommendation exists for patients who already have a pacemaker. Methods We undertook a random-effects meta-analysis of all RCTs and observational studies covering device upgrade to biventricular pacing or conduction system pacing. Results 6 RCTs assessing effect of upgrade to BiV pacing randomising 161 patients were eligible for analysis. Eligible observational studies included 46 of BiV upgrade and 7 of CSP upgrade totalling 2795 patients. Mean LVEF improved by +8.3% from 34.4% in BiV upgrade RCTs (p=0.001) and +8.3% from 25.7% in BiV upgrade observational studies (p In observational studies of upgrade to CSP, LVEF increased by +10.1% from 38.4% (p=0.001) despite less severe LV impairment at baseline (p=0.004 vs mean EF in BiV RCTs and p LVESV decreased significantly by −25.4 ml, −23.7 ml, and −19.8 ml in BiV RCTs, BiV observational studies and CSP observational studies. Significant changes were also seen in NYHA class (decreased by −0.4, −0.8 and −1.0 respectively). Minnesota Heart Failure Score (−6.9 points) and peak oxygen uptake (+1.1 ml/kg/min) increased significantly in RCTs of BiV upgrade. This was also seen in observational studies of BiV upgrade (−21.0 points and +2.63 ml/kg/min respectively). Conclusions RCTs and observational studies of upgrade to BiV pacing show significant physiological and symptomatic benefit. Observational studies of CSP upgrade show similar benefit with significant improvements in LVEF, LVESV and NYHA class in patients with an even milder degree of baseline LV impairment. Funding Acknowledgement Type of funding sources: None.

Published
2022
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2. Observational study of the medical management of patients with peripheral artery disease

Author

David Sidloff, Jannick A N Dorresteijn, V Htun, Ruth A. Benson, Z Mera, Athanasios Saratzis, Brenig L. Gwilym, R Lefroy, David C. Bosanquet, Toby Richards, Frank L.J. Visseren, A Tsui, A Thatcher, George Dovell, Nikesh Dattani, M Parks, N E M Jaspers, Rachael O. Forsythe, O Thomas, Joseph Shalhoub, and Tristan R A Lane

Subjects
Male, medicine.medical_specialty, Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use, Platelet Aggregation Inhibitors/therapeutic use, Blood Pressure, 030204 cardiovascular system & hematology, Peripheral Arterial Disease, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Internal medicine, Journal Article, medicine, Humans, Prospective Studies, 030212 general & internal medicine, Cardiovascular Diseases/etiology, Risk factor, Prospective cohort study, 11 Medical and Health Sciences, Aged, Aspirin, Lipids/blood, business.industry, Absolute risk reduction, Guideline, Middle Aged, Guideline Adherence/statistics & numerical data, Lipids, United Kingdom, Blood pressure, Cardiovascular Diseases, Cohort, Peripheral Arterial Disease/complications, Female, Smoking Cessation, Surgery, Guideline Adherence, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Vascular and Endovascular Research Network (VERN) Collaborators, business, Risk Reduction Behavior, Platelet Aggregation Inhibitors, Fibrinolytic agent, medicine.drug
Abstract

Background Previous research has suggested that patients with peripheral artery disease (PAD) are not offered adequate risk factor modification, despite their high cardiovascular risk. The aim of this study was to assess the cardiovascular profiles of patients with PAD and quantify the survival benefits of target-based risk factor modification. Methods The Vascular and Endovascular Research Network (VERN) prospectively collected cardiovascular profiles of patients with PAD from ten UK vascular centres (April to June 2018) to assess practice against UK and European goal-directed best medical therapy guidelines. Risk and benefits of risk factor control were estimated using the SMART-REACH model, a validated cardiovascular prediction tool for patients with PAD. Results Some 440 patients (mean(s.d.) age 70(11) years, 24·8 per cent women) were included in the study. Mean(s.d.) cholesterol (4·3(1·2) mmol/l) and LDL-cholesterol (2·7(1·1) mmol/l) levels were above recommended targets; 319 patients (72·5 per cent) were hypertensive and 343 (78·0 per cent) were active smokers. Only 11·1 per cent of patients were prescribed high-dose statin therapy and 39·1 per cent an antithrombotic agent. The median calculated risk of a major cardiovascular event over 10 years was 53 (i.q.r. 44–62) per cent. Controlling all modifiable cardiovascular risk factors based on UK and European guidance targets (LDL-cholesterol less than 2 mmol/l, systolic BP under 140 mmHg, smoking cessation, antiplatelet therapy) would lead to an absolute risk reduction of the median 10-year cardiovascular risk by 29 (20–38) per cent with 6·3 (4·0–9·3) cardiovascular disease-free years gained. Conclusion The medical management of patients with PAD in this secondary care cohort was suboptimal. Controlling modifiable risk factors to guideline-based targets would confer significant patient benefit.

Published
2019
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3. Upgrading right ventricular pacemakers to biventricular pacing or conduction system pacing: a systematic review and meta-analysis.

Author

Kaza N, Htun V, Miyazawa A, Simader F, Porter B, Howard JP, Arnold AD, Naraen A, Luria D, Glikson M, Israel C, Francis DP, Whinnett ZI, Shun-Shin MJ, and Keene D

Subjects
Humans, Cardiac Pacing, Artificial adverse effects, Cardiac Conduction System Disease therapy, Heart Conduction System, Ventricular Function, Left, Stroke Volume physiology, Treatment Outcome, Cardiac Resynchronization Therapy adverse effects, Pacemaker, Artificial, Ventricular Dysfunction, Left, Heart Failure diagnosis, Heart Failure therapy
Abstract

Guidelines recommend patients undergoing a first pacemaker implant who have even mild left ventricular (LV) impairment should receive biventricular or conduction system pacing (CSP). There is no corresponding recommendation for patients who already have a pacemaker. We conducted a meta-analysis of randomized controlled trials (RCTs) and observational studies assessing device upgrades. The primary outcome was the echocardiographic change in LV ejection fraction (LVEF). Six RCTs (randomizing 161 patients) and 47 observational studies (2644 patients) assessing the efficacy of upgrade to biventricular pacing were eligible for analysis. Eight observational studies recruiting 217 patients of CSP upgrade were also eligible. Fourteen additional studies contributed data on complications (25 412 patients). Randomized controlled trials of biventricular pacing upgrade showed LVEF improvement of +8.4% from 35.5% and observational studies: +8.4% from 25.7%. Observational studies of left bundle branch area pacing upgrade showed +11.1% improvement from 39.0% and observational studies of His bundle pacing upgrade showed +12.7% improvement from 36.0%. New York Heart Association class decreased by -0.4, -0.8, -1.0, and -1.2, respectively. Randomized controlled trials of biventricular upgrade found improvement in Minnesota Heart Failure Score (-6.9 points) and peak oxygen uptake (+1.1 mL/kg/min). This was also seen in observational studies of biventricular upgrades (-19.67 points and +2.63 mL/kg/min, respectively). In studies of the biventricular upgrade, complication rates averaged 2% for pneumothorax, 1.4% for tamponade, and 3.7% for infection over 24 months of mean follow-up. Lead-related complications occurred in 3.3% of biventricular upgrades and 1.8% of CSP upgrades. Randomized controlled trials show significant physiological and symptomatic benefits of upgrading pacemakers to biventricular pacing. Observational studies show similar effects between biventricular pacing upgrade and CSP upgrade., Competing Interests: Conflict of interest: none declared., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Published
2023
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4. Proteomic profiling of cellular steatosis with concomitant oxidative stress in vitro.

Author

Lockman KA, Htun V, Sinha R, Treskes P, Nelson LJ, Martin SF, Rogers SM, Le Bihan T, Hayes PC, and Plevris JN

Subjects
Aldehyde Reductase genetics, Aldehyde Reductase metabolism, Aldo-Keto Reductases, Cell Line, Tumor, Cholesterol biosynthesis, Fatty Acids, Nonesterified metabolism, Gene Expression Profiling, Gene Expression Regulation, Gene Ontology, Hepatocytes cytology, Hepatocytes metabolism, Histones genetics, Histones metabolism, Humans, Lipid Peroxidation, Lipogenesis drug effects, Lipogenesis genetics, Models, Biological, Molecular Sequence Annotation, Non-alcoholic Fatty Liver Disease genetics, Non-alcoholic Fatty Liver Disease metabolism, Non-alcoholic Fatty Liver Disease pathology, Oxidative Stress, Protein Biosynthesis drug effects, Ammonia pharmacology, Caprylates pharmacology, Hepatocytes drug effects, Lactic Acid pharmacology, Proteomics, Pyruvic Acid pharmacology
Abstract

Background: Nutrient excess underpins the development of nonalcoholic fatty liver disease (NAFLD). The ensuing metabolic derangement is characterised by increased cellular respiration, oxidative stress and mitochondrial impairment. We have previously recapitulated these events in an in vitro cellular steatosis model. Here, we examined the distinct patterns of protein expression involved using a proteomics approach., Methods: Human hepatoblastoma C3A cells were treated with a combination of energy substrates; lactate (L), pyruvate (P), octanoate (O) and ammonia (N). Proteins extracts were trypsinized and analyzed on a capillary HPLC OrbitrapXL mass spectrometer. Proteins were quantified using a label-free intensity based approach. Functional enrichment analysis was performed using ToppCluster via Gene Ontology (GO) database., Results: Of the 1327 proteins identified, 104 were differentially expressed between LPON and untreated cells (defined as: ≥2 peptides; fold change ≥1.5; p-value <0.05). Seventy of these were upregulated with LPON. Functional enrichment analysis revealed enhanced protein biosynthesis accompanied by downregulation of histones H2A type 1-A, H1.2, H1.5 and H1.0I in LPON cells. Lipid binding annotations were also enriched as well as proteins involved in cholesterol synthesis, uptake and efflux. Increased expression of aldo-keto reductase family 1, member C1 and C3 suggests enhanced sterol metabolism and increased ROS-mediated lipid peroxidation., Conclusions: The surge of energy substrates diverts free fatty acid metabolism towards pathways that can mitigate lipotoxicity. The histones depletion may represent an adaptation to increased protein synthesis. However, this can also expose DNA to oxidative stress thus should be explored further in the context of NAFLD progression.

Published
2016
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