A5000336640- Cardiac electrophysiology and arrhythmias
- Ion channel regulation and function
- Cardiac Arrhythmias and Treatments
- Cardiac pacing and defibrillation studies
- Atrial Fibrillation Management and Outcomes
- Cardiomyopathy and Myosin Studies
- Receptor Mechanisms and Signaling
- ECG Monitoring and Analysis
- Cardiovascular Effects of Exercise
- Cardiovascular Function and Risk Factors
- Cardiac Ischemia and Reperfusion
- Advanced MRI Techniques and Applications
- Cardiac Imaging and Diagnostics
- Neuroscience and Neural Engineering
- Neuroscience and Neuropharmacology Research
- TGF-β signaling in diseases
- Adipose Tissue and Metabolism
- Neurological disorders and treatments
- Viral Infections and Immunology Research
- Fuel Cells and Related Materials
- Electrochemical Analysis and Applications
- Mitochondrial Function and Pathology
- RNA and protein synthesis mechanisms
- Pancreatic and Hepatic Oncology Research
- Cardiac Arrest and Resuscitation
University of Cambridge
2015-2024
Papworth Hospital NHS Foundation Trust
2013-2023
Villanova University
2023
Addenbrooke's Hospital
1998-2022
Papworth Hospital
2010-2022
University of Ulster
2020-2022
Royal Victoria Hospital
2020-2022
Aalborg University
2021
Polskie Towarzystwo Gastroenterologii
2019
Grace (United States)
2011-2019
The ESC Guidelines represent the views of and were produced after careful consideration scientific medical knowledge, evidence available at time their publication.The is not responsible in event any contradiction, discrepancy, and/or ambiguity between other official recommendations or guidelines issued by relevant public health authorities, particular relation to good use healthcare therapeutic strategies.Health professionals are encouraged take fully into account when exercising clinical...
Implantable cardioverter-defibrillators (ICDs) prevent sudden death from cardiac causes in selected patients but require the use of transvenous lead systems. To eliminate need for venous access, we designed and tested an entirely subcutaneous ICD system.First, conducted two short-term clinical trials to identify a suitable device configuration assess energy requirements. We evaluated four configurations 78 who were candidates implantation subsequently best 49 additional determine...
Voltage-gated sodium channels drive the initial depolarization phase of cardiac action potential and therefore critically determine conduction excitation through heart. In patients, deletions or loss-of-function mutations channel gene, SCN5A , have been associated with a wide range arrhythmias including bradycardia (heart rate slowing), atrioventricular delay, ventricular fibrillation. The pathophysiological basis these clinical conditions is unresolved. Here we show that disruption mouse...
The purpose of this Consensus Statement is to focus on implantable cardioverter-defibrillator (ICD) deactivation in patients with irreversible or terminal illness. This statement summarizes the opinions Task Force members, convened by European Heart Rhythm Association (EHRA) and Society (HRS), based ethical legal principles, as well their own clinical, scientific, technical experience. It directed all healthcare professionals who treat implanted ICDs, nearing end life, order improve patient...
Background— We have previously linked hereditary progressive cardiac conduction defect (hereditary Lenègre’s disease) to a loss-of-function mutation in the gene encoding main Na + channel, SCN5A . In present study, we investigated heterozygous Scn5a -knockout mice ( +/− mice) as model for disease. Methods and Results— mice, surface ECG recordings showed age-related lengthening of P-wave PR- QRS-interval duration, coinciding with previous observations patients Old but not young extensive...
AimsThe subcutaneous implantable cardioverter defibrillator (S-ICD) was introduced to overcome complications related transvenous leads. Adoption of the S-ICD requires implanters learn a new implantation technique. The aim this study assess learning curve for with respect implant-related complications, procedure time, and inappropriate shocks (IASs).
Background Identification and elimination of nonpulmonary vein targets may improve clinical outcomes in patients with persistent atrial fibrillation (AF). We report on the use a novel, noncontact imaging mapping system that uses ultrasound to reconstruct chamber anatomy measures timing density dipolar, ionic activation (ie, charge density) across myocardium guide ablation arrhythmias. Methods The prospective, nonrandomized UNCOVER AF trial (Utilizing Novel Dipole Density Capabilities...
BACKGROUND. Spatial resolution in cardiac activation maps based on voltage measurement is limited by far-field interference. Precise characterization of electrical sources would resolve this limitation; however, practical charge-based mapping has not been achieved.
A Na(+)-HCO3- coinflux carrier and the Na(+)-H+ antiport have both been shown to contribute recovery from intracellular acidosis in cardiac tissue. We investigated participation of these mechanisms as well metabolite (lactate CO2) washout pHi after myocardial ischemia. Isovolumic ferret hearts were Langendorff-perfused with either HCO3(-)-buffered or nominally HCO3(-)-free (HEPES-buffered) medium at 30 degrees C. was estimated chemical shift 31P-nuclear magnetic resonance signal PO4-, net H+...
The SCN5A sodium channel is a major determinant for cardiac impulse propagation. We used epicardial mapping of the atria, ventricles, and septae to investigate conduction velocity (CV) in Scn5a heterozygous young old mice.Mice were divided into 4 groups: (1) (3 months) wild-type littermates (WT); (2) Scn5a-knockout mice (HZ); (3) (12 17 WT; (4) HZ. In HZ hearts, CV right but not left ventricle was reduced agreement with rightward rotation QRS axes; fibrosis virtually absent both pattern...
We have examined sino-atrial node (SAN) function in hearts from adult mice with heterozygous targeted disruption of the Scn5a gene to clarify role Scn5a-encoded cardiac Na+ channels normal SAN and mechanism(s) by which reduced channel might cause sinus dysfunction. Scn5a+/- showed depressed heart rates occasional (SA) block. Their isolated peripheral pacemaker cells a expression slowed intrinsic rates. Wild-type (WT) preparations exhibited similar activation patterns but significantly slower...
Mutations in glycerol-3-phosphate dehydrogenase 1-like (GPD1-L) protein reduce cardiac Na+ current (I(Na)) and cause Brugada Syndrome (BrS). GPD1-L has >80% amino acid homology with dehydrogenase, which is involved NAD-dependent energy metabolism.Therefore, we tested whether NAD(H) could regulate human sodium channels (Na(v)1.5).HEK293 cells stably expressing Na(v)1.5 rat neonatal cardiomyocytes were used. The influence of NADH/NAD+ on arrhythmic risk was evaluated wild-type or SCN5A(+/-)...
Mutations in the cardiac Na(+) channel gene (SCN5A) can adversely affect electric function heart, but effects be age dependent. We explored interacting of Scn5a disruption and aging on pathogenesis sinus node dysfunction a heterozygous knockout (Scn5a(+/-)) mouse model.We compared functional, histological, molecular features young (3 to 4 month) old (1 year) wild type Scn5a(+/-) mice. Both were associated with decreased heart rate variability, reduced sinoatrial automaticity, slowed...
Cell-cell and cell-matrix interactions guide organ development homeostasis by controlling lineage specification maintenance, but the underlying molecular principles are largely unknown. Here, we show that in human developing cardiomyocytes cell-cell contacts at intercalated disk connect to remodeling of actin cytoskeleton regulating RhoA-ROCK signaling maintain an active MRTF/SRF transcriptional program essential for cardiomyocyte identity. Genetic perturbation this mechanosensory pathway...
Loss-of-function mutations in SCN5A, the gene encoding Na(v)1.5 Na+ channel, are associated with inherited cardiac conduction defects and Brugada syndrome, which both exhibit variable phenotypic penetrance of defects. We investigated mechanisms this heterogeneity a mouse model heterozygous targeted disruption Scn5a (Scn5a(+/-) mice) compared our results to those obtained patients loss-of-function SCN5A.Based on ECG, 10-week-old Scn5a(+/-) mice were divided into 2 subgroups, one displaying...
Abstract Aims RECOVER AF evaluated the performance of whole-chamber non-contact charge-density mapping to guide ablation non-pulmonary vein (PV) targets in persistent atrial fibrillation (AF) patients following either a first or second failed procedure. Methods and results was prospective, non-randomized trial that enrolled scheduled for retreatment recurrent AF. The PVs were assessed re-isolated if necessary. maps used non-PV through elimination pathologic conduction patterns (PCPs)....
ABSTRACT Variations in the levels of smooth muscle-specific isoforms contractile proteins have been reported to occur many different vascular diseases. However, although much work has done vitro investigate regulation muscle cell differentiation, molecular mechanisms which regulate differentiation tissue vivo are unknown. Using quantitative immunofluorescence, we show that rat arteries markers correlate with cytokine TGF-β. In young mice one allele TGF-β1 gene deleted, both and reduced...
The recently described exchange protein directly activated by cAMP (Epac) has been implicated in distinct kinase A-independent cellular signalling pathways. We investigated the role of Epac activation adrenergically mediated ventricular arrhythmogenesis. In contrast to observations control conditions (n = 20), monophasic action potentials recorded 2 10 intrinsically beating and 5 20 extrinsically paced Langendorff-perfused wild-type murine hearts perfused with activator 8-pCPT-2'-O-Me-cAMP...