Larissa Fabritz

Larissa Fabritz
University of Birmingham · Institute of Cardiovascular Sciences

Professor Dr

About

264
Publications
28,171
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6,118
Citations
Additional affiliations
September 2011 - present
University of Birmingham
Position
  • Lecturer

Publications

Publications (264)
Preprint
Androgenic anabolic steroids (AAS) are commonly abused by young men. Male sex associates with earlier manifestation of common and rare cardiac conditions including atrial fibrillation and arrhythmogenic right ventricular cardiomyopathy (ARVC). Clinical data suggest an atrial involvement in ARVC. The disease is caused by desmosomal gene defects such...
Article
ZUSAMMENFASSUNG Gegenstand und Ziel Aufgrund der erhöhten Rate für Morbidität und Mortalität durch thrombembolische Ereignisse bei Vorhofflimmern ist die frühe Erkennung und Antikoagulation die zentrale Strategie zur Prävention von Schlaganfällen und systemischen Embolien. Wegen der steigenden Prävalenz von Vorhofflimmern, insbesondere in höherem L...
Article
Funding Acknowledgements Type of funding sources: Public grant(s) – EU funding. Main funding source(s): European Union Horizon 2020 CATCH ME; Cardiovascular Research Netherlands RACE V Background Little is known about changes in the atrial transcriptome associated with paroxysmal and persistent atrial fibrillation (AF). Purpose To identify major...
Article
Funding Acknowledgements Type of funding sources: Public grant(s) – EU funding. Main funding source(s): Horizon 2020 Background Risk factors for atrial fibrillation (AF), such as ageing, heart failure and AF itself, enhance AF propensity partly by inducing atrial fibrosis. Atrial endomysial fibrosis, a type of reactive fibrosis occurring between c...
Article
Funding Acknowledgements Type of funding sources: Private company. Main funding source(s): FARAPULSE, Inc. Introduction Thermal energy sources damage the entire atrial tissue during pulmonary vein isolation (PVI) including cardiac nerves and ganglia. This induces a postinterventional increase in heart rate. Pulsed-field ablation (PFA), a new non-t...
Article
Full-text available
Optical mapping of animal models is a widely used technique in pre-clinical cardiac research. It has several advantages over other methods, including higher spatial resolution, contactless recording and direct visualisation of action potentials and calcium transients. Optical mapping enables simultaneous study of action potential and calcium transi...
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Full-text available
Introduction: Screening for atrial fibrillation and timely initiation of oral anticoagulation, rhythm management, and treatment of concomitant cardiovascular conditions can improve outcomes in high-risk populations. Whether wearables can facilitate screening in older adults is not known. Methods and analyses: The multicenter, international, inve...
Article
Background Natriuretic peptides are routinely quantified to diagnose heart failure (HF). Their concentrations are also elevated in atrial fibrillation (AF). To clarify their value in predicting future cardiovascular events, we measured natriuretic peptides in unselected patients with cardiovascular conditions and related their concentrations to AF...
Article
Atrial fibrillation (AF) affects over 1% of the population and is a leading cause of stroke and heart failure in the elderly. A feared side effect of sodium channel blocker therapy, ventricular pro-arrhythmia, appears to be relatively rare in patients with AF. The biophysical reasons for this relative safety of sodium blockers are not known. Our da...
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Full-text available
We report a family with heterozygous deletion of exons 3–6 of the LMNA gene. The main presentation of affected family members was characterized by ventricular and supraventricular arrhythmias, atrioventricular (AV) block and sudden cardiac death (SCD) but also by severe dilative cardiomyopathy (DCM). We report on two siblings, a 36-year-old female...
Article
Cardiovascular diseases represent a major cause of morbidity and mortality, necessitating research to improve diagnostics, and to discover and test novel preventive and curative therapies. All of which warrant experimental models that recapitulate human disease. The translation of basic science results to clinical practice is a challenging task. In...
Article
Aims Natriuretic peptides are routinely quantified to diagnose heart failure (HF). Their concentrations are also elevated in atrial fibrillation (AF). To clarify their interpretation, we measured natriuretic peptides in unselected patients with cardiovascular conditions and related their concentrations to AF and HF status and to outcomes. Methods...
Article
Background/Introduction Cardiovascular (CV) diseases including atrial fibrillation and arteriosclerosis are associated with impaired cognitive function. Cognitive dysfunction can impact the process of shared clinical decision making, reduce adherence to polypharmacy, and decrease quality of life. The prevalence of cognitive dysfunction in contempor...
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Introduction AF increases the risk of stroke by a factor of five [1], oral anticoagulants (OACs) can reduce stroke by ∼60% and death by ∼25% [2]. Pharmacists, especially those based in primary care are well placed to support patients in this therapeutic area. However, research indicates that pharmacists do not always feel confident in supporting pa...
Article
Background The dynamic changes and stability of blood biomarkers over time and after treatment are not well known. In this study, we describe changes in 12 centrally quantified known and novel cardiovascular biomarkers, prior to and 3 months after ablation for atrial fibrillation (AF). Purpose In patients enrolled in the AXAFA-AFNET5 trial, we 1)...
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Aim Due to improved therapy in childhood, many patients with congenital heart disease reach adulthood and are termed adults with congenital heart disease (ACHD). ACHD often develop heart failure (HF) as a consequence of initial palliative surgery or complex anatomy and subsequently require advanced HF therapy. ACHD are usually excluded from trials...
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Full-text available
Rationale: Fibrosis promotes the maintenance of atrial fibrillation (AF), making it resistant to therapy. Improved understanding of the molecular mechanisms leading to atrial fibrosis will open new pathways towards effective antifibrotic therapies. Objective: This study aims to decipher the mechanistic interplay between polo-like kinase 2 (PLK2) an...
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Full-text available
Cardiac arrhythmias are a major cause of death and disability. A large number of experimental cell and animal models have been developed to study arrhythmogenic diseases. These models have provided important insights into the underlying arrhythmia mechanisms and translational options for their therapeutic management. This position paper from the ES...
Article
Objective The pharmacological management of atrial fibrillation (AF) comprises anticoagulation, for stroke prophylaxis, and rate or rhythm control drugs to alleviate symptoms and prevent heart failure. The aim of this study was to investigate trends in the proportion of patients with AF prescribed pharmacological therapies in the UK between 2008 an...
Conference Paper
Full-text available
Background Uraemic cardiomyopathy is present in >70% of patients with end-stage renal disease (ESRD). Myocardial fibrosis is a hallmark of uraemic cardiomyopathy and is associated with an increased risk of heart failure and sudden cardiac death. Coronary microvascular dysfunction (CMD) is common in ESRD and is an adverse prognostic marker that may...
Article
Full-text available
Background Adherence rates of preventative medication for cardiovascular disease (CVD) have been reported as 57%, and approximately 9% of all CVD events in Europe are attributable to poor medication adherence. Mobile health technologies, particularly mobile apps, have the potential to improve medication adherence and clinical outcomes. Objective T...
Article
Funding Acknowledgements Type of funding sources: Public grant(s) – EU funding. Main funding source(s): CATCH ME Foundation Leducq BACKGROUND In cardiac myocytes, desmosomal proteins and ion channels form macromolecular complexes important for maintaining cell adhesion and electrical integrity. High serum levels of androgenic anabolic steroids (AA...
Article
Funding Acknowledgements Type of funding sources: Public grant(s) – EU funding. Main funding source(s): CATCH ME Horizon 2020, EU-H2020-PHC-RIA (633196) CVON2014-09, RACE V: Reappraisal of Atrial Fibrillation: Interaction between hyperCoagulability, Electrical remodeling, and Vascular Destabilisation in the Progression of AF Background Atrial fibr...
Conference Paper
Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): BHF MRC Introduction Cardiac fibroblasts (cFbs) are responsible for deposition of extracellular matrix in the heart, providing support to the contracting myocardium and contributing to a myriad of physiological signalling processes. Prolonged and exces...
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Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): British Heart Foundation Leducq Foundation Background The point mutation M1875T in the SCN5A gene, which encodes the pore-forming α-subunit of the cardiac voltage-gated Na+ channel Nav1.5, has been associated with familial atrial fibrillation (AF), but its effect...
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Funding Acknowledgements Type of funding sources: Public grant(s) – EU funding. Main funding source(s): TRAIN-HEART Innovative Training Network, funded by the European Union’s Horizon 2020 research and innovation program (under the Marie Sklodowska-Curie grant agreement no. 813716) Characterizing Atrial fibrillation by Translating its Causes into H...
Article
Funding Acknowledgements Type of funding sources: Public grant(s) – EU funding. Main funding source(s): CATCH ME European Commission H2020 grant (no. 633196) Background Several novel blood biomarkers were recently found to reflect underlying pathophysiology implicated in atrial fibrillation (AF). These biomarkers could be used for stratifying pati...
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Full-text available
Background Coronary microvascular dysfunction (CMD) is common in end-stage renal disease (ESRD) and is an adverse prognostic marker. Coronary flow velocity reserve (CFVR) is a measure of coronary microvascular function and can be assessed using Doppler echocardiography. Reduced CFVR in ESRD has been attributed to factors such as diabetes, hypertens...
Article
Full-text available
Background Although atrial fibrillation (AF) ablation is increasingly used for rhythm control therapy, antiarrhythmic drugs (AADs) are commonly used, either alone or in combination with ablation. The effectiveness of AADs is highly variable. Prior work from our group suggests that alterations in the atrial resting membrane potential (RMP) induced b...
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Funding Acknowledgements Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): (1) University Hospitals Birmingham Charity (2) Metchley Park Medical Society Introduction Coronary microvascular dysfunction (CMD) is common among patients with end-stage renal disease (ESRD) and confers poor prognosis. Coronary flow ve...
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Background Large-scale screening for atrial fibrillation (AF) requires reliable methods to identify at-risk populations. Using an experimental semi-quantitative biomarker assay, B-type natriuretic peptide (BNP) and fibroblast growth factor 23 (FGF23) were recently identified as the most suitable biomarkers for detecting AF in combination with simpl...
Article
The prejunctional norepinephrine transporter (NET) is responsible for the clearance of released norepinephrine (NE) back into the sympathetic nerve terminal. NET regulation must be tightly controlled as variations could have important implications for neurotransmission. Thus far, the effects of sympathetic neuronal activity on NET function have bee...
Article
Aims Genetically altered mice are powerful models to investigate mechanisms of atrial arrhythmias, but normal ranges for murine atrial electrophysiology have not been robustly characterized. Methods and results We analyzed results from 221 electrophysiological (EP) studies in isolated, Langendorff-perfused hearts of wildtype mice (114 female, 107...
Article
Aims The risk of developing atrial fibrillation (AF) and its complications continues to increase, despite good progress in preventing AF-related strokes. Methods and results This article summarizes the outcomes of the 7th Consensus Conference of the Atrial Fibrillation NETwork (AFNET) and the European Heart Rhythm Association (EHRA) held in Lisbon...
Article
Full-text available
Background: Alström syndrome (ALMS) is a rare ciliopathy characterised by early onset insulin resistance, obesity, and dyslipidaemia and is a model for diseases that have huge social, health and economic impact. Cardiomyopathy develops in the majority, with high rates of morbidity and mortality, the definitive features of which are coarse replacem...
Article
Full-text available
Many cardiac pathologies involve changes in tissue structure. Conventional analysis of structural features is extremely time-consuming and subject to observer bias. The possibility to determine spatial interrelations between these features is often not fully exploited. We developed a staining protocol and an ImageJ-based tool (JavaCyte) for automat...
Article
Background: Kinase oxidation is a critical signalling mechanism through which changes in the intracellular redox state alter cardiac function. In the myocardium, type-1 protein kinase A (PKARIα) can be reversibly oxidized, forming interprotein disulfide bonds within the holoenzyme complex. However, the effect of PKARIα disulfide formation on downst...
Conference Paper
Full-text available
Background Studying cardiac electrophysiology in isolated perfused beating murine hearts is a well-established method. The ranges of normal values for left atrial (LA) action potential durations (LA-APD), activation times (LA-AT) and effective refractory periods (atrial ERP) in murine wildtype (WT) are not well known. Purpose This study aimed to e...
Preprint
BACKGROUND Adherence rates of preventative medication for cardiovascular disease (CVD) have been reported as 57%, and approximately 9% of all CVD events in Europe are attributable to poor medication adherence. Mobile health technologies, particularly mobile apps, have the potential to improve medication adherence and clinical outcomes. OBJECTIVE T...
Article
Full-text available
BACKGROUND Genomic and experimental studies suggest a role for PITX2 in atrial fibrillation (AF). To assess if this association is relevant for recurrent AF in patients, we tested whether left atrial PITX2 affects recurrent AF after AF ablation.METHOD SmRNA concentrations of PITX2 and its cardiac isoform, PITX2c, were quantified in left atrial appe...
Article
Full-text available
Background Coronary microvascular dysfunction is prevalent in chronic kidney disease (CKD), and may contribute to the development of myocardial dysfunction in CKD. Coronary flow velocity reserve (CFVR) is a marker of coronary microvascular function and falls with increasing CKD stage. Living kidney donors have renal function consistent with early s...
Article
Full-text available
Aims: Arrhythmias and sudden cardiac death (SCD) occur commonly in patients with heart failure. We found T-box 5 (TBX5) dysregulated in ventricular myocardium from heart failure patients and thus we hypothesized that TBX5 reduction contributes to arrhythmia development in these patients. To understand the underlying mechanisms, we aimed to reveal...
Article
Full-text available
Objective Circulating biomarkers are useful in detection and monitoring of cardiovascular diseases. However, their role in aortic valve disease is unclear. Mechanisms are rapidly elucidated and sex differences are suggested to be involved. Therefore, we sought to identify biomarkers involved in aortic valve calcification (AVC) stratified by sex.Met...
Article
Full-text available
Cardiac optical mapping utilises fluorescent dyes to directly image the electrical function of the heart at a high spatio-temporal resolution which far exceeds electrode techniques. It has therefore become an invaluable tool in cardiac electrophysiological research to map the propagation of heterogeneous electrical signals across the myocardium. In...
Article
Genome-wide association studies have uncovered over a 100 genetic loci associated with atrial fibrillation (AF), the most common arrhythmia. Many of the top AF-associated loci harbor key cardiac transcription factors, including PITX2, TBX5, PRRX1, and ZFHX3. Moreover, the vast majority of the AF-associated variants lie within noncoding regions of t...
Article
Despite recent progress in the understanding of cardiac ion channel function and its role in inherited forms of ventricular arrhythmias, the molecular basis of cardiac conduction disorders often remains unresolved. We aimed to elucidate the genetic background of familial atrioventricular block (AVB) using a whole exome sequencing (WES) approach. In...
Conference Paper
Background Studying cardiac electrophysiology in isolated perfused beating murine hearts is a well-established method. The range of normal values for left atrial action potential durations (LA-APD), activation times (LA-AT) and effective refractory periods (atrial ERP) in murine wildtype (WT) is not well known. Purpose This study aimed to establis...
Article
Full-text available
Objectives Prolonged ECG monitoring is clinically useful to detect unknown atrial fibrillation (AF) in stroke survivors. The diagnostic yield of prolonged ECG monitoring in other patient populations is less well characterised. We therefore studied the diagnostic yield of prolonged Holter ECG monitoring for AF in an unselected patient cohort referre...
Preprint
Full-text available
Background Alstrom syndrome (ALMS) is a rare ciliopathy characterised by early onset insulin resistance, obesity, and dyslipidaemia and is a model for diseases that have huge social, health and economic impact. Dilated cardiomyopathy develops in the majority, with high rates of morbidity and mortality, the definitive feature of which is the presenc...
Preprint
Full-text available
Background Alström syndrome (ALMS) is a rare ciliopathy characterised by early onset insulin resistance, obesity, and dyslipidaemia and is a model for diseases that have huge social, health and economic impact. Cardiomyopathy develops in the majority, with high rates of morbidity and mortality, the definitive feature of which is the presence of coa...
Preprint
Full-text available
Background Alström syndrome (ALMS) is a rare ciliopathy characterised by early onset insulin resistance, obesity, and dyslipidaemia and is a model for diseases that have huge social, health and economic impact. Cardiomyopathy develops in the majority, with high rates of morbidity and mortality, the definitive features of which are coarse replacemen...
Article
Full-text available
Aims: We assessed the performance of modelsf (risk scores) for predicting recurrence of atrial fibrillation (AF) in patients who have undergone catheter ablation. Methods and results: Systematic searches of bibliographic databases were conducted (November 2018). Studies were eligible for inclusion if they reported the development, validation, or...
Article
Full-text available
Chronic kidney disease is highly prevalent, affecting 10% to 15% of the adult population worldwide and is associated with increased cardiovascular morbidity and mortality. As chronic kidney disease worsens, a unique cardiovascular phenotype develops characterized by heart muscle disease, increased arterial stiffness, atherosclerosis, and hypertensi...
Article
Full-text available
Aims: Study sex-differences in efficacy and safety of atrial fibrillation (AF) ablation. Methods and results: We assessed first AF ablation outcomes on continuous anticoagulation in 633 patients [209 (33%) women and 424 (67%) men] in a pre-specified subgroup analysis of the AXAFA-AFNET 5 trial. We compared the primary outcome (death, stroke or t...