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The New England Journal of Medicine Apr 2024
Topics: Humans; Arrhythmias, Cardiac; Cardiomyopathies; Fibrosis; Heart Atria; Hypertension; Serine Endopeptidases
PubMed: 38657260
DOI: 10.1056/NEJMc2313870 -
The New England Journal of Medicine Apr 2024
Topics: Adult; Female; Humans; Alleles; Arrhythmias, Cardiac; Atrial Fibrillation; Cardiomyopathies; Fibrosis; Heart Atria; Hypertension; Loss of Function Mutation; Serine Endopeptidases; South Asian People
PubMed: 38657259
DOI: 10.1056/NEJMc2313870 -
The New England Journal of Medicine Apr 2024
Topics: Humans; Arrhythmias, Cardiac; Cardiomyopathies; Fibrosis; Heart Atria; Hypertension; Serine Endopeptidases
PubMed: 38657261
DOI: 10.1056/NEJMc2313870 -
Advances in Experimental Medicine and... 2012During the last decades Ca(2+) has been found to play a crucial role in cardiac arrhythmias associated with heart failure and a number of congenital arrhythmia... (Review)
Review
During the last decades Ca(2+) has been found to play a crucial role in cardiac arrhythmias associated with heart failure and a number of congenital arrhythmia syndromes. Recent studies demonstrated that altered atrial Ca(2+) cycling may promote the initiation and maintenance of atrial fibrillation, the most common clinical arrhythmia that contributes significantly to population morbidity and mortality. This article describes physiological Ca(2+) cycling mechanisms in atrial cardiomyocytes and relates them to fundamental cellular proarrhythmic mechanisms involving Ca(2+) signaling abnormalities in the atrium during atrial fibrillation.
Topics: Animals; Arrhythmias, Cardiac; Atrial Fibrillation; Calcium; Excitation Contraction Coupling; Heart Atria; Heart Diseases; Humans; Myocytes, Cardiac; Sarcoplasmic Reticulum Calcium-Transporting ATPases
PubMed: 22453988
DOI: 10.1007/978-94-007-2888-2_53 -
The New England Journal of Medicine Apr 2024
Topics: Humans; Cardiomyopathies; Fibrosis; Hypertension; Heart Atria; Arrhythmias, Cardiac
PubMed: 38657262
DOI: 10.1056/NEJMc2313870 -
Annals of Biomedical Engineering Jan 2021Atrial anisotropy affects electrical propagation patterns, anchor locations of atrial reentrant drivers, and atrial mechanics. However, patient-specific atrial fibre...
Atrial anisotropy affects electrical propagation patterns, anchor locations of atrial reentrant drivers, and atrial mechanics. However, patient-specific atrial fibre fields and anisotropy measurements are not currently available, and consequently assigning fibre fields to atrial models is challenging. We aimed to construct an atrial fibre atlas from a high-resolution DTMRI dataset that optimally reproduces electrophysiology simulation predictions corresponding to patient-specific fibre fields, and to develop a methodology for automatically assigning fibres to patient-specific anatomies. We extended an atrial coordinate system to map the pulmonary veins, vena cava and appendages to standardised positions in the coordinate system corresponding to the average location across the anatomies. We then expressed each fibre field in this atrial coordinate system and calculated an average fibre field. To assess the effects of fibre field on patient-specific modelling predictions, we calculated paced activation time maps and electrical driver locations during AF. In total, 756 activation time maps were calculated (7 anatomies with 9 fibre maps and 2 pacing locations, for the endocardial, epicardial and bilayer surface models of the LA and RA). Patient-specific fibre fields had a relatively small effect on average paced activation maps (range of mean local activation time difference for LA fields: 2.67-3.60 ms, and for RA fields: 2.29-3.44 ms), but had a larger effect on maximum LAT differences (range for LA 12.7-16.6%; range for RA 11.9-15.0%). A total of 126 phase singularity density maps were calculated (7 anatomies with 9 fibre maps for the LA and RA bilayer models). The fibre field corresponding to anatomy 1 had the highest median PS density map correlation coefficient for LA bilayer simulations (0.44 compared to the other correlations, ranging from 0.14 to 0.39), while the average fibre field had the highest correlation for the RA bilayer simulations (0.61 compared to the other correlations, ranging from 0.37 to 0.56). For sinus rhythm simulations, average activation time is robust to fibre field direction; however, maximum differences can still be significant. Patient specific fibres are more important for arrhythmia simulations, particularly in the left atrium. We propose using the fibre field corresponding to DTMRI dataset 1 for LA simulations, and the average fibre field for RA simulations as these optimally predicted arrhythmia properties.
Topics: Anisotropy; Arrhythmias, Cardiac; Atlases as Topic; Atrial Function; Diffusion Magnetic Resonance Imaging; Heart Atria; Humans; Patient-Specific Modeling
PubMed: 32458222
DOI: 10.1007/s10439-020-02525-w -
JAMA Internal Medicine Apr 2022
Topics: Arrhythmias, Cardiac; Electrocardiography; Heart Atria; Humans
PubMed: 35156997
DOI: 10.1001/jamainternmed.2021.8466 -
Circulation Research Apr 2014Atrial fibrillation (AF) is a complex disease with multiple inter-relating causes culminating in rapid, seemingly disorganized atrial activation. Therapy targeting AF is... (Review)
Review
Atrial fibrillation (AF) is a complex disease with multiple inter-relating causes culminating in rapid, seemingly disorganized atrial activation. Therapy targeting AF is rapidly changing and improving. The purpose of this review is to summarize current state-of-the-art diagnostic and therapeutic modalities for treatment of AF. The review focuses on reviewing treatment as it relates to the pathophysiological basis of disease and reviews preclinical and clinical evidence for potential new diagnostic and therapeutic modalities, including imaging, biomarkers, pharmacological therapy, and ablative strategies for AF. Current ablation and drug therapy approaches to treating AF are largely based on treating the arrhythmia once the substrate occurs and is more effective in paroxysmal AF rather than persistent or permanent AF. However, there is much research aimed at prevention strategies, targeting AF substrate, so-called upstream therapy. Improved diagnostics, using imaging, genetics, and biomarkers, are needed to better identify subtypes of AF based on underlying substrate/mechanism to allow more directed therapeutic approaches. In addition, novel antiarrhythmics with more atrial specific effects may reduce limiting proarrhythmic side effects. Advances in ablation therapy are aimed at improving technology to reduce procedure time and in mechanism-targeted approaches.
Topics: Action Potentials; Animals; Anti-Arrhythmia Agents; Atrial Fibrillation; Catheter Ablation; Diffusion of Innovation; Forecasting; Heart Atria; Heart Conduction System; Humans; Treatment Outcome
PubMed: 24763469
DOI: 10.1161/CIRCRESAHA.114.302362 -
Methods in Molecular Biology (Clifton,... 2022Gene therapy appears promising as a targeted treatment of cardiac diseases. Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and also a major...
Gene therapy appears promising as a targeted treatment of cardiac diseases. Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and also a major contributor to stroke, heart failure, and death. Mechanisms that initiate and sustain AF are associated with structural and electrophysiological remodeling in the whole atria. Selection of the appropriate gene delivery method is critical for transduction efficacy. The ideal gene delivery method to manage AF should provide widespread and sufficient exposure to the transgene in atria only that safely maintains the homeostasis of the heart without off-target expression. All these requirements can be achieved using atrial gene painting that is directly applied to the atrial epicardial surface. In this chapter, we present the advantages of atrial gene painting and the experimental method, as applied to a large animal model of AF.
Topics: Animals; Atrial Fibrillation; Disease Models, Animal; Heart Atria; Heart Diseases; Heart Failure
PubMed: 36040597
DOI: 10.1007/978-1-0716-2707-5_16 -
Acta Physiologica (Oxford, England) Feb 2013RyR2 mutations are associated with catecholaminergic polymorphic tachycardia, a condition characterized by ventricular and atrial arrhythmias. The present experiments...
AIM
RyR2 mutations are associated with catecholaminergic polymorphic tachycardia, a condition characterized by ventricular and atrial arrhythmias. The present experiments investigate the atrial electrophysiology of homozygotic murine RyR2-P2328S (RyR2(S/S)) hearts for ectopic triggering events and for conduction abnormalities that might provide a re-entrant substrate.
METHODS
Electrocardiograph recordings were made from regularly stimulated RyR2(S/S) and wild type (WT) hearts, perfused using a novel modified Langendorff preparation. This permitted the simultaneous use of either floating intracellular microelectrodes to measure action potential (AP) parameters, or a multielectrode array to measure epicardial conduction velocity (CV).
RESULTS
RyR2(S/S) showed frequent sustained tachyarrhythmias, delayed afterdepolarizations and ectopic APs, increased interatrial conduction delays, reduced epicardial CVs and reduced maximum rates of AP depolarization ((dV/dt)(max)), despite similar effective refractory periods, AP durations and AP amplitudes. Effective interatrial CVs and (dV/dt)(max) values of APs following ectopic (S2) stimulation were lower than those of APs following regular stimulation and decreased with shortening S1S2 intervals. However, although RyR2(S/S) atria showed arrhythmias over a wider range of S1S2 intervals, the interatrial CV and (dV/dt)(max) of S2 APs provoking such arrhythmias were similar in RyR2(S/S) and WT.
CONCLUSIONS
These results suggest that abnormal intracellular Ca(2+) homoeostasis produces both arrhythmic triggers and a slow-conducting arrhythmic substrate in RyR2(S/S) atria. A similar mechanism might also contribute to arrhythmogenesis in other conditions, associated with diastolic Ca(2+) release, such as atrial fibrillation.
Topics: Action Potentials; Animals; Arrhythmias, Cardiac; Calcium; Electrocardiography; Heart Atria; Mice; Mice, Mutant Strains; Organ Culture Techniques; Ryanodine Receptor Calcium Release Channel
PubMed: 22958452
DOI: 10.1111/apha.12006