-
Cells Sep 2021Around the world there are 33.5 million patients suffering from atrial fibrillation (AF) with an annual increase of 5 million cases. Most AF patients have an established... (Review)
Review
Around the world there are 33.5 million patients suffering from atrial fibrillation (AF) with an annual increase of 5 million cases. Most AF patients have an established form of an atrial cardiomyopathy. The concept of atrial cardiomyopathy was introduced in 2016. Thus, therapy of underlying diseases and atrial tissue changes appear as a cornerstone of AF therapy. Furthermore, therapy or prevention of atrial endocardial changes has the potential to reduce atrial thrombogenesis and thereby cerebral stroke. The present manuscript will summarize the underlying pathophysiology and remodeling processes observed in the development of an atrial cardiomyopathy, thrombogenesis, and atrial fibrillation. In particular, the impact of oxidative stress, inflammation, diabetes, and obesity will be addressed.
Topics: Atrial Fibrillation; Atrial Remodeling; Cardiomyopathies; Diabetes Mellitus; Heart Atria; Humans; Obesity
PubMed: 34685585
DOI: 10.3390/cells10102605 -
Basic Research in Cardiology Nov 2020The molecular mechanisms underlying atrial fibrillation (AF), the most common form of arrhythmia, are poorly understood and therefore target-specific treatment options... (Review)
Review
The molecular mechanisms underlying atrial fibrillation (AF), the most common form of arrhythmia, are poorly understood and therefore target-specific treatment options remain an unmet clinical need. Excitation-contraction coupling in cardiac myocytes requires high amounts of adenosine triphosphate (ATP), which is replenished by oxidative phosphorylation in mitochondria. Calcium (Ca) is a key regulator of mitochondrial function by stimulating the Krebs cycle, which produces nicotinamide adenine dinucleotide for ATP production at the electron transport chain and nicotinamide adenine dinucleotide phosphate for the elimination of reactive oxygen species (ROS). While it is now well established that mitochondrial dysfunction plays an important role in the pathophysiology of heart failure, this has been less investigated in atrial myocytes in AF. Considering the high prevalence of AF, investigating the role of mitochondria in this disease may guide the path towards new therapeutic targets. In this review, we discuss the importance of mitochondrial Ca handling in regulating ATP production and mitochondrial ROS emission and how alterations, particularly in these aspects of mitochondrial activity, may play a role in AF. In addition to describing research advances, we highlight areas in which further studies are required to elucidate the role of mitochondria in AF.
Topics: Animals; Atrial Fibrillation; Atrial Function; Calcium Signaling; Energy Metabolism; Heart Atria; Heart Rate; Humans; Mitochondria, Heart; Myocytes, Cardiac; Oxidative Stress; Reactive Oxygen Species
PubMed: 33258071
DOI: 10.1007/s00395-020-00827-7 -
JAMA Jun 2022Ablation of persistent atrial fibrillation (AF) remains a challenge. Left atrial fibrosis plays an important role in the pathophysiology of AF and has been associated... (Comparative Study)
Comparative Study Randomized Controlled Trial
Effect of MRI-Guided Fibrosis Ablation vs Conventional Catheter Ablation on Atrial Arrhythmia Recurrence in Patients With Persistent Atrial Fibrillation: The DECAAF II Randomized Clinical Trial.
IMPORTANCE
Ablation of persistent atrial fibrillation (AF) remains a challenge. Left atrial fibrosis plays an important role in the pathophysiology of AF and has been associated with poor procedural outcomes.
OBJECTIVE
To investigate the efficacy and adverse events of targeting atrial fibrosis detected on magnetic resonance imaging (MRI) in reducing atrial arrhythmia recurrence in persistent AF.
DESIGN, SETTING, AND PARTICIPANTS
The Efficacy of Delayed Enhancement-MRI-Guided Fibrosis Ablation vs Conventional Catheter Ablation of Atrial Fibrillation trial was an investigator-initiated, multicenter, randomized clinical trial involving 44 academic and nonacademic centers in 10 countries. A total of 843 patients with symptomatic or asymptomatic persistent AF and undergoing AF ablation were enrolled from July 2016 to January 2020, with follow-up through February 19, 2021.
INTERVENTIONS
Patients with persistent AF were randomly assigned to pulmonary vein isolation (PVI) plus MRI-guided atrial fibrosis ablation (421 patients) or PVI alone (422 patients). Delayed-enhancement MRI was performed in both groups before the ablation procedure to assess baseline atrial fibrosis and at 3 months postablation to assess for ablation scar.
MAIN OUTCOMES AND MEASURES
The primary end point was time to first atrial arrhythmia recurrence after a 90-day blanking period postablation. The primary safety composite outcome was defined by the occurrence of 1 or more of the following events within 30 days postablation: stroke, PV stenosis, bleeding, heart failure, or death.
RESULTS
Among 843 patients who were randomized (mean age 62.7 years; 178 [21.1%] women), 815 (96.9%) completed the 90-day blanking period and contributed to the efficacy analyses. There was no significant difference in atrial arrhythmia recurrence between groups (fibrosis-guided ablation plus PVI patients, 175 [43.0%] vs PVI-only patients, 188 [46.1%]; hazard ratio [HR], 0.95 [95% CI, 0.77-1.17]; P = .63). Patients in the fibrosis-guided ablation plus PVI group experienced a higher rate of safety outcomes (9 [2.2%] vs 0 in PVI group; P = .001). Six patients (1.5%) in the fibrosis-guided ablation plus PVI group had an ischemic stroke compared with none in PVI-only group. Two deaths occurred in the fibrosis-guided ablation plus PVI group, and the first one was possibly related to the procedure.
CONCLUSIONS AND RELEVANCE
Among patients with persistent AF, MRI-guided fibrosis ablation plus PVI, compared with PVI catheter ablation only, resulted in no significant difference in atrial arrhythmia recurrence. Findings do not support the use of MRI-guided fibrosis ablation for the treatment of persistent AF.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT02529319.
Topics: Ablation Techniques; Atrial Fibrillation; Catheter Ablation; Female; Fibrosis; Heart Atria; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Pulmonary Veins; Recurrence; Surgery, Computer-Assisted; Treatment Outcome
PubMed: 35727277
DOI: 10.1001/jama.2022.8831 -
Cardiovascular Diabetology Jan 2021Sodium-glucose linked transporter type 2 (SGLT-2) inhibition has been shown to reduce cardiovascular mortality in heart failure independently of glycemic control and...
BACKGROUND
Sodium-glucose linked transporter type 2 (SGLT-2) inhibition has been shown to reduce cardiovascular mortality in heart failure independently of glycemic control and prevents the onset of atrial arrhythmias, a common co-morbidity in heart failure with preserved ejection fraction (HFpEF). The mechanism behind these effects is not fully understood, and it remains unclear if they could be further enhanced by additional SGLT-1 inhibition. We investigated the effects of chronic treatment with the dual SGLT-1&2 inhibitor sotagliflozin on left atrial (LA) remodeling and cellular arrhythmogenesis (i.e. atrial cardiomyopathy) in a metabolic syndrome-related rat model of HFpEF.
METHODS
17 week-old ZSF-1 obese rats, a metabolic syndrome-related model of HFpEF, and wild type rats (Wistar Kyoto), were fed 30 mg/kg/d sotagliflozin for 6 weeks. At 23 weeks, LA were imaged in-vivo by echocardiography. In-vitro, Ca transients (CaT; electrically stimulated, caffeine-induced) and spontaneous Ca release were recorded by ratiometric microscopy using Ca-sensitive fluorescent dyes (Fura-2) during various experimental protocols. Mitochondrial structure (dye: Mitotracker), Ca buffer capacity (dye: Rhod-2), mitochondrial depolarization (dye: TMRE) and production of reactive oxygen species (dye: H2DCF) were visualized by confocal microscopy. Statistical analysis was performed with 2-way analysis of variance followed by post-hoc Bonferroni and student's t-test, as applicable.
RESULTS
Sotagliflozin ameliorated LA enlargement in HFpEF in-vivo. In-vitro, LA cardiomyocytes in HFpEF showed an increased incidence and amplitude of arrhythmic spontaneous Ca release events (SCaEs). Sotagliflozin significantly reduced the magnitude of SCaEs, while their frequency was unaffected. Sotagliflozin lowered diastolic [Ca] of CaT at baseline and in response to glucose influx, possibly related to a ~ 50% increase of sodium sodium-calcium exchanger (NCX) forward-mode activity. Sotagliflozin prevented mitochondrial swelling and enhanced mitochondrial Ca buffer capacity in HFpEF. Sotagliflozin improved mitochondrial fission and reactive oxygen species (ROS) production during glucose starvation and averted Ca accumulation upon glycolytic inhibition.
CONCLUSION
The SGLT-1&2 inhibitor sotagliflozin ameliorated LA remodeling in metabolic HFpEF. It also improved distinct features of Ca-mediated cellular arrhythmogenesis in-vitro (i.e. magnitude of SCaEs, mitochondrial Ca buffer capacity, diastolic Ca accumulation, NCX activity). The safety and efficacy of combined SGLT-1&2 inhibition for the treatment and/or prevention of atrial cardiomyopathy associated arrhythmias should be further evaluated in clinical trials.
Topics: Animals; Arrhythmias, Cardiac; Atrial Function, Left; Atrial Remodeling; Calcium Signaling; Disease Models, Animal; Glycosides; Heart Atria; Heart Failure; Metabolic Syndrome; Mitochondria, Heart; Mitochondrial Dynamics; Mitochondrial Swelling; Rats, Inbred WKY; Rats, Zucker; Reactive Oxygen Species; Sodium-Calcium Exchanger; Sodium-Glucose Transporter 1; Sodium-Glucose Transporter 2; Sodium-Glucose Transporter 2 Inhibitors; Rats
PubMed: 33413413
DOI: 10.1186/s12933-020-01208-z -
Journal of Cardiovascular... Oct 2021Atrial fibrillation (AF) is the most common arrhythmia among adults. While there have been incredible advances in the management of AF and its clinical sequelae,... (Review)
Review
Atrial fibrillation (AF) is the most common arrhythmia among adults. While there have been incredible advances in the management of AF and its clinical sequelae, investigation of atrial cardiomyopathies (ACMs) is becoming increasingly more prominent. ACM refers to the electromechanical changes-appreciated subclinically and/or clinically-that underlie atrial dysfunction and create an environment ripe for the development of clinically apparent AF. There are several subtypes of ACM, distinguished by histologic features. Recent progress in cardiovascular imaging, including echocardiography with speckle-tracking (e.g., strain analysis), cardiovascular magnetic resonance imaging (CMR), and atrial 4-D flow CMR, has enabled increased recognition of ACM. Identification of ACM and its features carry clinical implications, including elevating a patient's risk for development of AF, as well as associations with outcomes related to catheter-based and surgical AF ablation. In this review, we explore the definition and classifications of ACM, its complex relationship with clinical AF, imaging modalities, and clinical implications. We propose next steps for a more unified approach to ACM recognition that can direct further research into this complex field.
Topics: Adult; Atrial Fibrillation; Cardiomyopathies; Catheter Ablation; Echocardiography; Heart Atria; Humans
PubMed: 33993617
DOI: 10.1111/jce.15083 -
Circulation Aug 2023Atrial fibrillation (AF) is by far the most common cardiac arrhythmia. In about 3% of individuals, AF develops as a primary disorder without any identifiable trigger...
BACKGROUND
Atrial fibrillation (AF) is by far the most common cardiac arrhythmia. In about 3% of individuals, AF develops as a primary disorder without any identifiable trigger (idiopathic or historically termed lone AF). In line with the emerging field of autoantibody-related cardiac arrhythmias, the objective of this study was to explore whether autoantibodies targeting cardiac ion channels can underlie unexplained AF.
METHODS
Peptide microarray was used to screen patient samples for autoantibodies. We compared patients with unexplained AF (n=37 pre-existent AF; n=14 incident AF on follow-up) to age- and sex-matched controls (n=37). Electrophysiological properties of the identified autoantibody were then tested in vitro with the patch clamp technique and in vivo with an experimental mouse model of immunization.
RESULTS
A common autoantibody response against K3.4 protein was detected in patients with AF and even before the development of clinically apparent AF. K3.4 protein forms a heterotetramer that underlies the cardiac acetylcholine-activated inwardly rectifying K current, . Functional studies on human induced pluripotent stem cell-derived atrial cardiomyocytes showed that anti-K3.4 IgG purified from patients with AF shortened action potentials and enhanced the constitutive form of , both key mediators of AF. To establish a causal relationship, we developed a mouse model of K3.4 autoimmunity. Electrophysiological study in K3.4-immunized mice showed that K3.4 autoantibodies significantly reduced atrial effective refractory period and predisposed animals to a 2.8-fold increased susceptibility to AF.
CONCLUSIONS
To our knowledge, this is the first report of an autoimmune pathogenesis of AF with direct evidence of K3.4 autoantibody-mediated AF.
Topics: Humans; Animals; Mice; Atrial Fibrillation; G Protein-Coupled Inwardly-Rectifying Potassium Channels; Induced Pluripotent Stem Cells; Heart Atria; Autoantibodies
PubMed: 37401487
DOI: 10.1161/CIRCULATIONAHA.122.062776 -
Medical & Biological Engineering &... Apr 2023The inverse problem of electrocardiography or electrocardiographic imaging (ECGI) is a technique for reconstructing electrical information about cardiac surfaces from... (Review)
Review
The inverse problem of electrocardiography or electrocardiographic imaging (ECGI) is a technique for reconstructing electrical information about cardiac surfaces from noninvasive or non-contact recordings. ECGI has been used to characterize atrial and ventricular arrhythmias. Although it is a technology with years of progress, its development to characterize atrial arrhythmias is challenging. Complications can arise when trying to describe the atrial mechanisms that lead to abnormal propagation patterns, premature or tachycardic beats, and reentrant arrhythmias. This review addresses the various ECGI methodologies, regularization methods, and post-processing techniques used in the atria, as well as the context in which they are used. The current advantages and limitations of ECGI in the fields of research and clinical diagnosis of atrial arrhythmias are outlined. In addition, areas where ECGI efforts should be concentrated to address the associated unsatisfied needs from the atrial perspective are discussed.
Topics: Humans; Atrial Fibrillation; Body Surface Potential Mapping; Electrocardiography; Heart Atria; Diagnostic Imaging
PubMed: 36370321
DOI: 10.1007/s11517-022-02709-7 -
Open Heart Feb 2022
Topics: Atrial Fibrillation; Endurance Training; Exercise; Heart Atria; Humans; Organ Size; Risk Assessment; Risk Factors; Sedentary Behavior
PubMed: 35165169
DOI: 10.1136/openhrt-2022-001962 -
JACC. Cardiovascular Imaging Aug 2020
Topics: Atrial Fibrillation; Contrast Media; Fibrosis; Gadolinium; Heart Atria; Humans; Predictive Value of Tests
PubMed: 32682723
DOI: 10.1016/j.jcmg.2020.04.023 -
Medical Sciences (Basel, Switzerland) Apr 2023Atrial fibrillation (AF) is the most common pathological arrhythmia, and its complications lead to significant morbidity and mortality. However, patients with AF can... (Review)
Review
BACKGROUND
Atrial fibrillation (AF) is the most common pathological arrhythmia, and its complications lead to significant morbidity and mortality. However, patients with AF can often go undetected, especially if they are asymptomatic or have a low burden of paroxysms. Identification of those at high risk of AF development may help refine screening and management strategies.
METHODS
PubMed and Embase databases were systematically searched for studies looking at electrocardiographic predictors of AF from inception to August 2021.
RESULTS
A total of 115 studies were reported which examined a combination of atrial and ventricular parameters that could be electrocardiographic predictors of AF. Atrial predictors include conduction parameters, such as the PR interval, p-wave index and dispersion, and partial interatrial or advanced interatrial block, or morphological parameters, such as p-wave axis, amplitude and terminal force. Ventricular predictors include abnormalities in QRS amplitude, morphology or duration, QT interval duration, r-wave progression and ST segment, i.e., t-wave abnormalities.
CONCLUSIONS
There has been significant interest in electrocardiographic prediction of AF, especially in populations at high risk of atrial AF, such as those with an embolic stroke of undetermined source. This review highlights the breadth of possible predictive parameters, and possible pathological bases for the predictive role of each parameter are proposed.
Topics: Humans; Atrial Fibrillation; Electrocardiography; Heart Atria; Heart Rate; Heart Ventricles
PubMed: 37092499
DOI: 10.3390/medsci11020030