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JAMA Jan 2023Pulmonary vein isolation (PVI) alone is less effective in patients with persistent atrial fibrillation (AF) compared with paroxysmal AF. The left atrial posterior wall... (Comparative Study)
Comparative Study Randomized Controlled Trial
Effect of Catheter Ablation Using Pulmonary Vein Isolation With vs Without Posterior Left Atrial Wall Isolation on Atrial Arrhythmia Recurrence in Patients With Persistent Atrial Fibrillation: The CAPLA Randomized Clinical Trial.
IMPORTANCE
Pulmonary vein isolation (PVI) alone is less effective in patients with persistent atrial fibrillation (AF) compared with paroxysmal AF. The left atrial posterior wall may contribute to maintenance of persistent AF, and posterior wall isolation (PWI) is a common PVI adjunct. However, PWI has not been subjected to randomized comparison.
OBJECTIVE
To compare PVI with PWI vs PVI alone in patients with persistent AF undergoing first-time catheter ablation.
DESIGN, SETTING, AND PARTICIPANTS
Investigator initiated, multicenter, randomized clinical trial involving 11 centers in 3 countries (Australia, Canada, UK). Symptomatic patients with persistent AF were randomized 1:1 to either PVI with PWI or PVI alone. Patients were enrolled July 2018-March 2021, with 1-year follow-up completed March 2022.
INTERVENTIONS
The PVI with PWI group (n = 170) underwent wide antral pulmonary vein isolation followed by posterior wall isolation involving linear ablation at the roof and floor to achieve electrical isolation. The PVI-alone group (n = 168) underwent wide antral pulmonary vein isolation alone.
MAIN OUTCOMES AND MEASURES
Primary end point was freedom from any documented atrial arrhythmia of more than 30 seconds without antiarrhythmic medication at 12 months, after a single ablation procedure. The 23 secondary outcomes included freedom from atrial arrhythmia with/without antiarrhythmic medication after multiple procedures, freedom from symptomatic AF with/without antiarrhythmic medication after multiple procedures, AF burden between study groups at 12 months, procedural outcomes, and complications.
RESULTS
Among 338 patients randomized (median age, 65.6 [IQR, 13.1] years; 76.9% men), 330 (97.6%) completed the study. After 12 months, 89 patients (52.4%) assigned to PVI with PWI were free from recurrent atrial arrhythmia without antiarrhythmic medication after a single procedure, compared with 90 (53.6%) assigned to PVI alone (between-group difference, -1.2%; hazard ratio [HR], 0.99 [95% CI, 0.73-1.36]; P = .98). Of the secondary end points, 9 showed no significant difference, including freedom from atrial arrhythmia with/without antiarrhythmic medication after multiple procedures (58.2% for PVI with PWI vs 60.1% for PVI alone; HR, 1.10 [95% CI, 0.79-1.55]; P = .57), freedom from symptomatic AF with/without antiarrhythmic medication after multiple procedures (68.2% vs 72%; HR, 1.20 [95% CI, 0.80-1.78]; P = .36) or AF burden (0% [IQR, 0%-2.3%] vs 0% [IQR, 0%-2.8%], P = .47). Mean procedural times (142 [SD, 69] vs 121 [SD, 57] minutes, P < .001) and ablation times (34 [SD, 21] vs 28 [SD, 12] minutes, P < .001) were significantly shorter for PVI alone. There were 6 complications for PVI with PWI and 4 for PVI alone.
CONCLUSIONS AND RELEVANCE
In patients undergoing first-time catheter ablation for persistent AF, the addition of PWI to PVI alone did not significantly improve freedom from atrial arrhythmia at 12 months compared with PVI alone. These findings do not support the empirical inclusion of PWI for ablation of persistent AF.
TRIAL REGISTRATION
anzctr.org.au Identifier: ACTRN12616001436460.
Topics: Aged; Female; Humans; Male; Anti-Arrhythmia Agents; Atrial Fibrillation; Catheter Ablation; Heart Atria; Pulmonary Veins; Recurrence; Treatment Outcome; Middle Aged; Cardiac Surgical Procedures
PubMed: 36625809
DOI: 10.1001/jama.2022.23722 -
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 -
European Heart Journal Sep 2023This study aimed to histologically validate atrial structural remodelling associated with atrial fibrillation.
BACKGROUND AND AIMS
This study aimed to histologically validate atrial structural remodelling associated with atrial fibrillation.
METHODS AND RESULTS
Patients undergoing atrial fibrillation ablation and endomyocardial atrial biopsy were included (n = 230; 67 ± 12 years old; 69 women). Electroanatomic mapping was performed during right atrial pacing. Voltage at the biopsy site (Vbiopsy), global left atrial voltage (VGLA), and the proportion of points with fractionated electrograms defined as ≥5 deflections in each electrogram (%Fractionated EGM) were evaluated. SCZtotal was calculated as the total width of slow conduction zones, defined as regions with a conduction velocity of <30 cm/s. Histological factors potentially associated with electroanatomic characteristics were evaluated using multiple linear regression analyses. Ultrastructural features and immune cell infiltration were evaluated by electron microscopy and immunohistochemical staining in 33 and 60 patients, respectively. Fibrosis, intercellular space, myofibrillar loss, and myocardial nuclear density were significantly associated with Vbiopsy (P = .014, P < .001, P < .001, and P = .002, respectively) and VGLA (P = .010, P < .001, P = .001, and P < .001, respectively). The intercellular space was associated with the %Fractionated EGM (P = .001). Fibrosis, intercellular space, and myofibrillar loss were associated with SCZtotal (P = .028, P < .001, and P = .015, respectively). Electron microscopy confirmed plasma components and immature collagen fibrils in the increased intercellular space and myofilament lysis in cardiomyocytes, depending on myofibrillar loss. Among the histological factors, the severity of myofibrillar loss was associated with an increase in macrophage infiltration.
CONCLUSION
Histological correlates of atrial structural remodelling were fibrosis, increased intercellular space, myofibrillar loss, and decreased nuclear density. Each histological component was defined using electron microscopy and immunohistochemistry studies.
Topics: Humans; Female; Middle Aged; Aged; Atrial Fibrillation; Electrophysiologic Techniques, Cardiac; Heart Atria; Heart Rate; Fibrosis; Atrial Remodeling; Catheter Ablation
PubMed: 37350738
DOI: 10.1093/eurheartj/ehad396 -
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 -
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 -
Heart Rhythm May 2021Atrial fibrillation (AF) is the most common cardiac arrhythmia and an important cause of morbidity and mortality globally. Atrial remodeling includes changes in ion... (Review)
Review
Atrial fibrillation (AF) is the most common cardiac arrhythmia and an important cause of morbidity and mortality globally. Atrial remodeling includes changes in ion channel expression and function, structural alterations, and neural remodeling, which create an arrhythmogenic milieu resulting in AF initiation and maintenance. Current therapeutic strategies for AF involving ablation and antiarrhythmic drugs are associated with relatively high recurrence and proarrhythmic side effects, respectively. Over the last 2 decades, in an effort to overcome these issues, research has sought to identify the genetic basis for AF thereby gaining insight into the regulatory mechanisms governing its pathophysiology. Despite identification of multiple gene loci associated with AF, thus far none has led to a therapy, indicating additional contributors to pathology. Recently, in the context of expanding knowledge of the epigenome (DNA methylation, histone modifications, and noncoding RNAs), its potential involvement in the onset and progression of AF pathophysiology has started to emerge. Probing the role of various epigenetic mechanisms that contribute to AF may improve our knowledge of this complex disease, identify potential therapeutic targets, and facilitate targeted therapies. Here, we provide a comprehensive review of growing epigenetic features involved in AF pathogenesis and summarize the emerging epigenomic targets for therapy that have been explored in preclinical models of AF.
Topics: Atrial Fibrillation; Atrial Remodeling; Epigenomics; Heart Atria; Humans
PubMed: 33440248
DOI: 10.1016/j.hrthm.2021.01.007 -
Circulation. Cardiovascular Imaging Jun 2023Left atrial (LA) function following catheter or surgical ablation of de-novo long-standing persistent atrial fibrillation (AF) and its impact on AF recurrence was... (Clinical Trial)
Clinical Trial
BACKGROUND
Left atrial (LA) function following catheter or surgical ablation of de-novo long-standing persistent atrial fibrillation (AF) and its impact on AF recurrence was studied in patients participating in the CASA-AF trial (Catheter Ablation vs. Thoracoscopic Surgical Ablation in Long Standing Persistent Atrial Fibrillation).
METHODS
All patients underwent echocardiography preablation, 3 and 12 months post-ablation. LA structure and function were assessed by 2-dimensional volume and speckle tracking strain measurements of LA reservoir, conduit, and contractile strain. Left ventricular diastolic function was measured using transmitral Doppler filling velocities and myocardial tissue Doppler velocities to derive the e', E/e', and E/A ratios. Continuous rhythm monitoring was achieved using an implantable loop recorder.
RESULTS
Eighty-three patients had echocardiographic data suitable for analysis. Their mean age was 63.6±9.7 years, 73.5% were male, had AF for 22.8±11.6 months, and had a mean LA maximum volume of 48.8±13.8 mL/m. Thirty patients maintained sinus rhythm, and 53 developed AF recurrence. Ablation led to similar reductions in LA volumes at follow-up in both rhythm groups. However, higher LA emptying fraction (36.3±10.6% versus 27.9±9.9%; <0.001), reservoir strain (22.6±8.5% versus 16.7±5.7%; =0.001), and contractile strain (9.2±3.4% versus 5.6±2.5%; <0.001) were noted in the sinus rhythm compared with AF recurrence group following ablation at 3 months. Diastolic function was better in the sinus rhythm compared with the AF recurrence group with an E/A ratio of 1.5±0.5 versus 2.2±1.2 (<0.001) and left ventricular E/e' ratio of 8.0±2.1 versus 10.3±4.1 (<0.001), respectively. LA contractile strain at 3 months was the only independent predictor of AF recurrence.
CONCLUSIONS
Following ablation for long-standing persistent AF, improvement in LA function was greater in those who maintained sinus rhythm. LA contractile strain at 3 months was the most important determinant of AF recurrence following ablation.
REGISTRATION
URL: https://www.
CLINICALTRIALS
gov; Unique identifier: NCT02755688.
Topics: Aged; Female; Humans; Male; Middle Aged; Atrial Fibrillation; Atrial Function, Left; Catheter Ablation; Echocardiography; Heart Atria; Recurrence; Treatment Outcome
PubMed: 37288553
DOI: 10.1161/CIRCIMAGING.123.015352 -
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 -
Journal of Translational Medicine Jun 2023Epicardial adipose tissue (EAT) secretome induces fibrosis. Fibrosis, primarily extracellular matrix (ECM) produced by fibroblasts, creates a substrate for atrial...
BACKGROUND
Epicardial adipose tissue (EAT) secretome induces fibrosis. Fibrosis, primarily extracellular matrix (ECM) produced by fibroblasts, creates a substrate for atrial fibrillation (AF). Whether the EAT secretome from patients with AF activates human atrial fibroblasts and through which components, remains unexplored.
RESEARCH AIMS
(a) To investigate if the EAT secretome from patients with versus without AF increases ECM production in atrial fibroblasts. (b) To identify profibrotic proteins and processes in the EAT secretome and EAT from patients with, who will develop (future onset), and without AF.
METHODS
Atrial EAT was obtainded during thoracoscopic ablation (AF, n = 20), or open-heart surgery (future onset and non-AF, n = 35). ECM gene expression of human atrial fibroblasts exposed to the EAT secretome and the proteomes of EAT secretome and EAT were assessed in patients with and without AF. Myeloperoxidase and neutrophil extracellular traps (NETs) were assessed immunohistochemically in patients with paroxysmal, persistent, future onset, and those who remain free of AF (non-AF).
RESULTS
The expression of COL1A1 and FN1 in fibroblasts exposed to secretome from patients with AF was 3.7 and 4.7 times higher than in patients without AF (p < 0.05). Myeloperoxidase was the most increased protein in the EAT secretome and EAT from patients with versus without AF (FC 18.07 and 21.57, p < 0.005), as was the gene-set neutrophil degranulation. Immunohistochemically, myeloperoxidase was highest in persistent (FC 13.3, p < 0.0001) and increased in future onset AF (FC 2.4, p = 0.02) versus non-AF. Myeloperoxidase aggregated subepicardially and around fibrofatty infiltrates. NETs were increased in patients with persistent versus non-AF (p = 0.03).
CONCLUSION
In AF, the EAT secretome induces ECM gene expression in atrial fibroblasts and contains abundant myeloperoxidase. EAT myeloperoxidase was increased prior to AF onset, and both myeloperoxidase and NETs were highest in persistent AF, highlighting the role of EAT neutrophils in the pathophysiology of AF.
Topics: Humans; Adipose Tissue; Atrial Fibrillation; Fibrosis; Heart Atria; Pericardium; Peroxidase
PubMed: 37280612
DOI: 10.1186/s12967-023-04231-2 -
International Journal of Molecular... Mar 2021Atrial fibrillation (AF) is one of the most common tachyarrhythmias observed in the clinic and is characterized by structural and electrical remodelling. Atrial...
Atrial fibrillation (AF) is one of the most common tachyarrhythmias observed in the clinic and is characterized by structural and electrical remodelling. Atrial fibrosis, an emblem of atrial structural remodelling, is a complex multifactorial and patient‑specific process involved in the occurrence and maintenance of AF. Whilst there is already considerable knowledge regarding the association between AF and fibrosis, this process is extremely complex, involving intricate neurohumoral and cellular and molecular interactions, and it is not limited to the atrium. Current technological advances have made the non‑invasive evaluation of fibrosis in the atria and ventricles possible, facilitating the selection of patient‑specific ablation strategies and upstream treatment regimens. An improved understanding of the mechanisms and roles of fibrosis in the context of AF is of great clinical significance for the development of treatment strategies targeting the fibrous region. In the present review, a focus was placed on the atrial fibrosis underlying AF, outlining its role in the occurrence and perpetuation of AF, by reviewing recent evaluations and potential treatment strategies targeting areas of fibrosis, with the aim of providing a novel perspective on the management and prevention of AF.
Topics: Atrial Fibrillation; Atrial Remodeling; Fibrosis; Heart Atria; Heart Ventricles; Humans
PubMed: 33448312
DOI: 10.3892/ijmm.2020.4842