Pulmonary Veins Function as Echo Chambers in Persistent Atrial Fibrillation: Circuitous Re-Entry Generates Outgoing Wavefronts.

BACKGROUND: Although the substrate in persistent atrial fibrillation (PeAF) is not limited to the pulmonary veins (PVs), PV isolation (PVI) remains the cornerstone ablation strategy. OBJECTIVES: The aim of this study was to describe the mechanism of outgoing wavefronts (WFs) originating in the PV sleeves during PeAF. METHODS: Eleven patients presenting for first-time PeAF ablation were recruited (mean age 63.1 ± 10.9 years, 91% men). A 64-electrode catheter (Constellation; 38 mm) was positioned within the PV under fluoroscopic guidance. An inverse mapping technique was used to reconstruct unipolar atrial electrograms on the PV surface, and the resulting phase maps were used to identify incoming and outgoing WFs at the PV junction and to classify focal and re-entrant activity within the PV sleeves. RESULTS: During PeAF, the PVs gave rise to outgoing WFs with a frequency of 3.7 s-1 (Q1-Q3: 3.4-5.4 s-1) compared with 3.6 s-1 (Q1-Q3: 2.8-4.2 s-1) for incoming WFs. Circuitous macroscopic re-entry was the dominant mechanism driving outgoing WFs (frequency of re-entry 2.7 s-1 [Q1-Q3: 2.0-3.3 s-1] compared with focal activity 1.4 s-1 [Q1-Q3: 1.1-1.5 s-1]; P < 0.006). This was initiated by incoming WFs in 80% of cases. Consecutive focal activation from the same location was infrequent (10.0% ± 6.6%, n = 10). Rotors ≥360° were never observed. The median ratio (R) of outgoing to incoming WF frequency was 1.14 (Q1-Q3: 0.84-1.75), with R > 1 in 6 of 11 PVs. CONCLUSIONS: Electric activity generated by PV sleeves during PeAF is due mainly to circuitous re-entry initiated by incoming waves, frequently with R > 1. That is, the PVs act less as drivers of atrial fibrillation than as "echo chambers" that sustain and amplify fibrillatory activity.

Atrial Fibrillation Catheter Ablation vs Medical Therapy and Psychological Distress: A Randomized Clinical Trial.

Importance: The impact of atrial fibrillation (AF) catheter ablation on mental health outcomes is not well understood. Objective: To determine whether AF catheter ablation is associated with greater improvements in markers of psychological distress compared with medical therapy alone. Design, Setting, and Participants: The Randomized Evaluation of the Impact of Catheter Ablation on Psychological Distress in Atrial Fibrillation (REMEDIAL) study was a randomized trial of symptomatic participants conducted in 2 AF centers in Australia between June 2018 and March 2021. Interventions: Participants were randomized to receive AF catheter ablation (n = 52) or medical therapy (n = 48). Main Outcomes and Measures: The primary outcome was Hospital Anxiety and Depression Scale (HADS) score at 12 months. Secondary outcomes included follow-up assessments of prevalence of severe psychological distress (HADS score >15), anxiety HADS score, depression HADS score, and Beck Depression Inventory-II (BDI-II) score. Arrhythmia recurrence and AF burden data were also analyzed. Results: A total of 100 participants were randomized (mean age, 59 [12] years; 31 [32%] women; 54% with paroxysmal AF). Successful pulmonary vein isolation was achieved in all participants in the ablation group. The combined HADS score was lower in the ablation group vs the medical group at 6 months (8.2 [5.4] vs 11.9 [7.2]; P = .006) and at 12 months (7.6 [5.3] vs 11.8 [8.6]; between-group difference, -4.17 [95% CI, -7.04 to -1.31]; P = .005). Similarly, the prevalence of severe psychological distress was lower in the ablation group vs the medical therapy group at 6 months (14.2% vs 34%; P = .02) and at 12 months (10.2% vs 31.9%; P = .01), as was the anxiety HADS score at 6 months (4.7 [3.2] vs 6.4 [3.9]; P = .02) and 12 months (4.5 [3.3] vs 6.6 [4.8]; P = .02); the depression HADS score at 3 months (3.7 [2.6] vs 5.2 [4.0]; P = .047), 6 months (3.4 [2.7] vs 5.5 [3.9]; P = .004), and 12 months (3.1 [2.6] vs 5.2 [3.9]; P = .004); and the BDI-II score at 6 months (7.2 [6.1] vs 11.5 [9.0]; P = .01) and 12 months (6.6 [7.2] vs 10.9 [8.2]; P = .01). The median (IQR) AF burden in the ablation group was lower than in the medical therapy group (0% [0%-3.22%] vs 15.5% [1.0%-45.9%]; P < .001). Conclusion and Relevance: In this trial of participants with symptomatic AF, improvement in psychological symptoms of anxiety and depression was observed with catheter ablation, but not medical therapy. Trial Registration: ANZCTR Identifier: ACTRN12618000062224.

Gut Microbiota and Atrial Fibrillation: Pathogenesis, Mechanisms and Therapies.

Over the past decade there has been an interest in understanding the role of gut microbiota in the pathogenesis of AF. A number of studies have linked the gut microbiota to the occurrence of traditional AF risk factors such as hypertension and obesity. However, it remains unclear whether gut dysbiosis has a direct effect on arrhythmogenesis in AF. This article describes the current understanding of the effect of gut dysbiosis and associated metabolites on AF. In addition, current therapeutic strategies and future directions are discussed.

Impact of Catheter Ablation on Cognitive Function in Atrial Fibrillation: A Randomized Control Trial.

BACKGROUND: Early postoperative cognitive dysfunction (POCD) has been reported following atrial fibrillation (AF) ablation. However, whether POCD is persistent long-term is unknown. OBJECTIVES: The purpose of this study was to determine if AF catheter ablation is associated with persistent cognitive dysfunction at 12-month follow-up. METHODS: This is a prospective study of 100 patients with symptomatic AF who failed at least 1 antiarrhythmic drug randomized to either ongoing medical therapy or AF catheter ablation and followed up for 12 months. Changes in cognitive performance were assessed using 6 cognitive tests administered at baseline and during follow-up (3, 6, and 12 months). RESULTS: A total of 96 participants completed the study protocol. Mean age was 59 ± 12 years (32% women, 46% with persistent AF). The prevalence of new cognitive dysfunction in the ablation arm compared with the medical arm was as follows: at 3 months: 14% vs 2%; P = 0.03; at 6 months: 4% vs 2%; P = NS; and at 12 months: 0% vs 2%; P = NS. Ablation time was an independent predictor of POCD (P = 0.03). A significant improvement in cognitive scores was seen in 14% of the ablation arm patients at 12 months compared with no patients in the medical arm (P = 0.007). CONCLUSIONS: POCD was observed following AF ablation. However, this was transient with complete recovery at 12-month follow-up.

Impact of early vs. delayed atrial fibrillation catheter ablation on atrial arrhythmia recurrences.

BACKGROUND: Catheter ablation is an effective strategy in atrial fibrillation (AF). However, its timing in the course of management remains unclear. The aim of this study was to determine if an early vs. delayed AF ablation strategy is associated with differences in arrhythmia outcomes during 12-month follow-up. METHODS AND RESULTS: One hundred patients with symptomatic AF referred to a tertiary centre for management were randomized in a 1:1 ratio to either an early ablation strategy (within 1 month of recruitment) or a delayed ablation strategy (optimized medical therapy followed by catheter ablation at 12 months post recruitment). The primary endpoint was atrial arrhythmia free survival at 12 months post-ablation. Secondary outcomes included: (i) AF burden, (ii) AF burden by AF phenotype, and (iii) antiarrhythmic drug (AAD) use at 12 months. Overall, 89 patients completed the study protocol (Early vs. Delayed: 48 vs. 41). Mean age was 59 ± 12.9 years (29% women). Pulmonary vein isolation was achieved in 100% of patients. At 12 months, 56.3% of patients in the early ablation group were free from recurrent arrhythmia, compared with 58.6% in the delayed ablation group (HR 1.12, 95% CI 0.59-2.13, P = 0.7). All secondary outcomes showed no significant difference including median AF burden (Early vs. Delayed: 0% [IQR 3.2] vs. 0% [5], P = 0.66), median AF burden amongst paroxysmal AF patients (0% [IQR 1.1] vs. 0% [4.5], P = 0.78), or persistent AF patients (0% [IQR 22.8] vs. 0% [5.6], P = 0.45) or AAD use (33% vs. 37%, P = 0.8). CONCLUSION: Compared with an early ablation strategy, delaying AF ablation by 12 months for AAD management did not result in reduced ablation efficacy.

Insights From Simultaneous Left and Right Atrial Septal Mapping in Patients With Persistent Atrial Fibrillation.

BACKGROUND: The interatrial septum (IAS) is thought to be involved in the mechanism of persistent atrial fibrillation (PeAF). Simultaneous contact mapping of both sides of the IAS has not been performed previously. OBJECTIVES: The purpose of this study was to describe wave front (WF) activation patterns and extent of left and right atrial septal electrical dissociation in patients with PeAF. METHODS: Simultaneous mapping of both atrial septal surfaces using 2 high-density grid catheters was performed. Filtered electrograms of continuous atrial fibrillation, sinus rhythm (SR), and atrial pacing recordings were exported to MATLAB for off-line phase/activation analysis, and activation patterns on paired surfaces were analyzed. WF activation patterns between the 2 grids were evaluated to determine whether activation WFs were associated or dissociated. RESULTS: Eight patients with PeAF undergoing catheter ablation were included. Complete dissociation of WF activation patterns between the 2 sides of the septum existed throughout the mapping period with no 2 consecutive WF activation patterns matching. Single linear WFs were the most prevalent activation pattern on both septal grids. No focal breakthroughs were seen. Transient rotational activity was seen in 10% of phase activations. During SR and atrial pacing, both grids appeared to be activated independent of each other with no evidence of contralateral conduction across the 2 grids. CONCLUSIONS: Simultaneous biatrial septal mapping of human PeAF, SR, and atrial pacing shows complete WF dissociation between the left and right IAS with no evidence of trans-septal conduction, indicating that the 2 sides function as electrically discrete structures. No stable septal drivers were observed. These findings may have implications for mapping and ablation of PeAF.

Obesity and Atrial Fibrillation: Epidemiology, Pathogenesis and Effect of Weight Loss.

The obesity epidemic continues its relentless advance and is paralleled by an increase in the incidence of AF. Several epidemiological studies have highlighted obesity as an independent risk factor for the development of AF. This relationship is likely multifactorial through a number of interacting mechanisms. Weight loss through lifestyle changes or surgery has been associated with reverse remodelling of the atrial substrate and subsequent reduction in AF, making it an essential pillar in the management of AF in obese patients. In this review, the epidemiological data that support the obesity-AF relationship, the current insights into the underlying pathophysiological mechanism, the impact of weight loss on reverse remodelling and AF reduction, and the strategies to achieve weight loss in patients with AF are discussed.

Catheter ablation for atrial fibrillation: current indications and evolving technologies.

Catheter ablation for atrial fibrillation (AF) has emerged as an important rhythm-control strategy and is by far the most common cardiac ablation procedure performed worldwide. Current guidelines recommend the procedure in symptomatic patients with paroxysmal or persistent AF who are refractory or intolerant to antiarrhythmic drugs. The procedure might also be considered as a first-line approach in selected asymptomatic patients. Data from large registries indicate that AF ablation might reduce mortality and the risk of heart failure and stroke, but evidence from randomized controlled trials is mixed. Pulmonary vein isolation using point-by-point radiofrequency or with the cryoballoon remains the cornerstone technique in AF ablation. Additional atrial ablation can be performed in patients with persistent AF, but its benefits are largely unproven. Technological advances in the past decade have focused on achieving durable vein isolation, reducing procedure duration and improving safety. Numerous exciting new technologies are in various stages of development. In this Review, we discuss the relevant data to support the recommended and evolving indications for catheter ablation of AF, describe the different ablation techniques, and highlight the latest advances in technology that aim to improve its safety and efficacy. We also discuss lifestyle modification strategies to improve ablation outcomes.

Extensive right atrial free wall low-voltage zone as the substrate for atrial fibrillation: successful ablation by scar homogenization.

AIMS: Prior studies have described a variety of mechanisms for atrial fibrillation (AF) originating in the right atrium (RA). In this study, we report a series of patients in whom an extensive right atrial free wall low-voltage zone (LVZ) served as the AF substrate. METHODS AND RESULTS: Five patients with a clinical syndrome of paroxysmal AF and atrial tachycardia (AT) underwent electrophysiologic evaluation. Five patients (3 M; age 52 ± 7 years) had symptomatic paroxysmal AF for (28 ± 17 months) not responsive to medical therapy. At the initial EP study, AT was inducible in four patients and was spontaneous in one patient. In all patients, tachycardia instability precluded detailed AT mapping. Sinus or pace maps indicated an extensive LVZ in the lateral RA trabeculated free wall which consisted of regions of low amplitude complex signals interspersed between electrically silent areas. Radiofrequency ablation aimed at rendering the LVZ electrical inert was successful in eliminating AF in four of five patients. At a follow-up of 28 ± 15 months, one patient had an isolated recurrence of AF. However, two patients required repeat ablation for recurrent AT. CONCLUSION: An extensive LVZ in the trabeculated RA free wall constitutes an unusual substrate for AF. These patients also demonstrate unstable ATs originating from the same zone. Radiofrequency ablation to render the low-voltage zone electrically inert is an effective strategy to manage AF and AT.

Catheter Ablation Versus Medication in Atrial Fibrillation and Systolic Dysfunction: Late Outcomes of CAMERA-MRI Study.

OBJECTIVES: This study sought to determine the long-term outcomes of restoring sinus rhythm with catheter ablation (CA). BACKGROUND: The CAMERA-MRI (Catheter Ablation Versus Medical Rate Control in Atrial Fibrillation and Heart Failure-An MRI-Guided Multicenter Randomized Controlled Trial) study demonstrated that restoration of sinus rhythm with CA significantly improved left ventricular ejection fraction (LVEF) compared with medical rate control (MRC) at 6 months in persistent atrial fibrillation and otherwise unexplained systolic heart failure. However, the long-term outcomes have not been reported. METHODS: Patients enrolled in the CAMERA-MRI study were followed for 4 years with echocardiogram and cardiac magnetic resonance. CA involved pulmonary vein isolation and posterior left atrial wall isolation in 94%. Patients crossed over to CA after 6-month study duration. Arrhythmia burden was determined with implanted cardiac monitors or cardiac devices. RESULTS: Sixty-six patients (age 62 ± 10 years, atrial fibrillation duration of 22 ± 16 months, and LVEF 33 ± 9%) were randomized 1:1 to CA versus MRC. Eighteen of 33 patients crossed over from MRC group to CA group. At 4.0 ± 0.9 years, atrial fibrillation recurred in 27 patients (57%) in the CA group with a mean burden of 10.6 ± 21.2% after 1.4 ± 0.6 procedures. There was an absolute increase in LVEF with CA of 16.4 ± 13.3% compared with 8.6 ± 7.6% in MRC (p = 0.001). In the CA group, the absence of ventricular late gadolinium enhancement was associated with a greater improvement in absolute LVEF (19 ± 13% vs. 10 ± 11% in the late gadolinium enhancement-positive group; p = 0.04) and LVEF normalization in 19 patients (58%) versus 4 patients (18%) in the late gadolinium enhancement-positive group (p = 0.008) at 4.0 ± 0.9 years follow-up. CONCLUSIONS: CA is superior to MRC in improving LVEF in the long term in patients with atrial fibrillation and systolic heart failure. The greatest recovery in systolic function was demonstrated in the absence of ventricular fibrosis on cardiac magnetic resonance.

Atrial Fibrillation Structural Substrates: Aetiology, Identification and Implications.

Atrial remodelling in AF underlines the electrical, structural and mechanical changes in the atria of patients with AF. Several risk factors for AF contribute to the development of the atrial substrate, with some evidence that atrial remodelling reversal is possible with targeted intervention. In this article, the authors review the electrophysiological changes that characterise the atrial substrate in patients with AF risk factors. They also discuss the pitfalls of mapping the atrial substrate and the implications for developing tailored ablation strategies to improve outcomes in patients with AF.

Simultaneous epicardial-endocardial mapping of the sinus node in humans with structural heart disease: Impact of overdrive suppression on sinoatrial exits.

BACKGROUND: The 3-dimensional (3D) nature of sinoatrial node (SAN) function has not been characterized in the intact human heart. OBJECTIVE: The purpose of this study was to characterize the 3D nature of SAN function in patients with structural heart disease (SHD) using simultaneous endocardial-epicardial (endo-epi) phase mapping. METHODS: Simultaneous intraoperative endo-epi SAN mapping was performed during sinus rhythm at baseline (SRbaseline) and postoverdrive suppression at 600 ms (SRpost-pace600) and 400 ms (SRpost-pace400) using 2 Abbott Advisor HD Grid Mapping Catheters. Unipolar and bipolar electrograms (EGMs) were exported for phase analysis to determine (1) activation exits; (2) wavefront propagation sequence; (3) endo-epi dissociation; and (4) fractionation. Comparison of these variables was made among the 3 rhythms from an endo-epi perspective. RESULTS: Sixteen patients with SHD were included. SRbaseline activations were unicentric and predominantly exited cranially (87.5%) with endo-epi synchrony. However, with overdrive suppression, a tendency for caudal exit shift and endo-epi asynchrony was observed: SRpost-pace600 vs SRbaseline: cranial endo 75% vs 87.5% (P = .046); cranial epi 68.8% vs 87.5% (P = 0.002); caudal endo 12.5% vs 6.2% (P = 0.215); caudal epi 25% vs 6.2% (P = .0003); and SRpost-pace400 vs SRbaseline: cranial endo 81.3% vs 87.5% (P = 0.335); cranial epi 68.7% vs 87.5% (P = 0.0034; caudal endo 12.5% vs 6.2% (P = .148); caudal epi 31.2% vs 6.2% (P = 0.0017), consistent with multicentricity. EGM fractionation was more prevalent with overdrive suppression. CONCLUSION: During mapping of the intact human heart, SAN demonstrated redundancy of sinoatrial exits with postoverdrive shift in sites of earliest activation and epi-endo dissociation of sinoatrial exits.

Accuracy of wrist-worn heart rate monitors for rate control assessment in atrial fibrillation.

BACKGROUND: Wrist-worn heart rate (HR) monitors are increasingly popular. A paucity of data exists on their accuracy in atrial fibrillation (AF) in ambulatory patients. We sought to assess the HR accuracy of two commercially available smart watches [SW] (Fitbit Charge HR [FB] and Apple Watch Series 3 [AW]) compared with Holter monitoring in an ambulant patient cohort. METHODS: Thirty-two participants ≥18 years referred for 24-hour Holter monitoring were prospectively recruited. Each participant was randomly allocated to wear either a FB or AW along with their Holter monitor. RESULTS: Across all devices, 53,288 heart rate values were analysed from 32 participants. Twenty wore the AW (17 had persistent AF and 3 had sinus rhythm [SR]) while 12 participants wore the FB (9 in persistent AF and 3 in SR). Participants in SR demonstrated strong agreement compared to Holter monitoring (bias <1 beat, limits of agreement [LoA] -11 to 11 beats). In AF, both devices underestimated HR measurements (bias -9 beats, LoA -41 to 23). The degree of underestimation was more pronounced when HR > 100 bpm (bias of -28 beats for HR range 100-120 bpm, -48 for 120-140 bpm, and -69 for >140 bpm) compared to a slower HR (bias of -6 for HR range 80-100 bpm, <1 for 60-80 bpm, and -1 for <60 bpm). CONCLUSION: In ambulatory patients, smartwatches underestimated HR in AF particularly at HR ranges >100 bpm. Further improvements in device technology are needed before integrating them into the clinical management of rate control in AF.

An unusual presentation of atrial myxoma: thromboembolic phenomenon with a recent normal echocardiogram.

Atrial myxomas are the most common primary neoplasms of the heart. Clinical presentation varies from asymptomatic incidental masses to serious life-threatening cardiovascular complications. We describe the case of a 37-year-old man who presented with both coronary and cerebral embolisation secondary to an atrial myxoma in the context of a recent normal transthoracic echocardiogram.

Rare cause of pulmonary hypertension - pulmonary tumour thrombotic microangiopathy.

Pulmonary tumour thrombotic microangiopathy (PTTA) is a rare but lethal cause of pulmonary hypertension (PHT). Its underlying mechanism is believed to be fibrocellular intimal proliferation and microthrombosis. It has been reported in association with gastric adenocarcinoma and breast, pancreatic and lung cancers. The diagnosis is often made on postmortem examination due to the absence of diagnostic criteria and its rare occurrence. We describe the case of a middle-aged man who presented with rapidly progressive PHT. He deteriorated into multiorgan failure despite aggressive medical therapy and died 4 weeks after his initial presentation. A postmortem examination confirmed the diagnosis of PTTA in addition to the finding of signet cell gastric adenocarcinoma. This case highlights the lethal nature of this rare condition, the ongoing challenges in making an antemortem diagnosis, and the importance of postmortem examination in determining the cause of death to provide closure for both, the treating physician and the family.

Mitral and tricuspid valve repair in hypereosinophilic syndrome.

Hypereosinophilic syndrome (HES) is a rare systemic condition, defined as a persistently elevated eosinophil count associated with end organ damage and the absence of a primary cause. Cardiac involvement occurs in about 50% of patients with HES. Myocardial infiltration results in endomyocardial fibrosis, valve dysfunction and mural thrombus. The atrioventricular valves are almost always involved, resulting in regurgitation due to leaflet restriction, most commonly affecting the posterior mitral valve leaflet. Surgical management remains challenging in patients with HES with limited data on the choice of valve surgery. We describe the case of a 17-year-old woman with HES complicated by congestive cardiac failure secondary to severe mitral and tricuspid regurgitation. Because of refractory heart failure despite medical therapy, surgical mitral and tricuspid valve repair was performed, and an excellent 24-month outcome was achieved. We believe this is the first report of double valve repair in this rare condition.

Permanent pacing and conduction recovery in patients undergoing cardiac surgery for active infective endocarditis in an Australian Tertiary Center.

BACKGROUND: Postoperative heart block is common among patients undergoing surgery for infective endocarditis (IE). Limited data exists allowing cardiologists to predict who will require permanent pacemaker (PPM) implantation postoperatively. We aimed to determine the rate of postoperative PPM insertion, predictors for postoperative PPM, and describe PPM utilization and rates of device-related infection during follow-up. MATERIALS AND METHODS: A retrospective analysis was performed of 191 consecutive patients from a single institution who underwent cardiac surgery for IE between 2001 and 2017. Preoperative and operative predictors for postoperative PPM were evaluated using univariate and multivariate logistic regression. RESULTS: The rate of postoperative PPM implantation was 11% (17/154). The PPM group had more preoperative prolonged PR interval alone (33% vs 12%; P = .03), coexistent prolonged PR and QRS durations (13% vs 2%; P = .01), infection beyond the valve leaflets (82% vs 41%; P = .001), aortic root debridement (65% vs 23%; P = <.001), patch repair (47% vs 20%; P = .01), postoperative prolonged PR interval (50% vs 24%; P = .01), and prolonged QRS duration (47% vs 15%; P = .001). On multivariate analysis, infection beyond the valve leaflets emerged as an independent predictor for postoperative PPM (odds ratio, 1.94, 95% confidence interval, 1.14-3.28; P = .014). A reduction in PPM utilization was observed in five patients while eight patients continued to show significant ventricular pacing with no underlying rhythm at 12 months. There were no device-related infections. CONCLUSION: Postoperative PPM was required in 11% of patients undergoing surgery for IE over a 16-year period. Infection beyond the valve leaflet was an independent predictor for postoperative PPM insertion.