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.

Impact of CPAP on the Atrial Fibrillation Substrate in Obstructive Sleep Apnea: The SLEEP-AF Study.

BACKGROUND: Observational studies report that obstructive sleep apnea (OSA) is associated with an increasingly remodeled atrial substrate in atrial fibrillation (AF). However, the impact of OSA management on the electrophysiologic substrate has not been evaluated. OBJECTIVES: In this study, the authors sought to determine the impact of OSA management on the atrial substrate in AF. METHODS: We recruited 24 consecutive patients referred for AF management with at least moderate OSA (apnea-hypopnea index [AHI] ≥15). Participants were randomized in a 1:1 ratio to commence continuous positive airway pressure (CPAP) or no therapy (n = 12 CPAP; n = 12 no CPAP). All participants underwent invasive electrophysiologic study (high-density right atrial mapping) at baseline and after a minimum of 6 months. Outcome variables were atrial voltage (mV), conduction velocity (m/s), atrial surface area <0.5 mV (%), proportion of complex points (%), and atrial effective refractory periods (ms). Change between groups over time was compared. RESULTS: Clinical characteristics and electrophysiologic parameters were similar between groups at baseline. Compliance with CPAP therapy was high (device usage: 79% ± 19%; mean usage/day: 268 ± 91 min) and resulted in significant AHI reduction (mean reduction: 31 ± 23 events/h). There were no differences in blood pressure or body mass index between groups over time. At follow-up, the CPAP group had faster conduction velocity (0.86 ± 0.16 m/s vs 0.69 ± 0.12 m/s; P (time × group) = 0.034), significantly higher voltages (2.30 ± 0.57 mV vs 1.94 ± 0.72 mV; P < 0.05), and lower proportion of complex points (8.87% ± 3.61% vs 11.93% ± 4.94%; P = 0.011) compared with the control group. CPAP therapy also resulted in a trend toward lower proportion of atrial surface area <0.5 mV (1.04% ± 1.41% vs 4.80% ± 5.12%; P = 0.065). CONCLUSIONS: CPAP therapy results in reversal of atrial remodeling in AF and provides mechanistic evidence advocating for management of OSA in AF.

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.

Modified Precordial Lead R-Wave Deflection Interval Predicts Left- and Right-Sided Idiopathic Outflow Tract Ventricular Arrhythmias.

OBJECTIVES: This study evaluated if modifying electrocardiographic (ECG) precordial leads to a higher intercostal position improved the accuracy of outflow tract ventricular arrhythmia (OTVA) localization. BACKGROUND: Precordial ECG prediction algorithms that use a standard lead configuration localize OTVA with variable accuracy. METHODS: Patients who underwent OTVA ablation were prospectively enrolled to have a standard and modified (high) precordial ECG. R- and S-wave amplitudes and intervals were measured to develop an algorithm that differentiated the right ventricular outflow tract (RVOT) and the left ventricular outflow tract (LVOT) with high accuracy-the modified lead R-wave deflection interval (RWDI). This interval was defined from the earliest QRS onset (using all modified leads) to the lead with longest R-wave deflection. The RWDI was compared with all other ECG algorithms. RESULTS: A total of 50 patients (38 women; mean age 51 ± 17 years) had successful catheter ablation for OTVA (RVOT 60%, LVOT 40%). The modified lead RWDI was significantly shorter in the RVOT group (18.5 ms, interquartile range 25th to 75th percentile [IQR25-75]: 0 to 29.5 ms) compared with the LVOT group (67.5 ms, IQR25-75: 56.5 to 77 ms; p < 0.05). Using a RWDI ≤40 ms to predict an RVOT focus, the sensitivity and specificity of the modified lead RWDI were 100% and 95%, respectively; the area under the receiver-operating characteristic curve was 0.96. This was superior to all previously developed algorithms. In a computed tomography analysis (n = 50), the modified leads were significantly closer to the outflow tracts compared with the standard precordial leads. CONCLUSIONS: The modified lead RWDI is a simple, easily interpretable algorithm that can potentially differentiate a right- or left-sided origin of OTVA with high accuracy.

Symptom severity and quality of life in patients with atrial fibrillation: Psychological function outweighs clinical predictors.

BACKGROUND: The key drivers of symptom severity and health-related quality of life (hr-QOL) in patients with atrial fibrillation (AF) remain unclear. We aimed to determine the relative contribution to symptom severity and hr-QOL of clinical factors including left ventricular (LV) diastolic function and ventricular rate control during AF and of psychological functioning. METHODS: Seventy-eight consecutive patients with symptomatic AF and preserved LV systolic function underwent detailed evaluation of i) AF symptom severity and hr-QOL; ii) clinical factors including left ventricular (LV) diastolic function, AF burden, and ventricular rate during AF and iii) state and trait aspects of psychological functioning. RESULTS: Moderate-to-severe AF-related symptoms were reported by 64% of the study population whilst 36% reported no more than mild symptoms. Worse symptom severity was associated with a higher score on the Perceived Stress Scale (16.7 ±â€¯4.4 vs. 5.4 ±â€¯4.4, p < 0.0001) and higher prevalence of the Type D Personality (20/50 vs. 4/28, p = 0.012). In multivariable models, only a predisposition to subjectively appraise life situations as stressful (higher PSS score) and a personality with a higher degree of negative affectivity and social inhibition (higher TDPS score) were independent predictors of higher AF symptom severity and poorer hr-QOL. No clinical factors including AF burden, ventricular rates during AF or LV diastolic function were significant predictors of AF-specific symptoms or hr-QOL. CONCLUSION: In a tertiary AF population with preserved LV systolic function, only psychological functioning consistently predicts both AF-related symptoms and hr-QOL. LV diastolic function, AF burden, and ventricular rate during AF are not independent predictors.

Psychological Distress and Suicidal Ideation in Patients With Atrial Fibrillation: Prevalence and Response to Management Strategy.

Background An association between atrial fibrillation ( AF ), anxiety, and depression is recognized, but the spectrum of psychological distress remains unclear. We aimed to characterize the severity and predictors of distress associated with AF in a tertiary population and its response to AF management. Methods and Results Seventy-eight patients with symptomatic AF underwent evaluation, including of AF symptom severity, health-related quality of life, psychological distress, suicidal ideation, and specific personality traits. Twenty participants underwent AF ablation and 58 were managed medically, with repeat assessments at 4, 8, and 12 months. Severe distress (Hospital Anxiety and Depression Scale score, ≥15/42) was identified in 27 of 78 (35%). Independent predictors were a personality marked by vulnerability to stress (Perceived Stress Scale: R2, 0.54; ß=0.7±0.1; t=7.8; P<0.001) and 1 marked by negativity/social inhibition (Type D Personality Scale: R2, 0.47; ß=0.7±0.1; t=6.7; P<0.001). Suicidal ideation was reported by 16 of 78 (20%) and was predicted by personality traits (Perceived Stress Scale score: R2, 0.35; odds ratio, 1.22±0.06; P<0.001; Type D Personality Scale score: R2, 0.48; odds ratio, 1.43±0.14; P<0.001). Effective AF ablation (median AF burden 1% [0-1%] over 12 months) was associated with significant reductions in distress (Hospital Anxiety and Depression Scale score, 13.9±1.8 to 4.3±1.8; P<0.05) and prevalence of suicidal ideation (30-5%; P=0.02). Conclusions There was a high prevalence of severe psychological distress (35%) and of suicidal ideation (20%) in a tertiary AF population, with personality traits predicting both. Effective AF ablation was associated with significant improvements, suggesting AF itself may be a treatable causative factor of distress.

Low Rates of Major Complications for Radiofrequency Ablation of Atrial Fibrillation Maintained Over 14 Years: A Single Centre Experience of 2750 Consecutive Cases.

BACKGROUND: Despite technological advances, studies continue to report high complication rates for atrial fibrillation (AF) ablation. We sought to review complication rates for AF ablation at a high-volume centre over a 14-year period and identify predictors of complications. METHODS: We reviewed prospectively collected data from 2750 consecutive AF ablation procedures at our institution using radiofrequency energy (RF) between January 2004 and May 2017. All cases were performed under general anaesthetic with transoesophageal echocardiography (TEE), 3D-mapping and an irrigated ablation catheter. Double transseptal puncture was performed under TEE guidance. All patients underwent wide antral circumferential isolation of the pulmonary veins (30W anteriorly, 25W posteriorly) with substrate modification at operator discretion. RESULTS: Of 2255 initial and 495 redo procedures, ablation strategies were: pulmonary vein isolation (PVI) only 2097 (76.3%), PVI+ LA lines 368 (13.4%), PVI+posterior wall 191 (6.9%), PVI+cavotricuspid isthmus 277 (10.1%). There were 23 major (0.84%) and 20 minor (0.73%) complications. Cardiac tamponade (five cases - 0.18%) and phrenic nerve palsy (one case - 0.04%) rates were very low. Major vascular complications necessitating surgery or blood transfusion occurred in five patients (0.18%). There were no cases of death, permanent disability, atrio-oesophageal fistulae or symptomatic pulmonary vein (PV) stenosis, although there were five TEE probe-related complications (0.18%). Female gender (OR 2.14; 95% CI 1.07-4.26) but not age >70 (OR 1.01) was the only multivariate predictor of complications. CONCLUSIONS: Atrial fibrillation ablation performed at a high-volume centre using RF can be achieved with a low major complication rate in a representative AF population over a sustained period of time.

Temporal distribution of arrhythmic events in chronic kidney disease: Highest incidence in the long interdialytic period.

BACKGROUND: Chronic kidney disease (CKD) patients undergoing hemodialysis (HD) have a high risk of sudden cardiac death (SCD). A unique risk factor may be a longer interval between HD sessions (interdialytic period). Inherent in conventional HD (thrice-weekly) are two 48-hour short breaks (SIDP) and one 72-hour long break (LIDP) between HD sessions. OBJECTIVE: We used an implantable cardiac monitor (ICM) to define the incidence and timing of significant arrhythmias in an HD population. METHODS: Fifty CKD patients undergoing HD with left ventricular ejection fraction >35% had an ICM inserted, with intensive follow-up to record SCD events and predefined bradyarrhythmias and tachyarrhythmias. RESULTS: Mean age of the patients was 67 ± 11 years; 72% were male, and the mean follow-up was 18 ± 4 months. There were 8 unexpected SCDs (16%), all during the LIDP. The terminal event was severe bradycardia with asystole in each recorded case. No episodes of polymorphic ventricular tachycardia (VT) occurred. A total of 7686 arrhythmia events were recorded in 43 patients (86%), including bradycardia in 15 patients (30%), sinus arrest in 14 (28%), second-degree atrioventricular block in 4 (8%), nonsustained VT in 10 (20%), and new-onset paroxysmal atrial fibrillation in 14 (28%). The LIDP was the highest-risk period for all arrhythmias (P < .001). The arrhythmia event rate per hour was greatest during the first pre-HD period of the week compared with any other peri-HD period (P < .001). CONCLUSION: Risk of SCD and significant arrhythmias is greatest during the LIDP. SCD was attributable to severe bradycardia and asystole. Interventions to prevent this type of SCD or shorten the LIDP deserve further evaluation. CLINICAL TRIAL REGISTRATION INFORMATION: URL: https://www.anzctr.org.au (Unique identifier: ACTRN12613001326785).

Characterization of catheter-tissue contact force during epicardial radiofrequency ablation in an ovine model.

BACKGROUND: Contact force (CF) during radiofrequency ablation (RFA) is an important determinant of endocardial lesion size with limited data on epicardial RFA and CF. We evaluated CF characteristics using irrigated RFA on the epicardium in an ovine model. METHODS AND RESULTS: In 12 sheep, a 7-F irrigated RFA catheter with CF sensor was introduced via a pericardial incision onto/in parallel with ventricular epicardium. RFA (30 W per 30 second duration) was applied at 5g, 10g, 20g, 40g, and 70g: (1) over left and right ventricular myocardium with or without fat, (2) either directly over or adjacent to a coronary artery, or directly over the phrenic nerve. Force-time integral, lesion dimensions, and coronary artery/phrenic nerve injury were recorded. Lesion size, volume, and force-time integral progressively increased with higher CF (P<0.05). Steam pops occurred with high CF. Epicardial fat had an attenuating effect on RF penetration into myocardium (P<0.05); however, myocardial RF lesions could be created at sites with >3.5 mm epicardial fat. At sites with epicardial fat, each 10g increment in CF led to a 0.6 mm increase in lesion depth, whereas each 1 mm of fat reduced lesion depth into underlying myocardium by 0.7 mm. Extent of acute coronary injury with direct and indirect RFA and phrenic nerve palsy occurrence was proportional to CF. CONCLUSIONS: CF is a determinant of epicardial RF lesion size, steam pops, acute coronary artery injury, and phrenic nerve injury. Although epicardial fat limits lesion size, RFA with high CF can produce small myocardial RF lesions at sites of thick epicardial fat.