Left atrial strain and recurrence of atrial fibrillation after thoracoscopic surgical ablation: a subanalysis of the AFACT study.

To assess transthoracic echocardiographic (TTE) left atrial (LA) strain parameters and their association with atrial fibrillation (AF) recurrence after thoracoscopic surgical ablation (SA) in patients in sinus rhythm (SR) or in AF at baseline. Patients participating in the Atrial Fibrillation Ablation and Autonomic Modulation via Thoracoscopic Surgery trial were included. All patients underwent thoracoscopic pulmonary vein isolation with LA appendage exclusion and were randomized to ganglion plexus (GP) or no GP ablation. In TTEs performed before surgery, LA strain and mechanical dispersion (MD) of the LA reservoir and conduit phase in all patients, and of the contraction phase in patients in SR were obtained. Recurrence of AF was defined as any documented atrial tachyarrhythmia lasting > 30 s during one year of follow-up. Two hundred and four patients (58.6 ± 7.8 years, 73% male, 57% persistent AF) were included. At baseline TTE 121 (59%) were in SR and 83 (41%) had AF. Patients with AF recurrence had lower LA strain of the reservoir phase (13.0% vs. 16.6%; p = < 0.001) and a less decrease in strain of the conduit phase (-9.0% vs. -11.8%; p = 0.006), regardless of rhythm. MD of the conduit phase was larger in patients with AF recurrence (79.4 vs. 43.5 ms; p = 0.012). Multivariate cox regression analysis demonstrated solely an association between LA strain of the reservoir phase and AF recurrence in patients in SR (HR 0.95, p = 0.046) or with AF (HR 0.90, p = 0.038). A reduction in LA strain of the reservoir phase prior to SA predicts recurrence of AF in both patients with SR or AF. Left atrial strain assessment may therefore add to a better patient selection for SA.

Intermediate-term outcome of cryoballoon ablation of persistent atrial fibrillation and improvements in quality of life of patients.

BACKGROUND: Clinical outcome of pulmonary vein isolation (PVI) has been predominantly focused on the reoccurrence of atrial fibrillation (AF) and the maintenance of sinus rhythm. However, there has been a limited intermediate follow-up on health-related quality-of-life (HRQoL) of patients. Given the relatively high recurrence rate of persistent AF after PVI treatment, it is important to follow up with clinical outcomes on symptom improvement as well as health-related quality-of-life. This study was designed to investigate the recurrence rate of atrial tachyarrhythmia (ATa), AF-related symptoms and HRQoL after PVI in patients with persistent AF who were treated with the second generation cryoballoon. METHODS: Total 148 patients participated in the study who were treated by PVI between 2013 and 2017 for persistent AF. All patients visited the out-patient clinic 2-5 years after PVI. During this visit all patients filled-out an AF Effect on Quality-of-life (AFEQT) questionnaire and a seven-day Holter was applied. All rhythm recordings acquired post ablation were collected and analysed, and the modified European Heart Rhythm Association score (mEHRA) scores were calculated before and after the ablation. RESULTS: The average age of patients was 63±9 year old and 44 (27.9%) were female. Mean CHA2DS2 VASc score was 1.9±1.4, and moderate and severe left atrial (LA) dilation was present in 53 (36.1%) and 15 (10.2%) patients, respectively. After a follow-up of 3.7±1.0 years, 81 (54.7%) patients had an ATa recurrence and 35 (23.6%) patients underwent a repeat LA ablation. However, the mEHRA score significantly improved in 80.4% of the patients (p <0.001), with the median overall AFEQT score of 88.9 [70.4-97.2]. CONCLUSIONS: There is a considerable ATa recurrence rate after PVI of persistent AF at intermediate-term follow-up. However, our data indicate that PVI significantly improved AF-related symptoms and resulted in a high HRQoL for 2-5 years in patients with persistent AF.

Clinical course of sinus node dysfunction after thoracoscopic surgery for atrial fibrillation-analysis of the Atrial Fibrillation Ablation and Autonomic Modulation via Thoracoscopic Surgery (AFACT) study.

PURPOSE: Sinus node dysfunction (SND) may complicate thoracoscopic surgical atrial fibrillation (AF) ablation. Identifying patients at risk is important, as SND may require temporary or permanent pacing. To determine the incidence of postoperative SND and duration of symptoms in patients who underwent thoracoscopic surgical ablation. METHODS: Patients with paroxysmal or persistent AF included in the Atrial Fibrillation Ablation and Autonomic Modulation via Thoracoscopic Surgery (AFACT) study underwent pulmonary vein isolation and additional left atrial ablations on indication. Patients were randomized to ganglion plexus ablation or control. SND was defined as symptomatic or asymptomatic junctional rhythm exceeding sinus rate within 30 days postoperatively. The SND risk was assessed by using a univariable logistic regression model. The rate of pacemaker implantation was determined. RESULTS: The AFACT study included 240 patients. SND developed in 17 (7.1%) patients, not affected by randomized treatment, p = 0.18. SND patients more often had persistent AF (88.2%) than patients without SND (57.4%), p = 0.01. After univariable testing, persistent AF (OR 5.57 CI 1.52-35.90, p = 0.02) and additional left atrial ablations (OR 12.10 CI 2.40-220.20, p = 0.02) were associated with postoperative SND. Six (35.3%) patients needed temporary pacing for 1-7 days; permanent pacemakers (PMs) were implanted for SND in five (29.4%) patients. CONCLUSION: Additional left atrial ablations strongly increase the SND risk. The majority of SND was temporary, and sinus rhythm resolved within days, which indicates that a conservative approach with regard to pacemaker implantation should be considered.

PREventive left atrial appenDage resection for the predICtion of fuTure atrial fibrillation: design of the PREDICT AF study.

BACKGROUND: Atrial fibrillation is the most common cardiac arrhythmia, posing a heavy burden on patients' wellbeing and healthcare budgets. Patients undergoing cardiac surgery are at risk of developing postoperative atrial fibrillation (POAF), new-onset atrial fibrillation and subsequent atrial fibrillation-related complications, including stroke. Sufficient clinical identification of patients at risk fails while the pathological substrate changes that precede atrial fibrillation remain unknown. Here, we describe the PREDICT AF study design, which will be the first study to associate tissue pathophysiology and blood biomarkers with clinical profiling and follow-up of cardiothoracic surgery patients for the prediction of future atrial fibrillation. METHODS: PREDICT AF will include 150 patients without atrial fibrillation and a CHA2DS2-VASc score of at least 2 undergoing cardiac surgery. The left atrial appendage will be excised during surgery and blood samples will be collected before surgery and at 6 and 12 months' follow-up. Tissue and blood analysis will be used for the discovery of biomarkers including microRNAs and protein biomarkers. The primary study endpoint is atrial fibrillation, which will be objectified by 24 h Holters and ECGs after 30 days for POAF and after 6, 12 and 24 months for new-onset atrial fibrillation. Secondary endpoints include the dynamic changes of blood biomarkers over time and other atrial arrhythmias. PREDICT AF participants may benefit from extensive postoperative care with clinical phenotyping, rhythm monitoring and primary prevention of stroke. CONCLUSION: We here describe the PREDICT AF trial design, which will enable the discovery of biomarkers that truly predict POAF and new-onset atrial fibrillation by combining tissue and plasma-derived biomarkers with comprehensive clinical follow-up data. TRIAL REGISTRATION: Retrospectively registered NCT03130985 27 April 2017.

Additional Ganglion Plexus Ablation During Thoracoscopic Surgical Ablation of Advanced Atrial Fibrillation: Intermediate Follow-Up of the AFACT Study.

OBJECTIVES: The authors report the 2-year follow-up results of the AFACT (Atrial Fibrillation Ablation and Autonomic Modulation via Thoracoscopic Surgery) study. BACKGROUND: The AFACT study randomized patients with advanced atrial fibrillation (AF) to thoracoscopic AF ablation with or without additional ganglion plexus (GP) ablation. At 1 year, there was no difference in AF freedom between the groups, but autonomic modification may exert beneficial effects during longer follow-up. METHODS: Patients underwent thoracoscopic pulmonary vein isolation, with additional left atrial lines in persistent AF patients, and were randomized 1:1 to ablation of the 4 major GP and Marshall ligament or no GP ablation (control). Patients were followed every 3 months up to 18 months and at 24 months. After an initial 3-month blanking period, all antiarrhythmic drugs were discontinued. RESULTS: The authors randomized 240 patients (age 59 ± 8 years, 73% men, 68% enlarged left atrium, 60% persistent AF), of whom 228 patients (95%) completed follow-up. Freedom of any atrial tachyarrhythmia did not differ significantly between the GP group (55.6%) and control group (56.1%) (p = 0.91), with no difference in paroxysmal (p = 0.60) or persistent AF patients (p = 0.88). Documented AF recurrences were similar between treatment arms: 11.8% (GP) versus 11.0% (control) had >3 recurrences/year (p = 0.82). More persistent AF patients (17.0%) than paroxysmal (3.2%) had >3 recurrences per year (p < 0.01). Despite this, 78% of patients were off antiarrhythmic drugs after 2 years. No procedural-related complications occurred in the second year. CONCLUSIONS: Additional GP ablation during thoracoscopic surgery for advanced AF does not affect freedom of AF recurrence. As GP ablation is associated with more major procedural complications, it should not routinely be performed. (Atrial Fibrillation Ablation and Autonomic Modulation via Thorascopic Surgery [AFACT]; NCT01091389).

Persistent atrial fibrillation: A systematic review and meta-analysis of invasive strategies.

BACKGROUND: Persistent atrial fibrillation (AF) is associated with higher stroke and mortality risk than paroxysmal AF (pAF). Outcomes of catheter or surgical ablation are worse in patients with persistent AF than in pAF, and the optimal invasive rhythm control strategy has not been established. PURPOSE: We provide a contemporary systematic overview on efficacy and safety of catheter and minimally-invasive surgical ablation for persistent AF. METHODS: We systematically searched EMBASE, MEDLINE and CENTRAL from inception to July 2018 for randomized trials on surgical and catheter ablation, and included all study arms on persistent AF. Outcome was AF freedom after ≥12 months follow-up without AAD use. Random effects models were used to calculate proportions with 95%-confidence intervals. Safety consisted of adverse events during treatment and follow-up. RESULTS: We included 6 studies on minimally-invasive surgical ablation and 56 on catheter ablation, involving 7624 patients with persistent AF. AF Freedom at 12 months was 69% (95%CI 64-74%) after surgical and 51% (95%CI 46-56%) after catheter ablation. More severe procedural adverse events occurred with surgery than with catheter ablation. CONCLUSIONS: In persistent AF patients, minimally-invasive surgical ablation is associated with more procedural complications, but higher AF freedom. As adverse events after surgical ablation appear more severe than in catheter ablation, a patient-tailored therapy choice is warranted.

Comparison of non-triggered magnetic resonance imaging and echocardiography for the assessment of left atrial volume and morphology.

BACKGROUND: Advanced atrial fibrillation (AF) patients have persistent AF, failed previous catheter ablation and/or an enlarged left atrium (LA), which is associated with a reduced success of AF ablation. Transthoracic echocardiography (TTE) and contrast enhanced magnetic resonance angiography (CE-MRA) are available to assess LA volume. However, it is unknown how these modalities relate in patients with advanced AF. We therefore compared the reproducibility of TTE and non-triggered CE-MRA in advanced AF patients and their ability to select patients with successful thoracoscopic AF ablation. METHODS: Two independent observers measured LA volumes on 65 TTE and CE-MRA exams of advanced AF patients prior to AF ablation. Patients were followed after AF ablation with rhythm monitoring every 3 months for 1 year to determine AF recurrence. Inter-modality, inter- and intra-observer variability were determined using intraclass correlation coefficients (ICC). Receiver-operating characteristic (ROC) analysis was performed to determine sensitivity and specificity of TTE and CE-MRA volume and CE-MRA dimensions to identify patients with AF recurrence during follow-up. RESULTS: LA enlargement ≥ 34 ml/m2 was present in 60% of the patients. CE-MRA and TTE demonstrated a good correlation for LA volume assessment (intraclass correlation, ICC = 0.86; p < 0.001) with larger volumes consistently measured by CE-MRA. Major discrepancies were mostly attributed to TTE acquisition. Craniocaudal enlargement discriminated patients with AF recurrence (AUC 0.67 [95% CI 0.55-0.85], p = 0.01). CONCLUSIONS: Non-triggered CE-MRA is a viable and reproducible 3D alternative for 2D TTE to assess LA volume in advanced AF patients. Craniocaudal enlargement was the only discriminator of AF recurrence after AF ablation.

Quality of life improves after thoracoscopic surgical ablation of advanced atrial fibrillation: Results of the Atrial Fibrillation Ablation and Autonomic Modulation via Thoracoscopic Surgery (AFACT) study.

OBJECTIVE: We evaluated health-related quality of life at 12 months after thoracoscopic surgical ablation in patients enrolled in the Atrial Fibrillation Ablation and Autonomic Modulation via Thoracoscopic Surgery study. The Atrial Fibrillation Ablation and Autonomic Modulation via Thoracoscopic Surgery study assessed the efficacy and safety of ganglion plexus ablation in patients with symptomatic advanced atrial fibrillation undergoing thoracoscopic surgical ablation. METHODS: Patients (n = 240) underwent thoracoscopic pulmonary vein isolation with additional ablation lines in patients with persistent atrial fibrillation. Subjects were randomized to additional ganglion plexus ablation or control. Short Form 36 quality of life questionnaires were collected at baseline and at 6 and 12 months of follow-up. RESULTS: A total of 201 patients were eligible for quality of life analysis (age 59 ± 8 years, 72% were men, 68% had an enlarged left atrium, 57% had persistent atrial fibrillation). Patients improved in physical and mental health at 6 months (both P < .01) and 12 months (both P < .01) relative to baseline, with no difference between the ganglion plexus (n = 101) and control (n = 100) groups. Short Form 36 subscores in patients with 1 or no atrial fibrillation recurrences were similar to those in the general Dutch population after 12 months. Patients with multiple atrial fibrillation recurrences (30%) improved in mental (P < .01), but not physical health, and 6 of 8 Short Form 36 subscales remained below those of the general Dutch population. Patients with irreversible, but not with reversible procedural complications had persistently diminished quality of life scores at 12 months. CONCLUSIONS: Thoracoscopic surgery for advanced atrial fibrillation results in improvement in quality of life, regardless of additional ganglion plexus ablation. Quality of life in patients with no or 1 atrial fibrillation recurrence increased to the level of the general Dutch population, whereas in patients with multiple atrial fibrillation recurrences quality of life remained lower. Irreversible but not reversible procedural complications were associated with persistently lower quality of life.

The change in circulating galectin-3 predicts absence of atrial fibrillation after thoracoscopic surgical ablation.

Aims: Galectin-3 (Gal-3) is an important mediator of cardiac fibrosis, particularly in heart failure. Increased Gal-3 concentration (Gal-3), associated with increased risk of developing atrial fibrillation (AF), may reflect atrial fibrotic remodelling underlying AF progression. We aimed to investigate whether the change in serum Gal-3 reflects alterations of the arrhythmogenic atrial substrate following thoracoscopic AF surgery, and predicts absence of AF. Methods and results: Consecutive patients undergoing thoracoscopic AF surgery were included. Left atrial appendages (LAAs) and serum were collected during surgery and serum again 6 months thereafter. Gal-3 was determined in tissue and serum. Interstitial collagen in the LAA was quantified using Picrosirius red staining. Ninety-eight patients (76% male, mean age 60 ± 9 years) underwent thoracoscopic surgery for advanced AF. Patients with increased Gal-3 after ablation compared to baseline had a higher recurrence rate compared to patients with decreased or unchanged Gal-3 (HR 2.91, P = 0.014). These patients more frequently had persistent AF, longer AF duration and thick atrial collagen strands (P = 0.049). At baseline, Gal-3 was similar between patients with and without AF recurrence: 14.8 ± 3.9 µg/L vs. 13.7 ± 3.7 µg/L, respectively in serum (P = 0.16); 94.5 ± 19.4 µg/L vs. 93.3 ± 30.8µg/L, respectively in atrial myocardium (P = 0.83). There was no correlation between serum Gal-3 and left atrial Gal-3 (P = 0.20), nor between serum Gal-3 and the percentage of fibrosis in LAA (P = 0.18). Conclusion: The change of circulating Gal-3, rather than its baseline value, predicts AF recurrence after thoracoscopic ablation. Patients in whom Gal-3 increases after ablation have a high recurrence rate reflecting ongoing profibrotic signalling, irrespective of arrhythmia continuation.

Ganglion Plexus Ablation in Advanced Atrial Fibrillation: The AFACT Study.

BACKGROUND: Patients with long duration of atrial fibrillation (AF), enlarged atria, or failed catheter ablation have advanced AF and may require more extensive treatment than pulmonary vein isolation. OBJECTIVES: The aim of this study was to investigate the efficacy and safety of additional ganglion plexus (GP) ablation in patients undergoing thoracoscopic AF surgery. METHODS: Patients with paroxysmal AF underwent pulmonary vein isolation. Patients with persistent AF also received additional lines (Dallas lesion set). Patients were randomized 1:1 to additional epicardial ablation of the 4 major GPs and Marshall's ligament (GP group) or no extra ablation (control) and followed every 3 months for 1 year. After a 3-month blanking period, all antiarrhythmic drugs were discontinued. RESULTS: Two hundred forty patients with a mean AF duration of 5.7 ± 5.1 years (59% persistent) were included. Mean procedure times were 185 ± 54 min and 168 ± 54 min (p = 0.015) in the GP (n = 117) and control groups (n = 123), respectively. GP ablation abated 100% of evoked vagal responses; these responses remained in 87% of control subjects. Major bleeding occurred in 9 patients (all in the GP group; p < 0.001); 8 patients were managed thoracoscopically, and 1 underwent sternotomy. Sinus node dysfunction occurred in 12 patients in the GP group and 4 control subjects (p = 0.038), and 6 pacemakers were implanted (all in the GP group; p = 0.013). After 1 year, 4 patients had died (all in the GP group, not procedure related; p = 0.055), and 9 were lost to follow-up. Freedom from AF recurrence in the GP and control groups was not statistically different whether patients had paroxysmal or persistent AF. At 1 year, 82% of patients were not taking antiarrhythmic drugs. CONCLUSIONS: GP ablation during thoracoscopic surgery for advanced AF has no detectable effect on AF recurrence but causes more major adverse events, major bleeding, sinus node dysfunction, and pacemaker implantation. (Atrial Fibrillation Ablation and Autonomic Modulation via Thoracoscopic Surgery [AFACT]; NCT01091389).

Atrial fibrosis and conduction slowing in the left atrial appendage of patients undergoing thoracoscopic surgical pulmonary vein isolation for atrial fibrillation.

BACKGROUND: Atrial fibrosis is an important component of the arrhythmogenic substrate in patients with atrial fibrillation (AF). We studied the effect of interstitial fibrosis on conduction velocity (CV) in the left atrial appendage of patients with AF. METHODS AND RESULTS: Thirty-five left atrial appendages were obtained during AF surgery. Preparations were superfused and stimulated at 100 beats per minute. Activation was recorded with optical mapping. Longitudinal CV (CVL), transverse CV (CVT), and activation times (> 2 mm distance) were measured. Interstitial collagen was quantified and graded qualitatively. The presence of fibroblasts and myofibroblasts was assessed immunohistochemically. Mean CVL was 0.55 ± 0.22 m/s, mean CVT was 0.25 ± 0.15 m/s, and the mean activation time was 9.31 ± 5.45 ms. The amount of fibrosis was unrelated to CV or patient characteristics. CVL was higher in left atrial appendages with thick compared with thin interstitial collagen strands (0.77 ± 0.22 versus 0.48 ± 0.19 m/s; P = 0.012), which were more frequently present in persistent patients with AF. CVT was not significantly different (P = 0.47), but activation time was 14.93 ± 4.12 versus 7.95 ± 4.12 ms in patients with thick versus thin interstitial collagen strands, respectively (P = 0.004). Fibroblasts were abundantly present and were associated with the presence of thick interstitial collagen strands (P = 0.008). Myofibroblasts were not detected in the left atrial appendage. CONCLUSIONS: In patients with AF, thick interstitial collagen strands are associated with higher CVL and increased activation time. Our observations demonstrate that the severity and structure of local interstitial fibrosis is associated with atrial conduction abnormalities, presenting an arrhythmogenic substrate for atrial re-entry.

Disparate response of high-frequency ganglionic plexus stimulation on sinus node function and atrial propagation in patients with atrial fibrillation.

BACKGROUND: In patients with atrial fibrillation (AF), the autonomic nervous system is supposed to play an role in triggering AF; however, little is known of the effect on atrial conduction characteristics. OBJECTIVE: The purpose of this study was to study the effect of ganglionic plexus (GP) stimulation during sinus rhythm on atrial and pulmonary vein conduction in patients during thoracoscopic surgery for AF METHODS: In 25 patients, the anterior right ganglionic plexus (ARGP) was stimulated (16 Hz, at 1, 2, and 5 mA). Epicardial electrograms were recorded using a 48-electrode map from the right pulmonary vein (RPV) or right atrial (RA). Intra-atrial activation time (IAT), local activation time (LAT), and inhomogeneity of conduction (IIC) were determined. ECG parameters (P-P, P-R interval) were measured. RESULTS: P-P interval was 956 ± 157 ms (range 768-1368 ms), and P-R interval was 203 ± 37 ms (range 136-280 ms). After ARGP stimulation, a short-lasting increase of P-P interval was observed, more prominent at higher output (1 mA = 82 ms, 2 mA = 180 ms, 5 mA = 268 ms, all P <.01 vs baseline). P-R interval remained unchanged. IAT was 34.4 ms (range 5.6-50.3 ms) at the RA and 105.8 ms (range 79.7-163.3 ms) at the RPV. After 1-mA stimulation IAT increased, in patients taking beta-blockers (P = .001), or it decreased, and this change persisted after subsequent stimulation at higher current (1 mA, P = .001; 2 mA, P = .401; 5 mA, P = .593). Similar changes were observed for LAT and IIC. CONCLUSION: ARGP stimulation results in a short-lasting, output-dependent decrease in sinus node frequency due to a parasympathetic response. Stimulation of the ARGP induced a prolonged increase or decrease in conduction characteristics in patients with AF, consistent with a persistent differential parasympathetic and/or sympathetic response.

Electrophysiological Evaluation of Thoracoscopic Pulmonary Vein Isolation.

Although the majority of patients with atrial fibrillation and an indication for non-pharmacological therapy is treated with catheter ablation, thoracoscopic surgery is an emerging technique that aims at combining the results of the classic Cox Maze operation with a less invasive approach. Recurrences after thoracoscopic surgery have been mainly ascribed to incomplete ablation lines, but literature on electrophysiological confirmation of thoracoscopic pulmonary vein isolation is limited. Currently, surgical confirmation of uni- or bidirectional conduction block may be hampered by insufficient resolution of the mapping material available. Additionally uncertainty remains on the precise lesions sets required, and how to tailor them to individual patients. In hybrid procedures, electrophysiologists and surgeons join forces to combine their expertise and skills which may lead to increased procedural success rates by minimizing the chance of incomplete PV isolation or absence of conduction block across an alternative ablation line. Here we describe techniques for thoracoscopic mapping and present a literature review.