Advanced glycation end products predict long-term outcome of catheter ablation in paroxysmal atrial fibrillation.

PURPOSE: Oxidative stress is an important contributor to the etiology of atrial fibrillation (AF). Our aim was to study oxidative stress biomarkers in patients undergoing pulmonary vein isolation (PVI) for paroxysmal AF with radiofrequency catheter ablation and to assess its prognostic value in predicting long-term PVI outcome. METHODS: In this prospective cohort study, we included 62 patients (mean age 55±8 years, 12 females and 50 males) with paroxysmal AF and implanted ECG loop recorders who underwent PVI. Plasmatic concentrations of advanced glycation end-products (AGEs), fructosamine, advanced oxidation protein products, and thiobarbituric-acid reacting substances were measured before PVI. AF burden (percentage of time spent in AF) was continually assessed during the follow-up period (1063±271 days). RESULTS: Nineteen patients (31%) were defined as optimal responders (oR) with AF burden < 0.5% after PVI. Remaining 43 patients (69%) were defined as sub-optimal responders. Concentration of AGEs was significantly lower in oR by 3.7 g/g (CI: -6.5 to -1.7; P=0.0003). After adjustment for age, sex, BMI, left atrial size, arterial hypertension, and AF burden before PVI, only low concentration of AGEs remained significantly associated with oR (odds ratio: 1.3; P=0.04). AGEs concentration achieved area under the curve of 0.78 for predicting optimal long-term PVI response. CONCLUSIONS: AGEs concentration before PVI was associated with long-term PVI outcome in patients with paroxysmal AF. Further research will show if this biomarker could contribute to optimal patient selection for catheter ablation.

Adapting detection sensitivity based on evidence of irregular sinus arrhythmia to improve atrial fibrillation detection in insertable cardiac monitors.

Aims: Intermittent change in p-wave discernibility during periods of ectopy and sinus arrhythmia is a cause of inappropriate atrial fibrillation (AF) detection in insertable cardiac monitors (ICM). To address this, we developed and validated an enhanced AF detection algorithm. Methods and results: Atrial fibrillation detection in Reveal LINQ ICM uses patterns of incoherence in RR intervals and absence of P-wave evidence over a 2-min period. The enhanced algorithm includes P-wave evidence during RR irregularity as evidence of sinus arrhythmia or ectopy to adaptively optimize sensitivity for AF detection. The algorithm was developed and validated using Holter data from the XPECT and LINQ Usability studies which collected surface electrocardiogram (ECG) and continuous ICM ECG over a 24-48 h period. The algorithm detections were compared with Holter annotations, performed by multiple reviewers, to compute episode and duration detection performance. The validation dataset comprised of 3187 h of valid Holter and LINQ recordings from 138 patients, with true AF in 37 patients yielding 108 true AF episodes ≥2-min and 449 h of AF. The enhanced algorithm reduced inappropriately detected episodes by 49% and duration by 66% with <1% loss in true episodes or duration. The algorithm correctly identified 98.9% of total AF duration and 99.8% of total sinus or non-AF rhythm duration. The algorithm detected 97.2% (99.7% per-patient average) of all AF episodes ≥2-min, and 84.9% (95.3% per-patient average) of detected episodes involved AF. Conclusion: An enhancement that adapts sensitivity for AF detection reduced inappropriately detected episodes and duration with minimal reduction in sensitivity.

Detection of occult paroxysmal atrial fibrilation by implantable long-term electrocardiographic monitoring in cryptogenic stroke and transient ischemic attack population: a study protocol for prospective matched cohort study.

BACKGROUND: Cardio-embolic etiology is the most frequently predicted cause of cryptogenic stroke/TIA. Detection of occult paroxysmal atrial fibrillation is crucial for selection of appropriate medication. METHODS: Enrolment of eligible cryptogenic stroke and TIA patients began in 2014 and will continue until 2018. The patients undergo long-term (12 months) ECG monitoring (implantable loop recorder) and testing for PITX2 (chromosome 4q25) and ZFHX3 (chromosome 16q22) gene mutations. There will be an appropriate control group of age- and sex-matched healthy volunteers. To analyse the results descriptive statistics, statistical tests for group differences, and correlation analyses will be used. DISCUSSION: In our study we are focusing on a possible correlation between detection of atrial fibrillation by an implantable ECG recorder, and PITX2 and/or ZFHX3 gene mutations in cryptogenic stroke/TIA patients. A correlation could lead to implementation of this genomic approach to cryptogenic stroke/TIA diagnostics and management. The results will be published in 2018. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02216370 .

P-wave evidence as a method for improving algorithm to detect atrial fibrillation in insertable cardiac monitors.

BACKGROUND: Frequent premature atrial contractions and sick sinus syndrome are primary causes of inappropriate atrial fibrillation (AF) detection in insertable cardiac monitors (ICMs). OBJECTIVE: The study aimed to validate an algorithm designed to reduce inappropriate AF detection on the basis of the identification of a single P wave during the cardiac cycle. METHODS: The original detection algorithm looks for evidence of AF based on differences in the pattern of R-R intervals over a 2-minute period. The improved algorithm reduces evidence for AF detection if P waves are detected. The algorithm was validated by using Holter data, which collected 2 leads of surface electrocardiogram and continuously uplinked ICM electrocardiogram over a 46-hour period. ICM detections were compared with Holter annotations to compute episode and duration detection performance. RESULTS: Valid Holter recordings (8442 hours) were analyzed from 206 patients. True AF was observed in 76 patients, yielding 482 true AF episodes ≥2 minutes in duration and 1191 hours of AF. The algorithm correctly identified 97.8% of the total AF duration and 99.3% of the total sinus or non-AF rhythm duration. The algorithm detected 85% (90% per-patient average) of all AF episodes ≥2 minutes in duration, and 55% (78% per-patient average) of the detected episodes had AF. AF was found in 95% of the detected episodes >1 hour. The improved algorithm reduced inappropriate episodes and duration by 46% and 55%, respectively, while also reducing appropriate episodes and duration by 2% and 0.1%, respectively. CONCLUSION: An improvement in the ICM algorithm for AF detection incorporating P-wave information substantially reduced inappropriately detected episodes and duration, with minimal reduction in sensitivity for detecting AF.

Analysis of atrial fibrillatory rate during spontaneous episodes of atrial fibrillation in humans using implantable loop recorder electrocardiogram.

Atrial fibrillatory rate (AFR) can predict outcome of interventions for atrial fibrillation (AF); however, AFR behavior at AF onset in humans is poorly described. We studied AFR during spontaneous AF episodes in patients with lone paroxysmal AF who received implantable loop recorders and had AF episodes of 1 hour or more recorded (n = 4). Mean AFR per minute was assessed from continuous implantable loop recorder electrocardiogram using spatiotemporal QRST cancellation and time-frequency analysis. Atrial fibrillatory rate increased from 290 ± 20 to 326 ± 39 fibrillations per minute during the first 3 hours (P<.05) and reached plateau then. Atrial fibrillatory rate beyond the initial 3 hours can, therefore, be considered stable and may be evaluated for prediction of intervention effect.

Performance of a new leadless implantable cardiac monitor in detecting and quantifying atrial fibrillation: Results of the XPECT trial.

BACKGROUND: Current methods for detecting atrial fibrillation (AF) have limited diagnostic yield. Continuous monitoring with automatic arrhythmia detection and classification may improve detection of symptomatic and asymptomatic AF and subsequent patient treatment. The study purpose was to quantify the performance of the first implantable leadless cardiac monitor (ICM) with dedicated AF detection capabilities. METHODS AND RESULTS: Patients (n=247) with an implanted ICM (Reveal XT, Medtronic Inc, Minneapolis, Minn) who were likely to present with paroxysmal AF were selected. A special Holter device stored 46 hours of subcutaneously recorded ECG, ICM markers, and 2 surface ECG leads. The ICM automatic arrhythmia classification was compared with the core laboratory classification of the surface ECG. Of the 206 analyzable Holter recordings collected, 76 (37%) contained at least 1 episode of core laboratory classified AF. The sensitivity, specificity, positive predictive value, and negative predictive value for identifying patients with any AF were 96.1%, 85.4%, 79.3%, and 97.4%, respectively. The AF burden measured with the ICM was very well correlated with the reference value derived from the Holter (Pearson coefficient=0.97). The overall accuracy of the ICM for detecting AF was 98.5%. CONCLUSIONS: In this ICM validation study, the dedicated AF detection algorithm reliably detected the presence or absence of AF and the AF burden was accurately quantified. The ICM is a promising new diagnostic and monitoring tool for the clinician to treat AF patients independently of symptoms. Long-term studies are needed to evaluate the clinical benefits of the technology.

Reduction of atrial fibrillation burden by atrial overdrive pacing: experience with an improved algorithm to reduce early recurrences of atrial fibrillation.

AIMS: Two independent studies have revealed a potential limitation of post-mode switch overdrive pacing (PMOP), which is its delayed start. METHODS AND RESULTS: We conducted a prospective, randomized, single blind, crossover design study (the post-long pause overdrive pacing study) to test the efficacy of an improved version of PMOP (PMOP(enhanced)). A total of 45 patients were enrolled, of whom 41 were analysed. The median number of atrial tachycardia/atrial fibrillation (AT/AF) episodes per day (1.38 vs. 1.19), the median number of early recurrences of atrial fibrillation (ERAF) per day (0.56 vs. 0.51), and the median AT/AF burden (time per day spent in AT/AF) (2.47 vs. 2.51 h) were not significantly different during the control and active study periods. Based on the median number of episodes per week recorded 90 days prior to enrollment, the patients were stratified by the median and then split into two groups, Group A (lower 2-Quartiles) and Group B (upper 2-Quartiles). The median AT/AF burden was significantly lower in Group B during the active study period (3.71 vs. 1.71 h, P = 0.02).The median number of AT/AF episodes per day and the median number of ERAF per day in Group B showed a trend towards reduction when the algorithm was turned on (3.79 vs. 2.44 and 2.77 vs. 1.86, respectively). In contrast, in Group A we did not demonstrate any difference in AT/AF frequency, ERAF frequency, or burden. CONCLUSION: The main finding of this study is that temporary overdrive pacing at 90 bpm for 10 min starting just prior to device-classified AT/AF termination does not show a positive effect on the overall study population. However, when enabled in patients who suffer from a high percentage of ERAF, a significant reduction in the AT/AF burden could be demonstrated. Based on these findings, further prospective studies on a more targeted patient population are needed to confirm our results.

Reduction of atrial tachyarrhythmia episodes during the overdrive pacing period using the post-mode switch overdrive pacing (PMOP) algorithm.

BACKGROUND: Early recurrences within 10 minutes after termination of an atrial tachyarrhythmia, such as atrial tachycardia (AT), atrial flutter, or atrial fibrillation (AF) episodes, account for a large part of paroxysmal AT/AF episodes. It is unclear whether these arrhythmias can be suppressed by overdrive pacing. OBJECTIVE: We set out to prove that overdrive pacing is effective in preventing early recurrences of AT/AF. METHODS: This AT500 (DDDRP device, Bakken Research Center Medtronic, Maastricht, The Netherlands) post-mode switch overdrive pacing (PMOP) study is a randomized controlled trial designed to test the efficacy of overdrive pacing on the suppression of early recurring AT/AF episodes. With the PMOP feature, overdrive pacing is activated 12 ventricular beats after device-confirmed termination of an AT/AF episode with a programmed duration and rate. If at least four episodes of 1 minute in duration occurred within the run-in period of 1 month, patients were randomized to one of the three settings (PMOP off and PMOP 10 minutes at 90 bpm or 120 bpm) for 2 months. At 2 and 4 months, patients were crossed over to another arm. At 6 months, all patients were programmed with PMOP on at 90 bpm for 30 minutes. RESULTS: We enrolled 122 and randomized 50 patients. Sixty percent of all stored AT/AF episodes occurred within 10 minutes after a previous episode; 31% occurred after device-determined termination and before the device reached the overdrive rate (17-27 ventricular beats after termination), and 29% of the episodes occurred while the device was pacing at the programmed overdrive rate. Thirty-seven percent of the average percentage of episodes during the overdrive period was prevented by the randomized settings of PMOP 90 bpm/10 min (P = .01, paired t-test, n = 39) and 120 bpm/10 min (P = .03, n = 35). In addition, for the nonrandomized setting of PMOP 90 bpm/30 min, the average number of episodes during the overdrive period was significantly smaller than the percentage of episodes occurring during the corresponding off period of 30 minutes (P = .05, n = 33). No significant differences in burden and episodes were found between the PMOP settings and the corresponding off periods. CONCLUSIONS: This is the first randomized controlled clinical trial to prove that overdrive pacing is effective in preventing early recurrences of AT/AF. However, shortcomings of the PMOP algorithm, such as late activation, need further improvement.

Determination of repetitive slow pathway conduction for evaluation of the efficacy of radiofrequency ablation in AVNRT.

AIMS: To determine whether the loss of repetitive slow pathway conduction identifies a successful radiofrequency ablation of atrioventricular nodal reentry tachycardia (AVNRT). METHODS AND RESULTS: Thirty nine consecutive patients undergoing ablation of AVNRT using the slow pathway approach were included. At baseline and after each radiofrequency application with an episode of junctional rhythm, repetitive slow pathway conduction was assessed as follows: Effective refractory period of the fast pathway was determined. The coupling interval of the first atrial extrastimulus (A2) was set at 30 ms below the effective refractory period of the fast pathway to ensure its conduction via the slow pathway. The second atrial extrastimulus (A3) was introduced at progressively longer coupling intervals starting from 200 ms until: (1) it propagated to the His bundle or (2) an anterogradely blocked AV nodal echo of A2 appeared before a conducted A3 depolarized the atrium in the His bundle electrogram. The response was termed repetitive slow pathway conduction if A3 was conducted with an AH > 200 ms. Application was considered successful if no AVNRT could be induced. Repetitive slow pathway conduction was present after 1 of 39 successful and after 34 of 40 ineffective applications (P < 0.0001). Repetitive slow pathway conduction identified a successful application with 97% sensitivity, 86% specificity, 86% positive predictive value, and 97% negative predictive value. CONCLUSION: The presence of repetitive slow pathway conduction identifies an unsuccessful application with a clinically meaningful negative predictive value.