Directed networks as a novel way to describe and analyze cardiac excitation : directed graph mapping

Networks provide a powerful methodology with applications in a variety of biological, technological and social systems such as analysis of brain data, social networks, internet search engine algorithms, etc. To date, directed networks have not yet been applied to characterize the excitation of the human heart. In clinical practice, cardiac excitation is recorded by multiple discrete electrodes. During (normal) sinus rhythm or during cardiac arrhythmias, successive excitation connects neighboring electrodes, resulting in their own unique directed network. This in theory makes it a perfect fit for directed network analysis. In this study, we applied directed networks to the heart in order to describe and characterize cardiac arrhythmias. Proof-of-principle was established using in-silico and clinical data. We demonstrated that tools used in network theory analysis allow determination of the mechanism and location of certain cardiac arrhythmias. We show that the robustness of this approach can potentially exceed the existing state-of-the art methodology used in clinics. Furthermore, implementation of these techniques in daily practice can improve the accuracy and speed of cardiac arrhythmia analysis. It may also provide novel insights in arrhythmias that are still incompletely understood

Feasibility and performance of a device for automatic self-detection of symptomatic acute coronary artery occlusion in outpatients with coronary artery disease : a multicentre observational study

Background Time delay between onset of symptoms and seeking medical attention is a major determinant of mortality and morbidity in patients with acute coronary artery occlusion. Response time might be reduced by reliable self-detection. We aimed to formally assess the proof-of-concept and accuracy of self-detection of acute coronary artery occlusion by patients during daily life situations and during the very early stages of acute coronary artery occlusion. Methods In this multicentre, observational study, we tested the operational feasibility, specificity, and sensitivity of our RELF method, a three-lead detection system with an automatic algorithm built into a mobile handheld device, for detection of acute coronary artery occlusion. Patients were recruited continuously by physician referrals from three Belgian hospitals until the desired sample size was achieved, had been discharged with planned elective percutaneous coronary intervention, and were able to use a smartphone; they were asked to perform random ambulatory selfrecordings for at least 1 week. A similar self-recording was made before percutaneous coronary intervention and at 60 s of balloon occlusion. Patients were clinically followed up until 1 month after discharge. We quantitatively assessed the operational feasibility with an automated dichotomous quality check of self-recordings. Performance was assessed by analysing the receiver operator characteristics of the ST difference vector magnitude. This trial is registered with ClinicalTrials.gov, number NCT02983396. Findings From Nov 18, 2016, to April 25, 2018, we enrolled 64 patients into the study, of whom 59 (92%) were eligible for self-applications. 58 (91%) of 64 (95% CI 81.0-95.6) patients were able to perform ambulatory self-recordings. Of all 5011 self-recordings, 4567 (91%) were automatically classified as successful within 1 min. In 65 balloon occlusions, 63 index tests at 60 s of occlusion in 55 patients were available. The mean specificity of daily life recordings was 0.96 (0.95-0.97). The mean false positive rate during daily life conditions was 4.19% (95% CI 3.29-5.10). The sensitivity for the target conditions was 0.87 (55 of 63; 95% CI 0.77-0.93) for acute coronary artery occlusion, 0.95 (54 of 57; 0.86-0.98) for acute coronary artery occlusion with electrocardiogram (ECG) changes, and 1.00 (35 of 35) for acute coronary artery occlusion with ECG changes and ST-segment elevation myocardial infarction criteria (STEMI). The index test was more sensitive to detect a 60 s balloon occlusion than the STEMI criteria on 12-lead ECG (87% vs 56%; p<0.0001). The proportion of total variation in study estimates due to heterogeneity between patients (I-2) was low (12.6%). The area under the receiver operator characteristics curve was 0.973 (95% CI 0.956-0.990) for acute coronary artery occlusion at different cutoff values of the magnitude of the ST difference vector. No patients died during the study. Interpretation Self-recording with our RELF device is feasible for most patients with coronary artery disease. The sensitivity and specificity for automatic detection of the earliest phase of acute coronary artery occlusion support the concept of our RELF device for patient empowerment to reduce delay and increase Survival without overloading emergency services. Copyright (C) 2019 The Author(s). Published by Elsevier Ltd

First successful radiofrequency ablation of focal atrial tachycardia in a horse guided by a high density 3D electro-anatomical mapping system (Rhythmia®)

Transvenous electrical cardioversion (TVEC) has a 95% success rate for cardioversion of atrial tachyarrhythmia but recurrence rate is about 35%. A 5-year-old showjumper stallion with regular atrial tachyarrhythmia was treated successfully with TVEC twice but showed early recurrence each time. An electrophysiological study suggested a right sided atrial tachycardia and the option for ablation was taken. In the standing horse, a decapolar catheter and two TVEC catheters, in case atrial fibrillation would occur during the procedure, were inserted in the left jugular vein and placed in the coronary sinus, right atrium and left pulmonary artery, respectively. Subsequently, under general anesthesia, an electro-anatomical mapping catheter (Intellamap Orion, Boston Scientific) was inserted into the right jugular vein and used to create a 3D electro-anatomical map (Rhythmia, Boston Scientific) of right atrium and venae cavae. Activation mapping, whereby the coronary sinus signal served as time reference, revealed a focal atrial tachycardia with a cycle length of 400ms with earliest activity at the caudodorsal interatrial wall. An ablation catheter (Intellanav OI, Boston Scientific) was guided towards the site of earliest activation using the Rhythmia mapping system and targeted for ablation. During the 5th application (temperature-controlled 60W, maximal temperature 60°C), the atrial tachycardia terminated and became non-inducible. Total ablation time was 366 seconds. Recovery was uneventful. This is the first time that the exact origin of an atrial arrhythmia is identified by 3D electro-anatomical mapping and is successfully treated by radiofrequency ablation. This study proves that both techniques are technically feasible in adult horses

Prospective evaluation of entrainment mapping as an adjunct to new-generation high-density activation mapping systems of left atrial tachycardias

BACKGROUND Identification of atrial tachycardia (AT) mechanism remains challenging. OBJECTIVE We sought to investigate the added value of entrainment maneuvers (EM) when using new high-density activation mapping (HDAM) technologies for the identification of complex left ATs. METHODS Thirty-six consecutive complex ATs occurring after ablation of persistent atrial fibrillation were prospectively analyzed. The AT mechanism was diagnosed in 2 steps by 2 experts: (1) based on H DAM only (Coherent module, CARTO, Biosense Webster Inc., Irvine, CA) and (2) with additional analysis from EM. RESULTS EM resulted in atrial fibrillation in 1 patient, who was excluded from the analysis. Ten of 11 single loop macroreentries identified by HDAM were confirmed by EM. Only 4 of 14 double loop macroreentries identified by HDAM wereconfirmed by EM (in 10 patients, EM unmasked passive activation of one of the visual cir- cuits). One sole microreentry circuit identified by HDAM was confirmed by EM. A combination of macro- and microreentry circuits was visualized in 3 ATs using H DAM. However, EM revealed passive activation of the visual macroreentrant loop in 2 of these 3 cases. By using HDAM in 6 of 35 ATs (17%), no univocal mechanism could be identified, whereas EM finally enabled the diagnosis of 5 microreentry circuits and 1 macroreentrant AT. All the diagnoses made from EM in addition to HDAM were confirmed by ablation. CONCLUSION Entrainment maneuvers are still useful during mapping of complex left ATs, mostly to differentiate active from passive macroreentrant loops and to demonstrate microreentry circuits

Long-term outcomes of the pentaspline pulsed field ablation catheter for the treatment of paroxysmal atrial fibrillation: Results of the prospective, multicenter FARA-Freedom Study.

INTRODUCTION/OBJECTIVES Pulmonary vein isolation (PVI) is well-established strategy for the treatment of paroxysmal atrial fibrillation (PAF). Despite randomized controlled trials and real-world data showing the promise of pulsed-field ablation (PFA) for this treatment, long term efficacy and safety data demonstrating single procedure outcomes off antiarrhythmic drugs remain limited. The aim of the FARA-Freedom Study was to evaluate long-term efficacy and safety of PFA using the pentaspline catheter for PAF. METHODS FARA-Freedom, a prospective, non-randomized, multicenter study, enrolled patients with PAF undergoing de novo PVI with PFA, which were followed for 12 months with weekly transtelephonic monitoring (TTMs) and 72-hr Holter ECG at 6 and 12 months. The primary safety endpoint was a composite of device- or procedure-related serious adverse events out to 7 days post-ablation and PV stenosis or atrioesophageal (AE) fistula out to 12 months. Treatment success is a composite of acute PVI and chronic success; which includes freedom from any documented atrial tachyarrhythmia longer than 30 s, use of antiarrhythmic drugs or cardioversion after a 3-month blanking period, or use of amiodarone or repeat ablation at any time. RESULTS The study enrolled 179 PAF patients (62 ± 10 yr, 39% female) at 13 centers. At index procedure, all PVs were successfully isolated with the pentaspline PFA catheter. Procedure and left atrial dwell times, with a 20 min waiting period, were 71.9 ± 17.6 and 41.0 ± 13.3 min, respectively. Fluoroscopy time was 11.5 ± 7.4 min. Notably, monitoring compliance was high with 88.4% and 90.3% with weekly event and 72-hour Holter monitors, respectively. Freedom from composite primary effectiveness endpoint was 66.6%, 41 patients had atrial tachyarrhythmia recurrence: mostly recurrent atrial fibrillation (31 patients). The composite safety endpoint occurred in 2 patients (1.1%), 1 tamponade and 1 TIA. There was no coronary spasm, PV stenosis, or AE fistula. There were 4 cases of transient phrenic nerve palsy, but all resolved during index procedure. CONCLUSIONS In this prospective, non-randomized, multicenter study, PVI using a pentaspline PFA catheter was effective in treating PAF patients despite rigorous endpoint definitions and high monitoring compliance and demonstrated favorable safety

Antithrombotic management and outcomes of patients with atrial fibrillation treated with NOACs early at the time of market introduction:Main results from the PREFER in AF Prolongation Registry

International audienceAbstract The management of patients with atrial fibrillation (AF) has rapidly changed with increasing use of non-vitamin K antagonist oral anticoagulants (NOACs) and changes in the use of rhythm control therapy. The prevention of thromboembolic events European Registry in Atrial Fibrillation Prolongation Registry (PREFER Prolongation) enrolled consecutive patients with AF on NOACs between 2014 and 2016 in a multicentre, prospective, observational study with one-year follow-up, focusing on the time of introduction of NOACs. Overall, 3783 patients were enrolled, with follow-up information available in 3223 (85%). Mean age was 72.2 ± 9.4 years, 40% were women, mean CHA 2 DS 2 VASc score was 3.4 ± 1.6, and 2587 (88.6%) had a CHA 2 DS 2 VASc score ≥ 2. Rivaroxaban was used in half of patients, and dabigatran and apixaban were used in about a quarter of patients each; edoxaban was not available for use in Europe at the time. Major cardiovascular event rate was low: serious events occurred in 74 patients (84 events, 2%), including 24 strokes (1%), 62 major bleeds (2%), of which 30 were life-threatening (1%) and 3 intracranial (0.1%), and 28 acute coronary syndromes (1%). Mortality was 2%. Antiarrhythmic drugs were used in about 50% of patients, catheter ablation in 5%. Adverse events were low in this contemporary European cohort of unselected AF patients treated with NOACs already at the time of their first introduction, despite high thromboembolic risk

Association of atrial tissue fibrosis identified by delayed enhancement MRI and atrial fibrillation catheter ablation: the DECAAF study

IMPORTANCE: Left atrial fibrosis is prominent in patients with atrial fibrillation (AF). Extensive atrial tissue fibrosis identified by delayed enhancement magnetic resonance imaging (MRI) has been associated with poor outcomes of AF catheter ablation. OBJECTIVE: To characterize the feasibility of atrial tissue fibrosis estimation by delayed enhancement MRI and its association with subsequent AF ablation outcome. DESIGN, SETTING, AND PARTICIPANTS: Multicenter, prospective, observational cohort study of patients diagnosed with paroxysmal and persistent AF (undergoing their first catheter ablation) conducted between August 2010 and August 2011 at 15 centers in the United States, Europe, and Australia. Delayed enhancement MRI images were obtained up to 30 days before ablation. MAIN OUTCOMES AND MEASURES: Fibrosis quantification was performed at a core laboratory blinded to the participating center, ablation approach, and procedure outcome. Fibrosis blinded to the treating physicians was categorized as stage 1 (<10% of the atrial wall), 2 (≥10%-<20%), 3 (≥20%-<30%), and 4 (≥30%). Patients were followed up for recurrent arrhythmia per current guidelines using electrocardiography or ambulatory monitor recording and results were analyzed at a core laboratory. Cumulative incidence of recurrence was estimated by stage at days 325 and 475 after a 90-day blanking period (standard time allowed for arrhythmias related to ablation-induced inflammation to subside) and the risk of recurrence was estimated (adjusting for 10 demographic and clinical covariates). RESULTS: Atrial tissue fibrosis estimation by delayed enhancement MRI was successfully quantified in 272 of 329 enrolled patients (57 patients [17%] were excluded due to poor MRI quality). There were 260 patients who were followed up after the blanking period (mean [SD] age of 59.1 [10.7] years, 31.5% female, 64.6% with paroxysmal AF). For recurrent arrhythmia, the unadjusted overall hazard ratio per 1% increase in left atrial fibrosis was 1.06 (95% CI, 1.03-1.08; P < .001). Estimated unadjusted cumulative incidence of recurrent arrhythmia by day 325 for stage 1 fibrosis was 15.3% (95% CI, 7.6%-29.6%); stage 2, 32.6% (95% CI, 24.3%-42.9%); stage 3, 45.9% (95% CI, 35.5%-57.5%); and stage 4, 51.1% (95% CI, 32.8%-72.2%) and by day 475 was 15.3% (95% CI, 7.6%-29.6%), 35.8% (95% CI, 26.2%-47.6%), 45.9% (95% CI, 35.6%-57.5%), and 69.4% (95% CI, 48.6%-87.7%), respectively. Similar results were obtained after covariate adjustment. The addition of fibrosis to a recurrence prediction model that includes traditional clinical covariates resulted in an improved predictive accuracy with the C statistic increasing from 0.65 to 0.69 (risk difference of 0.05; 95% CI, 0.01-0.09). CONCLUSIONS AND RELEVANCE: Among patients with AF undergoing catheter ablation, atrial tissue fibrosis estimated by delayed enhancement MRI was independently associated with likelihood of recurrent arrhythmia. The clinical implications of this association warrant further investigation