Markers of Left Atrial Fibrosis in Atrial Fibrillation and Prediction of Successful Rhythm Control Intervention

Introduction Methods to restore atrial fibrillation (AF) to sinus rhythm include catheter ablation and electrical cardioversion. Myocardial fibrosis is associated with recurrence and may be measurable using circulating biomarkers. Other methods include cardiac magnetic resonance (CMR) and electro-anatomical mapping. The aims were: 1) Compare biomarkers in AF patients and controls. 2) Assess biomarker levels at multiple sampling sites. 3) Determine associations between methods of fibrosis quantification. 4) Determine their predictive value for arrhythmia recurrence. Methods 93 AF ablation patients, 79 cardioversion patients, and 40 control patients were enrolled. Enzyme-linked immunosorbent assay was used to determine peripheral serum levels of galectin-3 (gal-3), type I collagen C terminal peptide (ICTP), type III procollagen N terminal peptide (PIIINP), and fibroblast growth factor 23 (FGF-23). Additionally, in ablation patients, levels were measured in the coronary sinus and both atria. 31 ablation patients underwent CMR. Follow up was 12 months. Results ICTP levels were higher in ablation patients than in controls (p=0.007). Peripheral ICTP levels were higher than intracardiac levels (p<0.001), and CS levels were higher than atrial levels (p<0.001). Peripheral gal-3 levels were higher than left atrial levels (p=0.001). FGF-23 was weakly predictive of AF recurrence after cardioversion (HR 1.003 p=0.012). No other biomarkers predicted AF recurrence. Low voltage in the left atrium was the only independent predictor of AF recurrence, mapped in sinus rhythm (HR 4.323 p=0.014) or AF (HR 5.195 p=0.046). LV extracellular volume was associated with LA pressure (beta 0.49, P=0.008) and coronary sinus ICTP (beta 0.75, P<0.001). Conclusion There is no clinically useful predictive effect of the biomarkers in this study. Further research into FGF-23 is warranted. Associations between LV extracellular volume, ICTP and LA pressure may suggest elevated ventricular myocardial turnover of type I collagen in this cohort, and a possible link with atrial pathology

Efficacy and safety of ablation for people with non-paroxysmal atrial fibrillation.

: The optimal rhythm management strategy for people with non-paroxysmal (persistent or long-standing persistent) atrial fibrilation is currently not well defined. Antiarrhythmic drugs have been the mainstay of therapy. But recently, in people who have not responded to antiarrhythmic drugs, the use of ablation (catheter and surgical) has emerged as an alternative to maintain sinus rhythm to avoid long-term atrial fibrillation complications. However, evidence from randomised trials about the efficacy and safety of ablation in non-paroxysmal atrial fibrillation is limited. : To determine the efficacy and safety of ablation (catheter and surgical) in people with non-paroxysmal (persistent or long-standing persistent) atrial fibrillation compared to antiarrhythmic drugs. : We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE Ovid, Embase Ovid, conference abstracts, clinical trial registries, and Health Technology Assessment Database. We searched these databases from their inception to 1 April 2016. We used no language restrictions. : We included randomised trials evaluating the effect of radiofrequency catheter ablation (RFCA) or surgical ablation compared with antiarrhythmic drugs in adults with non-paroxysmal atrial fibrillation, regardless of any concomitant underlying heart disease, with at least 12 months of follow-up. : Two review authors independently selected studies and extracted data. We evaluated risk of bias using the Cochrane 'Risk of bias' tool. We calculated risk ratios (RRs) for dichotomous data with 95% confidence intervals (CIs) a using fixed-effect model when heterogeneity was low (I² &lt;= 40%) and a random-effects model when heterogeneity was moderate or substantial (I² &gt; 40%). Using the GRADE approach, we evaluated the quality of the evidence and used the GRADE profiler (GRADEpro) to import data from Review Manager 5 to create 'Summary of findings' tables. : We included three randomised trials with 261 participants (mean age: 60 years) comparing RFCA (159 participants) to antiarrhythmic drugs (102) for non-paroxysmal atrial fibrillation. We generally assessed the included studies as having low or unclear risk of bias across multiple domains, with reported outcomes generally lacking precision due to low event rates. Evidence showed that RFCA was superior to antiarrhythmic drugs in achieving freedom from atrial arrhythmias (RR 1.84, 95% CI 1.17 to 2.88; 3 studies, 261 participants; low-quality evidence), reducing the need for cardioversion (RR 0.62, 95% CI 0.47 to 0.82; 3 studies, 261 participants; moderate-quality evidence), and reducing cardiac-related hospitalisation (RR 0.27, 95% CI 0.10 to 0.72; 2 studies, 216 participants; low-quality evidence) at 12 months follow-up. There was substantial uncertainty surrounding the effect of RFCA regarding significant bradycardia (or need for a pacemaker) (RR 0.20, 95% CI 0.02 to 1.63; 3 studies, 261 participants; low-quality evidence), periprocedural complications, and other safety outcomes (RR 0.94, 95% CI 0.16 to 5.68; 3 studies, 261 participants; very low-quality evidence). : In people with non-paroxysmal atrial fibrillation, evidence suggests a superiority of RFCA to antiarrhythmic drugs in achieving freedom from atrial arrhythmias, reducing the need for cardioversion, and reducing cardiac-related hospitalisations. There was uncertainty surrounding the effect of RFCA with significant bradycardia (or need for a pacemaker), periprocedural complications, and other safety outcomes. Evidence should be interpreted with caution, as event rates were low and quality of evidence ranged from moderate to very low.<br/

A new minimally invasive heart surgery instrument for atrial fibrillation treatment : first in vitro and animal tests.

International audienceThe paper presents a new robotic system for beating heart surgery. The final goal of this project is to develop a tele-operated system for the thoracoscopic treatment of patients with atrial fibrillation. The system consists of a robot that moves an innovative end-effector used to perform lines as in the Cox-Maze technique. This device is an electrode mesh that is introduced in the thorax through a trocar and is deployed inside the left atrium, where it can create selective ablation lines at any atrial region, using radio frequency. The current version of the umbrella has 22 electrodes. Using visual feedback from an ultrasound based navigation system, the surgeon can choose which electrodes on the mesh to activate. Once the umbrella is in contact with the endocardium of the left atrium, at the expected position, the surgeon activates the chosen electrodes sequentially. The umbrella can then be moved to another position. In vitro and in vivo animal tests have been carried out in order to test and improve the instrument, the robotic system and the operative procedure

Automated algorithm-driven methods of localising drivers of persistent atrial fibrillation using atrial fibrillation cycle length and atrial fibrillation voltage

The assessment of atrial fibrillation cycle length has played a role in the development of atrial fibrillation ablation by pulmonary vein isolation (PVI) and has also been used to assess response to ablation. Areas of rapid rotational activity in the left atrium have been implied to act as drivers of persistent atrial fibrillation and several methods have been developed to identify these potential drivers. Unprocessed atrial fibrillation electrograms show large variation in cycle length and signal amplitude. Current methods of localising driver regions rely on complex pattern recognition and subjective assessment of operators. The main hypotheses of this thesis were as follows: 1) a technique can be developed to ascertain a clinically relevant, dominant cycle length for any AF segment, 2) the automated technique, can be used to map rapid and regular activity in the left atrium, 3) a patient-tailored definition of rapid activity and low AF voltage, calculated based on patient-specific parameters is feasible; 4) paired with automated low voltage substrate analysis, dominant cycle length analysis is able to provide a framework for localising drivers of AF that is objective, transparent and requires no complex pattern recognition of subjective judgement. To test the hypotheses, a technique was developed based on manual annotation of real-world AF electrograms that was able to ascertain cycle length independent of missing segments or variable cycle length or signal amplitude. Following this, an automated algorithm was validated to determine dominant cycle length. In the following chapter, the nature of AF cycle length was investigated by investigating the patterns of rapid activity with extended AF segments and the concept of patient-tailored definitions of rapid activity was introduced. In the subsequent analysis, the effect of PVI was examined on AF voltage and the AF cycle length, focusing on rapid and regular areas and low voltage zones, and their changes. The last chapter utilised the accumulated information to test the sensitivity and specificity of a percentile-based, patient-tailored approach to low AF voltage and to present an objective, automated method of localising rapid and regular areas within low voltage zones within the left atrium. In summary, it is feasible to assess and locate rapid and regular areas, and localise low voltage zones in persistent AF with a completely automated algorithm, and patient-tailored definitions of low voltage rapid AF activity are a preferable alternative to absolute cut offs.Open Acces