In this study, we describe a novel, non-invasive method of using DE-MRI to detect pathologic regions of LA tissue in patients with AF. Our results also indicate that an increased amount of enhancement within the LA is strongly associated with AF recurrence following PVAI. If substantiated, this method would provide guidance in determining appropriate candidates for catheter ablation of AF.
The results presented here also correlate well with other studies that considered pre-existent LA low voltage tissue and scarring (determined by invasive EP study) as an independent predictor of procedural failure and eventual AF recurrence.11
Our results also demonstrate that not only the extent but also the locations of LA enhancement appear to be important predictors of ablation success (). Patients who suffered recurrent AF showed enhancement in all portions of the LA while patients who responded successfully to ablation showed enhancement primarily limited to the posterior wall and septum.
Results of DE-MRI Analysis and Patient Outcome
The presence of fibrosis/low voltage tissue has been postulated as a potential cause of the abnormalities in atrial activation that may underlie the initiation and maintenance of fibrillation.22, 23
Animal studies have confirmed an increased tendency for AF when atrial fibrosis is experimentally induced.24–26
Increased fibrosis has also been clearly demonstrated in human LA tissue specimens of patients with AF 27–28
and correlations have been seen between serum markers of atrially selective fibroblasts and clinical AF.29
Other studies have shown that atrial fibrosis can lead to AF induction by burst or premature atrial pacing that would otherwise fail to cause AF in normal hearts.25, 30
Spatial distribution and degree of fibrosis/low voltage tissue appears to have an important influence in fibrillatory dynamics, including both the location and variability of wavefront breakthroughs.31
By altering the LA substrate, it is therefore likely that fibrotic change and structural remodeling aid in the formation of circuits needed for re-entry, thus perpetuating the atrial arrhythmia. These findings are consistent with the trends noted in this study. In multivariate analysis, the extent of LA wall enhancement seemed to be most associated with the more persistent form of the atrial arrhythmia ().
DE-MRI is a well-established method for characterizing fibrosis and tissue remodeling in the ventricle. It is commonly employed to characterize tissue heterogeneity in ventricular myocardium that may increase arrhythmia generation and to differentiate hibernating muscle from nonviable tissue in the setting of myocardial ischemia.32–34
Despite its success, however, the use of DE-MRI has largely been confined to the ventricle due to the challenges in spatial resolution required to image the LA wall. This study presents an imaging methodology for successfully obtaining DE-MRI scans with sufficient spatial resolution and signal to noise ratio for visualization and analysis of LA tissue. In addition to its non-invasive nature, DE-MRI offers other advantages over invasive EA mapping studies to assess LA tissue health. For example, CARTO based mapping studies have been associated with a high degree of spatial error, from 0.5 to 1.0 cm, in comparative studies.35, 36
In contrast, reconstruction utilizing DE-MRI provides information regarding both anatomy and the location of pathology without spatial distortion.
AF is a progressive disease, which suggest the presence of a self-perpetuating cycle and there is evidence that causality between fibrillation and fibrosis may be bidirectional. Rapidly paced cardiac myocytes have been shown to release factors that induce a nearly four-fold increase in collagen-1 and fibronectin-1 in atrial tissue.37
In this study, patients suffering recurrence exhibited a significant difference in the amount of structural remodeling as compared to individuals without recurrence. This observation helps corroborate the link between the degree of fibrosis and the disease severity in AF. In our study, patients with extensive enhancement presented exclusively with persistent forms of the disease. Further, multivariate analysis demonstrated that the greatest degree of variance for ablation outcome and response to medical therapy were explained by the degree of fibrotic enhancement in the LA wall (). This and the other associated findings therefore present a disease model that supports the importance of early intervention.
Determining the extent of low voltage tissue prior to ablative treatment provides an opportunity to characterize the stage of disease in patients with AF. Based upon the results of this study, ablative treatment of AF in patients with extensive LA enhancement should be offered with a reduced expectation of long-term success. Additional research is necessary to determine whether ablation represents a viable treatment option in patients with extensive enhancement or whether additional medical therapy should be further investigated in these patients.11
DE-MRI screening will likely allow for better patient selection and may aid in identifying candidates for repeat procedures who still have patches of tissue suitable for ablation.
Though statistically significant differences in the degree of enhancement were seen between patients with paroxysmal and persistent AF, those patients who responded to medical therapy and those who did not, and patients who suffered a recurrence of AF; the sample size is relatively small and these findings will need to be verified in larger patient cohorts. Larger studies are also needed to improve the value of the c-statistic in order to make it a stronger prognostic indicator in clinical practice. In addition, MR imaging in this study was performed on a 1.5 Tesla scanner and significant improvements in LA wall imaging with greater spatial resolution and improved signal to noise ratio are expected at higher magnetic field (3 Tesla). The presence of respiratory navigator artifacts and other MRI noise may lead to the inappropriate detection and quantification of fibrosis, though such effects appeared to be minimal in this study. Finally, the algorithm used to detect and quantify fibrosis requires an experienced observer to choose threshold levels.