Detection and Quantification of Left Atrial Structural Remodeling With Delayed-Enhancement Magnetic Resonance Imaging in Patients With Atrial Fibrillation
Background— Atrial fibrillation (AF) is associated with diffuse left atrial fibrosis and a reduction in endocardial voltage. These changes are indicators of AF severity and appear to be predictors of treatment outcome. In this study, we report the utility of delayed-enhancement magnetic resonance imaging (DE-MRI) in detecting abnormal atrial tissue before radiofrequency ablation and in predicting procedural outcome.
Methods and Results— Eighty-one patients presenting for pulmonary vein antrum isolation for treatment of AF underwent 3-dimensional DE-MRI of the left atrium before the ablation. Six healthy volunteers also were scanned. DE-MRI images were manually segmented to isolate the left atrium, and custom software was implemented to quantify the spatial extent of delayed enhancement, which was then compared with the regions of low voltage from electroanatomic maps from the pulmonary vein antrum isolation procedure. Patients were assessed for AF recurrence at least 6 months after pulmonary vein antrum isolation, with an average follow-up of 9.6±3.7 months (range, 6 to 19 months). On the basis of the extent of preablation enhancement, 43 patients were classified as having minimal enhancement (average enhancement, 8.0±4.2%), 30 as having moderate enhancement (21.3±5.8%), and 8 as having extensive enhancement (50.1±15.4%). The rate of AF recurrence was 6 patients (14.0%) with minimal enhancement, 13 (43.3%) with moderate enhancement, and 6 (75%) with extensive enhancement (P<0.001).
Conclusions— DE-MRI provides a noninvasive means of assessing left atrial myocardial tissue in patients suffering from AF and might provide insight into the progress of the disease. Preablation DE-MRI holds promise for predicting responders to AF ablation and may provide a metric of overall disease progression.
Received March 27, 2008; accepted January 21, 2009.
Pulmonary vein (PV) antrum isolation (PVAI) is effective in treating patients with paroxysmal, persistent, and long-standing persistent forms of atrial fibrillation (AF).1–4 PVAI helps restore normal sinus rhythm in a majority of patients independently of the effects of antiarrhythmic drug therapy, cardioversion, or both.5,6
Clinical Perspective p 1767
Recent breakthroughs in the understanding of the pathophysiology of AF have suggested structural and functional characteristics that relate to treatment. This progress was initiated by identifying focal points of electric activity within the PVs as a causative factor of the arrhythmia.1 Subsequent exploration of the left atrial (LA) substrate has suggested that AF may be a self-perpetuating disease wherein chronic or recurrent fibrillatory activation induces progressive electrical and tissue structural remodeling.7,8 Although the mechanisms underlying the remodeling are complex, the changes in electric activation manifest as a reduction in myocardial voltage and a decrease in the effective refractory period.9,10 The degree of voltage reduction may help grade the severity of tissue pathology underlying AF, and preliminary results suggest that the success of PVAI is reduced when substantial low-voltage tissue or preexisting scar is present.11 Histological examination of LA tissue has confirmed the presence of fibrosis in regions of low-voltage tissue,12 but determining the extent and location of fibrosis in the LA without invasive techniques has not been possible. As a result, the effects of such structural remodeling on patient outcome to treatment are poorly understood.
Delayed-enhancement magnetic resonance imaging (DE-MRI) is an established method for visualizing tissue necrosis in cardiac disease processes, including myocardial infarction and myocarditis.13–15 Contrast enhancement occurs as a result of altered washout kinetics of gadolinium relative to normal surrounding tissue, which may reflect increased fibrosis or tissue remodeling of the myocardium.13 In this study, we assessed the feasibility of a new DE-MRI acquisition and processing protocol to detect fibrosis in the LA before ablation and its potential to predict PVAI procedural outcome.
Patients in this study presented to the University of Utah for PVAI of symptomatic AF from December 2006 to January 2008. The study protocol was reviewed and approved by the University of Utah Institutional Review Board and was HIPAA compliant. During the course of the study, DE-MRI scans were performed on 118 patients. Fifteen of the scans were not interpretable because of significant wraparound artifact or substantial blurring caused by patient motion. An additional 22 patients were removed from analysis because of an incorrect choice of inversion time or other concerns about DE-MRI quality, leaving 81 patients in the clinical cohort. Table 1 lists the demographics of the study patients. After providing informed consent, patients underwent MRI scanning to define PV anatomy, LA area, and LA wall thickness. LA appendage thrombus was ruled out by transesophageal echocardiogram. Left ventricular ejection fraction was obtained by biplane transthoracic echocardiogram. LA volume was determined by segmentation of the blood volume on MRI angiography images.
The baseline AF type was categorized as either paroxysmal AF (episode of AF that self-terminated within 7 days) or persistent AF (episode of AF lasting >7 days). Patients who required either pharmacological treatment or medical or electric cardioversion were classified as having persistent AF. All antiarrhythmic medications were stopped 24 or 48 hours before the procedure. Amiodarone was discontinued at least 3 month before the procedure. The data on the patient’s response to antiarrhythmic drugs were assessed through retrospective chart review. Failure to respond to a given medication was defined as having an episode of breakthrough AF while on the antiarrhythmic drug.
Six healthy volunteers without a history of AF or other cardiac arrhythmias also underwent DE-MRI acquisition in the same manner as patients presenting for PVAI. The volunteers included 4 men and 2 women with a mean age of 44.2±21.2 years (range, 26 to 81 years). The volunteers did not undergo electroanatomic mapping.
All patients underwent MRI studies on a 1.5-T Avanto clinical scanner (Siemens Medical Solutions, Erlangen, Germany) using a TIM phased-array receiver coil or 32-channel cardiac coil (In Vivo Corp, Gainesville, Fla). DE-MRI was acquired ≈15 minutes after the contrast agent injection (dose, 0.1 mmol/kg body weight; Multihance, Braco Diagnostic Inc, Princeton, NJ) using 3-dimensional (3D) inversion-recovery-prepared, respiration-navigated, ECG-gated, gradient-echo pulse sequence with fat saturation. Typical acquisition parameters were as follows: free breathing using navigator gating, a transverse imaging volume with true voxel size of 1.25×1.25×2.5 mm, flip angle of 22°, repetition time/echo time of 6.1/2.4 ms, inversion time of 230 to 320 ms, and parallel imaging with GRAPPA technique with R=2 and 42 reference lines. ECG gating was used to acquire a subset of phase-encoding views during the diastolic phase of the LA cardiac cycle. Typical scan time for the DE-MRI study was 5 to 9 minutes, depending on the subject’s respiration and heart rate. Of 81 patients, 73 (90.1%) were in normal sinus rhythm during MRI acquisition. Patients who were in AF at the time of clinical presentation were often cardioverted to restore normal sinus rhythm before MRI acquisition. Additional details of MRI acquisition methods and data documenting interobserver and intraobserver variability of the quantification methodology may be found in the online-only Data Supplement.
In the volunteer group, the DE-MRI scans were acquired at 15 and again at 30 minutes after contrast injection. In a subset of 4 patients, a third DE-MRI scan was acquired 45 minutes after contrast injection. In total, 16 DE-MRI scans from the healthy volunteers were acquired and analyzed. Image processing and quantification were performed in the same manner as for AF patients.
Three-Dimensional Electroanatomic Mapping
At the beginning of the PVAI procedure, a detailed voltage map of the LA was obtained in all patients with the 3D electroanatomic mapping system CARTOMERGE (Biosense Webster, Diamond Bar, Calif). The physician performing the PVAI procedure was blinded to the DE-MRI results. Mapping was performed in sinus rhythm whenever possible. Efforts were made to distribute measurement points evenly throughout the LA, and bipolar voltage was measured from peak to peak with the signal filtered from 30 to 400 Hz. Endocardial contact of the mapping catheter (Navistar-ThermoCool, Biosense Webster) was confirmed visually with fluoroscopy and intracardiac echocardiography and through the CARTO 3D navigation system to indicate that the catheter was stable in space and in good contact with the LA wall. Of 81 patients, 48 (59.3%) were in normal sinus rhythm during electroanatomic mapping, 27 (33.3%) were in AF during electroanatomic mapping, and 6 (7.4%) were in atrial flutter.
AF Ablation Procedure
Ablation was performed under intracardiac echocardiography in all study patients as described previously.11,16,17 Briefly, a 10F, 64-element, phased-array ultrasound catheter (AcuNav, Siemens Medical Solutions USA, Malvern, Pa) was used to visualize the interatrial septum and to guide the transseptal puncture. A circular mapping catheter (Lasso, Biosense Webster) and an ablation catheter were inserted into the LA. Intracardiac echocardiography was used to define the PV ostia, their antra, and the posterior wall. Intracardiac echocardiography also was used to position the circular mapping catheter and ablation catheter. All study patients underwent PVAI, defined as electric disconnection of the PV antrum from the LA, together with posterior wall and septal debulking.
After the procedure, all patients were observed on a telemetry unit for 24 hours. After discharge, patients underwent 8 weeks of patient-triggered and autodetected event monitoring and were instructed to activate the monitors anytime they felt symptoms. Patients continued anticoagulation therapy with warfarin (international normalized ratio, 2.0 to 3.0) for a minimum of 3 months. Patients were assessed for AF recurrence at 3 months, 6 months, and 1 year after the procedure. The average follow-up in this study was 9.6±3.7 months (range, 6 to 19 months).
Procedural success was defined as freedom from AF, atrial tachycardia, and atrial flutter while off antiarrhythmic medications 3 months after PVAI (ie, blanking period of 90 days).18 To confirm the absence of asymptomatic AF, all patients received a 48-hour Holter ECG recording within 24 hours after the procedure and an 8-day Holter ECG at the 3-, 6-, and 12-month follow-up. Recurrences were therefore determined from patient reporting, event monitoring, Holter monitoring, and ECG data and were defined as any symptomatic or asymptomatic detected episode of AF, atrial tachycardia, or atrial flutter lasting >30 seconds.
Analysis of DE-MRI Images
Three-dimensional visualization and segmentation of the MRI were performed with OsiriX 220.127.116.11 The LA was segmented manually in all patients and verified visually in the original image stack before rendering. Initial visualization used a maximum intensity projection to assess contrast consistency, followed by volume rendering with a ray-cast engine with linear table opacity. A color lookup table mask was applied to better differentiate between enhanced and nonenhanced tissue.
In all images, the epicardial and endocardial borders were manually contoured with image display and analysis software written in MATLAB (The Mathworks Inc, Natick, Mass). The relative extent of fibrosis was quantified within the LA wall with a threshold-based algorithm (see the Appendix in the online-only Data Supplement). Patients were assigned to 1 of 3 groups on the basis of the extent (percentage of LA myocardium) of enhancement. The extent of enhancement was entered into analysis as a categorical variable. Patients with mild enhancement showed abnormal enhancement in <15% of the LA wall. Moderate enhancement was considered to be between 15% and 35% of the LA wall. Extensive enhancement was considered to be >35% LA wall enhancement. LA volume also was entered into the predictive model as a categorical variable, with patients divided into 4 separate groups based on the quartile cutoff points. Quartile 1 included patients with LA volume <59.89 mL; quartile 2, patients with LA volume between 59.9 and 85.9 mL; quartile 3, patients with LA volume between 85.91 to 116.12 mL; and quartile 4, patients with LA volume >116.13 mL.
Correlation With Electroanatomic Maps
A quantitative and qualitative analysis was performed to correlate low-voltage regions on electroanatomic maps and enhancement on DE-MRI. Fifty-four patients with high-quality CartoXP maps (defined as >100 voltage points spread evenly throughout the atrium) were selected. The LA on the electroanatomic map and 3D DE-MRI was subdivided into 18 specific regions: 9 on the posterior wall and 9 on the anterior and septal walls. Four blinded reviewers (2 experts in cardiac MRI and 2 experts in AF ablation) scored the MRI models and electroanatomic maps on a scale of 0 to 3. For MRI models, 0 was no enhancement, 1 was mild enhancement, 2 was moderate enhancement, and 3 was extensive enhancement. For the electroanatomic maps, 0 was considered healthy tissue (voltage >1 mV, purple on electroanatomic maps), 1 was mild illness (voltage >0.1 to <0.5 mV), 2 was moderate illness (presence of low-voltage tissue [voltage >0.1 mV to <0.5 mV] and fibrotic scar [voltage <0.1 mV]), and 3 was considered diseased tissue with significant scarring (voltage <0.1 mV, red on electroanatomic maps). The overall score was an average sum of all 9 regions for both the posterior wall and the septum.
The reviewers then qualitatively assessed the relationship between electroanatomic maps and MRI models. The relationship was rated on a scale of 0 to 4: 0 was coded as no relationship, 1 as poor, 2 as mediocre, 3 as good, and 4 as excellent.
Normal continuous variables are presented as mean±SD. Continuous data were analyzed by 1-way ANOVA to test for significant differences. Recurrence was analyzed in a time-to-event Cox regression model. Recurrence after the blanking period was considered the failure variable; category of fibrosis (mild, moderate, severe) was considered the predictor variable; and available follow-up duration was used as the time variable. A test of the proportional hazards, a required assumption of Cox regression, was performed for each covariate and globally with a formal significance test based on the unscaled and scaled Schoenfeld residuals.20 A quantitative analysis of the relationship between DE-MRI and electroanatomic maps was performed with linear regression.
Multivariate analysis was conducted with a logistic regression model reporting odds ratios (ORs). Predictor variables included extent of LA wall enhancement, LA volume, AF type, and age. Differences were considered significant at values of P<0.05. Statistical analysis was performed with the SPSS 15.0 statistical package (SPSS Inc, Chicago, Ill), STATA 9 (Stata Corp, College Station, Tex), and Microsoft Excel 2007 (Microsoft Corp, Redmond, Wash). In addition, a Harrell’s c statistic was calculated for the Cox regression model.21
The authors had full access to and take full responsibility for the integrity of the data. All authors have read and agree to the manuscript as written.
Eighty-one patients underwent PVAI for treatment of AF. Forty-one patients were classified as having paroxysmal AF and 40 patients as having persistent AF. Forty-three patients were identified with mild enhancement, 30 with moderate enhancement, and 8 with extensive enhancement. Table 1 lists the patient demographics for the 3 patient groups and overall demographics for the clinical cohort. Twenty-five patients were placed back on antiarrhythmic medications after the procedure and continued therapy for a total of 8 weeks after the procedure.
Among the healthy volunteers, the average extent of LA wall enhancement was 1.7±0.3%. In the 43 patients classified as having mild LA enhancement, the average LA wall enhancement was 8.0±4.2%. In the 30 patients with moderate enhancement, average LA wall enhancement was 21.3±5.8%. In the 8 patients with extensive enhancement, the average LA wall enhancement was significantly higher at 50.1±15.4%. All patients with extensive enhancement presented with persistent AF. Although all groups had similar population characteristics at baseline, a statistically significant difference in LA volume was noted between those with mild or moderate enhancement and individuals with extensive enhancement (P<0.001).
DE-MRI and Electroanatomic Maps
DE-MRI detected enhancement in all patients presenting for PVAI. Figure 1 shows the 3D segmented MRI (Figure 1A) and color model (Figure 1B) for 1 patient. Discrete patches of enhancement/fibrosis (green) can be seen in the posterior wall and septum on both the MRI and the electroanatomic map. In comparison, the healthy volunteers showed little to no abnormal enhancement. Figure 2 shows MRI models for 2 individuals who lacked the type of enhancement seen in patients with AF.
Figure 3 shows 3D MRI models in patients with mild structural remodeling. The minimal contrast is suggestive of largely viable and electrically normal atrial myocardium, a finding verified by comparison with electroanatomic maps obtained during the procedure (Figure 3D). In all patients, a correlation between regions of enhancement on DE-MRI and low-voltage regions on electroanatomic maps was seen (Figures 1 and 3 through 5⇓⇓⇓). Quantitative analysis of this relationship demonstrated a positive correlation of R2=0.61 (Figure 6).
In addition to the extent of LA wall enhancement, the primary location of enhancement differed among the 3 patient groups. Among patients with mild and moderate LA wall enhancement, it was seen primarily in the posterior wall and interatrial septum (Figures 3 and 4⇑). Among patients with extensive low-voltage tissue (Figure 5), enhancement was seen in all portions of the LA wall, including the posterior wall, interatrial septum, and anterior wall. This difference resulted in a large, statistically significant difference in the location of LA wall enhancement (P<0.001). Compared with the electroanatomic maps, 2 distinct patterns emerged: Some patients exhibited continuous regions of enhancement (patient 1, Figure 5), whereas others showed a scattered pattern enhancement (patient 2, Figure 5).
DE-MRI Quantification and Patient Outcome
Of 81 patients, 56 (69.1%) remained free of AF recurrence while off antiarrhythmic drugs. Only 6 patients (14.0%) with minimal enhancement suffered AF recurrence, whereas 13 (43.3%) of the moderate and 6 (75%) of the extensive group suffered AF recurrence (Cox regression, P<0.05). Patients who suffered AF recurrences were placed back on antiarrhythmic drugs, and of these, 21 of 25 (84%) responded favorably to antiarrhythmic drug therapy after ablation and maintained normal sinus rhythm.
Before ablation, 70 patients were tried on antiarrhythmic drugs; 32 patients responded favorably to antiarrhythmic drugs, and 38 patients did not. A statistically significant difference in the extent of LA enhancement also was noted between patients who responded to medical therapy (13.3±9.9%) and those who did not (21.2±18.7%; logistic regression P=0.038). The extent of delayed enhancement as a single predictor achieved a c statistic of 0.62. Table 2 shows that the extent of LA wall enhancement was the strongest predictor of response to rhythm control response with antiarrhythmic drugs and ablation.
Figure 7 shows the Cox regression analysis of patients in normal sinus rhythm after ablation of the LA grouped by the extent of enhancement. In addition to the overall differences in AF recurrence, patients with moderate and extensive enhancement often suffered recurrence at later time points than those with mild enhancement. Of special note, after the 6-month follow-up, no recurrences were noted in the mild enhancement group.
The cutoff points between mild and moderate enhancement (15%) and between moderate and extensive enhancement (35%) were chosen after manual review of the data distribution—and before outcome analysis—as natural breakpoints between populations.
Table 2 shows the results of the 3 multivariate models. For all 3 outcome metrics of interest, the extent of LA wall enhancement was the most statistically significant predictor. For baseline AF, both the extent of LA wall enhancement and LA volume remained statistically significant predictors of persistent forms of the arrhythmia, although extent of LA wall enhancement had a greater adjusted OR (3.47; 95% confidence interval, 1.32 to 9.16) than LA volume (adjusted OR, 1.02; 95% confidence interval, 1.01 to 1.04). This finding may reflect the fact that both variables likely have a degree of correlation with each another; they are both predictors of severe and persistent forms of the disease. Extent of LA wall enhancement was the most statistically significant predictor of the patient’s response to both drug and ablation therapies for AF. After the effect of LA wall enhancement in the drug therapy model was controlled for, none of the other variables achieved statistical significance.
In the present study, we describe a novel noninvasive method of using DE-MRI to detect pathological 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 after 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 preexistent LA low-voltage tissue and scarring (determined by invasive electrophysiological study) independent predictors 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 (Table 3). Patients who suffered recurrent AF showed enhancement in all portions of the LA, whereas patients who responded successfully to ablation showed enhancement limited primarily to the posterior wall and septum.
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 appear to have an important influence in fibrillatory dynamics, including both the location and variability of wave-front breakthroughs.31 Therefore, by altering the LA substrate, fibrotic change and structural remodeling probably aid in the formation of circuits needed for reentry, 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 (Table 2).
DE-MRI is a well-established method for characterizing fibrosis and tissue remodeling in the ventricle. It is commonly used 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 been confined largely to the ventricle because of 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 noninvasive nature, DE-MRI offers other advantages over invasive electroanatomic 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 with DE-MRI provides information on both the anatomy and the location of pathology without spatial distortion.
AF is a progressive disease, which suggests the presence of a self-perpetuating cycle, and evidence exists that causality between fibrillation and fibrosis may be bidirectional. Rapidly paced cardiac myocytes have been shown to release factors that induce a nearly 4-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 compared with 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. Furthermore, multivariate analysis demonstrated that the greatest degree of variance for ablation outcome and response to medical therapy was explained by the degree of fibrotic enhancement in the LA wall (Table 2). 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 before ablative treatment provides an opportunity to characterize the stage of disease in patients with AF. On the basis of 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 better patient selection and may aid in identifying candidates for repeat procedures who still have patches of tissue suitable for ablation.
Although statistically significant differences in the degree of enhancement were seen between patients with paroxysmal and patients with persistent AF, those patients who responded to medical therapy and those who did not, and patients who suffered a recurrence of AF and those who did not, the sample size is relatively small, and these findings need to be verified in larger patient cohorts. Larger studies are needed to improve the value of the c statistic to make it a stronger prognostic indicator in clinical practice. In addition, MRIs in this study were performed on a 1.5-T scanner, and significant improvements in LA wall imaging with greater spatial resolution and improved signal-to-noise ratio are expected at a higher magnetic field (3 T). The presence of respiratory navigator artifacts and other MRI noise may lead to the inappropriate detection and quantification of fibrosis, although 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.
DE-MRI of the LA, coupled with advanced image analysis techniques, provides a noninvasive method for quantifying and localizing LA changes associated with AF. Patients with a greater extent of delayed enhancement in the LA wall suffer much higher recurrence rates after PVAI for AF. DE-MRI holds great promise for guiding physicians in recommending catheter ablation or medical management for patients with AF.
We gratefully acknowledge the aid of Josh Bertola, Duane Richins, and Judy Eldredge, who assisted with the acquisition of the MRI scans.
Sources of Funding
National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases grant 5T35 HL00774-15, Short-Term Training: Students in Health Professional Schools, provided the funding for R.S. Oakes during this study. The Scientific Computing and Imaging Institute and the National Institutes of Health National Center for Research Resources, Center for Integrative Biomedical Computing (http://www.sci.utah.edu/cibc), grant 5P41RR012553-02, provided computational support and resources.
Drs Kholmovski, DiBella, Parker, and Marrouche are partially supported by grants from Siemens Medical and Surgivision. The other authors report no conflicts.
Marrouche NF, Martin DO, Wazni O, Gillinov AM, Klein A, Bhargava M, Saad E, Bash D, Yamada H, Jaber W, Schweikert R, Tchou P, Abdul-Karim A, Saliba W, Natale A. Phased-array intracardiac echocardiography monitoring during pulmonary vein isolation in patients with atrial fibrillation: impact on outcome and complications. Circulation. 2003; 107: 2710–2716.
Marrouche NF, Dresing T, Cole C, Bash D, Saad E, Balaban K, Pavia SV, Schweikert R, Saliba W, Abdul-Karim A, Pisano E, Fanelli R, Tchou P, Natale A. Circular mapping and ablation of the pulmonary vein for treatment of atrial fibrillation: impact of different catheter technologies. J Am Coll Cardiol. 2002; 40: 464–474.
Pappone C, Oreto G, Rosanio S, Vicedomini G, Tocchi M, Gugliotta F, Salvati A, Dicandia C, Calabro MP, Mazzone P, Ficarra E, Di Gioia C, Gulletta S, Nardi S, Santinelli V, Benussi S, Alfieri O. Atrial electroanatomic remodeling after circumferential radiofrequency pulmonary vein ablation: efficacy of an anatomic approach in a large cohort of patients with atrial fibrillation. Circulation. 2001; 104: 2539–2544.
Lemola K, Desjardins B, Sneider M, Case I, Chugh A, Good E, Han J, Tamirisa K, Tsemo A, Reich S, Tschopp D, Igic P, Elmouchi D, Bogun F, Pelosi F Jr, Kazerooni E, Morady F, Oral H. Effect of left atrial circumferential ablation for atrial fibrillation on left atrial transport function. Heart Rhythm. 2005; 2: 923–928.
Wijffels MC, Kirchhof CJ, Dorland R, Allessie MA. Atrial fibrillation begets atrial fibrillation: a study in awake chronically instrumented goats. Circulation. 1995; 92: 1954–1968.
Morillo CA, Klein GJ, Jones DL, Guiraudon CM. Chronic rapid atrial pacing: structural, functional, and electrophysiological characteristics of a new model of sustained atrial fibrillation. Circulation. 1995; 91: 1588–1595.
Verma A, Wazni OM, Marrouche NF, Martin DO, Kilicaslan F, Minor S, Schweikert RA, Saliba W, Cummings J, Burkhardt JD, Bhargava M, Belden WA, Abdul-Karim A, Natale A. Pre-existent left atrial scarring in patients undergoing pulmonary vein antrum isolation: an independent predictor of procedural failure. J Am Coll Cardiol. 2005; 45: 285–292.
Boldt A, Wetzel U, Lauschke J, Weigl J, Gummert J, Hindricks G, Kottkamp H, Dhein S. Fibrosis in left atrial tissue of patients with atrial fibrillation with and without underlying mitral valve disease. Heart. 2004; 90: 400–405.
De Cobelli F, Pieroni M, Esposito A, Chimenti C, Belloni E, Mellone R, Canu T, Perseghin G, Gaudio C, Maseri A, Frustaci A, Del Maschio A. Delayed gadolinium-enhanced cardiac magnetic resonance in patients with chronic myocarditis presenting with heart failure or recurrent arrhythmias. J Am Coll Cardiol. 2006; 47: 1649–1654.
Marrouche NF, Guenther J, Segerson NM, Daccarett M, Rittger H, Marschang H, Schibgilla V, Schmidt M, Ritscher G, Noelker G, Brachmann J. Randomized comparison between open irrigation technology and intracardiac-echo-guided energy delivery for pulmonary vein antrum isolation: procedural parameters, outcomes, and the effect on esophageal injury. J Cardiovasc Electrophysiol. 2007; 18: 583–588.
Calkins H, Brugada J, Packer DL, Cappato R, Chen SA, Crijns HJ, Damiano RJ Jr, Davies DW, Haines DE, Haissaguerre M, Iesaka Y, Jackman W, Jais P, Kottkamp H, Kuck KH, Lindsay BD, Marchlinski FE, McCarthy PM, Mont JL, Morady F, Nademanee K, Natale A, Pappone C, Prystowsky E, Raviele A, Ruskin JN, Shemin RJ. HRS/EHRA/ECAS expert consensus statement on catheter and surgical ablation of atrial fibrillation: recommendations for personnel, policy, procedures and follow-up: a report of the Heart Rhythm Society (HRS) Task Force on Catheter and Surgical Ablation of Atrial Fibrillation developed in partnership with the European Heart Rhythm Association (EHRA) and the European Cardiac Arrhythmia Society (ECAS); in collaboration with the American College of Cardiology (ACC), American Heart Association (AHA), and the Society of Thoracic Surgeons (STS): endorsed and approved by the governing bodies of the American College of Cardiology, the American Heart Association, the European Cardiac Arrhythmia Society, the European Heart Rhythm Association, the Society of Thoracic Surgeons, and the Heart Rhythm Society. Europace. 2007; 9: 335–379.
Ratib O. OSIRIX: an open source platform for advanced multimodality medical imaging. Paper presented at: 4th International Conference on Information & Communications Technology; December 10–12, 2006; Cairo, Egypt.
Grambsch PM, Therneau TM. Proportional hazards tests and diagnostics based on weighted residuals. Biometrika. 1994; 81: 515–526.
Li D, Fareh S, Leung TK, Nattel S. Promotion of atrial fibrillation by heart failure in dogs: atrial remodeling of a different sort. Circulation. 1999; 100: 87–95.
Verheule S, Sato T, Everett Tt, Engle SK, Otten D, Rubart-von der Lohe M, Nakajima HO, Nakajima H, Field LJ, Olgin JE. Increased vulnerability to atrial fibrillation in transgenic mice with selective atrial fibrosis caused by overexpression of TGF-beta1. Circ Res. 2004; 94: 1458–1465.
Kostin S, Klein G, Szalay Z, Hein S, Bauer EP, Schaper J. Structural correlate of atrial fibrillation in human patients. Cardiovasc Res. 2002; 54: 361–379.
Tanaka K, Zlochiver S, Vikstrom KL, Yamazaki M, Moreno J, Klos M, Zaitsev AV, Vaidyanathan R, Auerbach DS, Landas S, Guiraudon G, Jalife J, Berenfeld O, Kalifa J. Spatial distribution of fibrosis governs fibrillation wave dynamics in the posterior left atrium during heart failure. Circ Res. 2007; 101: 839–847.
Schmidt A, Azevedo CF, Cheng A, Gupta SN, Bluemke DA, Foo TK, Gerstenblith G, Weiss RG, Marban E, Tomaselli GF, Lima JA, Wu KC. Infarct tissue heterogeneity by magnetic resonance imaging identifies enhanced cardiac arrhythmia susceptibility in patients with left ventricular dysfunction. Circulation. 2007; 115: 2006–2014.
Malchano ZJ, Neuzil P, Cury RC, Holmvang G, Weichet J, Schmidt EJ, Ruskin JN, Reddy VY. Integration of cardiac CT/MR imaging with three-dimensional electroanatomical mapping to guide catheter manipulation in the left atrium: implications for catheter ablation of atrial fibrillation. J Cardiovasc Electrophysiol. 2006; 17: 1221–1229.
Burstein B, Qi XY, Yeh YH, Calderone A, Nattel S. Atrial cardiomyocyte tachycardia alters cardiac fibroblast function: a novel consideration in atrial remodeling. Cardiovasc Res. 2007; 76: 442–452.
Catheter ablation has become an increasingly popular and acceptable treatment option for the atrial fibrillation patient. Nevertheless, many questions remain about preprocedural predictors of ablation failure. Here, we describe a novel delayed-enhancement magnetic resonance imaging–based method to detect and quantify preexistent left atrial structural remodeling in patients undergoing ablation of atrial fibrillation. We found that patients with extensive preablation left atrial enhancement were more likely to suffer atrial fibrillation recurrence after ablation than those with minimal or moderate degrees of enhancement. This noninvasive modality would allow patients to be selectively screened before ablation to determine whether they are appropriate candidates for the procedure. The ability to properly select ablation patients will reduce the unnecessary risks and costs to those patients who stand to benefit little from the procedure.
The online-only Data Supplement is available with this article at http://circ.ahajournals.org/cgi/content/full/CIRCULATIONAHA.108. 811877/DC1.