Robert S. MacLeod

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.

Influence of tissue conductivity anisotropy on EEG/MEG field and return current computation in a realistic head model: a simulation and visualization study using high-resolution finite element modeling.

To achieve a deeper understanding of the brain, scientists, and clinicians use electroencephalography (EEG) and magnetoencephalography (MEG) inverse methods to reconstruct sources in the cortical sheet of the human brain. The influence of structural and electrical anisotropy in both the skull and the white matter on the EEG and MEG source reconstruction is not well understood. In this paper, we report on a study of the sensitivity to tissue anisotropy of the EEG/MEG forward problem for deep and superficial neocortical sources with differing orientation components in an anatomically accurate model of the human head. The goal of the study was to gain insight into the effect of anisotropy of skull and white matter conductivity through the visualization of field distributions, isopotential surfaces, and return current flow and through statistical error measures. One implicit premise of the study is that factors that affect the accuracy of the forward solution will have at least as strong an influence over solutions to the associated inverse problem. Major findings of the study include (1) anisotropic white matter conductivity causes return currents to flow in directions parallel to the white matter fiber tracts; (2) skull anisotropy has a smearing effect on the forward potential computation; and (3) the deeper a source lies and the more it is surrounded by anisotropic tissue, the larger the influence of this anisotropy on the resulting electric and magnetic fields. Therefore, for the EEG, the presence of tissue anisotropy both for the skull and white matter compartment substantially compromises the forward potential computation and as a consequence, the inverse source reconstruction. In contrast, for the MEG, only the anisotropy of the white matter compartment has a significant effect. Finally, return currents with high amplitudes were found in the highly conducting cerebrospinal fluid compartment, underscoring the need for accurate modeling of this space.

Left atrial strain and strain rate in patients with paroxysmal and persistent atrial fibrillation: relationship to left atrial structural remodeling detected by delayed-enhancement MRI.

Background—Atrial fibrillation (AF) is a progressive condition that begins with hemodynamic and/or structural changes in the left atrium (LA) and evolves through paroxysmal and persistent stages. Because of limitations with current noninvasive imaging techniques, the relationship between LA structure and function is not well understood. Methods and Results—Sixty-five patients (age, 61.2±14.2 years; 67% men) with paroxysmal (44%) or persistent (56%) AF underwent 3D delayed-enhancement MRI. Segmentation of the LA wall was performed and degree of enhancement (fibrosis) was determined using a semiautomated quantification algorithm. Two-dimensional echocardiography and longitudinal LA strain and strain rate during ventricular systole with velocity vector imaging were obtained. Mean fibrosis was 17.8±14.5%. Log-transformed fibrosis values correlated inversely with LA midlateral strain (r=−0.5, P=0.003) and strain rate (r=−0.4, P<0.005). Patients with persistent AF as compared with paroxysmal AF had more fibrosis (22±17% versus 14±9%, P=0.04) and lower midseptal (27±14% versus 38±16%, P=0.01) and midlateral (35±16% versus 45±14% P=0.03) strains. Multivariable stepwise regression showed that midlateral strain (r=−0.5, P=0.006) and strain rate (r=−0.4, P=0.01) inversely predicted the extent of fibrosis independent of other echocardiographic parameters and the rhythm during imaging. Conclusions—LA wall fibrosis by delayed-enhancement MRI is inversely related to LA strain and strain rate, and these are related to the AF burden. Echocardiographic assessment of LA structural and functional remodeling is quick and feasible and may be helpful in predicting outcomes in AF.

New magnetic resonance imaging-based method for defining the extent of left atrial wall injury after the ablation of atrial fibrillation.

OBJECTIVES We describe a noninvasive method of detecting and quantifying left atrial (LA) wall injury after pulmonary vein antrum isolation (PVAI) in patients with atrial fibrillation (AF). Using a 3-dimensional (3D) delayed-enhancement magnetic resonance imaging (MRI) sequence and novel processing methods, LA wall scarring is visualized at high resolution after radiofrequency ablation (RFA). BACKGROUND Radiofrequency ablation to achieve PVAI is a promising approach to curing AF. Controlled lesion delivery and scar formation within the LA are indicators of procedural success, but the assessment of these factors is limited to invasive methods. Noninvasive evaluation of LA wall injury to assess permanent tissue injury may be an important step in improving procedural success. METHODS Imaging of the LA wall with a 3D delayed-enhanced cardiac MRI sequence was performed before and 3 months after ablation in 46 patients undergoing PVAI for AF. Our 3D respiratory-navigated MRI sequence using parallel imaging resulted in 1.25 x 1.25 x 2.5 mm (reconstructed to 0.6 x 0.6 x 1.25 mm) spatial resolution with imaging times ranging 8 to 12 min. RESULTS Radiofrequency ablation resulted in hyperenhancement of the LA wall in all patients post-PVAI and may represent tissue scarring. New methods of reconstructing the LA in 3D allowed quantification of LA scarring using automated methods. Arrhythmia recurrence at 3 months correlated with the degree of wall enhancement with >13% injury predicting freedom from AF (odds ratio: 18.5, 95% confidence interval: 1.27 to 268, p = 0.032). CONCLUSIONS We define noninvasive MRI methods that allow for the detection and quantification of LA wall scarring after RF ablation in patients with AF. Moreover, there seems to be a correlation between the extent of LA wall injury and short-term procedural outcome.

Atrial Fibrosis Helps Select the Appropriate Patient and Strategy in Catheter Ablation of Atrial Fibrillation: A DE-MRI Guided Approach

MRI for AF Patient Selection and Ablation Approach. Introduction: Left atrial (LA) fibrosis and ablation related scarring are major predictors of success in rhythm control of atrial fibrillation (AF). We used delayed enhancement MRI (DE‐MRI) to stratify AF patients based on pre‐ablation fibrosis and also to evaluate ablation‐induced scarring in order to identify predictors of a successful ablation.

Evaluation of the left atrial substrate in patients with lone atrial fibrillation using delayed-enhanced MRI: Implications for disease progression and response to catheter ablation

BACKGROUND Lone atrial fibrillation (AF) is thought to be a benign type or an early stage of the disease. OBJECTIVE This study sought to compare the left atrium (LA) substrate using delayed-enhanced magnetic resonance imaging (DE-MRI) in patients with lone AF versus those with comorbidities. METHODS Forty of 333 included patients met criteria for lone AF. All patients underwent DE-MRI to quantify atrial fibrosis as a marker for structural remodeling (SRM) and underwent catheter ablation. Based on the degree of SRM, patients were staged into 4 groups: Utah I (≤5% LA wall enhancement), Utah II (>5% to ≤20%), Utah III (>20% to ≤35%), or Utah IV (>35%). RESULTS Distribution in Utah I to IV was comparable in patients with lone AF and non-lone AF. In both groups, a number of patients showed extensive SRM. Mean enhancement (14.08 ± 8.94 vs. 16.94 ± 11.37) was not significantly different between the 2 groups (P = .0721). In the lone AF group, catheter ablation was successful in suppressing AF in all of Utah I, 81.82% of Utah II, 62.5% of Utah III, and none of Utah IV patients. Similar results were achieved in the non-lone AF group. Outcome after ablation was significantly dependent on the SRM of the LA (P < .001). CONCLUSION The degree of LA structural remodeling as detected using DE-MRI is independent of AF type and associated comorbidities. Selecting appropriate treatment candidates based on the quality and quantity of atrial fibrosis using DE-MRI would improve procedural outcome and avoid unnecessary intervention.

Association of Left Atrial Fibrosis Detected by Delayed-Enhancement Magnetic Resonance Imaging and the Risk of Stroke in Patients With Atrial Fibrillation

OBJECTIVES This study tried to determine the association between left atrial (LA) fibrosis, detected using delayed-enhanced magnetic resonance imaging (DE-MRI), and the CHADS(2) score (point system based on individual clinical risk factors including congestive heart failure, hypertension, age, diabetes, and prior stroke) variables, specifically stroke. BACKGROUND In patients with atrial fibrillation (AF), conventional markers for the risk of stroke base their higher predictive effect on clinical features, particularly previous stroke history, and not individual LA pathophysiological properties. We aimed to determine the association between LA fibrosis, detected using DE-MRI, and the CHADS(2) score variables, specifically stroke. METHODS Patients with AF who presented to the AF clinic and received a DE-MRI of the LA were evaluated. Their risk factor profiles, including a CHADS(2) score, were catalogued. The degree of LA fibrosis was determined as a percentage of the LA area. Any history of previous strokes, warfarin use, or cerebrovascular disease was recorded. RESULTS A total of 387 patients, having a mean age of 65 ± 12 years, 36.8% female, were included in this study. A history of previous stroke was present in 36 (9.3%) patients. Those patients with previous strokes had a significantly higher percentage of LA fibrosis (24.4 ± 12.4% vs. 16.2 ± 9.9%, p < 0.01). A larger amount of LA fibrosis was also seen in those patients with a higher CHADS(2) score (≥ 2: 18.7 ± 11.4 vs. <2: 14.7 ± 9.2, p < 0.01). A logistic regression analysis of all variables except strokes (CHAD score) demonstrated that LA fibrosis independently predicted cerebrovascular events (p = 0.002) and significantly increased the predictive performance of the score (area under the curve = 0.77). CONCLUSIONS Our preliminary, multicenter results suggest DE-MRI-based detection of LA fibrosis is independently associated with prior history of strokes. We propose that the amount of DE-MRI-determined LA fibrosis could represent a marker for stroke and a possible therapeutic target with potential applicability for clinical treatment for patients with AF.

Inverse electrocardiography by simultaneous imposition of multiple constraints

The authors describe two new methods for the inverse problem of electrocardiography. Both employ regularization with multiple constraints, rather than the standard single-constraint regularization. In one method, multiple constraints on the spatial behavior of the solution are used simultaneously. In the other, spatial constraints are used simultaneously with constraints on the temporal behavior of the solution. The specific cases of two spatial constraints and one spatial and one temporal constraint are considered in detail. A new method, the L-Surface, is presented to guide the choice of the required pairs of regularization parameters. In the case when both spatial and temporal regularization are used simultaneously, there is an increased computational burden, and two methods are presented to compute solutions efficiently. The methods are verified by simulations using both dipole sources and measured canine epicardial data.

Atrial Fibrillation Ablation Outcome Is Predicted by Left Atrial Remodeling on MRI

Background—Although catheter ablation therapy for atrial fibrillation (AF) is becoming more common, results vary widely, and patient selection criteria remain poorly defined. We hypothesized that late gadolinium enhancement MRI (LGE-MRI) can identify left atrial (LA) wall structural remodeling (SRM) and stratify patients who are likely or not to benefit from ablation therapy. Methods and Results—LGE-MRI was performed on 426 consecutive patients with AF without contraindications to MRI before undergoing their first ablation procedure and on 21 non-AF control subjects. Patients were categorized by SRM stage (I–IV) based on the percentage of LA wall enhancement for correlation with procedure outcomes. Histological validation of SRM was performed comparing LGE-MRI with surgical biopsy. A total of 386 patients (91%) with adequate LGE-MRI scans were included in the study. After ablation, 123 patients (31.9%) experienced recurrent atrial arrhythmias during the 1-year follow-up. Recurrent arrhythmias (failed ablations) occurred at higher SRM stages with 28 of 133 (21.0%) in stage I, 40 of 140 (29.3%) in stage II, 24 of 71 (33.8%) in stage III, and 30 of 42 (71.4%) in stage IV. In multivariate analysis, ablation outcome was best predicted by advanced SRM stage (hazard ratio, 4.89; P<0.0001) and diabetes mellitus (hazard ratio, 1.64; P=0.036), whereas increased LA volume and persistent AF were not significant predictors. LA wall enhancement was significantly greater in patients with AF versus non-AF controls (16.6±11.2% versus 3.1±1.9%; P<0.0001). Histological evidence of remodeling from surgical biopsy specimens correlated with SRM on LGE-MRI. Conclusions—Atrial SRM is identified on LGE-MRI, and extensive LGE (≥30% LA wall enhancement) predicts poor response to catheter ablation therapy for AF.

Evaluation of left atrial lesions after initial and repeat atrial fibrillation ablation: lessons learned from delayed-enhancement MRI in repeat ablation procedures.

Background—We evaluated scar lesions after initial and repeat catheter ablation of atrial fibrillation (AF) and correlated these regions to low-voltage tissue on repeat electroanatomic mapping. We also identified gaps in lesion sets that could be targeted and closed during repeat procedures. Methods and Results—One hundred forty-four patients underwent AF ablation and received a delayed-enhancement MRI at 3 months after ablation. The number of pulmonary veins (PV) with circumferential lesions were assessed and correlated with procedural outcome. Eighteen patients with AF recurrence underwent repeat ablation. MRI scar regions were compared with electroanatomic maps during the repeat procedure. Regions of incomplete scar around the PVs were then identified and targeted during repeat ablation to ensure complete circumferential lesions. After the initial procedure, complete circumferential scarring of all 4 PV antrum (PVA) was achieved in only 7% of patients, with the majority of patients (69%) having <2 completely scarred PVA. After the first procedure, the number of PVs with complete circumferential scarring and total left atrial wall (LA) scar burden was associated with better clinical outcome. Patients with successful AF termination had higher average total left atrial wall scar of 16.4%±9.8 (P=0.004) and percent PVA scar of 66.2±25.4 (P=0.01) compared with patients with AF recurrence who had an average total LA wall scar 11.3%±8.1 and PVA percent scar 50.0±24.7. In patients who underwent repeat ablation, the PVA scar percentage was 56.1%±21.4 after the first procedure compared with 77.2%±19.5 after the second procedure. The average total LA scar after the first ablation was 11.0%±4.1, whereas the average total LA scar after second ablation was 21.2%±7.4. All patients had an increased number of completely scarred pulmonary vein antra after the second procedure. MRI scar after the first procedure and low-voltage regions on electroanatomic mapping obtained during repeat ablation demonstrated a positive quantitative correlation of R2=0.57. Conclusions—Complete circumferential PV scarring difficult to achieve but is associated with better clinical outcome. Delayed-enhancement MRI can accurately define scar lesions after AF ablation and can be used to target breaks in lesion sets during repeat ablation.Background— We evaluated scar lesions after initial and repeat catheter ablation of atrial fibrillation (AF) and correlated these regions to low-voltage tissue on repeat electroanatomic mapping. We also identified gaps in lesion sets that could be targeted and closed during repeat procedures. Methods and Results— One hundred forty-four patients underwent AF ablation and received a delayed-enhancement MRI at 3 months after ablation. The number of pulmonary veins (PV) with circumferential lesions were assessed and correlated with procedural outcome. Eighteen patients with AF recurrence underwent repeat ablation. MRI scar regions were compared with electroanatomic maps during the repeat procedure. Regions of incomplete scar around the PVs were then identified and targeted during repeat ablation to ensure complete circumferential lesions. After the initial procedure, complete circumferential scarring of all 4 PV antrum (PVA) was achieved in only 7% of patients, with the majority of patients (69%) having <2 completely scarred PVA. After the first procedure, the number of PVs with complete circumferential scarring and total left atrial wall (LA) scar burden was associated with better clinical outcome. Patients with successful AF termination had higher average total left atrial wall scar of 16.4%±9.8 ( P =0.004) and percent PVA scar of 66.2±25.4 ( P =0.01) compared with patients with AF recurrence who had an average total LA wall scar 11.3%±8.1 and PVA percent scar 50.0±24.7. In patients who underwent repeat ablation, the PVA scar percentage was 56.1%±21.4 after the first procedure compared with 77.2%±19.5 after the second procedure. The average total LA scar after the first ablation was 11.0%±4.1, whereas the average total LA scar after second ablation was 21.2%±7.4. All patients had an increased number of completely scarred pulmonary vein antra after the second procedure. MRI scar after the first procedure and low-voltage regions on electroanatomic mapping obtained during repeat ablation demonstrated a positive quantitative correlation of R 2=0.57. Conclusions— Complete circumferential PV scarring difficult to achieve but is associated with better clinical outcome. Delayed-enhancement MRI can accurately define scar lesions after AF ablation and can be used to target breaks in lesion sets during repeat ablation.