Atrial fibrosis quantified using late gadolinium enhancement MRI is associated with sinus node dysfunction requiring pacemaker implant.

INTRODUCTION: Sinus node dysfunction (SND) commonly manifests with atrial arrhythmias alternating with sinus pauses and sinus bradycardia. The underlying process is thought to be because of atrial fibrosis. We assessed the value of atrial fibrosis, quantified using late gadolinium enhanced-MRI (LGE-MRI), in predicting significant SND requiring pacemaker implant. METHODS: Three hundred forty-four patients with atrial fibrillation (AF) presenting for catheter ablation underwent LGE-MRI. Left atrial (LA) fibrosis was quantified in all patients and right atrial (RA) fibrosis in 134 patients. All patients underwent catheter ablation with pulmonary vein isolation with posterior wall and septal debulking. Patients were followed prospectively for 329 ± 245 days. Ambulatory monitoring was instituted every 3 months. Symptomatic pauses and bradycardia were treated with pacemaker implantation per published guidelines. RESULTS: The average patient age was 65 ± 12 years. The average wall fibrosis was 16.7 ± 11.1% in the LA, and 5.3 ± 6.4% in the RA. RA fibrosis was correlated with LA fibrosis (R(2) = 0.26; P < 0.01). Patients were divided into 4 stages of LA fibrosis (Utah I: <5%, Utah II: 5-20%, Utah III: 20-35%, Utah IV: >35%). Twenty-two patients (mean atrial fibrosis, 23.9%) required pacemaker implantation during follow-up. Univariate and multivariate analysis identified LA fibrosis stage (OR, 2.2) as a significant predictor for pacemaker implantation with an area under the curve of 0.704. CONCLUSIONS: In patients with AF presenting for catheter ablation, LGE-MRI quantification of atrial fibrosis demonstrates preferential LA involvement. Significant atrial fibrosis is associated with clinically significant SND requiring pacemaker implantation.

Atrial fibrosis helps select the appropriate patient and strategy in catheter ablation of atrial fibrillation: a DE-MRI guided approach.

UNLABELLED: 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. METHODS AND RESULTS: One hundred and forty-four patients were staged by percent of fibrosis quantified with DE-MRI, relative to the LA wall volume: minimal or Utah stage 1; <5%, mild or Utah stage 2; 5-20%, moderate or Utah stage 3; 20-35%, and extensive or Utah stage 4; >35%. All patients underwent pulmonary vein (PV) isolation and posterior wall and septal debulking. Overall, LA scarring was quantified and PV antra were evaluated for circumferential scarring 3 months post ablation. LA scarring post ablation was comparable across the 4 stages. Most patients had either no (36.8%) or 1 PV (32.6%) antrum circumferentially scarred. Forty-two patients (29%) had recurrent AF over 283 ± 167 days. No recurrences were noted in Utah stage 1. Recurrence was 28% in Utah stage 2, 35% in Utah stage 3, and 56% in Utah stage 4. Recurrence was predicted by circumferential PV scarring in Utah stage 2 and by overall LA wall scarring in Utah stage 3. No recurrence predictors were identified in Utah stage 4. CONCLUSIONS: Circumferential PV antral scarring predicts ablation success in mild LA fibrosis, while posterior wall and septal scarring is needed for moderate fibrosis. This may help select the proper candidate and strategy in catheter ablation of AF.

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.

Echocardiographic left atrial reverse remodeling after catheter ablation of atrial fibrillation is predicted by preablation delayed enhancement of left atrium by magnetic resonance imaging.

BACKGROUND: Atrial fibrosis is a hallmark of atrial structural remodeling (SRM) and leads to structural and functional impairment of left atrial (LA) and persistence of atrial fibrillation (AF). This study was conducted to assess LA reverse remodeling after catheter ablation of AF in mild and moderate-severe LA SRM. METHODS: Catheter ablation was performed in 68 patients (age 62 ± 14 years, 68% males) with paroxysmal (n = 26) and persistent (n = 42) AF. The patients were divided into group 1 with mild LA SRM (<10%, n = 31) and group 2 with moderate-severe LA SRM (>10%, n = 37) by delayed enhancement magnetic resonance imaging (DEMRI). Two-dimensional echocardiography, LA strain, and strain rate during left ventricular systole by velocity vector imaging were performed pre and at 6 ± 3 months postablation. The long-term outcome was monitored for 12 months. RESULTS: Patients in group 1 were younger (57 ± 15 vs 66 ± 13 years, P = .009) with a male predominance (80% vs 57%, P < .05) as compared to group 2. Postablation, group 1 had significant increase in average LA strain (Δ↑: 14% vs 4%, P < .05) and strain rate (Δ↑: 0.5 vs 0.1 cm/s, P < .05) as compared to group 2. There was a trend toward more patients with persistent AF in group 2 (68% vs 55%, P = .2), but it was not statistically significant. Group 2 had more AF recurrences (41% vs 16%, P = .02) at 12 months after ablation. CONCLUSION: Mild preablation LA SRM by DEMRI predicts favorable LA structural and functional reverse remodeling and long-term success after catheter ablation of AF, irrespective of the paroxysmal or persistent nature of AF.

Magnetic resonance imaging-confirmed ablative debulking of the left atrial posterior wall and septum for treatment of persistent atrial fibrillation: rationale and initial experience.

INTRODUCTION: Though pulmonary vein (PV) isolation has been widely adopted for treatment of atrial fibrillation (AF), recurrence rates remain unacceptably high with persistent and longstanding AF. As evidence emerges for non-PV substrate changes in the pathogenesis of AF, more extensive ablation strategies need further study. METHODS: We modified our PV antrum isolation procedure to include abatement of posterior and septal wall potentials. We also employed recently described image-processing techniques using delayed-enhancement (DE) MRI to characterize tissue injury patterns 3 months after ablation, to assess whether each PV was encircled with scar, and to assess the impact of these parameters on procedural success. RESULTS: 118 consecutive patients underwent debulking procedure and completed follow-up, of which 86 underwent DE-MRI. The total left atrial (LA) radiofrequency delivery correlated with percent LA scarring by DE-MRI (r = 0.6, P < 0.001). Based on DE patterns, complete encirclement was seen in only 131 of 335 PVs (39.1%). As expected, Cox regression analysis showed a significant relationship between the number of veins encircled by delayed enhancement and clinical success (hazard ratio of 0.62, P = 0.015). Also, progressive quartile increases in postablation posterior and septal wall scarring reduced recurrences rates with a HR of 0.65, P = 0.022 and 0.66, P = 0.026, respectively. CONCLUSION: Pathologic remodeling in the septal and posterior walls of the LA helps form the pathogenic substrate for AF, and these early results suggest that more aggressive treatment of these regions appears to correlate with improved ablation outcomes. Noninvasive imaging to characterize tissue changes after ablation may prove essential to stratifying recurrence risk.

Direct toxic effects of aqueous extract of cigarette smoke on cardiac myocytes at clinically relevant concentrations.

AIMS: Our goal was to determine if clinically relevant concentrations of aqueous extract of cigarette smoke (CSE) have direct deleterious effects on ventricular myocytes during simulated ischemia, and to investigate the mechanisms involved. METHODS: CSE was prepared with a smoking chamber. Ischemia was simulated by metabolic inhibition (MI) with cyanide (CN) and 0 glucose. Adult rabbit and mouse ventricular myocyte [Ca(2+)](i) was measured by flow cytometry using fluo-3. Mitochondrial [Ca(2+)] was measured with confocal microscopy, and Rhod-2 fluorescence. The mitochondrial permeability transition (MPT) was detected by TMRM fluorescence and myocyte contracture. Myocyte oxidative stress was quantified by dichlorofluorescein (DCF) fluorescence with confocal microscopy. RESULTS: CSE 0.1% increased myocyte contracture caused by MI. The nicotine concentration (HPLC) in 0.1% CSE was 15 ng/ml, similar to that in humans after smoking cigarettes. CSE 0.1% increased mitochondrial Ca(2+) uptake, and increased the susceptibility of mitochondria to the MPT. CSE 0.1% increased DCF fluorescence in isolated myocytes, and increased [Ca(2+)](i) in paced myocytes exposed to 2.0 mM CN, 0 glucose (P-MI). These effects were inhibited by the superoxide scavenger Tiron. The effect of CSE on [Ca(2+)](i) during P-MI was also prevented by ranolazine. CONCLUSIONS: CSE in clinically relevant concentrations increases myocyte [Ca(2+)](i) during simulated ischemia, and increases myocyte susceptibility to the MPT. These effects appear to be mediated at least in part by oxidative radicals in CSE, and likely contribute to the effects of cigarette smoke to increase myocardial infarct size, and to decrease angina threshold.

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.

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.

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.

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 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.

MRI in cardiac electrophysiology: the emerging role of delayed-enhancement MRI in atrial fibrillation ablation.

Catheter ablation of atrial fibrillation has emerged as a viable therapeutic option for those patients who have failed conventional medical therapy. This treatment strategy has been introduced in the past decade following the discovery of ectopic foci in the pulmonary veins capable of initiating this arrhythmia. The basis of current ablation techniques relies on inducing myocardial necrosis at distinct anatomical landmarks in order to electrically isolate these ectopic foci and to disrupt pulmonary vein and left atrial conduction pathways. The recent introduction of a delayed-enhancement cardiac MRI sequence now allows for the noninvasive assessment of the location and extent of left atrial scarring following the ablation procedure. In this review, we describe this novel scan sequence and its current and potential role in catheter ablation of atrial fibrillation.

Initial experience of assessing esophageal tissue injury and recovery using delayed-enhancement MRI after atrial fibrillation ablation.

BACKGROUND: Esophageal wall thermal injury after atrial fibrillation ablation is a potentially serious complication. However, no noninvasive modality has been used to describe and screen patients to examine whether esophageal wall injury has occurred. We describe a noninvasive method of using delayed-enhancement MRI to detect esophageal wall injury and subsequent recovery after atrial fibrillation ablation. METHODS AND RESULTS: We analyzed the delayed-enhancement MRI scans of 41 patients before ablation and at 24 hours and 3 months after ablation to determine whether there was evidence of contrast enhancement in the esophagus after atrial fibrillation ablation. In patients with contrast enhancement, 3D segmentation of the esophagus was performed using a novel image processing method. Upper gastrointestinal endoscopy was then performed. Repeat delayed-enhancement MRI and upper gastrointestinal endoscopy was performed 1 week later to track changes in lesions. The wall thickness of the anterior and posterior wall of the esophagus was measured at 3 time points: before ablation, 24 hours after ablation, and 3 months after ablation. Evaluation of preablation MRI scans demonstrated no cases of esophageal enhancement. At 24 hours, 5 patients showed contrast enhancement. Three of these patients underwent upper gastrointestinal endoscopy, which demonstrated esophageal lesions. Repeat upper gastrointestinal endoscopy and MRI 1 week later demonstrated resolution of the lesions. All 5 patients had confirmed resolution of enhancement at 3 months. All patients with esophageal tissue enhancement demonstrated left atrial wall enhancement directly adjacent to the regions of anterior wall esophageal enhancement. CONCLUSIONS: Our preliminary results indicate delayed-enhancement MRI can assess the extent and follow progression of esophageal wall injury after catheter ablation of atrial fibrillation. It appears that acute esophageal injury recovers within 1 week of the procedure.

Temporal left atrial lesion formation after ablation of atrial fibrillation.

BACKGROUND: Atrial fibrillation (AF) ablation uses radiofrequency (RF) energy to induce thermal damage to the left atrium (LA) in an attempt to isolate AF circuits. This injury can be seen using delayed enhancement magnetic resonance imaging (DE-MRI). OBJECTIVE: The purpose of this study was to describe DE-MRI findings of the LA in the acute and chronic stages postablation. METHODS: Twenty-five patients were scanned at two time points postablation. The first group (n = 10) underwent DE-MRI at 24 hours and at 3 months. The second group (n = 16) was scanned at 3 months and at 6 or 9 months. One patient had three scans (24 hours, 3 months, 9 months) and was included in both groups. The location and extent of enhancement were then analyzed between both groups. RESULTS: The median change in LA wall injury between 24 hours and 3 months was -6.38% (range -11.7% to 12.58%). The median change in LA wall injury between 3 months and later follow-up was +2.0% (range -4.0% to 6.58%). There appears to be little relationship between the enhancement at 24 hours and 3 months (R(2) = 0.004). In contrast, a strong correlation is seen at 3 months and later follow-up (R(2) = 0.966). Qualitative comparison revealed a stronger qualitative relationship between MRI findings at 3 months and later follow-up than at 24 hours and 3 months. CONCLUSION: RF-induced scar appears to have formed by 3 months postablation. At 24 hours postablation, DE-MRI enhancement appears consistent with a transient inflammatory response rather than stable LA scar formation.

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.