Degree Of Left Atrial Fibrosis Research Articles

Curcumin, novel application in reversing myocardial fibrosis in the treatment for atrial fibrillation from the perspective of transcriptomics in rat model

In order to explore the possible mechanism of curcumin in the treatment of AF, we focused on the myocardial fibrosis in the pathogenesis of atrial fibrillation to explore whether curcumin could play a role in the treatment of AF by reducing myocardial fibrosis.Rats were given daily gavage of saline (control and AF groups) or curcumin (4 mL/kg, concentration: 50 mg/mL, curcumin groups) during days 4–28. The rat model of AF was induced by Ach - CaCl2, and evaluate the therapeutic effect of curcumin on the duration of AF rhythm, the degree of myocardial fibrosis and the secretion of inflammatory factors in serum. RNA-seq to explore the possible mechanism of curcumin alleviating myocardial fibrosis of AF. curcumin significantly inhibits the duration of AF and reduces the degree of left atrial fibrosis. ELISA results showed curcumin could significantly reduce the secretion of IL-17A, IL-1β, IL -6 and TGF-β1. Bioinformatics analyses revealed that the IL-17 signaling pathway are involved in the therapeutic mechanism of curcumin. Furthermore, The genes encoding Col1a1, Fasn, Pck1, Bmp10, IL33 and Figf were pivotal and possible key genes for the therapeutic mechanisms of curcumin.Curcumin can reduce the degree of left atrial fibrosis of AF and the secretion of inflammatory factors. The therapeutic effect of curcumin on AF was attributed to its effect on the IL-17 signaling pathway. Besides, COL1A1, FASN, PCK1, BMP10, IL33 and FIGF were the pivotal genes associated with mechanisms of action of curcumin on AF.

B-PO02-096 PREDICTION OF ATRIAL FIBRILLATION RECURRENCE POST-ABLATION BASED ON ATRIAL FIBROSIS BY LATE GADOLINIUM ENHANCEMENT: A META-ANALYSIS

The degree of left atrial fibrosis has been identified as one of the independent predictors of the recurrence of atrial fibrillation (AF) post-ablation. Late gadolinium enhancement magnetic resonance imaging (LGE-MRI) has been known to predict the recurrence of AF post-ablation based on left atrial fibrosis in various observational studies. In this paper, we have systematically combined the studies performed that used LGE-MRI to quantify atrial fibrosis based on the different stages of fibrosis before ablation to predict AF's recurrence. This meta-analysis aims to investigate the recurrence of atrial AF post-ablation based on the various stages of fibrosis seen in the late gadolinium enhancement magnetic resonance imaging (LGE-MRI). Electronic databases were searched nine studies that met the inclusion criteria were identified. A total of 1,787 patients underwent LGE-MRI to assess atrial fibrosis before catheter ablation for AF. We performed three sets of analyses: first, compared stage IV versus stage I (reference group). The second set examined the combined stages III and IV versus stages I and II (reference group). The third set compared stage IV versus combined stages I, II, and III. The metanalysis relied on a random-effects model to pool the odds ratios (OR) and 95% confidence intervals (CI) using the DerSimonian and Laird method. The data was analyzed using StatsDirect software, England. The study showed a higher rate of AF recurrence after ablation in stage IV atrial fibrosis compared with those in stage I (OR, 9.54; 95% CI, 3.81 to 28.89; P<00001). Also, in patients with combined stages III & IV of atrial fibrosis, AF recurrence was significantly higher after ablation than stages I & II groups (OR, 2.37; 95% CI, 1.61 to 3.50; P<00001). Similarly, patients with stage IV compared to combined stages I, II, and III have higher odds of recurrence post-ablation (OR, 4.24; 95% CI, 2.39- 7.52, P < 0.001). This metanalysis demonstrates the strong association of left atrial fibrosis seen in LGE-MRI and AF post-ablation recurrence. The finding of this study will further assist clinicians in predicting the rate of recurrence of AF based on the amount of fibrosis and tailor therapeutic decisions for further management.

Impaired left atrial reservoir and conduit strain in patients with atrial fibrillation and extensive fibrosis

Abstract Funding Acknowledgements Type of funding sources: None. Background Atrial fibrillation (AF) is associated with profound structural and functional changes in the atria. Timely interventions may decelerate and perhaps reverse this pathophysiologic process and improve clinical outcome. In this regard, detailed characterization of the atrial remodeling process, and understanding of the interplay between structural remodeling and function is essential. Purpose In the present study, we investigated the association between left atrial (LA) phasic function and the extent of LA fibrosis using advanced cardiovascular magnetic resonance (CMR) imaging techniques, including 3-dimensional (3D) late gadolinium enhancement (LGE) and Feature Tracking. Methods Patients with paroxysmal and persistent AF (n = 93) underwent CMR in sinus rhythm. LA global reservoir strain, conduit strain and contractile strain were derived from cine CMR images using Feature Tracking. The extent of LA fibrosis was assessed from 3D LGE images. Healthy volunteers underwent CMR and served as controls (n = 19). Results Significantly lower reservoir strain, conduit strain and contractile strain were found in AF patients, as compared to controls (-15.7 ± 3.9% vs. -21.1 ± 3.6% P &amp;lt; 0.001, -8.6 ± 2.9% vs. -12.6 ± 2.5% P &amp;lt; 0.001 and -7.1 ± 2.4% vs. -8.6 ± 2.2% P = 0.02, respectively) (Figure A, B, C). Patients with a high degree of LA fibrosis (dichotomized by the median value) had lower reservoir strain and conduit strain compared to patients with a low degree of LA fibrosis (-14.7 ± 4.0% vs. -16.8 ± 3.5%, P = 0.02 and -7.7 ± 2.7% vs. -9.5 ± 2.9%, P &amp;lt; 0.01, respectively). In contrast, no difference was found for LA contractile strain (-7.0 ± 2.3% vs. -7.3 ± 2.5%, P = 0.62) (Figure D, E, F). Conclusions This study shows impaired LA reservoir and conduit strain in AF patients with extensive atrial fibrosis. Of interest, LA contractile function was largely unaffected. Future studies are required to study the biologic nature of this association and possible therapeutic implications. Abstract Figure.

P1020Persistent AF patients with limited areas of low voltage have a similar benefit from pulmonary vein isolation as compared to paroxysmal AF patients: insight from the SMOP study

Abstract Background Pulmonary vein isolation (PVI) performed with radio-frequency catheter ablation (CA) is an effective therapy for atrial fibrillation (AF). However previous data have suggested that PVI is less effective in persistent (PER) vs. paroxysmal (PAR) AF. Atrial fibrosis and scar, indeed, are an important substrate involved in persistent AF, and some author correlate them to an increased rate of recurrences after CA. For this reason several adjunctive ablation strategies have been suggested for invasive treatment in PER AF pts. However, there is a lack of evidence on their effectivness in current literature. Objective the aim of our study was to assess the rate of AF recurrences in PAR and PER AF patients after a first pulmonary vein isolation (IVP) procedure, and their relationship with low voltage areas of the left atrium assessed by means of high density mapping performed before CA. Methods we analyzed 214 patients of the SMOP-AF study (Substrate Mapping as Outcome Predictor in Atrial Fibrillation Ablation), a prospective multi-centric registry enrolling patients with both PAR and PER AF undergoing a first radio-frequency CA procedure aimed to obtain permanent PVI . High-density mapping was performed in sinus rhythm using the CARTO system before PVI. Areas with less than 0,5 mV on mapping were defined as low voltage zone (LVZ); LVZ was indexed on the atrial area. Comparisons were made by cross-tables and Chi-square test or Student T test. Results Patients with PER AF (n = 44, 21%) were older (63 ± 9 vs 58 ± 10 yrs, p = 0.01), but notably with no difference in LVEF and atrial dimensions as compared to pts with PAR AF. In addition no statistical difference was observed in procedural variables, except for a greater LVZ area on atrial mapping (8 ± 18 % vs. 5 ± 15 %, p = 0.04) and a longer p wave duration (115 ± 21 msec vs. 103 ± 18 msec, p = 0.01) in pts with PER AF. The incidence of recurrence in the overall population was 15.3% at 3 months and 13.7% from 3 to 12 months: there was no statistical difference in success-rate between PER and PAR pts (respectively 79,5% vs 86% p value = 0.315 in blanking period and 85,3% vs 86,5% p value = 0.8 at 3-12 months follow-up). No statistical difference was observed for ablation variables (number of lesion, contact force, force time integral) in pts with vs. without recurrences. Conclusion Our study showed that pulmonary vein isolation alone seems to be as effective in paroxismal and persistent AF patients with low degree of left atrial fibrosis. Our data call into question the idea that PVI alone is not effective in PER AF. High density mapping of the LA could help to identify a subset of PER AF patients with a limited extension of low voltage areas (i.e around 10% of the overall LA surface) that could benefit from PVI without adjunctive ablation strategies. Our data needs to be confirmed in a longer follow-up.

P333Left atrial function by echocardiography is independent of degree of left atrial electrical scar

Abstract Introduction Assessment of left atrial function via transthoracic echocardiography (TTE) is performed most commonly by measuring the transmitral A wave in sinus rhythm. Left atrial (LA) fibrosis plays an important role in the pathogenesis and perpetuation of Atrial Fibrillation (AF). It may be identified by bipolar voltage (BiV) mapping, which can easily be performed at the beginning of a Pulmonary Vein Isolation (PVI) procedure. The relationship between the degree of LA fibrosis, characterised with mapping, and LA function, determined by echocardiography, has not previously been elucidated. Methods Patients were enrolled in a project to evaluate the degree of fibrosis during PVI procedures. Pre-procedure TTEs of those presenting in sinus rhythm were assessed and the transmitral A wave was measured and compared to the degree of scarring seen. The high density electroanatomic maps (HD-EAMs) created during the PVIs were analysed using a novel VHA algorithm after the procedure. All points with voltages &amp;lt; 0.5mV were defined to have electrical scar. Patients were classified into 4 quartiles based on the levels of scar seen (Figure 1). Results 39 patients were included in the evaluation. Average age was 60.6 +/- 13.2 years. 32 (82.0%) of the patients were male. Mean CHADS2VASc score was 1.5. The mean percentage of scar was calculated as 19.6 +/- 15.9%. The average A wave was 0.62 +/- 0.18 ms-1. Pearson’s correlation coefficient showed no relationship between LA scar and either A wave velocities (r = 0.26, p = 0.11) or E:A ratio (r=-0.02, p = 0.91). A significant correlation between A wave velocity and CHADS2VASc was observed (r = 0.49, p = 0.001). Conclusion Our study demonstrates no relationship between degree of LA scarring and reduced LA function on TTE as assessed by the A wave. It has been established that structural remodelling in AF (such as atrial dilatation) may occur independently of the electrical remodelling. A potential explanation for our findings is that the electrical scarring in AF, which results in alterations in refractory periods, precedes the negative remodelling which ultimately results in reduced atrial function. This hypothesis would need to be further evaluated in larger studies. Abstract Figure 1

High-intensity endurance training is associated with left atrial fibrosis

Endurance athletes are at higher risk for developing atrial fibrillation as compared to the general population. The exact mechanism to explain this observation is incompletely understood. Our study aimed to determine whether degree of left atrial fibrosis detected by late gadolinium-enhancement magnetic resonance imaging (LGE-MRI) differed between Masters athletes and non-athlete controls. We recruited 20 endurance healthy Masters athletes and 20 healthy control subjects who underwent cardiac MRI. Healthy controls were recruited during screening colonoscopies and Masters athletes were recruited through word of mouth and at competitions. The two groups were age and gender matched. None of the participants were known to have an arrhythmia. Fibrosis, as measured by late gadolinium-enhancement, was measured in each participant by blinded readers. The degree of left atrial fibrosis was compared between the two groups. All participants were recruited from the Salt Lake City region and scanned at the University of Utah healthcare complex. Left ventricular function was normal in all study participants. Left atrial volumes were significantly larger in the athletes (74.2 ml ± 14.4) as compared to the healthy control subjects (60.8 mL ± 21.4) (P = .02). Mean left atrial fibrosis score, reported as a percentage of the LA, was 15.5% ± 5.9 in the athlete cohort compared to 9.6% ± 4.9 in the controls (P = .002). To our knowledge this is the first study that describes, characterizes and specifically quantifies fibrotic changes within the left atrium of highly trained endurance athletes. Increased atrial fibrosis seen in this population may be an early indicator for endurance athletes at risk of developing atrial arrhythmias.

P5651Association of left atrial fibrosis extent with left ventricular geometric remodeling and diastolic dysfunction in patients with paroxysmal atrial fibrillation

Abstract Introduction Whether left atrial fibrosis (LAf) in patients with atrial fibrillation (AF) is a consequence of left ventricular (LV) diastolic dysfunction or primary atrial pathology continues to be a debatable issue. Electroanatomical mapping (EAM) allows to image and to define LAf as a substrate of AF. Purpose To study the relationship of LAf extent with LV diastolic function and geometric remodeling in patients (pts) with paroxysmal AF. Methods 56 pts with paroxysmal AF (mean age 57.1±8.4 years, 31 males), undergone catheter ablation, were enrolled in the study, including 30 pts with arterial hypertension (AH), 15 – with coronary artery disease (CAD) and AH. Comprehensive transthoracic echocardiography was carried out in all pts to assess chamber volumes, systolic and LV diastolic functions and geometry patterns according to Recommendations of ASE and EACVI. Before ablation, EAM was performed in sinus rhythm. The bipolar low voltage areas of LAf were identified with the cut-off &lt;0.5 mV. For the LAf quantification following indicators were calculated: total square of LAf (Sf, cm2) and LAf degree, estimated as an analog of the UTAH staging system, by selection of UTAH I: &lt;5% fibrosis; II: 5–19%; III: 20–35% and IV: &gt;35%. Results All patients had preserved systolic LV function. To assess the influence of LV geometry on LAf extent all pts were distributed in accordance to LV geometry patterns (p): normal geometry (pI) – 27 pts, concentric remodeling (pII) – 13, eccentric hypertrophy (pIII) – 10, concentric hypertrophy (pIV) – 6. Pts with pIII were older than pI pts: 60.8±6.4 vs 53.9±10.4 (p=0.048). All pts with pIII and pIV had AH. From 11 pts without AH, 10 had pI of LV geometry. PIII was revealed more often in CAD pts compared to those without CAD: 29.2 vs 10.5% (p=0.04). PIII pts had bigger LA volume compared to pI pts (74.3±22.5 vs 58.8±19.4 ml, p=0.019) and pII pts (61.9±14.9, p=0.05), but LA volume of pIII pts didn't differ from pIV pts (71.9±14.5, p=0.78). PIII pts had more extent Sf than pI pts (28.32±8.9 vs 13.4±6.5, p=0.05), while Sf of pII (17.3±8.7, p=0.495) and pIV pts (16.4±9.5, p=0.699) didn't differ significantly from Sf of pI pts. As for the degree of LAf, UTAH I was absent in pts with pIII and UTAH IV was revealed in 40% of these pts, while in pts with pI UTAH I was in 26% and UTAH IV - in 14.8% (p=0.049). However, Sf and UTAH degree did not depend on age, CAD and heart failure presence. As for diastolic dysfunction, in pIII and pIV pts e∼septal and e∼lateral were lower compared to pI pts: 6.3±1.9, 5.5±2.4 vs 8.5±2.2 (p&lt;0.01) and 8.2±2.7, 8.0±3.8 vs 11.3±2.9 (p&lt;0.01), respectively, while E/e∼ in pIII pts didn't differ from pI pts (8.0±1.6 vs 7.2±1.6, p=0.17), but in pIV was more than in pI pts (10.4±2.8, p=0.003). Conclusion LAf extent in paroxysmal AF is associated more with such LV geometry pattern as eccentric hypertrophy, than with diastolic disorders, which accompany both eccentric and concentric hypertrophy.

ASSOCIATION OF LEFT ATRIAL FIBROSIS EXTENT WITH LEFT VENTRICULAR STRUCTURAL AND FUNCTIONAL REMODELLING IN PATIENTS WITH ATRIAL FIBRILLATION

Aim.To investigate the relationships between left atrial (LA) fibrosis extent and left ventricular (LV) structural and functional status in patients (pts) with nonvalvular atrial fibrillation (AF).Material and Methods.The study enrolled 56 pts (mean age 57.1±8.4 years, 25 females), admitted to hospital for primary catheter ablation (CA), including 47 pts with paroxysmal AF and 9 pts with persistent AF. All pts had scheduled transthoracic echocardiography to measure size and volume of cardiac chambers and systolic and diastolic functions of the left ventricle. Based on the calculation of the LV mass index (LVMI) and relative wall thickness (RWT), we categorized all pts into 4 groups: (1) normal geometry (n=27); (2) concentric remodeling (normal LVMI and high RWT, n=13); (3) concentric hypertrophy (high LVMI and high RWT, n=6); and (4) eccentric remodeling (high LVMI and normal RWT, n=10). The assessment of LA fibrosis sizes was based on the allocation of low voltage zones (&lt;0.5 mV) in the process of voltage electroanatomic mapping (VEM) as the first stage of CA. Following indicators were calculated: total square of fibrosis (Sf), % of fibrosis from the total LA square (Sf%), the degree of LA fibrosis (an analog of the UTAH score), and number of LA fibrosis zones. Level of NT-proBNP in blood was determined among other laboratory tests. All pts had preserved LV ejection fraction (LVEF).Results.Results of the study confirmed positive relationships between Sf, Sf% and LA diameter, LVMI, and NT-proBNP level. Negative relationship was noted between Sf, Sf%, the UTAH degree and LVEF. Such LV geometry type as eccentric hypertrophy was associated with a higher number of LA fibrosis zones compared to the normal LV geometry, while significant differences in other types of geometry were not found.Conclusion. Thus, LA fibrosis extent was associated with LA size, LV function, and LV geometric remodeling pattern.

Left atrial fibrosis correlates with extent of left ventricular myocardial delayed enhancement and left ventricular strain in hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is associated with increased left ventricular (LV) mass, decreased myocardial strain, and the presence of LV fibrosis and scar. The relationship between LV scar and fibrosis with left atrial (LA) fibrosis in the setting of HCM has not been examined. The purpose of this study is to demonstrate a correlation between the degree of LA fibrosis and LV parameters in subjects with HCM. Twenty-eight subjects with HCM were imaged on a 1.5T MRI scanner with cine, LV and LA late gadolinium enhancement (LGE) sequences. LA LGE and LA measurements were correlated with LV measurements of volumes, mass, strain, and LGE. Other clinical conditions and medication usage were also examined and evaluated for correlation with LA and LV parameters. LV LGE was identified in 24 (86%) of the cases and LA LGE was identified in all of the cases. Extent of LA fibrosis significantly correlated with percent LV LGE (r = 0.64, p = 0.001), but not with indexed LV mass or maximum wall thickness. Extent of LA fibrosis also moderately correlated with decreased LV global strain (radial, r = - 0.50, p = 0.013; circumferential, r = 0.47, p = 0.02; longitudinal, r = 0.52, p = 0.013). Increased LA systolic volume correlated moderately with LV end diastolic volume (r = 0.50, p = 0.006). Patients on therapy with Renin-Angiotensin-Aldosterone System (RAAS) Inhibition had significantly less LA LGE compared to those without (18.6% vs 10.8%, p = 0.023). LA fibrosis, as measured by LGE, is prevalent in HCM and is correlated with LV LGE. The correlation between LA and LV LGE might suggest either that LA fibrosis is a consequence of LV remodeling, or that LA and LV fibrosis are both manifestations of the same cardiomyopathic process. Further study is warranted to determine the causality of LA scar in this population.

Atrial Fibrosis by Late Gadolinium Enhancement Magnetic Resonance Imaging and Catheter Ablation of Atrial Fibrillation: 5-Year Follow-Up Data.

BackgroundLate gadolinium enhancement magnetic resonance imaging is an effective tool for assessment of atrial fibrosis. The degree of left atrial fibrosis is a good predictor of atrial fibrillation (AF) ablation success at 1 year, but the association between left atrial fibrosis and long‐term ablation success has not been studied.Methods and ResultsLate gadolinium enhancement magnetic resonance images of sufficient quality to quantify atrial fibrosis were obtained before the first AF ablation in 308 consecutive patients. Left atrial fibrosis was classified in 4 Utah stages (I, 0–10%; II, 10–20%; III, 20–30%; and IV, >30%). Patients were followed up for up to 5 years until the time of first arrhythmia recurrence or second ablation. A total of 308 patients were included; the mean age was 64.5±12.1 years, and 63.4% were men. During follow‐up, 157 patients experienced an arrhythmia recurrence and 106 patients underwent a repeated ablation. A graded effect was observed in which patients with more advanced atrial fibrosis were more likely to experience recurrent AF (hazard ratio for stage IV versus stage I, 2.73; 95% confidence interval, 1.57–4.75) and undergo a repeated ablation (proportional odds ratio for stage IV versus stage I, 5.19; 95% confidence interval, 2.12–12.69).ConclusionsThe degree of left atrial fibrosis predicts the success of AF ablation at up to 5 years follow‐up. In patients with advanced atrial fibrosis, AF ablation is associated with a high procedural failure rate.

Increased serum lysyl oxidase-like 2 levels correlate with the degree of left atrial fibrosis in patients with atrial fibrillation.

Atrial fibrillation (AF) progression is generally accompanied by increased atrial fibrosis and atrial structural remodeling. Lysyl oxidase-like 2 (LOXL2) is known to play an important role in many fibrotic conditions, including cardiac fibrosis. The present study aimed to explore the relationship between serum LOXL2 levels and AF. Fifty-four AF patients and 32 control subjects were enrolled in the study. High-density three-dimensional electroanatomic mapping was performed, and mean bipolar voltage was assessed in AF patients. LOXL2 levels were measured by enzyme-linked immunosorbent assay. All patients underwent echocardiography to assess left atrium size and left ventricle function. Serum LOXL2 levels were significantly elevated in AF patients compared with the control group (526.81 ± 316.82 vs 240.94 ± 92.51 pg/ml, P<0.01). In addition, serum LOXL2 level was significantly correlated with the size of the left atrium (LAD) (r2 = 0.38, P<0.01). Furthermore, the serum LOXL2 levels were significantly higher in AF patients with LAD ≥ 40 mm compared with those with LAD < 40 mm (664.34 ± 346.50 vs 354.90 ± 156.23 pg/ml, P<0.01). And the Spearman’s correlation analysis further revealed that the mean bipolar left atrial voltage was inversely correlated with the LOXL2 (r2 = −0.49, P<0.01) in AF patients. Multivariate regression analysis further demonstrated that serum LOXL2 [odds ratio (OR) 1.013, 95% confidence interval (CI) 1.002–1.024, P<0.05] and LAD (OR 1.704, 95% CI 1.131–2.568, P<0.01) were independent predictors of AF. In conclusion, serum LOXL2 levels were significantly elevated and were correlated with the degree of left atrial fibrosis in AF patients.

The degree of left atrial structural remodeling impacts left ventricular ejection fraction in patients with atrial fibrillation

The extent of left atrial (LA) wall structural remodeling (fibrosis) detected by late gadolinium enhancement-magnetic resonance imaging (LGE-MRI) is correlated with advanced atrial fibrillation (AF). The concomitant occurrence of AF and left ventricular (LV) dysfunction is not uncommon. We studied the effect of LA fibrosis, a confounder of both AF and LV dysfunction, on LV ejection fraction (EF). For the analysis, we identified and included 384 patients from our retrospective AF database who underwent LGE-MRI and transthoracic echocardiography prior to AF ablation. Based on the degree of LA fibrosis, patients were categorized into four stages as: Utah 1 (<5% LA fibrosis), Utah 2 (5-20% fibrosis), Utah 3 (20-35% fibrosis), and Utah 4 (>35% fibrosis). The average pre-ablation LVEF was 60.5%±8.5% (n=24) in Utah stage 1 patients, 55.7%±10.3% (n=240) in Utah stage 2 patients, 51.7±11.5% (n=90) in Utah stage 3 patients, and 48.9%±11.6% (n=30) in Utah stage 4 patients (p<0.001, one-way ANOVA). The percentage of LA fibrosis was significantly negatively correlated to LVEF pre-ablation in a univariate analysis (p<0.001). In a multivariate model accounting for age, gender, AF type, and comorbidities such as diabetes and hypertension, Utah stage remained a significant predictor of pre-ablation EF (p<0.001). Patients with extensive LA fibrosis appear to have depressed LV function pre-ablation, suggesting that structural remodeling in the LA may also be triggering and promoting remodeling within the ventricular myocardium.

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

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. 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. 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. 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). 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.

Abstract 2156: Left Atrial Fibrosis Impacts Left Ventricular Ejection Fraction in Patients with Atrial Fibrillation

Background. The extent of left atrial (LA) wall fibrosis detected by delayed enhancement MRI (DE-MRI) appears to be correlated with advanced atrial fibrillation (AF). However, the effect of LA fibrosis on left ventricular function (LVEF) is not well understood. We report the relationship between left atrial fibrosis and LVEF in patients with AF. Methods. Sixty-seven patients underwent DE-MRI and 2-dimensional trans-thoracic echocardiography prior to ablation for AF. Three dimensional segmentation of the LA was performed and the extent of fibrosis was quantified using a semi-automated algorithm. Patients were assigned to one of three groups based on the degree of LA fibrosis; 1) mild enhancement where the fibrosis &lt; 15% of the LA wall, 2) moderate enhancement where fibrosis &gt; 15% and &lt; 35%, and extensive where fibrosis &gt; 35% of the LA wall. LVEF was determined both prior to and 3 months following pulmonary vein antrum isolation with posterior wall and septal debulking. Results. The average pre-ablation LVEF among patients with mild fibrosis was 53.2% ± 9.9% (n = 41), 52.3% ± 7.4% (n = 19) among patients with moderate fibrosis and 42.1% ± 9.9% (n = 7) among those with extensive enhancement (p = 0.01,one way ANOVA). The difference remains significant after controlling for patient age, gender, hypertension, MI, AF type, mitral valve regurgitation, CAD and the presence of non-AF related CHF. Following ablation, all groups had an increase in the LVEF. The greatest increase occurred among patients in the extensive group. On average, this group experienced an overall improvement of 10.8% ± 14.1%. Patients in the mild enhancement group had an average improvement of 3.3% ± 11.1% and those in the moderate group had an average improvement of 3.8% ± 5.6%. The post-ablation LVEF among patients with mild fibrosis was 56.6% ± 8.3%, 56.2% ± 6.4% among patients with moderate fibrosis and 53.0% ± 15.4% among patients with extensive fibrosis. Conclusion. From our preliminary experience with DE-MRI fibrosis detection, patients with extensive LA fibrosis appear to have depressed LV function pre-ablation. This group of patients seems to experience a large improvement (~11%) in LV function post-ablation compared to patients with less LA fibrosis.