Extent Of Left Atrial Fibrosis Research Articles

The role and implications of left atrial fibrosis in surgical mitral valve repair as assessed by CMR: the ALIVE study design and rationale.

Patients with mitral regurgitation (MR) commonly suffer from left atrial (LA) remodeling. LA fibrosis is considered to be a key player in the LA remodeling process, as observed in atrial fibrillation (AF) patients. Literature on the presence and extent of LA fibrosis in MR patients however, is scarce and its clinical implications remain unknown. Therefore, the ALIVE trial was designed to investigate the presence of LA remodeling including LA fibrosis in MR patients prior to and after mitral valve repair (MVR) surgery. The ALIVE trial is a single center, prospective pilot study investigating LA fibrosis in patients suffering from MR in the absence of AF (identifier NCT05345730). In total, 20 participants will undergo a CMR scan including 3D late gadolinium enhancement (LGE) imaging 2 week prior to MVR surgery and at 3 months follow-up. The primary objective of the ALIVE trial is to assess the extent and geometric distribution of LA fibrosis in MR patients and to determine effects of MVR surgery on reversed atrial remodelling. This study will provide novel insights into the pathophysiological mechanism of fibrotic and volumetric atrial (reversed) remodeling in MR patients undergoing MVR surgery. Our results may contribute to improved clinical decision making and patient-specific treatment strategies in patients suffering from MR.

MicroRNA-21 mediated cross-talk between cardiomyocytes and fibroblasts in patients with atrial fibrillation.

Atrial fibrosis represents a major hallmark in disease progression of atrial fibrillation (AF). We have previously shown that circulating microRNA-21 (miR-21) correlates with the extent of left atrial fibrosis in patients undergoing catheter ablation for AF and can serve as a biomarker to predict ablation success. In this study, we aimed to validate the role of miR-21-5p as a biomarker in a large cohort of AF patients and to investigate its pathophysiological role in atrial remodeling. For the validation cohort, we included 175 patients undergoing catheter ablation for AF. Bipolar voltage maps were obtained, circulating miR-21-5p was measured, and patients were followed-up for 12 months including ECG holter monitoring. AF was simulated by tachyarrhythmic pacing of cultured cardiomyocytes, the culture medium was transferred to fibroblast, and fibrosis pathways were analysed. 73.3% of patients with no/minor LVAs, 51.4% of patients with moderate LVAs and only 18.2% of patients with extensive LVAs were in stable sinus rhythm (SR) 12 months after ablation (p < 0.01). Circulating miR-21-5p levels significantly correlated with the extent of LVAs and event-free survival. In-vitro tachyarrhythmic pacing of HL-1 cardiomyocytes resulted in an increased miR-21-5p expression. Transfer of the culture medium to fibroblasts induced fibrosis pathways and collagen production. The HDAC1 inhibitor mocetinostat was found to inhibit atrial fibrosis development. We validated miR-21-5p as a biomarker that reflects the extent of left atrial fibrosis in AF patients. Furthermore, we found that miR-21-5p is released in-vitro from cardiomyocytes under tachyarrhythmic conditions and stimulates fibroblasts in a paracrine mode to induce collagen production.

Extent of Left Atrial Fibrosis Correlates with Descending Aorta Proximity at 3D Late Gadolinium Enhancement Cardiac MRI in Patients with Atrial Fibrillation.

To determine whether the distance between the descending aorta and left atrial (LA) wall correlates with the amount of fibrosis quantified in the posterior left inferior pulmonary vein (LIPV) area of the LA in patients with atrial fibrillation (AF). In this retrospective study, patients with AF underwent cardiac MRI in sinus rhythm prior to a pulmonary vein isolation procedure (July 2018 to February 2020). The mean distance (distancemean) and shortest distance (distanceshort) between the descending aorta and the LA wall were measured on three-dimensional (3D) contrast-enhanced MR angiograms; distancemean was defined as the average of five measurements at different levels between the descending aorta and the LA wall. The extent of LA fibrosis, both global fibrosis and regional fibrosis within the LIPV area, was derived from postprocessed, 3D, late gadolinium-enhanced images. Associations between the extent of fibrosis and the proximity of the descending aorta were analyzed by using correlative and multivariable analyses. A total of 47 (mean age, 60 years ± 8 [standard deviation]; 31 men) patients were included for analysis. The extent of fibrosis in the posterior LIPV area was correlated with the distancemean (r s = -0.48; P < .01) and distanceshort (r s = -0.49; P < .01). Patients with a short distance between the descending aorta and LA wall (defined as a distanceshort < 2 mm) had a higher percentage of fibrosis in the posterior LIPV area than patients with a distanceshort greater than 2 mm (38.7% ± 22.7 vs 21.2% ± 17.8; P < .01). The distance between the descending aorta and LA was correlated with the extent of quantified fibrosis within the posterior LIPV area.Keywords: MRI, Cardiac, Left Atrium Supplemental material is available for this article. © RSNA, 2022.

Classification of Left Atrial Diseased Tissue Burden Determined by Automated Voltage Analysis Predicts Outcomes after Ablation for Atrial Fibrillation.

Background The burden and persistence of atrial fibrillation (AF) have been associated with the presence and extent of left atrial (LA) fibrosis. Recent reports have implicated an association between the extent of LA fibrosis and the outcome of pulmonary vein isolation (PVI). We aimed to analyse the value of an automated scar quantification method in the prediction of success following PVI. Methods One hundred and nine consecutive patients undergoing PVI for paroxysmal or persistent AF were included in our observational study with a 2-year follow-up. Prior to PVI, patients underwent high-definition LA electroanatomical mapping, and scar burden was quantified by automated software (Voltage Histogram Analysis, CARTO 3, Biosense Webster), then classified into 4 subgroups (Dublin Classes I-IV). Recurrence rates were analysed on and off antiarrhythmic drug therapy (AAD), respectively. Results The overall success rate was 74% and 67% off AAD at 1- and 2-year follow-up, respectively. Patients with Dublin Class IV had significantly lower success rates (p = 0.008, off AAD). Dublin Class IV (OR = 2.27, p = 0.022, off AAD) and the presence of arrhythmia in the blanking period (OR = 3.28, p = 0.001, off AAD) were the only significant predictors of recurrence. The use of AAD did not affect these results. Conclusions We propose a classification of low voltage areas based on automated quantification by software during 3D mapping prior to PVI. Patients with high burden of low voltage areas (>31% of <0.5 mV, Dublin Class IV) have a higher risk of recurrence following PVI. Information gathered during electroanatomical mapping may have important prognostic value.

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.

Is the extent of left atrial fibrosis associated with body mass index in patients undergoing pulmonary vein isolation for atrial fibrillation?

Left atrial (LA) fibrosis is associated with a higher rate of recurrence of atrial fibrillation (AF) after pulmonary vein isolation (PVI). Body mass index (BMI) is strongly associated with the prevalence of AF, but there is insufficient data about the association between BMI and LA fibrosis. The aim of the study was to examine the association between LA fibrosis and BMI in patients with AF undergoing PVI. In 114 patients an electro-anatomical voltage map was created using the CARTO 3 three-dimensional system before PVI. The total fibrosis area (voltage criteria ≤0.5 mV), percentage, and the number of fibrotic areas were calculated. A general linear model was used to determine the differences in BMI with confounders between groups of patients with differing extents of fibrosis and numbers of focuses. Advanced fibrosis was found in 53 (47%) patients, in up to 9 areas with a median of 2 and an interquartile range (IQR) of 0-3. The median total fibrotic area was 27.3 cm2 with an IQR of 0.1-30.3 cm2. Patients were stratified by percentage of fibrotic area: <5%, 5%-20%, 20%-35%, and above 35%; no significant difference in mean BMI was found between the groups (P = 0.57). When stratified by the number of fibrotic areas (0, 1, 2, and ≥3 fibrotic areas), no difference in BMI was noted between the groups (P = 0.67). Fibrosis of the LA, as the strongest predictor of AF recurrence after PVI, does not correlate with BMI in patients with AF where PVI is indicated.

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

BackgroundAtrial fibrillation (AF) is associated with profound structural and functional changes in the atria. 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.MethodsPatients with paroxysmal and persistent AF (n = 105) underwent CMR in sinus rhythm. LA global reservoir strain, conduit strain and contractile strain were derived from cine CMR images using CMR feature tracking. The extent of LA fibrosis was assessed from 3D LGE images. Healthy subjects underwent CMR and served as controls (n = 19).ResultsSignificantly lower LA reservoir strain, conduit strain and contractile strain were found in AF patients, as compared to healthy controls (− 15.9 ± 3.8% vs. − 21.1 ± 3.6% P < 0.001, − 8.7 ± 2.7% vs. − 12.6 ± 2.5% P < 0.001 and − 7.2 ± 2.3% vs. − 8.6 ± 2.2% P = 0.02, respectively). 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 (− 15.0 ± 3.9% vs. − 16.9 ± 3.3%, P = 0.02 and − 7.9 ± 2.7% vs. − 9.5 ± 2.6%, P = 0.01, respectively). In contrast, no difference was found for LA contractile strain (− 7.1 ± 2.4% vs. − 7.4 ± 2.3%, P = 0.55).ConclusionsImpaired LA reservoir and conduit strain are present in AF patients with extensive atrial fibrosis. Future studies are needed to examine the biologic nature of this association and possible therapeutic implications.

Quantification of Left Atrial Fibrosis in Patients After Pulmonary Vein Isolation Using the Second-Generation Cryoballoon

Left atrial (LA) fibrosis is associated with a poor outcome after atrial fibrillation (AF) ablation. This study examined the extent of low-voltage areas in patients with recurrence of atrial tachyarrhythmia (ATA) after CB-based pulmonary vein isolation (PVI).Sixty patients (mean age 67 ± 10 years, n = 32 female; n = 34 paroxysmal AF) who received radiofrequency redo-procedure due to recurrence of ATA within 6 months after CB-based PVI were included. A point-by point 3D-map was performed, and low-voltage sites were delineated based on bipolar voltage < 0.5 mV. The extent of fibrosis was categorized as stage A (0-10% of the LA wall), stage B (10-30%), stage C (30-50%), and stage D (> 50%).The median area of LA low-voltage sites was 28.9 (9; 50.3) cm2, corresponding to 17.4 (6; 30.6) % of the LA wall surface. 17/60 (28.3%) patients were categorized as fibrosis stage A, 21/60 (35%) as stage B, 18/60 (30%) as stage C, and 4/60 (6.7%) as stage D. Patient age and LA diameter were associated with more pronounced LA fibrosis; the extent of LA fibrosis was significantly higher in patients with LA tachycardia (LAT) during redo-procedures (P < 0.01), and ablation of linear lesions was more often performed (P < 0.01).In patients after CB2-based PVI, expanded LA tissue fibrosis was associated with the occurrence of LAT and more extensive LA ablation during redo-procedures.

Atrial fibrillation is not associated with altered left atrial microRNA expression profile in ischemic end-stage human heart failure

Abstract Introduction In patients with chronic heart failure (CHF) left ventricular dysfunction results in elevated left atrial (LA) pressure, triggering pathological atrial remodelling and atrial fibrillation (AF). Nevertheless, it has been reported that some patients with CHF remain in sinus rhythm (SR) despite of the pathological structural alterations (e.g. dilation and fibrosis) of the LA. Of particular interest, data is scarce regarding the molecular explanation for the observed variability in AF development among CHF patients. Recent studies have indicated that alterations in microRNA (miRNA) expression might contribute to the pathogenesis of AF. However, the majority of previous studies focusing on miRNA expression compared healthy LA with SR to pathologically remodelled, dilated LA with AF. Consequently, whether dysregulation of miRNA expression directly contribute to AF and not only to pathological LA remodelling has not been tested before. Purpose The present study aimed to investigate miRNA expression in comparably remodelled LA from end-stage CHF patients with permanent AF (CHF-AF) or SR (CHF-SR). Methods LA samples were collected from male, non-diabetic, ischemic end-stage CHF patients undergoing heart transplantation (n=24). Patients were carefully selected to avoid any differences in age (55±2 vs. 54±2 years, CHF-AF vs. CHF-SR, n.s.), ejection fraction ([EF]: 22.5±1.8 vs. 23.3±2.5%, CHF-AF vs. CHF-SR, n.s.) LA diameters (longitudinal LA diameter: 56±4 vs. 48±5mm.; CHF-AF vs. CHF-SR, n.s.; horizontal LA diameter: 61±2 vs. 54±3, CHF-AF vs. CHF-SR, n.s.) and NYHA stage. As a molecular marker of atrial load, the mRNA expression of atrial natriuretic peptide (ANP) was measured with qRT-PCR. The extent of left atrial fibrosis was assessed on picrosirius red stained histological sections. Global LA miRNA expression profiling (including the measurement of 800 human miRNA) was carried out using a commercially available kit. Results LA mRNA expression of ANP was comparable between the AF-CHF and the SR-CHF groups, suggesting that atrial load occurred to the same level in the two experimental groups. Furthermore, no differences could be observed in the extent of atrial collagen content between the AF-CHF and the SR-CHF groups (collagen area: 20.3±1.3% vs. 23.9±3.1%, n.s.), providing evidence that fibrotic remodelling had occurred to a similar magnitude. The high-throughput miRNA measurement revealed no differences in atrial miRNA expression between the two study groups. Conclusion The present study provides evidence for the first time that AF is not associated with different LA miRNA expression in end-stage CHF patients with comparable level of LA dilatation, ANP expression (atrial load) and interstitial fibrosis. Based on these findings, the potential of miRNA-based therapeutic interventions might be limited in AF patients with ischemic end-stage CHF. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): NVKP_16-1-2016-0017

The association of growth differentiation factor 15 (GDF-15) level with extent of left atrial fibrosis in patients with nonvalvular atrial fibrillation

Aim To study the relationship between the serum level of growth differentiation factor 15 (GDF-15) and clinical and functional characteristics and severity of left atrial (LA) fibrosis in patients with nonvalvular atrial fibrillation (AF).Material and methods The study included 87 patients with nonvalvular AF (62 patients with paroxysmal AF and 25 patients with persistent AF) aged 27 to 72 years (mean age, 56.9±9.2 years, 32 women). 85 % of these patients had arterial hypertension (AH), 33 % had AH and ischemic heart disease, and 12.6 % had isolated AF and were hospitalized for primary catheter ablation. General clinical evaluation, echocardiography, laboratory tests including measurement of GDF-15 and NT-proBNP concentrations in blood were performed. As a surrogate substrate of LA fibrosis during the electroanatomical voltage mapping, the area of low-voltage (&lt;0.5 mV) zones in LA was calculated, including the total LA fibrosis area (Sf, cm2) and a percentage of fibrosis of the total LA area (Sf%).Results Median concentration of GDF-15 was 767.5 [590.0; 951.0] pg /ml. The GDF-15 level positively correlated with age, presence and severity of AH and chronic heart failure, body mass index, and degree of obesity, CHA2DS2 VASc score, level of NT-proBNP, and LA fibrosis area (Sf and Sf%) and negatively correlated with the indexes of left ventricular diastolic function, e' septal and e' lateral. The area of fibrosis increased with increasing GDF-15 concentrations divided into quartiles; Sf% exceeded 20 % at GDF-15 levels higher than median. After a comparative analysis of patients with Sf% ≤20 % and &gt;20 %, statistically significantly different variables were included into a stepwise logistic regression analysis. Two independent predictors of LA fibrosis &gt;20% were identified: a concentration of GDF-15 higher than median (odd ratio (OR), 3.318, 95 % confidence interval (CI): 1.184-9.298) and LA volume index (OR, 1.079, 95 % CI: 1.014-1.147). According to results of the ROC analysis, the area under the curve (AUC) was 0.762 (p=0.000), the model specificity was 72.3 %, sensitivity was 72.4 %, and the prediction accuracy was 72.4 %.Conclusion Blood levels of GDF-15 were associated with the presence and severity of major risk factors for AF and the area of LA fibrosis. In this study, a level of GDF-15 above the median and the LA volume index were independent predictors of LA fibrosis &gt; 20% of the LA area.

P457Incidence of LA fibrosis and substrate-based AF ablation success rates in HF patients

Abstract Funding Acknowledgements The author(s) received no specific funding for this work. Background In heart failure (HF) patients, sinus rhythm maintenance after catheter ablation for atrial fibrillation (AF) is mandatory to achieve better long-term outcome. Presence of left atrial (LA) fibrosis significantly attenuates ablation success rates. Incidence of LA fibrosis and the effect of an individualized substrate-based ablation concept on rhythm outcome in HF patients with AF is unclear. Methods This study investigated 103 patients (64 years, 69% men) with persistent AF (79%) and left ventricular (LV) dysfunction (EF 33% IQR [25; 38]) undergoing first time AF ablation. Identification of LA fibrosis and selection of ablation strategy were based on sinus rhythm voltage mapping. All patients received pulmonary vein isolation (PVI). LA fibrosis ablation was individualized by (i) homogenization of small areas, (ii) linear lesions connecting fibrosis and anatomical obstacles and (iii) linear lesions isolating large fibrotic areas. Rhythm outcome was measured by continuous device monitoring (AF detection ≥ 6 min) or Holter-ECG. A total post-procedural AF burden &amp;lt; 0.1% was defined as successful rhythm control. Results LA fibrosis in the overall cohort, in paroxysmal and persistent AF patients was detected in 39/103 (38%), 6/22 (27%) and 33/81 (41%), respectively. After 11 ± 5 months and 1.2 procedures/patient, freedom from AF recurrence was similar between patients with and without LA fibrosis (33/39 (84%) vs. 54/64 (84%); p = 0.485). With continuous monitoring, 73/87 (84%) patients recorded a total AF burden &amp;lt; 0.1%. There was no significant difference in AF burden outcome between patients with and without LA fibrosis (3.1% SD ±17.4 vs. 2.2% SD ±8.1; p = 0.4). No correlation between presence or extent of LA fibrosis and AF burden was found; p = 0.299. Conclusion A substantial number of HF patients with AF have no evidence of LA fibrosis. Among HF patients with LA fibrosis, individualized substrate-based AF ablation beyond PVI was able to achieve similar ablation success.

Atrial Fibrosis: Translational Considerations for the Management of AF Patients.

Fibrosis plays a fundamental role in the initiation and maintenance of AF, mainly due to enhanced automaticity and anisotropy-related re-entry. The identification and quantification of atrial fibrosis is achieved either preprocedurally by late gadolinium enhancement MRI or intraprocedurally using electroanatomic voltage mapping. The presence and extent of left atrial fibrosis among AF patients may influence relevant decision making regarding the need for anticoagulation, the adoption of rate versus rhythm control and mainly the type of ablation strategy that will be followed during interventional treatment. Several types of individualised substrate modifications targeting atrial fibrotic areas have been proposed, although their impact on patient outcome needs to be further investigated in adequately powered prospective randomised controlled clinical trials.

Noninvasive assessment of left atrial fibrosis. Correlation between echocardiography, biomarkers, and electroanatomical mapping.

Left atrial (LA) fibrosis promotes atrial fibrillation (AF), may predict poor radiofrequency catheter ablation (RFCA) outcome, and may be assessed invasively using electroanatomical mapping (EAM). Speckle tracking echocardiography (STE) enables quantitative assessment of LA function. The aim was to assess the relationship between LA fibrosis derived from EAM and LA echocardiographic parameters as well as biomarkers of fibrosis in patients with AF. Sixty-six patients (64% males, mean age 56±10) with nonvalvular AF treated with first RFCA were prospectively studied. Seventy-three percent of patients were in sinus rhythm at the time of examination. LA geometry, systolic, and diastolic function were assessed. In STE global, peak atrial longitudinal (PALS) and contractile (PACS) strain were calculated. LA stiffness index (LAs) - the ratio of E/e' to PALS - was assessed. The EAM of LA was build using Carto System before RFCA. Low amplitude potentials area (LAPA) was quantitatively analyzed and expressed as a percentage of LA surface using the cut-off <0.5mV to detect potential sites of fibrosis. The serum concentrations of MMP-9, PIIINP, and TGFβ1were estimated before RFCA. Pearson correlation analysis showed a significant correlation between LA diastolic function parameters: PALS (-0.54, P<.001), LAs (0.65, P<.001), and LAPA in patients who were in sinus rhythm. Also LA volume significantly correlated with LAPA (0.44, P<.002). None of biomarkers correlated with LAPA. Left atrial diastolic parameters derived from STE correlate well with the extent of LA fibrosis. Thus, STE may be useful in the noninvasive assessment of LA fibrosis and selection of candidates for RFCA.

Abstract 20912: The Impact of Mitral Valve Disease on Atrial Fibrillation Ablation Outcome

Introduction: Mitral Valve Disease (MVD) is associated with atrial fibrillation (AF) and can worsen its prognosis. Left Atrial (LA) fibrosis is a known substrate for AF and its extent affects the management. Hypothesis: We hypothesize MVD increases LA fibrosis in AF patients and the chance of AF ablation failure. Secondly, even in patients with low levels of LA fibrosis that are optimal candidates for ablation, presence of MVD still worsens the outcome. Methods: Patients were categorized in two groups: 140 patients had coexisting MVD and AF, and 100 patients AF without MVD. MVD was defined as any dysfunctionality of mitral valve including mitral stenosis, mitral regurgitation, and history of previous mitral valve surgery . LA fibrosis was quantified by Late Gadolinium Enhancement MRI (LGE-MRI). Baseline characteristics were gathered through chart reviewing. Following ablation, patients were followed for median of 71 months for AF recurrence. Results: Patients were 76.4 ± 10.7 years of age in MVD+AF group and 64.2 ± 14.7 in AF group (p &lt; 0.0001). Extent of LA fibrosis was 18.1% ± 9.3 and 10.3% ± 5.3 in MVD+AF and AF group, respectively (p &lt; 0.0001). The result of our statistical model adjusted for possible cofounders showed that coexistence of MVD in AF patients result in presence of 6.4% more LA fibrosis (p &lt; 0.00001) and lowered the chance of remaining AF free after the ablation (recurrence-free ratio of 0.554 vs 0.757 in MVD+AF and AF group respectively, P &lt; 0.05) (Figure 1). In patients with LA fibrosis less than 20% who would be ideal AF ablation candidate, the presence of MVD decreased the chance to remain AF free (0.574 vs 0.775 in MVD+AF and AF respectively, p &lt; 0.05) (Figure 2). Conclusions: MVD increases LA fibrosis in AF patients and the chance of AF recurrence post-ablation.

Serum YKL-40 as a Marker of Left Atrial Fibrosis Assessed by Delayed Enhancement MRI in Lone Atrial Fibrillation.

Assessment of the left atrial (LA) fibrosis by using delayed-enhanced magnetic resonance imaging (DE-MRI) in atrial fibrillation (AF) patients is a pioneering noninvasive method. Serum YKL-40 is a novel marker for inflammation and known to play a role in ongoing tissue fibrosis. However, its role in LA fibrosis is unclear. We aimed to investigate the association of serum YKL-40 with the presence and extent of LA fibrosis. A total of 50 patients with lone paroxysmal AF (62% male; age: 47.2 ± 7.0 years) underwent cardiac DE-MRI according to study protocol. Cardiac DE-MRI at 1.5 Tesla scanner was used to quantify LA fibrosis. Serum YKL-40 levels and clinical and echocardiographic data were recorded in all participants. DE-MRI revealed any degree of LA fibrosis in 31 (62%) patients. Median serum YKL-40 was significantly higher (P = 0.008) and left venticular ejection fraction was lower (P = 0.047) in patients with LA fibrosis as compared to patients without LA fibrosis. Extent of LA fibrosis was significantly correlated with age, duration of AF history, serum C-reactive protein, and serum YKL-40 levels. Only log (YKL-40) level was found as independent predictor for the presence of LA fibrosis (odds ratio: 1.626, P = 0.022). Multivariate linear regression analysis pointed out that duration of AF history (β = 0.330, P = 0.003) and serum log (YKL-40) levels (β = 0.546, P < 0.001) were significantly and independently associated with the extent of LA fibrosis. Higher levels of serum YKL-40 are associated with the presence and more extensive LA fibrosis in patients with lone AF. As a marker of inflammation, serum YKL-40 may also be used as an indicator for the degree of LA fibrosis.

Left atrial volume, congestive heart failure, and obesity are associated with extent of left atrial fibrosis by late gadolinium enhancement

Background The cardiovascular MRI late gadolinium enhancement (LGE) sequence has developed as a tool to evaluate fibrosis in the atrial walls. LA remodelling and fibrosis is theorized to precede the onset of and to increase with the persistence of AF. Pathological studies have demonstrated that other cardiac diseases are associated with LA fibrosis regardless of the presence of AF. Identifying conditions associated with LA LGE in the general population could be important for risk stratification of atrial fibrosis and AF development in patients with such comorbidities. This study aims to identify common clinical conditions associated with greater LA LGE.

The association of pre-existing left atrial fibrosis with clinical variables in patients referred for catheter ablation of atrial fibrillation.

INTRODUCTIONAtrial fibrillation (AF) recurrence after ablation is associated with left atrial (LA) fibrosis on late gadolinium enhanced (LGE) magnetic resonance imaging (MRI). We sought to determine pre-ablation, clinical characteristics that associate with the extent of LA fibrosis in patients undergoing catheter ablation for AF.METHODS AND RESULTSConsecutive patients presenting for catheter ablation of AF were enrolled and underwent LGE-MRI prior to initial AF ablation. The extent of fibrosis as a percentage of total LA myocardium was calculated in all patients prior to ablation. The cohort was divided into quartiles based on the percentage of fibrosis. Of 60 patients enrolled in the cohort, 13 had <5% fibrosis (Group 1), 15 had 5–7% fibrosis (Group 2), 17 had 8–13% fibrosis (Group 3), and 15 had 14–36% fibrosis (Group 4). The extent of LA fibrosis was positively associated with time in continuous AF, and the presence of persistent or longstanding persistent AF. However, no statistically significant difference was observed in the presence of comorbid conditions, age, BMI, LA volume, or family history of AF among the four groups. After adjusting for diabetes and hypertension in a multivariable linear regression model, paroxysmal AF remained independently and negatively associated with the extent of fibrosis (−4.0 ± 1.8, P = 0.034).CONCLUSIONThe extent of LA fibrosis in patients undergoing AF ablation is associated with AF type and time in continuous AF. Our results suggest that the presence and duration of AF are primary determinants of increased atrial LGE.

Usefulness of Atrial Deformation Analysis to Predict Left Atrial Fibrosis and Endocardial Thickness in Patients Undergoing Mitral Valve Operations for Severe Mitral Regurgitation Secondary to Mitral Valve Prolapse

In patients with severe mitral regurgitation (MR) referred for cardiac surgery, left atrial (LA) remodeling and enlargement are accompanied by mechanical stress, mediated cellular hypertrophy, and interstitial fibrosis that finally lead to LA failure. Speckle tracking echocardiography is a novel non-Doppler-based method that allows an objective quantification of LA myocardial deformation, becoming useful for LA functional analysis. We conducted a study to evaluate the relation between the traditional and novel atrial indexes and the extent of ultrastructural alterations, obtained from patients with severe MR who were undergoing surgical correction of the valvular disease. The study population included 46 patients with severe MR, referred to our echocardiographic laboratory for a diagnostic examination before cardiac surgery. The global peak atrial longitudinal strain (PALS) was measured in all subjects by averaging all atrial segments. LA tissue samples were obtained from all patients. Masson's trichrome staining was performed to assess the extent of the fibrosis. The LA endocardial thickness was measured. A close negative correlation between the global PALS and grade of LA myocardial fibrosis was found (r=-0.82, p <0.0001), with poorer correlations for the LA indexed volume (r= 0.51, p= 0.01), LA ejection fraction (r= 0.61, p= 0.005), and E/E' ratio (0.14, p= NS). Of these indexes, global PALS showed the best diagnostic accuracy to detect LA fibrosis (area under the curve 0.89), and it appears to be a strong and independent predictor of LA fibrosis. Furthermore, we also demonstrated an inverse correlation between the global PALS and LA endocardial thickness (r=-0.66, p= 0.0001). In conclusion, in patients with severe MR referred for cardiac surgery, impairment of LA longitudinal deformation, as assessed by the global PALS, correlated strongly with the extent of LA fibrosis and remodeling.