Fibrotic Atrial Cardiomyopathy Research Articles

Characterization of conduction recovery and atrial electrophysiological properties after pulmonary vein isolation using pulsed field ablation

Abstract Background Pulsed field ablation (PFA) is a relatively new technology for isolation of pulmonary veins in patients with atrial fibrillation (AF). Data addressing reasons for recurrent atrial fibrillation despite primarily successful pulmonary vein isolation (PVI) using PFA are scarce, due to an up to date limited number of patients treated this way. Objective The aim of this study was to analyze electrophysiological characteristics of reconduction and / or left atrial substrate of patients referred to our center for Re-Do procedures for recurrent AF after an initial PVI using PFA. Methods 90 patients (mean age 66±9 years, 69 male (77%)) had been treated in our center from November 2021 to July 2023 with PVI using PFA. 9 (10%) of these patients were referred for Re-Do procedures. These were performed by radiofrequency ablation (RFA) using Carto system including high density mapping and high power / short duration (HPSD) ablation. We analyzed location of PV reconnection and low voltage areas (LVA) in the left atria. Results 7 out of 9 patients (77%) presented with reconnections of pulmonary veins. In one patient a single vein showed reconduction (RSPV), in 5 patients 2 veins were conducting (1x LSPV, 3x LIPV, 1 left sided common os (LCo), 1x RSPV, 3x RIPV). None of the patients showed 3 or 4 reconnected veins. Areas of reconduction in each vein were: LSPV 1x ridge, 1x posterior; LIPV 1x posterior, 1x anterior and posterior; LCo 1x posterior, RSPV 1x anterior, 2x carina, 1x anterior and posterior; RIPV 1x complete, 2x carina. In 7 patients a fibrotic atrial cardiomyopathy (FACM) was diagnosed via high density mapping of LVA’s. In 2 of these patients all 4 pulmonary veins were chronically isolated after the initial PVI. All patients except one (very small anterior LVA) with FACM ≥1 were treated with additional linear or encircling lesions according to the individual extent of the fibrotic areas. 2 patients had no LVA’s detectable. In one of those 2 patients 2 veins had reconnected. The other patient had chronically isolated veins (no proof of dormant conduction with adenosine) and no detectable non-PV-triggers under isoprenaline. Conclusion In the population of patients undergoing PVI using PFA in our center, only 10% had clinically relevant recurrences leading to the necessity of a Re-Do procedure. Most patients (77%) in this setting had reconnections of pulmonary veins. There is a tendency of posterior reconnections of the left pulmonary veins and reconnections of the carina of the right pulmonary veins, but the number of patients is too small to clearly define predilection sites that have to be paid attention to when using PFA. Additionally, left atrial substrate is an important problem in patients with recurrent AF despite primarily successful PVI and has to be considered and thoroughly addressed in Re-Do procedures.Reconnection of LSPV and anterior LVAAblation of RSPV and LSPV (posterior)

Interatrial Block, Bayés Syndrome, Left Atrial Enlargement, and Atrial Failure

Interatrial block (IAB) is defined by the presence of a P-wave ≥120 ms. Advanced IAB is diagnosed when there is also a biphasic morphology in inferior leads. The cause of IAB is complete block of Bachmann’s bundle, resulting in retrograde depolarization of the left atrium from areas near the atrioventricular junction. The anatomic substrate of advanced IAB is fibrotic atrial cardiomyopathy. Dyssynchrony induced by advanced IAB is frequently a trigger and maintenance mechanism of atrial fibrillation (AF) and other atrial arrhythmias. Bayés syndrome is characterized by the association of advanced IAB with atrial arrhythmias. This syndrome is associated with an increased risk of stroke, dementia, and mortality. Advanced IAB frequently produces an alteration of the atrial architecture. This atrial remodeling may promote blood stasis and hypercoagulability, triggering the thrombogenic cascade, even in patients without AF. In addition, atrial remodeling may ultimately lead to mechanical dyssynchrony and enlargement. Atrial enlargement is usually the result of prolonged elevation of atrial pressure due to various underlying conditions such as IAB, diastolic dysfunction, left ventricular hypertrophy, valvular heart disease, hypertension, and athlete’s heart. Left atrial enlargement (LAE) may be considered present if left atrial volume indexed to body surface is > 34 mL/m2; however, different cut-offs have been used. Finally, atrial failure is a global clinical entity that includes any atrial dysfunction that results in impaired cardiac performance, symptoms, and decreased quality of life or life expectancy.

Optimizing fibrosis detection: a comparison of electroanatomical mapping and late enhancement gadolinium magnetic resonance imaging.

Fibrotic atrial cardiomyopathy plays an important role in determining the outcome of ablation in patients with atrial fibrillation (AF). Two main methods are being used for the evaluation of fibrosis: voltage-based high-density (HD) electroanatomical mapping (EAM) and late gadolinium enhancement MRI (LGE-MRI). The comparability between both methods in detecting fibrosis has not been systematically investigated. LGE-MRIs of the left atrium (LA) were performed in 21 patients. LA-fibrosis was evaluated using a custom-designed software generating a 3D-model of the LA. HD-electroanatomical maps were recorded in each patient. After processing the maps and the MRI models by excluding the mitral valve, pulmonary veins, and the left atrial appendage, the LGE areas were measured and compared to the low voltage areas (LVA) in the HD maps using three different cutoff values of 0.5 mV, 0.7 mV, and 1.0 mV. The analysis revealed significant differences between EAM and LGE-MRI in assessing LA-fibrosis at 0.5-mV (for anterior and posterior walls) and 1.0-mV cutoffs (for anterior and posterior wall and septum). However, no significant differences were found between EAM and LGE-MRI when using a 0.7-mV cutoff for all the investigated areas. A voltage cutoff of 0.7 mV provided the best correlation between EAM and LGE MRI for detecting left atrial fibrosis. It supports the idea that a 0.5-mV cutoff may underestimate fibrosis, as areas with local signal voltages between 0.6 and 0.8 mV could also show LGE on MRI. Further research is needed to determine the ideal voltage cutoff for detecting left atrial fibrosis.

Left atrial conduction times and regional velocities in persistent atrial fibrillation patients with and without fibrotic atrial cardiomyopathy

Despite the progress in understanding left atrial substrate and arrhythmogenesis, only little is known about conduction characteristics in atrial fibrillation patients with various stages of fibrotic atrial cardiomyopathy (FACM). This study evaluates left atrial conduction times and conduction velocities based on high-density voltage and activation maps in sinus rhythm (CARTO®3 V7) of 53 patients with persistent atrial fibrillation (LVEF 60% (55–60 IQR), LAVI 39 ml/m2 (31–47 IQR), LApa 24 ± 6 cm2). Measurements were made in low voltage areas (LVA ≤ 0.5 mV) and normal voltage areas (NVA ≥ 1.5 mV) at the left atrial anterior and posterior walls. Maps of 28 FACM and 25 no FACM patients were analyzed (19 FACM I/II, 9 FACM III/IV, LVA 14 ± 11 cm2). Left atrial conduction time averaged to 110 ± 24 ms but was shown to be prolonged in FACM (119 ms, + 17%) when compared to no FACM patients (101 ms, p = 0.005). This finding was pronounced in high-grade FACM (III/IV) (133 ms, + 31.2%, p = 0.001). In addition, the LVA extension correlated significantly with the left atrial conduction time (r = 0.56, p = 0.002). Conduction velocities were overall slower in LVA than in NVA (0.6 ± 0.3 vs. 1.3 ± 0.5 m/s, -51%, p < 0.001). Anterior conduction appeared slower than posterior, which was significant in NVA (1 vs. 1.4 m/s, -29%, p < 0.001) but not in LVA (0.6 vs. 0.8 m/s, p = 0.096). FACM has a significant influence on left atrial conduction characteristics in patients with persistent atrial fibrillation. Left atrial conduction time prolongs with the grade of FACM and the quantitative expanse of LVA up to 31%. LVAs show a 51% conduction velocity reduction compared to NVA. Moreover, regional conduction velocity differences are present in the left atrium when comparing anterior to posterior walls. Our data may influence individualized ablation strategies.

Myosin light-chain 4 gene-transfer attenuates atrial fibrosis while correcting autophagic flux dysregulation

ObjectivesTo determine the role of MYL4 regulation of lysosomal function and its disturbance in fibrotic atrial cardiomyopathy. BackgroundWe have previously demonstrated that the atrial-specific essential light chain protein MYL4 is required for atrial contractile, electrical, and structural integrity. MYL4 mutation/dysfunction leads to atrial fibrosis, standstill, and dysrhythmia. However, the underlying pathogenic mechanisms remain unclear. Methods and resultsRats subjected to knock-in of a pathogenic MYL4 mutant (p.E11K) developed fibrotic atrial cardiomyopathy. Proteome analysis and single-cell RNA sequencing indicate enrichment of autophagy pathways in mutant-MYL4 atrial dysfunction. Immunofluorescence and electron microscopy revealed undegraded autophagic vesicles accumulated in MYL4p.E11K rat atrium. Next, we identified that dysfunctional MYL4 protein impairs autophagy flux in vitro and in vivo. Cardiac lysosome positioning and mobility were regulated by MYL4 in cardiomyocytes, which affected lysosomal acidification and maturation of lysosomal cathepsins. We then examined the effects of MYL4 overexpression via adenoviral gene-transfer on atrial cardiomyopathy induced by MYL4 mutation: MYL4 protein overexpression attenuated atrial structural remodeling and autophagy dysfunction. ConclusionsMYL4 regulates autophagic flux in atrial cardiomyocytes via lysosomal mobility. MYL4 overexpression attenuates MYL4 p.E11K induced fibrotic atrial cardiomyopathy, while correcting autophagy and lysosomal function. These results provide a molecular basis for MYL4-mutant induced fibrotic atrial cardiomyopathy and identify a potential biological-therapy approach for the treatment of atrial fibrosis.

Electrophysiological insights into left atrial conduction times and regional velocities in atrial fibrillation patients with and without fibrotic atrial cardiomyopathy

Abstract Background Although considerable progress has been made in understanding the process of arrhythmogenesis in atrial fibrillation (AF) patients and the role of atrial substrate, little is known about atrial conduction characteristics in different grades of fibrotic atrial cardiomyopathy (FACM) and specific left atrial (LA) regions. Purpose The aim of this study was to evaluate left atrial conduction times (LACT) and -velocities (CV) in electroanatomical high density maps during sinus rhythm in AF patients with and without signs of atrial fibrosis. Methods Before radiofrequency catheter ablation electroanatomical high density mapping was performed in 41 AF patients (n=38 persistent, n=3 paroxysmal) using a 10-polar circular mapping catheter and the CARTO3 V7 navigation system (Biosense Webster, Diamond Bar, CA). We evaluated the size of low voltage areas (LVA ≤0.5mV), LACTs and local CVs at the anterior and posterior wall in low voltage areas and normal voltage areas (NVA ≥1.5mV). The latter were specifically calculated in the direction of wave-front propagation (coherent algorithm) by using 3-dimensional coordinates and local activation times of triads of sites. Results 20 FACM and 21 non-FACM maps were analysed (1823±1031 points, n=16 low grade FACM I+II, n=4 high grade FACM III+IV, EF 57.24±6,18%, LAVI 43.01±15,63 ml/m2). The mean total size of LVA in FACM patients was 12.06 cm2 (anterior wall 9.51 cm2, posterior wall 2.55 cm2). LACT was 109.15±25.30 ms in our AF population, whereby LACT was shown to be longer (118.79ms, +18%) in FACM patients compared to patients without substrate (100.40 ms, p=0.01), particularly pronounced in high grade FACM (III–IV) (146 ms, +46%, p=0.001). The extension of LVA fairly strong correlated with LACT duration (Spearman ρ= 0.76). Conduction velocities in LVA revealed significantly lower (−55%) than those in NVA (0.61±0.11m/s vs. 1.34±0.30m/s, p=0.000). When comparing the anterior to the posterior wall, anterior conduction appeared slower than posterior conduction, which was significant in NVA (−12%, 1.02 vs. 1.16 m/s, p=0.0053) and failed to reach statistical significance in LVA (−11.6%, 0.61 vs. 0.069 m/s, p=0.39). See Figure 1 and Table 1 for more clinical and electrophysiological characteristics in FACM vs. non FACM patients. Conclusion Total LACT is significantly prolonged in FACM patients and seems to correlate with LVA size. Compared to areas with a normal bipolar voltage (≥1.5mV) LVAs (≤0.5mV) show a 55% CV reduction. Furthermore, regional CVs were shown to differ between the anterior and the posterior LA wall. Those findings might have an impact on developing substrate-based ablation strategies in catheter ablation of FACM patients. Funding Acknowledgement Type of funding sources: None.

Genetic findings in patients with primary fibrotic atrial cardiomyopathy

Primary fibrotic atrial cardiomyopathy (PF-ACM) is a novel type of cardiomyopathy characterized by primary atrial fibrosis with arrhythmogenicity and increased stroke risk without ventricular myocardium involvement. However, genetic analysis regarding PF-ACM and genotype–phenotype correlations is lacking. A cohort of PF-ACM patients was recruited and followed up. Whole-exome sequencing (WES) was applied, and genes were screened using a cardiovascular disease (CVD)-related gene panel. Echocardiography and cardiac magnetic resonance (CMR) were performed. The pathogenicity of the identified mutations was evaluated using in silico analysis. Thirty-three unrelated patients were referred for WES. Thirty-three rare variants of 19 CVD-related genes were identified in 21 patients, with 10 patients harboring more than one variation. TTN was the most frequent gene observed. Further analysis demonstrated that variations in sarcomeric (SV) or non-sarcomeric (NSV) genes were found in 16 and 10 patients, respectively. Patients carrying variants regardless of SV or NSV had larger left atrial dimensions determined by echo and larger left atrium areas determined by CMR. There was no discrepancy in disease severity between SV carriers and NSV carriers. Our genetic investigation into PF-ACM has identified several genetic culprits, providing further insight into its underlying pathophysiology and emphasizing a potential role for genetic testing for this condition.

Abstract 11178: Non-Invasive Identification of Fibrotic Atrial Cardiomyopathy with Neural Networks Based on 642,400 12-Lead Ecgs from an Extensive Cohort Simulation Study

The clinical picture of fibrotic atrial cardiomyopathy is caused by a partial replacement of atrial myocardial tissue with fibrotic substrate. Being subject to electrical and structural remodeling processes, the substrate provides the necessary properties for the maintenance of atrial fibrillation and could thus be a good risk marker. We hypothesize that the P waves in the 12-lead ECG present a non-invasive and cost-effective tool to quantify the extent of atrial fibrosis as an alternative to state-of-the-art approaches. Our virtual patient cohort comprised a combination of 80 atrial, 25 thoracic geometries and 27 rotation angle variations of the atria. For each atrial model, 10 stages of fibrosis were defined by replacing different fractions of the myocardial volume with fibrotic tissue patches exhibiting remodeled ionic and conduction velocity properties. Conducting electrophysiological simulations in sinus rhythm on each model combination with one to three different healthy baseline conduction velocities yielded 642,400 synthetic ECGs. P wave duration, dispersion, peak-to-peak amplitudes and terminal force in V1 were calculated and served, together with atrial volumes and torso sizes, as an input for a regression neural network to estimate the volume fraction of atrial fibrosis. The root mean square error between the ground truth and the estimated extent of fibrosis was 8.74% left atrial fibrotic volume. Based on the regression results, a distinction between the healthy and the diseased cohorts was possible with an accuracy of 99.01%, a sensitivity of 99.57% and a specificity of 62.38%. In conclusion, we have gauged the potential of the 12-lead ECG for estimating fibrotic atrial volume fractions in an extensive cohort simulation study comprising both, functional and anatomical inter-subject variability. As a next step, the methods need to be validated with clinical data for which robust feature extraction algorithms are required.

Detection of left atrial fibrosis in LGE-MRI and high-density electroanatomical mapping: finding a threshold for the best match

Abstract Background Fibrotic atrial cardiomyopathy plays an important role in determining the outcome of ablation in patients with atrial fibrillation (AF). Two main methods are being used for the evaluation of fibrosis: voltage based high-density (HD) electroanatomical mapping (EAM) and late gadolinium enhancement MRI (LGE-MRI). The comparability between both methods in detecting fibrosis has not been systematically investigated. Method LGE-MRIs of the left atrium (LA) were performed in 21 patients (pts). The extent and distribution of fibrosis were evaluated using a custom-designed software generating a 3D model of the LA. HD-electroanatomical maps were recorded in each patient using a 3D mapping software (CARTO3, Biosense Webster). The MRI-3D-model of the LA was then integrated in the 3D mapping system. After processing the HD maps and the MRI models by excluding the mitral valve, pulmonary veins and the left atrial appendage, the atrium was then divided into three independent areas: anterior and posterior wall, and intra-atrial-septum. The LGE areas were then measured using the 3D surface measurement tool. These were then compared to the low voltage areas (LVA) measured in the HD maps using three different cut-off values of 0.5 mV, 0.7 mV, and 1.0 mV. Results In MRI 5 pts had no significant fibrosis (fibrotic area ≤1 cm2). 16 pts showed fibrosis on the anterior wall (7.3 cm2±6.2 cm2). 15 pts showed fibrosis at the septum (5 cm2±2.9 cm2) and 9 pts showed fibrosis on the posterior wall (3.9 cm2±2.5 cm2). Using EAM with a cut-off voltage value of 0.7 mV, 3 pts had no fibrosis. 15 pts showed fibrosis on the anterior wall (7.7 cm2±6.8 cm2). 16 pts showed fibrosis at the septum (5.3 cm2±4.1 cm2) and 8 patient showed fibrosis on the posterior wall (3.5 cm2±1.8 cm2). Using a lower voltage cut-off value of 0.5 mV, fibrosis was evident in less patients with smaller fibrotic areas in LA. Whereas when using a cut-off value of 1.0 mV more patients showed a greater extent of the LA fibrosis. We found significant differences between the two methods (MRI vs. 3D-mapping) when using a cut-off value of 0.5 mV (Wilcoxon, p&amp;lt;0.001 for the anterior and posterior wall and the septum). A cut-off value of 1.0 mV also showed significant differences on the anterior and posterior walls (Wilcoxon, p&amp;lt;0.001). When using a cut-off value of 0.7 mV we did not find a significant difference between the two groups (Wilcoxon, p=0.365) with a correlation coefficient of 0.97 (Pearson; p&amp;lt;0.001) for the anterior wall, 0.69 (Pearson; p=0.007) for the posterior wall, and 0.81 (Pearson; p=0.002) for the septum. Conclusion A cut-off value of 0.7 mV in EAM correlated best with the findings in LGE-MRI. The currently used predefined cut-off value of 0.5 mV in EAM may lead to an underestimation of the actual extent of the fibrosis. Increasing the voltage cut-off value towards 0.7 mV may therefore lead to a better characterisation of fibrotic atrial cardiomyopathy. Funding Acknowledgement Type of funding sources: None.

Non-Invasive and Quantitative Estimation of Left Atrial Fibrosis Based on P Waves of the 12-Lead ECG-A Large-Scale Computational Study Covering Anatomical Variability.

The arrhythmogenesis of atrial fibrillation is associated with the presence of fibrotic atrial tissue. Not only fibrosis but also physiological anatomical variability of the atria and the thorax reflect in altered morphology of the P wave in the 12-lead electrocardiogram (ECG). Distinguishing between the effects on the P wave induced by local atrial substrate changes and those caused by healthy anatomical variations is important to gauge the potential of the 12-lead ECG as a non-invasive and cost-effective tool for the early detection of fibrotic atrial cardiomyopathy to stratify atrial fibrillation propensity. In this work, we realized 54,000 combinations of different atria and thorax geometries from statistical shape models capturing anatomical variability in the general population. For each atrial model, 10 different volume fractions (0–45%) were defined as fibrotic. Electrophysiological simulations in sinus rhythm were conducted for each model combination and the respective 12-lead ECGs were computed. P wave features (duration, amplitude, dispersion, terminal force in V1) were extracted and compared between the healthy and the diseased model cohorts. All investigated feature values systematically in- or decreased with the left atrial volume fraction covered by fibrotic tissue, however value ranges overlapped between the healthy and the diseased cohort. Using all extracted P wave features as input values, the amount of the fibrotic left atrial volume fraction was estimated by a neural network with an absolute root mean square error of 8.78%. Our simulation results suggest that although all investigated P wave features highly vary for different anatomical properties, the combination of these features can contribute to non-invasively estimate the volume fraction of atrial fibrosis using ECG-based machine learning approaches.

Coexistence of sinus bradycardia and junctional tachycardia in a patient with fibrotic atrial cardiomyopathy

A 65-year-old woman was referred for catheter ablation in the treatment of persistent tachycardia after surgery for atrial fibrillation and mitral regurgitation. Bipolar voltage mapping of both atria revealed that severe and extensive atrial fibrosis isolated the sinoatrial node from the atrioventricular junction and led to the coexistence of sinus bradycardia and persistent junctional tachycardia.

What every clinician should know about Bayés syndrome.

Bayés syndrome is a new clinical entity, characterized by the association of advanced interatrial block (IAB) on surface electrocardiogram with atrial fibrillation (AF) and other atrial arrhythmias. This syndrome is associated with an increased risk of stroke, dementia, and mortality. Advanced IAB is diagnosed by the presence of a P-wave ≥ 120ms with biphasic morphology (±) in inferior leads. The cause of IAB is complete Bachmann bundle blockade, leading to retrograde depolarization of the left atrium from areas near the atrioventricular junction. The anatomic substrate of advanced IAB is fibrotic atrial cardiomyopathy. Dyssynchrony induced by advanced IAB is a trigger and maintenance mechanism of AF. This alteration of the atrial architecture produces atrial remodeling, blood stasis and hypercoagulability, triggering the thrombogenic cascade. The presence of advanced IAB, even in patients without documented atrial arrhythmias, has also been associated with AF, stroke, dementia, and mortality. However, in these patients, there is no evidence to support the use of anticoagulation. Therefore, in patients with advanced IAB, a proactive search for AF is recommended.

Left Atrial Structural Remodelling in Non-Valvular Atrial Fibrillation: What Have We Learnt from CMR?

Left atrial structural, functional and electrical remodelling are linked to atrial fibrillation (AF) pathophysiology and mirror the phrase “AF begets AF”. A structurally remodelled left atrium (LA) is fibrotic, dysfunctional and enlarged. Fibrosis is the hallmark of LA structural remodelling and is associated with increased risk of stroke, heart failure development and/or progression and poorer catheter ablation outcomes with increased recurrence rates. Moreover, increased atrial fibrosis has been associated with higher rates of stroke even in sinus-rhythm individuals. As such, properly assessing the fibrotic atrial cardiomyopathy in AF patients becomes necessary. In this respect, late-gadolinium enhancement cardiac magnetic resonance (LGE-CMR) imaging is the gold standard in imaging myocardial fibrosis. LA structural remodelling extension offers both diagnostic and prognostic information and influences therapeutic choices. LGE-CMR scans can be used before the procedure to better select candidates and to aid in choosing the ablation technique, during the procedure (full CMR-guided ablations) and after the ablation (to assess the ablation scar). This review focuses on imaging several LA structural remodelling CMR parameters, including size, shape and fibrosis (both extension and architecture) and their impact on procedure outcomes, recurrence risk, as well as their utility in relation to the index procedure timing.

Incidence of Atrial Fibrosis in Non-Valvular Atrial Fibrillation Patients and its Impact on Recurrence after Pulmonary Vein Antral Isolation.

Atrial fibrillation (AF) is the most common sustained arrhythmia; it affects 1%-2% of the general population [1]. Many studies demonstrated an association between atrial fibrosis and AF [2]. There is increasing evidence that even in patients with lone AF; the AF is an arrhythmic manifestation of a structural atrial disease which has been described as fibrotic atrial cardiomyopathy [3]. It is unknown whether the presence of atrial fibrosis has any impact on post pulmonary vein antrum isolation outcome. This study aims to determine the incidence of atrial fibrosis in patients with non-valvular AF and its impact on recurrence after pulmonary vein antrum isolation. This study included twenty eight consecutive patients referred for first-time pulmonary vein antrum isolation for the treatment of symptomatic recurrent non-valvular AF not responding to medical treatment, Isolation of the pulmonary veins antra was performed using three dimensional electroanatomical mapping, detailed voltage map was done in the right and left atrium, before ablation and Low-voltage zones were identified. Follow up of the patients was done for 6 months after the procedure to detect recurrence of AF. Left atrium fibrosis was present in 6 (21.4%) cases, right atrium fibrosis was present only in 1 (3.6%) case and recurrence of atrial fibrillation after 6 months occurred in 12 (42.9%) cases. AF burden was significantly higher in the recurrence group [50.33 ±19.7 (48) (hour/month)] as compared to no recurrence group [29.5 ± 6.99 (32) (hour/month)] with P-value 0.002 and the incidence of left atrium fibrosis was significantly higher in the recurrence group as compared to no recurrence group with P-value 0.024. The only significant predictors of recurrence were the presence of left atrium fibrosis (OR 10.71, 95% CI 1.05 to 109.78; P=0.046) and AF burden (OR 1.14, 95% CI 1.02 to 1.27; P=0.023). The only significant predictor of the presence of left atrium fibrosis was AF burden (OR 1.06, 95% CI 1.01 to 1.13; P=0.031). The presence of the atrial fibrosis in the left atrium is an independent predictor of atrial fibrillation recurrence after pulmonary vein antrum isolation after 6 months without left atium substrate modification.

Atrial remodeling and metabolic dysfunction in idiopathic isolated fibrotic atrial cardiomyopathy

BackgroundIdiopathic isolated fibrotic atrial cardiomyopathy (IIF-ACM) is a novel subtype of cardiomyopathy characterized by atrial fibrosis that does not involve the ventricular myocardium and is associated with significant atrial tachyarrhythmia. The mechanisms underlying its pathogenesis are unknown. MethodsAtrium samples were obtained from 3 patients with IIF-ACM via surgical intervention. Control samples were consisted of 3 atrium biopsies from patients with congenital heart disease and normal sinus rhythm, matched for gender, age and basic clinical characteristics. Comparative histology, immunofluorescence staining, electron microscopy and proteomics analyses were carried out to explore the unique pathogenesis of IIF-ACM. ResultsIIF-ACM atria displayed disordered myofibrils, profound fibrosis and mitochondrial damages compared to the control atria. Proteomics profiling identified metabolic pathways as the most profound changes in IIF-ACM. ConclusionsOur study suggested that metabolic changes in the atrial myocardium caused mitochondrial oxidative stress and potential cell damage, which further led to atrial fibrosis and myofibril disorganization, the characteristic phenotype of IIF-ACM.

Idiopathic isolated fibrotic atrial cardiomyopathy underlies unexplained scar-related atrial tachycardia in younger patients.

Unexplained scar-related atrial tachycardia (AT) has been frequently encountered in clinical practice. We hypothesized that idiopathic, isolated fibrotic atrial cardiomyopathy (ACM) underlies this rhythm disorder. This study was aimed to characterize the underlying substrate and to explore the aetiology of this unexplained scar-related AT. Twenty-six (11 men, aged 46 ± 13 years) of 52 non-surgical scar-related AT patients identified by three-dimensional voltage mapping were enrolled in this prospective observational study. Multimodality image examinations (echocardiography, cardiac magnetic resonance, 99Tc single-photon emission computed tomography), ventricular voltage mapping, and intracardiac pressure curve recording ruled out ventricular involvement. Catheter ablation was acutely successful for all the patients, and pacemaker implantation was performed in seven patients who presented sinus node dysfunction or atrial standstill after termination of the AT. In three patients with multiple AT recurrences, the diseased areas of the right atrium were resected and dechannelled via mini-invasive surgical interventions. Histological examinations revealed profound fibrosis without amyloidosis or adipose deposition. Viral and familial investigations yielded negative results. Fibrosis progression over a median of 45 (5-109) months of follow-up manifested as atrial arrhythmia recurrence in seven patients and atrial lead non-capture due to newly developed atrial standstill in two patients. Two patients suffered four ischaemic stroke events before receiving anticoagulation treatment. Isolated, fibrotic ACM may underlie the idiopathic scar-related ATs. This novel cardiomyopathy has unique clinical characteristics with high morbidity including stroke and warrants specific therapeutic strategies. Further investigations are required to determine the aetiology and mechanism.

Catheter ablation of atrial fibrillation with box isolation of fibrotic areas: Lessons on fibrosis distribution and extent, clinical characteristics, and their impact on long-term outcome.

The BIFA concept (box isolation of fibrotic areas) supplementing pulmonary vein isolation (PVI) was implemented in atrial fibrillation (AF) patients with fibrotic atrial cardiomyopathy (FACM) to improve catheter ablation outcomes. Ninety-two patients with FACM underwent PVI + BIFA. We investigated patient characteristics (58 persistent/34 paroxysmal, 68±8 years, LA 44±7 mm, CHA2 DS2 -VASc 2.6±1.3, FACM I: 15.2%, II: 53.3%, III: 26.1%, IV: 5.4%), periprocedural data concerning fibrosis extent/distribution, and their impact on outcome. Based on severe fibrosis areas (SFAs) of 13.5±13.9 cm2 detected by voltage mapping, 1.4±0.5 boxes (n=1-3, 2.2-35.3 cm2 ) were applied in the left atrium. With higher grade FACM, SFAs increased and maximum voltage decreased (I/IV: 6.29/3.18 mV). Anterior (ant.) SFAs were found to be more common and larger than posterior (post.) SFAs (58.3% vs. 42.6%, ant. 8.0±8.0 vs. post. 4.7±6.8 cm2 ). In 40 of 92 (43%) patients, both atrial walls were affected with rare cases of solely post. fibrosis (6 of 92, 6.6%). Women (39 of 92, 42%) showed FACM III+IV more often than men (P = 0.022) and can still present paroxysmal while persistent males are more likely to have FACM I-II. Single and multiple procedure (1.2/patient) success was 69% and 83% after 16±8 months with an unfavorable impact of large SFA size, both-sided fibrosis and reduced maximum voltage, independently of patient characteristics and AF type. FACM patients are a challenging AF subgroup for catheter ablation. Women seem to show FACM III+IV more often than men. The distribution of left atrial fibrosis is variable but more pronounced anteriorly. Atrial disease is characterized by SFA size but also maximum voltage reduction, both with implications on ablation outcome. Using BIFA, success rates of patients without fibrosis can be approached but are limited in FACM III+IV.

Sinus Node and Atrial Arrhythmias.

Although sinus node dysfunction (SND) and atrial arrhythmias frequently coexist and interact, the putative mechanism linking the 2 remain unclear. Although SND is accompanied by atrial myocardial structural changes in the right atrium, atrial fibrillation (AF) is a disease of variable interactions between left atrial triggers and substrate most commonly of left atrial origin. Significant advances have been made in our understanding of the genetic and pathophysiologic mechanism underlying the development and progression of SND and AF. Although some patients manifest SND as a result of electric remodeling induced by periods of AF, others develop progressive atrial structural remodeling that gives rise to both conditions together. The treatment strategy will thus vary according to the predominant disease phenotype. Although catheter ablation will benefit patients with predominantly AF and secondary SND, cardiac pacing may be the mainstay of therapy for patients with predominant fibrotic atrial cardiomyopathy. This contemporary review summarizes current knowledge on sinus node pathophysiology with the broader goal of yielding insights into the complex relationship between sinus node disease and atrial arrhythmias.

Prediction of atrial fibrillation development and progression: Current perspectives.

Atrial fibrillation (AF) is the most common arrhythmia in clinical practice. Several conventional and novel predictors of AF development and progression (from paroxysmal to persistent and permanent types) have been reported. The most important predictor of AF progression is possibly the arrhythmia itself. The electrical, mechanical and structural remodeling determines the perpetuation of AF and the progression from paroxysmal to persistent and permanent forms. Common clinical scores such as the hypertension, age ≥ 75 years, transient ischemic attack or stroke, chronic obstructive pulmonary disease, and heart failure and the congestive heart failure, hypertension, age ≥ 75 years, diabetes mellitus, stroke/transient ischemic attack, vascular disease, age 65-74 years, sex category scores as well as biomarkers related to inflammation may also add important information on this topic. There is now increasing evidence that even in patients with so-called lone or idiopathic AF, the arrhythmia is the manifestation of a structural atrial disease which has recently been defined and described as fibrotic atrial cardiomyopathy. Fibrosis results from a broad range of factors related to AF inducing pathologies such as cell stretch, neurohumoral activation, and oxidative stress. The extent of fibrosis as detected either by late gadolinium enhancement-magnetic resonance imaging or electroanatomic voltage mapping may guide the therapeutic approach based on the arrhythmia substrate. The knowledge of these risk factors may not only delay arrhythmia progression, but also reduce the arrhythmia burden in patients with first detected AF. The present review highlights on the conventional and novel risk factors of development and progression of AF.

Abstract 15018: Idiopathic, Isolated, Fibrotic Atrial Cardiomyopathy: An Overlooked Type of Cardiomyopathy

Introduction Myocardium fibrosis is a hallmark of cardiomyopathy and a proposed substrate for cardiac arrhythmias. Nevertheless, fibrosis of atrial myocardium and fibrotic atrial cardiomyopathy has not been systemically addressed. Hypothesis We hypothesized that idiopathic, isolated, fibrotic atrial cardiomyopathy (IIF-ACM) is a specific cardiomyopathy, which is characterized by atrial fibrosis and related arrhythmias. Methods In the past 8 years, 34 patients (male 13, mean age 46.5±13.3 yrs) were diagnosed with IIF-ACM based on: 1) clinical evaluation; 2) cardiac image examination; and 3) electro-anatomic mapping detected atrial scarring. Serum biomarkers of collagen metabolism and cardiomyopathy-related genetic screening were performed. Tissue pathology and virus detections were done for two patients. Results During clinical evaluation, electric silent areas were detected in all patients by intra-cardiac electro-anatomical mapping. Among 34 patients, 26 presented with atrial tachycardia (AT), 5 with sick sinus syndrome (SSS) and 3 with atrial standstill. 5 AT patients further developed SSS during the correction of AT by radiofrequency ablation. Late gadolinium-enhancement cardiovascular magnet resonance showed mild to severely dilated atria, without bilateral ventricular scarring or functional impairment. Serum biomarkers of collagen screening demonstrated significant increased collagen synthesis than collagen degradation in IIF-ACM patients. Cardiomyopathy-related genetic screening depicted no clinically relevant mutation. Histological studies showed global fibrosis of atria (Fig. 1). Conclusions We systemically reported 34 patients with IIF-ACM, which is characterized by atrial scarring and relevant arrhythmias. Ventricular functions of note were preserved in all patients. However, the underlying etiology of IIF-ACM remains to be investigated.