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Background and Purpose: A recent paradigm shift in proarrhythmic risk assessment suggests that the integration of clinical, non-clinical, and computational evidence can be used to reach a comprehensive understanding of the proarrhythmic potential of drug candidates. While current computational methodologies focus on predicting the incidence of proarrhythmic events after drug administration, the objective of this study is to predict concentration-response relationships of QTc as a clinical endpoint., Experimental Approach: Full heart computational models reproducing human cardiac populations were created to predict the concentration-response relationship of changes in the QT interval as recommended for clinical trials. The concentration-response relationship of the QT-interval prolongation obtained from the computational cardiac population was compared against the relationship from clinical trial data for a set of well-characterized compounds: moxifloxacin, dofetilide, verapamil, and ondansetron., Key Results: Computationally derived concentration-response relationships of QT interval changes for three of the four drugs had slopes within the confidence interval of clinical trials (dofetilide, moxifloxacin and verapamil) when compared to placebo-corrected concentration-ΔQT and concentration-ΔQT regressions. Moxifloxacin showed a higher intercept, outside the confidence interval of the clinical data, demonstrating that in this example, the standard linear regression does not appropriately capture the concentration-response results at very low concentrations. The concentrations corresponding to a mean QTc prolongation of 10 ms were consistently lower in the computational model than in clinical data. The critical concentration varied within an approximate ratio of 0.5 (moxifloxacin and ondansetron) and 1 times (dofetilide, verapamil) the critical concentration observed in human clinical trials. Notably, no other in silico methodology can approximate the human critical concentration values for a QT interval prolongation of 10 ms., Conclusion and Implications: Computational concentration-response modelling of a virtual population of high-resolution, 3-dimensional cardiac models can provide comparable information to clinical data and could be used to complement pre-clinical and clinical safety packages. It provides access to an unlimited exposure range to support trial design and can improve the understanding of pre-clinical-clinical translation., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Elem Biotech owns the commercial rights to Alya, the computational finite element solver employed in this study. However, any other commercial or academic finite element solver could be employed to reproduce this work. Elem Biotech owns the commercial rights to Alya, the solver employed in this study., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Following the 3 R's principles of animal research-replacement, reduction, and refinement-a high-performance computational framework was produced to generate a platform to perform human cardiac in-silico clinical trials as means to assess the pro-arrhythmic risk after the administrations of one or combination of two potentially arrhythmic drugs. The drugs assessed in this study were hydroxychloroquine and azithromycin. The framework employs electrophysiology simulations on high-resolution three-dimensional, biventricular human heart anatomies including phenotypic variabilities, so as to determine if differential QT-prolongation responds to drugs as observed clinically. These simulations also reproduce sex-specific ionic channel characteristics. The derived changes in the pseudo-electrocardiograms, calcium concentrations, as well as activation patterns within 3D geometries were evaluated for signs of induced arrhythmia. The virtual subjects could be evaluated at two different cycle lengths: at a normal heart rate and at a heart rate associated with stress as means to analyze the proarrhythmic risks after the administrations of hydroxychloroquine and azithromycin. Additionally, a series of experiments performed on reanimated swine hearts utilizing Visible Heart ® methodologies in a four-chamber working heart model were performed to verify the arrhythmic behaviors observed in the in silico trials.The obtained results indicated similar pro-arrhythmic risk assessments within the virtual population as compared to published clinical trials (21% clinical risk vs 21.8% in silico trial risk). Evidence of transmurally heterogeneous action potential prolongations after providing a large dose of hydroxychloroquine was found as the observed mechanisms for elicited arrhythmias, both in the in vitro and the in silico models. The proposed workflow for in silico clinical drug cardiotoxicity trials allows for reproducing the complex behavior of cardiac electrophysiology in a varied population, in a matter of a few days as compared to the months or years it requires for most in vivo human clinical trials. Importantly, our results provided evidence of the common phenotype variants that produce distinct drug-induced arrhythmogenic outcomes., (© 2024. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Stroke is the second leading cause of death worldwide. Nearly two-thirds of strokes are produced by cardioembolisms, and half of cardioembolic strokes are triggered by Atrial Fibrillation (AF), the most common type of arrhythmia. A more recent cause of cardioembolisms is Transcatheter Aortic Valve Replacements (TAVRs), which may onset post-procedural adverse events such as stroke and Silent Brain Infarcts (SBIs), for which no definitive treatment exists, and which will only get worse as TAVRs are implanted in younger and lower risk patients. It is well known that some specific characteristics of elderly patients may lower the safety and efficacy of anticoagulation therapy, making it a real urgency to find alternative therapies. We propose a device consisting of a strut structure placed at the base of the treated artery to model the potential risk of cerebral embolisms caused by dislodged debris of varying sizes. This work analyzes a design based on a patented medical device, intended to block cardioembolisms from entering the cerebrovascular system, with a particular focus on AF, and potentially TAVR patients. The study has been carried out in two stages. Both of them based on computational fluid dynamics (CFD) coupled with Lagrangian particle tracking method. The first stage of the work evaluates a variety of strut thicknesses and inter-strut spacings, contrasting with the device-free baseline geometry. The analysis is carried out by imposing flowrate waveforms characteristic of both healthy and AF patients. Boundary conditions are calibrated to reproduce physiological flowrates and pressures in a patient's aortic arch. In the second stage, the optimal geometric design from the first stage was employed, with the addition of lateral struts to prevent the filtration of particles and electronegatively charged strut surfaces, studying the effect of electrical forces on the clots if they are considered charged. Flowrate boundary conditions were used to emulate both healthy and AF conditions. Results from numerical simulations coming form the first stage indicate that the device blocks particles of sizes larger than the inter-strut spacing. It was found that lateral strut space had the highest impact on efficacy. Based on the results of the second stage, deploying the electronegatively charged device in all three aortic arch arteries, the number of particles entering these arteries was reduced on average by 62.6% and 51.2%, for the healthy and diseased models respectively, matching or surpassing current oral anticoagulant efficacy. In conclusion, the device demonstrated a two-fold mechanism for filtering emboli: while the smallest particles are deflected by electrostatic repulsion, avoiding microembolisms, which could lead to cognitive impairment, the largest ones are mechanically filtered since they cannot fit in between the struts, effectively blocking the full range of particle sizes analyzed in this study. The device presented in this manuscript offers an anticoagulant-free method to prevent stroke and SBIs, imperative given the growing population of AF and elderly patients., Competing Interests: DO, MF, ACM and MV are employed by ELEM Biotech. MV is an investor of ELEM Biotech. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Eguzkitza, Oks, Navia, Houzeaux, Butakoff, Fisa, Campoy Millán and Vázquez.)

The aim of this work was to analyze the influence of sex hormones and anatomical details (trabeculations and false tendons) on the electrophysiology of healthy human hearts. Additionally, sex- and anatomy-dependent effects of ventricular tachycardia (VT) inducibility are presented. To this end, four anatomically normal, human, biventricular geometries (two male, two female), with identifiable trabeculations, were obtained from high-resolution, ex-vivo MRI and represented by detailed and smoothed geometrical models (with and without the trabeculations). Additionally one model was augmented by a scar. The electrophysiology finite element model (FEM) simulations were carried out, using O'Hara-Rudy human myocyte model with sex phenotypes of Yang and Clancy. A systematic comparison between detailed vs smooth anatomies, male vs female normal hearts was carried out. The heart with a myocardial infarction was subjected to a programmed stimulus protocol to identify the effects of sex and anatomical detail on ventricular tachycardia inducibility. All female hearts presented QT-interval prolongation however the prolongation interval in comparison to the male phenotypes was anatomy-dependent and was not correlated to the size of the heart. Detailed geometries showed QRS fractionation and increased T-wave magnitude in comparison to the corresponding smoothed geometries. A variety of sustained VTs were obtained in the detailed and smoothed male geometries at different pacing locations, which provide evidence of the geometry-dependent differences regarding the prediction of the locations of reentry channels. In the female phenotype, sustained VTs were induced in both detailed and smooth geometries with RV apex pacing, however no consistent reentry channels were identified. Anatomical and physiological cardiac features play an important role defining risk in cardiac disease. These are often excluded from cardiac electrophysiology simulations. The assumption that the cardiac endocardium is smooth may produce inaccurate predictions towards the location of reentry channels in in-silico tachycardia inducibility studies., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Gonzalez-Martin et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

This work intends to study the effect of aortic annulus eccentricity and leaflet rigidity on the performance, thrombogenic risk and calcification risk in bioprosthetic aortic valve replacements (BAVRs). To address these questions, a two-way immersed fluid-structure interaction (FSI) computational model was implemented in a high-performance computing (HPC) multi-physics simulation software, and validated against a well-known FSI benchmark. The aortic valve bioprosthesis model is qualitatively contrasted against experimental data, showing good agreement in closed and open states. Regarding the performance of BAVRs, the model predicts that increasing eccentricities yield lower geometric orifice areas (GOAs) and higher normalized transvalvular pressure gradients (TPGs) for healthy cardiac outputs during systole, agreeing with in vitro experiments. Regions with peak values of residence time are observed to grow with eccentricity in the sinus of Valsalva, indicating an elevated risk of thrombus formation for eccentric configurations. In addition, the computational model is used to analyze the effect of varying leaflet rigidity on both performance, thrombogenic and calcification risks with applications to tissue-engineered prostheses. For more rigid leaflets it predicts an increase in systolic and diastolic TPGs, and decrease in systolic GOA, which translates to decreased valve performance. The peak shear rate and residence time regions increase with leaflet rigidity, but their volume-averaged values were not significantly affected. Peak solid stresses are also analyzed, and observed to increase with rigidity, elevating risk of valve calcification and structural failure. To the authors' knowledge this is the first computational FSI model to study the effect of eccentricity or leaflet rigidity on thrombogenic biomarkers, providing a novel tool to aid device manufacturers and clinical practitioners., (© 2022 The Authors. International Journal for Numerical Methods in Biomedical Engineering published by John Wiley & Sons Ltd.)

Background: Left ventricular assist devices (LVADs) are implantable pumps that act as a life support therapy for patients with severe heart failure. Despite improving the survival rate, LVAD therapy can carry major complications. Particularly, the flow distortion introduced by the LVAD in the left ventricle (LV) may induce thrombus formation. While previous works have used numerical models to study the impact of multiple variables in the intra-LV stagnation regions, a comprehensive validation analysis has never been executed. The main goal of this work is to present a model of the LV-LVAD system and to design and follow a verification, validation and uncertainty quantification (VVUQ) plan based on the ASME V&V40 and V&V20 standards to ensure credible predictions., Methods: The experiment used to validate the simulation is the SDSU cardiac simulator, a bench mock-up of the cardiovascular system that allows mimicking multiple operation conditions for the heart-LVAD system. The numerical model is based on Alya, the BSC's in-house platform for numerical modelling. Alya solves the Navier-Stokes equation with an Arbitrary Lagrangian-Eulerian (ALE) formulation in a deformable ventricle and includes pressure-driven valves, a 0D Windkessel model for the arterial output and a LVAD boundary condition modeled through a dynamic pressure-flow performance curve. The designed VVUQ plan involves: (a) a risk analysis and the associated credibility goals; (b) a verification stage to ensure correctness in the numerical solution procedure; (c) a sensitivity analysis to quantify the impact of the inputs on the four quantities of interest (QoIs) (average aortic root flow [Formula: see text], maximum aortic root flow [Formula: see text], average LVAD flow [Formula: see text], and maximum LVAD flow [Formula: see text]); (d) an uncertainty quantification using six validation experiments that include extreme operating conditions., Results: Numerical code verification tests ensured correctness of the solution procedure and numerical calculation verification showed a grid convergence index (GCI)95% <3.3%. The total Sobol indices obtained during the sensitivity analysis demonstrated that the ejection fraction, the heart rate, and the pump performance curve coefficients are the most impactful inputs for the analysed QoIs. The Minkowski norm is used as validation metric for the uncertainty quantification. It shows that the midpoint cases have more accurate results when compared to the extreme cases. The total computational cost of the simulations was above 100 [core-years] executed in around three weeks time span in Marenostrum IV supercomputer., Conclusions: This work details a novel numerical model for the LV-LVAD system, that is supported by the design and execution of a VVUQ plan created following recognised international standards. We present a methodology demonstrating that stringent VVUQ according to ASME standards is feasible but computationally expensive., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: AS, MV, BE and CB have acted as consultants for Medtronic PLC related to Medtronic’s HVAD. KMN and VV have an ongoing research study for Abbott, Inc for work on Abbott’s HeartMate III. RG and PP need to include the following statement: “The mention of commercial products, their sources, or their use in connection with material reported herein is not to be construed as either an actual or implied endorsement of such products by the U.S. Department of Health and Human Services”.

Venous-arterial extracorporeal membrane oxygenation (VA-ECMO) treatment for acute cardiogenic shock in patients who also have acute lung injury predisposes development of a serious complication called "north-south syndrome" (NSS) which causes cerebral hypoxia. NSS is poorly characterized and hemodynamic studies have focused on cerebral perfusion ignoring the heart. We hypothesized in NSS the heart would be more likely to receive hypoxemic blood than the brain due to the proximity of the coronary arteries to the aortic annulus. To test this, we conducted a computational fluid dynamics simulation of blood flow in a human supported by VA-ECMO. Simulations quantified the fraction of blood at each aortic branching vessel originating from residual native cardiac output versus VA-ECMO. As residual cardiac function was increased, simulations demonstrated myocardial hypoxia would develop prior to cerebral hypoxia. These results illustrate the conditions where NSS will develop and the relative cardiac function that will lead to organ-specific hypoxia. Illustration of the impact of north-south syndrome on organ-specific oxygen delivery. Patients on VA-ECMO have two sources of blood flow, one from the VA-ECMO circuit and one from the residual cardiac function. When there is no residual cardiac function, all organs are perfused with oxygenated blood. As myocardial recovery progresses, blood supply from the two sources will begin to mix resulting in non-homogeneous mixing and differential oxygenation based upon the anatomical site of branching vessels., (© 2021. The Author(s).)

Importance: Being born small for gestational age (SGA), approximately 10% of all births, is associated with increased risk of cardiovascular mortality in adulthood, but mechanistic pathways are unclear. Cardiac remodeling and dysfunction occur in fetuses SGA and children born SGA, but it is uncertain whether and how these changes persist into adulthood., Objective: To evaluate baseline cardiac function and structure and exercise capacity in young adults born SGA., Design, Setting, and Participants: This cohort study conducted from January 2015 to January 2018 assessed a perinatal cohort born at a tertiary university hospital in Spain between 1975 and 1995. Participants included 158 randomly selected young adults aged 20 to 40 years born SGA (birth weight below the 10th centile) or with intrauterine growth within standard reference ranges (controls). Participants provided their medical history, filled out questionnaires regarding smoking and physical activity habits, and underwent incremental cardiopulmonary exercise stress testing, cardiac magnetic resonance imaging, and a physical examination, with blood pressure, glucose level, and lipid profile data collected., Exposure: Being born SGA., Main Outcomes and Measures: Cardiac structure and function assessed by cardiac magnetic resonance imaging, including biventricular end-diastolic shape analysis. Exercise capacity assessed by incremental exercise stress testing., Results: This cohort study included 81 adults born SGA (median age at study, 34.4 years [IQR, 30.8-36.7 years]; 43 women [53%]) and 77 control participants (median age at study, 33.7 years [interquartile range (IQR), 31.0-37.1 years]; 33 women [43%]). All participants were of White race/ethnicity and underwent imaging, whereas 127 participants (80% of the cohort; 66 control participants and 61 adults born SGA) completed the exercise test. Cardiac shape analysis showed minor changes at rest in right ventricular geometry (DeLong test z, 2.2098; P = .02) with preserved cardiac function in individuals born SGA. However, compared with controls, adults born SGA had lower exercise capacity, with decreased maximal workload (mean [SD], 180 [62] W vs 214 [60] W; P = .006) and oxygen consumption (median, 26.0 mL/min/kg [IQR, 21.5-33.5 mL/min/kg vs 29.5 mL/min/kg [IQR, 24.0-36.0 mL/min/kg]; P = .02). Exercise capacity was significantly correlated with left ventricular mass (ρ = 0.7934; P < .001)., Conclusions and Relevance: This cohort of young adults born SGA had markedly reduced exercise capacity. These results support further research to clarify the causes of impaired exercise capacity and the potential association with increased cardiovascular mortality among adults born SGA.

Statistical shape analysis is a powerful tool to assess organ morphologies and find shape changes associated to a particular disease. However, imbalance in confounding factors, such as demographics might invalidate the analysis if not taken into consideration. Despite the methodological advances in the field, providing new methods that are able to capture complex and regional shape differences, the relationship between non-imaging information and shape variability has been overlooked. We present a linear statistical shape analysis framework that finds shape differences unassociated to a controlled set of confounding variables. It includes two confounding correction methods: confounding deflation and adjustment. We applied our framework to a cardiac magnetic resonance imaging dataset, consisting of the cardiac ventricles of 89 triathletes and 77 controls, to identify cardiac remodelling due to the practice of endurance exercise. To test robustness to confounders, subsets of this dataset were generated by randomly removing controls with low body mass index, thus introducing imbalance. The analysis of the whole dataset indicates an increase of ventricular volumes and myocardial mass in athletes, which is consistent with the clinical literature. However, when confounders are not taken into consideration no increase of myocardial mass is found. Using the downsampled datasets, we find that confounder adjustment methods are needed to find the real remodelling patterns in imbalanced datasets., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests., (Copyright © 2020. Published by Elsevier B.V.)

Two-dimensional representation of 3D anatomical structures is a simple and intuitive way for analysing patient information across populations and image modalities. While cardiac ventricles, especially the left ventricle, have an established standard representation (bull's eye plot), the 2D depiction of the left atrium (LA) remains challenging due to its sub-structural complexity including the pulmonary veins (PV) and the left atrial appendage (LAA). Quasi-conformal flattening techniques, successfully applied to cardiac ventricles, require additional constraints in the case of the LA to place the PV and LAA in the same geometrical 2D location for different cases. Some registration-based methods have been proposed but surface registration is time-consuming and prone to errors when the geometries are very different. We propose a novel atrial flattening methodology where a 2D standardised map of the LA is obtained quickly and without errors related to registration. The LA is divided into five regions which are then mapped to their analogue two-dimensional regions. 67 human left atria from magnetic resonance images (MRI) were studied to derive a population-based template representing the averaged relative locations of the PVs and LAA. The clinical application of our methodology is illustrated on different use cases including the integration of MRI and electroanatomical data.

Aims: Late gadolinium enhancement cardiac magnetic resonance (LGE-CMR) may define left atrial (LA) anatomy and structural remodelling, and facilitate atrial fibrillation (AF) ablation. We aimed to assess the intra- and inter-observer reproducibility and agreement of LGE-CMR parameters with direct application to AF ablation techniques., Methods and Results: One experienced and one non-experienced observer performed complete LGE-CMR data analysis twice, on different days, in 40 randomly selected LGE-CMR examinations [20 performed before ablation (pre-ablation) and 20 performed 3 months after ablation (post-ablation)]. Four additional observers (two experienced and two non-experienced) performed complete LGE-CMR data analysis in a subgroup of 30 patients (15 pre-ablation and 15 post-ablation). All LGE-CMR were performed in sinus rhythm. Intra- and inter-observer reproducibility of LA volume, LA area, and sphericity index (SI) was high: coefficient of variation <10% and intraclass correlation coefficient >0.71. Geometric congruency of repeated reconstruction of LA shape was high: maximal error <5 mm for intra-observer and <8 mm for inter-observer. The precision of scar location increased with extent of scar, and was high (Dice coefficient >0.75) when the scar area was >5 cm2 for a single observer and >15 cm2 for multiple observers. Non-experienced observers performed equally well to experienced observers., Conclusion: Late gadolinium enhancement cardiac magnetic resonance measurements of LA area, volume, and SI were reproducible, and geometric congruency of LA shape was high. Location of scar was precise for scar areas >5 cm2 for single observers and >15 cm2 for multiple observers, regardless of the observers' experience. These results may serve as a reference for future studies on the role for substrate-based AF ablation procedures., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

Aims: We tested the hypothesis that a machine learning (ML) algorithm utilizing both complex echocardiographic data and clinical parameters could be used to phenogroup a heart failure (HF) cohort and identify patients with beneficial response to cardiac resynchronization therapy (CRT)., Methods and Results: We studied 1106 HF patients from the Multicenter Automatic Defibrillator Implantation Trial with Cardiac Resynchronization Therapy (MADIT-CRT) (left ventricular ejection fraction ≤ 30%, QRS ≥ 130 ms, New York Heart Association class ≤ II) randomized to CRT with a defibrillator (CRT-D, n = 677) or an implantable cardioverter defibrillator (ICD, n = 429). An unsupervised ML algorithm (Multiple Kernel Learning and K-means clustering) was used to categorize subjects by similarities in clinical parameters, and left ventricular volume and deformation traces at baseline into mutually exclusive groups. The treatment effect of CRT-D on the primary outcome (all-cause death or HF event) and on volume response was compared among these groups. Our analysis identified four phenogroups, significantly different in the majority of baseline clinical characteristics, biomarker values, measures of left and right ventricular structure and function and the primary outcome occurrence. Two phenogroups included a higher proportion of known clinical characteristics predictive of CRT response, and were associated with a substantially better treatment effect of CRT-D on the primary outcome [hazard ratio (HR) 0.35; 95% confidence interval (CI) 0.19-0.64; P = 0.0005 and HR 0.36; 95% CI 0.19-0.68; P = 0.001] than observed in the other groups (interaction P = 0.02)., Conclusions: Our results serve as a proof-of-concept that, by integrating clinical parameters and full heart cycle imaging data, unsupervised ML can provide a clinically meaningful classification of a phenotypically heterogeneous HF cohort and might aid in optimizing the rate of responders to specific therapies., (© 2018 The Authors. European Journal of Heart Failure © 2018 European Society of Cardiology.)

Pulmonary vein isolation (PVI) is a common procedure for the treatment of atrial fibrillation (AF) since the initial trigger for AF frequently originates in the pulmonary veins. A successful isolation produces a continuous lesion (scar) completely encircling the veins that stops activation waves from propagating to the atrial body. Unfortunately, the encircling lesion is often incomplete, becoming a combination of scar and gaps of healthy tissue. These gaps are potential causes of AF recurrence, which requires a redo of the isolation procedure. Late-gadolinium enhanced cardiac magnetic resonance (LGE-CMR) is a non-invasive method that may also be used to detect gaps, but it is currently a time-consuming process, prone to high inter-observer variability. In this paper, we present a method to semi-automatically identify and quantify ablation gaps. Gap quantification is performed through minimum path search in a graph where every node is a scar patch and the edges are the geodesic distances between patches. We propose the Relative Gap Measure (RGM) to estimate the percentage of gap around a vein, which is defined as the ratio of the overall gap length and the total length of the path that encircles the vein. Additionally, an advanced version of the RGM has been developed to integrate gap quantification estimates from different scar segmentation techniques into a single figure-of-merit. Population-based statistical and regional analysis of gap distribution was performed using a standardised parcellation of the left atrium. We have evaluated our method on synthetic and clinical data from 50 AF patients who underwent PVI with radiofrequency ablation. The population-based analysis concluded that the left superior PV is more prone to lesion gaps while the left inferior PV tends to have less gaps (p < .05 in both cases), in the processed data. This type of information can be very useful for the optimization and objective assessment of PVI interventions., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Aims: Left atrial (LA) fibrosis can be identified by late gadolinium enhancement cardiac magnetic resonance (LGE-CMR) in patients with atrial fibrillation (AF). However, there is limited information about anatomical fibrosis distribution in the left atrium. The aim is to determine whether there is a preferential spatial distribution of fibrosis in the left atrium in patients with AF., Methods and Results: A 3-Tesla LGE-CMR was performed in 113 consecutive patients referred for AF ablation. Images were post-processed and analysed using ADAS-AF software (Galgo Medical), which allows fibrosis identification in 3D colour-coded shells. A regional semiautomatic LA parcellation software was used to divide the atrial wall into 12 segments: 1-4, posterior wall; 5-6, floor; 7, septal wall; 8-11, anterior wall; 12, lateral wall. The presence and amount of fibrosis in each segment was obtained for analysis. After exclusions for artefacts and insufficient image quality, 76 LGE-MRI images (68%) were suitable for fibrosis analysis. Segments 3 and 5, closest to the left inferior pulmonary vein, had significantly higher fibrosis (40.42% ± 23.96 and 25.82% ± 21.24, respectively; P < 0.001), compared with other segments. Segments 8 and 10 in the anterior wall contained the lowest fibrosis (2.54% ± 5.78 and 3.82% ± 11.59, respectively; P < 0.001). Age >60 years was significantly associated with increased LA fibrosis [95% confidence interval (CI) 0.19-8.39, P = 0.04] and persistent AF approached significance (95% CI -0.19% to 7.83%, P = 0.08)., Conclusion: In patients with AF, the fibrotic area is preferentially located at the posterior wall and floor around the antrum of the left inferior pulmonary vein. Age >60 years was associated with increased fibrosis.