Charles Sillett

All Publications

• Representation of women in cardiovascular disease management: a systematic analysis of ESC guidelines. Open heart Lashkarinia, S. S., Lee, A. W., Baptiste, T. M., Barrows, R. K., Sillett, C. P., Rodero, C., Tayal, U., de Marvao, A., Panay, N., Williamson, C., Blomstrom-Lundqvist, C., Haugaa, K., Casadei, B., Maleckar, M. M., Strocchi, M., Niederer, S. A. 2025; 12 (2)

  Abstract

  Sex differences play a critical role in the presentation, progression and treatment outcomes of cardiac diseases. However, historical male predominance in clinical studies has led to disparities in evidence supporting care for both sexes. Clinical guidelines are essential for cardiovascular care, shaping practice and influencing patient outcomes. In this study, we reviewed 34 European Society of Cardiology (ESC) guidelines between 2002 and 2024 to evaluate the representation of women and the inclusion of female-specific recommendations.We compiled 136 gender-related keywords, validated by six clinicians, and quantified their occurrence across guidelines. While our primary analysis focused on female-specific keywords, we also identified male-specific terms as a comparison point to help quantitatively interpret the representation of female-specific terminology in the guidelines. Each guideline underwent independent review by two auditors who used structured questions to assess its sensitivity to female-specific differences in disease presentation, diagnosis, management and treatment.The most frequent terms were 'pregnancy', 'women' and 'sex', with 1768 (17.9%), 1573 (15.9%) and 676 (6.8%) overall repetitions, respectively, contrasted against 'cardiac' (6932 occurrences) as a baseline. Results showed inconsistency in addressing female-specific factors and health considerations in ESC guidelines. We were able to assess the relative frequency of female-specific language and highlight in contrast areas where female representation in cardiovascular guidelines may be insufficient. Most guidelines (24/34) mentioned pregnancy and provided related recommendations, with one of the guidelines entirely dedicated to cardiovascular disease (CVD) in pregnancy (2018) and a new one planned for 2025. Only 10/30 guidelines acknowledged menopause as a CVD risk factor and offered recommendations for clinical practice.These findings highlight the need for systematic integration of female-specific considerations across all guidelines. In the wider context, there is also a need for improved representation of women in clinical trials and for making the available evidence on which the guidelines are based less biased toward men.

  View details for DOI 10.1136/openhrt-2025-003320

  View details for PubMedID 40889952

• Three-dimensional left atrial strain from retrospective gated computed tomography: Comparison with speckle-tracking echocardiography in patients with aortic stenosis. Journal of cardiovascular computed tomography Sillett, C., Androshchuk, V., Long, E., Baptiste, T. M., Strocchi, M., Solis Lemus, J. A., Lee, A. W., Roney, C. H., Rajani, R., Patterson, T., Redwood, S., Niederer, S. A. 2025

  Abstract

  Three-dimensional (3D) left atrial (LA) deformation assessment beyond the two-dimensional (2D) apical views circumvents atrial foreshortening and can be quantified from four-dimensional (4D) retrospective gated computed tomography (CT) using novel feature tracking methods. However, the consistency between CT-derived 3D and echocardiographic 2D peak left atrial longitudinal strain (PALS) has not been reported. We aimed to compare CT-derived 3D and echocardiographic 2D PALS in patients undergoing transcatheter aortic valve implantation (TAVI).Eighty patients (81.8 ​± ​5.8 years, 30 ​% female) who underwent CT and transthoracic echocardiography (TTE) before TAVI were included. CT images were reconstructed at 5 ​% increments over the R-R interval. 4D CT-derived deformation was evaluated using novel feature tracking, from which 2D and 3D PALSCT were measured and compared with 2D PALSTTE.2D PALSTTE and 2D PALSCT measurements were strongly correlated (Pearson coefficient ​= ​0.84) and comparable (mean bias ​= ​-0.8; 95 ​% confidence interval, CI: -1.9 to 0.3), whereas 2D PALSTTE exhibited systematic overestimation compared with 3D PALSCT (mean bias ​= ​-3.6; 95 ​% CI: -4.7 to -2.5; P ​< ​0.001). 3D PALSCT and 2D PALSTTE exhibited comparable correlations with exercise capacity and quality of life scores and prediction of elevated brain natriuretic peptide (area under the curve, AUC: 0.84, 0.79, respectively) and diastolic filling pressures (AUC: 0.65, 0.69, respectively).2D PALSCT and 2D PALSTTE showed good agreement, whereas 2D PALSTTE was systemically larger than 3D PALSCT which may be attributed to atrial foreshortening. 3D PALSCT circumvents limitations of 2D echocardiography and may offer adjunctive evaluation of atrial reservoir function in patients with valvular heart disease.

  View details for DOI 10.1016/j.jcct.2025.08.003

  View details for PubMedID 40846525

• Is regional atrial strain a useful surrogate of regional atrial fibrosis in atrial cardiomyopathy? European heart journal. Imaging methods and practice Lee, A. W., Sillett, C., Solis-Lemus, J. A., Kessler Iglesias, C., Hopman, L. H., Hua, A., Wheen, P., Qayyum, A., Strocchi, M., Roney, C., Booth, T., Ismail, T. F., Chubb, H., Ennis, D. B., Jabbour, A., Fatkin, D., Götte, M. J., Niederer, S. A. 2025; 3 (2): qyaf068

  Abstract

  To determine whether atrial biomechanics measured using 3D regional strain, left atrial volume (LAV), and left atrial emptying fraction (LAEF) are associated with atrial fibrosis in patients with suspected atrial cardiomyopathy.Cardiovascular magnetic resonance (CMR) was performed in atrial fibrillation (AF) patients (n = 47). Healthy volunteer (n = 41) and familial dilated cardiomyopathy (DCM) (n = 31) cohorts were acquired for normalization and validation, respectively. Fibrosis was quantified using late gadolinium enhancement (LGE)-CMR, and 3D regional strain was quantified using feature tracking. Machine learning classifiers were used to classify regional severe fibrosis (>30% LGE enhancement) using regional strain and global measures of atrial anatomy and function. 3D regional strain measures (peak reservoir strain or first/second strain principal component) alone were not associated with regional fibrosis (accuracies ≤ 56.0%) in the AF cohort. Severe fibrosis was found primarily in the lateral (85.1% of AF patients) and posterior (66.0%) regions. In AF patients, the classifier incorporating LAV, LAEF, and regional location was associated with severe regional fibrosis (AUC = 0.86 ± 0.06, accuracy = 79.4 ± 6.2%), while in familial DCM patients, the accuracy was lower (62.8%).There is a distinctive pattern of fibrosis that develops with progression of atrial cardiomyopathy, irrespective of cause. Global measures reflecting overall atrial anatomy (LAV) and function (LAEF), rather than localized regional 3D strain, were associated with severe regional fibrosis. These data suggest that regional atrial 3D strain alone is not a reliable surrogate for severe regional fibrosis.

  View details for DOI 10.1093/ehjimp/qyaf068

  View details for PubMedID 40641661

  View details for PubMedCentralID PMC12242763

• Identification of atrial myopathy and atrial fibrillation recurrence after ablation using 3D left atrial phasic strain from retrospective gated computed tomography. European heart journal. Imaging methods and practice Sillett, C., Razeghi, O., Baptiste, T. M., Lee, A. W., Solis Lemus, J. A., Rodero, C., Roney, C. H., Feng, R., Ganesan, P., Chang, H. J., Clopton, P., Linton, N., Rajani, R., Rogers, A. J., Narayan, S. M., Niederer, S. A. 2025; 3 (1): qyaf027

  Abstract

  Reduced left atrial (LA) mechanical function associates with atrial myopathy and adverse clinical endpoints in atrial fibrillation (AF) patients; however, conventional 2D imaging modalities are limited by atrial foreshortening and sub-optimally capture 3D LA motion.We set out to test the hypothesis that 3D LA motion features from 4D (3D + time) retrospective gated computed tomography (RGCT) associate with AF phenotypes and predict AF recurrence in patients undergoing catheter ablation.Sixty-nine AF patients (60.8 ± 12.2 years, 39% female, 30% non-paroxysmal AF) who were indicated for CT coronary angiography including a RGCT protocol in sinus rhythm prior to ablation were included. We measured 3D LA endocardial motion by optimized 3D feature tracking and calculated 3D global and regional phasic strain and peak strain rates (SRs). AF recurrence was observed in 18 patients (26%) at 1-year. Global reservoir strain (P < 0.05) and contractile strain and SR (both P < 0.01) were reduced in patients with vs. those without recurrent AF. Global and anterior wall contractile SR were more predictive of recurrent AF than LA volume index (area under the curve, AUC: 0.74, 0.77, and 0.68, respectively). Reduced global conduit SR and septal reservoir strain were more strongly associated with non-paroxysmal AF than CHADS2-VASc (AUCs: 0.74, 0.75, and 0.59, respectively).Reduced passive and active 3D LA motion from 4D RGCT associates with more advanced AF and AF recurrence post-ablation, respectively. Future work should extend this approach to larger populations, with new low-radiation CT technologies to widen its applicability.

  View details for DOI 10.1093/ehjimp/qyaf027

  View details for PubMedID 40171523

  View details for PubMedCentralID PMC11959267

• A three-dimensional left atrial motion estimation from retrospective gated computed tomography: application in heart failure patients with atrial fibrillation FRONTIERS IN CARDIOVASCULAR MEDICINE Sillett, C., Razeghi, O., Lee, A. W. C., Solis Lemus, J., Roney, C., Mannina, C., de Vere, F., Ananthan, K., Ennis, D. B., Haberland, U., Xu, H., Young, A., Rinaldi, C. A., Rajani, R., Niederer, S. A. 2024; 11: 1359715

  Abstract

  A reduced left atrial (LA) strain correlates with the presence of atrial fibrillation (AF). Conventional atrial strain analysis uses two-dimensional (2D) imaging, which is, however, limited by atrial foreshortening and an underestimation of through-plane motion. Retrospective gated computed tomography (RGCT) produces high-fidelity three-dimensional (3D) images of the cardiac anatomy throughout the cardiac cycle that can be used for estimating 3D mechanics. Its feasibility for LA strain measurement, however, is understudied.The aim of this study is to develop and apply a novel workflow to estimate 3D LA motion and calculate the strain from RGCT imaging. The utility of global and regional strains to separate heart failure in patients with reduced ejection fraction (HFrEF) with and without AF is investigated.A cohort of 30 HFrEF patients with (n = 9) and without (n = 21) AF underwent RGCT prior to cardiac resynchronisation therapy. The temporal sparse free form deformation image registration method was optimised for LA feature tracking in RGCT images and used to estimate 3D LA endocardial motion. The area and fibre reservoir strains were calculated over the LA body. Universal atrial coordinates and a human atrial fibre atlas enabled the regional strain calculation and the fibre strain calculation along the local myofibre orientation, respectively.It was found that global reservoir strains were significantly reduced in the HFrEF + AF group patients compared with the HFrEF-only group patients (area strain: 11.2 ± 4.8% vs. 25.3 ± 12.6%, P = 0.001; fibre strain: 4.5 ± 2.0% vs. 15.2 ± 8.8%, P = 0.001), with HFrEF + AF patients having a greater regional reservoir strain dyssynchrony. All regional reservoir strains were reduced in the HFrEF + AF patient group, in whom the inferior wall strains exhibited the most significant differences. The global reservoir fibre strain and LA volume + posterior wall reservoir fibre strain exceeded LA volume alone and 2D global longitudinal strain (GLS) for AF classification (area-under-the-curve: global reservoir fibre strain: 0.94 ± 0.02, LA volume + posterior wall reservoir fibre strain: 0.95 ± 0.02, LA volume: 0.89 ± 0.03, 2D GLS: 0.90 ± 0.03).RGCT enables 3D LA motion estimation and strain calculation that outperforms 2D strain metrics and LA enlargement for AF classification. Differences in regional LA strain could reflect regional myocardial properties such as atrial fibrosis burden.

  View details for DOI 10.3389/fcvm.2024.1359715

  View details for Web of Science ID 001198345000001

  View details for PubMedID 38596691

  View details for PubMedCentralID PMC11002108

• Novel Regional Analysis of Left Atrial Strain From Computed Tomography Separates Patients With Persistent versus Paroxysmal Atrial Fibrillation Sillett, C., Razeghi, O., Lee, A., Lemus, J., Roney, C., Ganesan, P., Feng, R., Chubb, H., Nieman, K., Rogers, A. J., Rajani, R. LIPPINCOTT WILLIAMS & WILKINS. 2023

  View details for DOI 10.1161/circ.148.suppl_1.13321

  View details for Web of Science ID 001157891302197

• Evaluation of an open-source pipeline to create patient-specific left atrial models: A reproducibility study. Computers in biology and medicine Solís-Lemus, J. A., Baptiste, T., Barrows, R., Sillett, C., Gharaviri, A., Raffaele, G., Razeghi, O., Strocchi, M., Sim, I., Kotadia, I., Bodagh, N., O'Hare, D., O'Neill, M., Williams, S. E., Roney, C., Niederer, S. 2023; 162: 107009

  Abstract

  This work presents an open-source software pipeline to create patient-specific left atrial models with fibre orientations and a fibrDEFAULTosis map, suitable for electrophysiology simulations, and quantifies the intra and inter observer reproducibility of the model creation. The semi-automatic pipeline takes as input a contrast enhanced magnetic resonance angiogram, and a late gadolinium enhanced (LGE) contrast magnetic resonance (CMR). Five operators were allocated 20 cases each from a set of 50 CMR datasets to create a total of 100 models to evaluate inter and intra-operator variability. Each output model consisted of: (1) a labelled surface mesh open at the pulmonary veins and mitral valve, (2) fibre orientations mapped from a diffusion tensor MRI (DTMRI) human atlas, (3) fibrosis map extracted from the LGE-CMR scan, and (4) simulation of local activation time (LAT) and phase singularity (PS) mapping. Reproducibility in our pipeline was evaluated by comparing agreement in shape of the output meshes, fibrosis distribution in the left atrial body, and fibre orientations. Reproducibility in simulations outputs was evaluated in the LAT maps by comparing the total activation times, and the mean conduction velocity (CV). PS maps were compared with the structural similarity index measure (SSIM). The users processed in total 60 cases for inter and 40 cases for intra-operator variability. Our workflow allows a single model to be created in 16.72 ± 12.25 min. Similarity was measured with shape, percentage of fibres oriented in the same direction, and intra-class correlation coefficient (ICC) for the fibrosis calculation. Shape differed noticeably only with users' selection of the mitral valve and the length of the pulmonary veins from the ostia to the distal end; fibrosis agreement was high, with ICC of 0.909 (inter) and 0.999 (intra); fibre orientation agreement was high with 60.63% (inter) and 71.77% (intra). The LAT showed good agreement, where the median ± IQR of the absolute difference of the total activation times was 2.02 ± 2.45 ms for inter, and 1.37 ± 2.45 ms for intra. Also, the average ± sd of the mean CV difference was -0.00404 ± 0.0155 m/s for inter, and 0.0021 ± 0.0115 m/s for intra. Finally, the PS maps showed a moderately good agreement in SSIM for inter and intra, where the mean ± sd SSIM for inter and intra were 0.648 ± 0.21 and 0.608 ± 0.15, respectively. Although we found notable differences in the models, as a consequence of user input, our tests show that the uncertainty caused by both inter and intra-operator variability is comparable with uncertainty due to estimated fibres, and image resolution accuracy of segmentation tools.

  View details for DOI 10.1016/j.compbiomed.2023.107009

  View details for PubMedID 37301099

  View details for PubMedCentralID PMC10790305

• A systematic review of cardiac in-silico clinical trials. Progress in biomedical engineering (Bristol, England) Rodero, C., Baptiste, T. M., Barrows, R. K., Keramati, H., Sillett, C. P., Strocchi, M., Lamata, P., Niederer, S. A. 2023; 5 (3): 032004

  Abstract

  Computational models of the heart are now being used to assess the effectiveness and feasibility of interventions through in-silico clinical trials (ISCTs). As the adoption and acceptance of ISCTs increases, best practices for reporting the methodology and analysing the results will emerge. Focusing in the area of cardiology, we aim to evaluate the types of ISCTs, their analysis methods and their reporting standards. To this end, we conducted a systematic review of cardiac ISCTs over the period of 1 January 2012-1 January 2022, following the preferred reporting items for systematic reviews and meta-analysis (PRISMA). We considered cardiac ISCTs of human patient cohorts, and excluded studies of single individuals and those in which models were used to guide a procedure without comparing against a control group. We identified 36 publications that described cardiac ISCTs, with most of the studies coming from the US and the UK. In 75% of the studies, a validation step was performed, although the specific type of validation varied between the studies. ANSYS FLUENT was the most commonly used software in 19% of ISCTs. The specific software used was not reported in 14% of the studies. Unlike clinical trials, we found a lack of consistent reporting of patient demographics, with 28% of the studies not reporting them. Uncertainty quantification was limited, with sensitivity analysis performed in only 19% of the studies. In 97% of the ISCTs, no link was provided to provide easy access to the data or models used in the study. There was no consistent naming of study types with a wide range of studies that could potentially be considered ISCTs. There is a clear need for community agreement on minimal reporting standards on patient demographics, accepted standards for ISCT cohort quality control, uncertainty quantification, and increased model and data sharing.

  View details for DOI 10.1088/2516-1091/acdc71

  View details for PubMedID 37360227

  View details for PubMedCentralID PMC10286106

• Applications of multimodality imaging for left atrial catheter ablation. European heart journal. Cardiovascular Imaging Roney, C. H., Sillett, C., Whitaker, J., Lemus, J. A., Sim, I., Kotadia, I., O'Neill, M., Williams, S. E., Niederer, S. A. 2021; 23 (1): 31-41

  Abstract

  Atrial arrhythmias, including atrial fibrillation and atrial flutter, may be treated through catheter ablation. The process of atrial arrhythmia catheter ablation, which includes patient selection, pre-procedural planning, intra-procedural guidance, and post-procedural assessment, is typically characterized by the use of several imaging modalities to sequentially inform key clinical decisions. Increasingly, advanced imaging modalities are processed via specialized image analysis techniques and combined with intra-procedural electrical measurements to inform treatment approaches. Here, we review the use of multimodality imaging for left atrial ablation procedures. The article first outlines how imaging modalities are routinely used in the peri-ablation period. We then describe how advanced imaging techniques may inform patient selection for ablation and ablation targets themselves. Ongoing research directions for improving catheter ablation outcomes by using imaging combined with advanced analyses for personalization of ablation targets are discussed, together with approaches for their integration in the standard clinical environment. Finally, we describe future research areas with the potential to improve catheter ablation outcomes.

  View details for DOI 10.1093/ehjci/jeab205

  View details for PubMedID 34747450

  View details for PubMedCentralID PMC8685603

• Optimisation of Left Atrial Feature Tracking Using Retrospective Gated Computed Tomography Images. Functional imaging and modeling of the heart : ... International Workshop, FIMH ..., proceedings. FIMH Sillett, C., Razeghi, O., Strocchi, M., Roney, C. H., O'Brien, H., Ennis, D. B., Haberland, U., Rajani, R., Rinaldi, C. A., Niederer, S. A. 2021; 12738: 71-83

  Abstract

  Retrospective gated cardiac computed tomography (CCT) images can provide high contrast and resolution images of the heart throughout the cardiac cycle. Feature tracking in retrospective CCT images using the temporal sparse free-form deformations (TSFFDs) registration method has previously been optimised for the left ventricle (LV). However, there is limited work on optimising nonrigid registration methods for feature tracking in the left atria (LA). This paper systematically optimises the sparsity weight (SW) and bending energy (BE) as two hyperparameters of the TSFFD method to track the LA endocardium from end-diastole (ED) to end-systole (ES) using 10-frame retrospective gated CCT images. The effect of two different control point (CP) grid resolutions was also investigated. TSFFD optimisation was achieved using the average surface distance (ASD), directed Hausdorff distance (DHD) and Dice score between the registered and ground truth surface meshes and segmentations at ES. For baseline comparison, the configuration optimised for LV feature tracking gave errors across the cohort of 0.826 ± 0.172mm ASD, 5.882 ± 1.524mm DHD, and 0.912 ± 0.033 Dice score. Optimising the SW and BE hyperparameters improved the TSFFD performance in tracking LA features, with case specific optimisations giving errors across the cohort of 0.750 ± 0.144mm ASD, 5.096 ± 1.246mm DHD, and 0.919 ± 0.029 Dice score. Increasing the CP resolution and optimising the SW and BE further improved tracking performance, with case specific optimisation errors of 0.372 ± 0.051mm ASD, 2.739 ± 0.843mm DHD and 0.949 ± 0.018 Dice score across the cohort. We therefore show LA feature tracking using TSFFDs is improved through a chamber-specific optimised configuration.

  View details for DOI 10.1007/978-3-030-78710-3_8

  View details for PubMedID 35727914

  View details for PubMedCentralID PMC9170531