Publications
463 results found
Balaban G, Halliday B, Bradley P, et al., 2021, Late-gadolinium enhancement interface area and electrophysiological simulations predict arrhythmic events in non-ischemic dilated cardiomyopathy patients, JACC: Clinical Electrophysiology, Vol: 7, Pages: 238-249, ISSN: 2405-5018
BACKGROUND: The presence of late-gadolinium enhancement (LGE) predicts life threatening ventricular arrhythmias in non-ischemic dilated cardiomyopathy (NIDCM); however, risk stratification remains imprecise. LGE shape and simulations of electrical activity may be able to provide additional prognostic information.OBJECTIVE: This study sought to investigate whether shape-based LGE metrics and simulations of reentrant electrical activity are associated with arrhythmic events in NIDCM patients.METHODS: CMR-LGE shape metrics were computed for a cohort of 156 NIDCM patients with visible LGE and tested retrospectively for an association with an arrhythmic composite end-point of sudden cardiac death and ventricular tachycardia. Computational models were created from images and used in conjunction with simulated stimulation protocols to assess the potential for reentry induction in each patient’s scar morphology. A mechanistic analysis of the simulations was carried out to explain the associations. RESULTS: During a median follow-up of 1611 [IQR 881-2341] days, 16 patients (10.3%) met the primary endpoint. In an inverse probability weighted Cox regression, the LGE-myocardial interface area (HR:1.75; 95% CI:1.24-2.47; p=0.001), number of simulated reentries (HR: 1.4; 95% CI: 1.23-1.59; p<0.01) and LGE volume (HR:1.44; 95% CI:1.07-1.94; p=0.02) were associated with arrhythmic events. Computational modeling revealed repolarisation heterogeneity and rate-dependent block of electrical wavefronts at the LGE-myocardial interface as putative arrhythmogenic mechanisms directly related to LGE interface area.CONCLUSION: The area of interface between scar and surviving myocardium, as well as simulated reentrant activity, are associated with an elevated risk of major arrhythmic events in NIDCM patients with LGE and represent novel risk predictors.
Mazzarotto F, Hawley MH, Beltrami M, et al., 2021, Systematic large-scale assessment of the genetic architecture of left ventricular non-compaction reveals diverse aetiologies, Genetics in Medicine, Vol: 23, Pages: 856-864, ISSN: 1098-3600
Purpose: To characterise the genetic architecture of left ventricular non-compaction (LVNC) and investigate the extent to which it may represent a distinct pathology or a secondary phenotype associated with other cardiac diseases.Methods: We performed rare variant association analysis with 840 LVNC cases and 125,748 gnomAD population controls, and compared results to similar analyses on dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM). Results: We observed substantial genetic overlap indicating that LVNC often represents a phenotypic variation of DCM or HCM. In contrast, truncating variants (TV) in MYH7, ACTN2 and PRDM16 were uniquely associated with LVNC and may reflect a distinct LVNC aetiology. In particular, MYH7 TV, generally considered non-pathogenic for cardiomyopathies, were 20-fold enriched in LVNC cases over controls. MYH7 TV heterozygotes identified in the UK Biobank and healthy volunteer cohorts also displayed significantly greater non-compaction compared to matched controls. RYR2 exon deletions and HCN4 transmembrane variants were also enriched in LVNC, supporting prior reports of association with arrhythmogenic LVNC phenotypes.Conclusions: LVNC is characterised by substantial genetic overlap with DCM/HCM but is also associated with distinct non-compaction and arrhythmia aetiologies. These results will enable enhanced application of LVNC genetic testing and help to distinguish pathological from physiological non-compaction.
Harper AR, Goel A, Grace C, et al., 2021, Common genetic variants and modifiable risk factors underpin hypertrophic cardiomyopathy susceptibility and expressivity, Nature Genetics, Vol: 53, Pages: 135-142, ISSN: 1061-4036
Hypertrophic cardiomyopathy (HCM) is a common, serious, genetic heart disorder. Rare pathogenic variants in sarcomere genes cause HCM, but with unexplained phenotypic heterogeneity. Moreover, most patients do not carry such variants. We report a genome-wide association study of 2,780 cases and 47,486 controls that identified 12 genome-wide-significant susceptibility loci for HCM. Single-nucleotide polymorphism heritability indicated a strong polygenic influence, especially for sarcomere-negative HCM (64% of cases; h2g = 0.34 ± 0.02). A genetic risk score showed substantial influence on the odds of HCM in a validation study, halving the odds in the lowest quintile and doubling them in the highest quintile, and also influenced phenotypic severity in sarcomere variant carriers. Mendelian randomization identified diastolic blood pressure (DBP) as a key modifiable risk factor for sarcomere-negative HCM, with a one standard deviation increase in DBP increasing the HCM risk fourfold. Common variants and modifiable risk factors have important roles in HCM that we suggest will be clinically actionable.
Ware J, Tadros R, Francis C, et al., 2021, Shared genetic pathways contribute to risk of hypertrophic and dilated cardiomyopathies with opposite directions of effect, Nature Genetics, Vol: 53, Pages: 128-134, ISSN: 1061-4036
The heart muscle diseases hypertrophic (HCM) and dilated (DCM) cardiomyopathies are leading causes of sudden death and heart failure in young otherwise healthy individuals. We conducted genome-wide association studies (GWAS) and multi-trait analyses in HCM (1,733 cases), DCM (5,521 cases), and nine left ventricular (LV) traits in 19,260 UK Biobank participants with structurally-normal hearts. We identified 16 loci associated with HCM, 13 with DCM, and 23 with LV traits. We show strong genetic correlations between LV traits and cardiomyopathies, with opposing effects in HCM and DCM. Two-sample Mendelian randomization supports a causal association linking increased contractility with HCM risk. A polygenic risk score (PRS) explains a significant portion of phenotypic variability in carriers of HCM-causing rare variants. Our findings thus provide evidence that PRS may account for variability in Mendelian diseases. More broadly, we provide insights into how genetic pathways may lead to distinct disorders through opposing genetic effects.
Hammersley DJ, Jones RE, Mach L, et al., 2021, Cardiovascular Magnetic Resonance in Heritable Cardiomyopathies, HEART FAILURE CLINICS, Vol: 17, Pages: 25-39, ISSN: 1551-7136
Raphael CE, Liew AC, Mitchell F, et al., 2020, Predictors and Mechanisms of Atrial Fibrillation in Patients With Hypertrophic Cardiomyopathy, AMERICAN JOURNAL OF CARDIOLOGY, Vol: 136, Pages: 140-148, ISSN: 0002-9149
- Author Web Link
- Cite
- Citations: 6
Balaban G, Costa CM, Porter B, et al., 2020, 3D Electrophysiological Modeling of Interstitial Fibrosis Networks and Their Role in Ventricular Arrhythmias in Non-Ischemic Cardiomyopathy, IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING, Vol: 67, Pages: 3125-3133, ISSN: 0018-9294
- Author Web Link
- Cite
- Citations: 5
Halliday B, Vazir A, Owen R, et al., 2020, Heart rate as a marker of relapse during withdrawal of heart failure therapy in patients with recovered dilated cardiomyopathy: an analysis from TRED-HF, European-Society-of-Cardiology (ESC) Congress, Publisher: OXFORD UNIV PRESS, Pages: 1057-1057, ISSN: 0195-668X
- Author Web Link
- Cite
- Citations: 1
Zemrak F, Raisi-Estabragh Z, Khanji MY, et al., 2020, Left Ventricular Hypertrabeculation Is Not Associated With Cardiovascular Morbity or Mortality: Insights From the Eurocmr Registry, FRONTIERS IN CARDIOVASCULAR MEDICINE, Vol: 7, ISSN: 2297-055X
- Author Web Link
- Cite
- Citations: 5
Celutkiene J, Pudil R, Lopez-Fernandez T, et al., 2020, Role of cardiovascular imaging in cancer patients receiving cardiotoxic therapies: a position statement on behalf of the Heart Failure Association (HFA), the European Association of Cardiovascular Imaging (EACVI) and the Cardio-Oncology Council of the European Society of Cardiology (ESC), EUROPEAN JOURNAL OF HEART FAILURE, Vol: 22, Pages: 1504-1524, ISSN: 1388-9842
- Author Web Link
- Cite
- Citations: 183
Meyer H, Dawes T, Serrani M, et al., 2020, Genetic and functional insights into the fractal structure of the heart, Nature, Vol: 584, Pages: 589-594, ISSN: 0028-0836
The inner surfaces of the human heart are covered by a complex network of muscular strands that is thought to be a vestigeof embryonic development.1,2 The function of these trabeculae in adults and their genetic architecture are unknown. Toinvestigate this we performed a genome-wide association study using fractal analysis of trabecular morphology as animage-derived phenotype in 18,096 UK Biobank participants. We identified 16 significant loci containing genes associatedwith haemodynamic phenotypes and regulation of cytoskeletal arborisation.3,4 Using biomechanical simulations and humanobservational data, we demonstrate that trabecular morphology is an important determinant of cardiac performance. Throughgenetic association studies with cardiac disease phenotypes and Mendelian randomisation, we find a causal relationshipbetween trabecular morphology and cardiovascular disease risk. These findings suggest an unexpected role for myocardialtrabeculae in the function of the adult heart, identify conserved pathways that regulate structural complexity, and reveal theirinfluence on susceptibility to disease
Sintou A, Mansfield C, Iacob A-O, et al., 2020, Mediastinal lymphadenopathy, class-switched auto-antibodies and myocardial immune-complexes during heart failure in rodents and humans, Frontiers in Cell and Developmental Biology, Vol: 8, Pages: 1-12, ISSN: 2296-634X
Mediastinal lymphadenopathy and auto-antibodies are clinical phenomena during ischemicheart failure pointing to an autoimmune response against the heart. T and B cell have beenconvincingly demonstrated to be activated after myocardial infarction, a prerequisite for thegeneration of mature auto-antibodies. Yet, little is known about the immunoglobulin isotyperepertoire thus pathological potential of anti-heart auto-antibodies during heart failure.We obtained human myocardial tissue from ischemic heart failure patients and inducedexperimental MI in rats. We found that anti-heart autoimmunity persists during heart failure.Rat mediastinal lymph nodes are enlarged and contain active secondary follicles with matureisotype-switched IgG2a B cells. Mature IgG2a auto-antibodies specific for cardiac antigens arepresent in rat heart failure serum, and IgG and complement C3 deposits are evident in heartfailure tissue of both rats and human patients.Previously established myocardial inflammation, and the herein provided proof of B cellmaturation in lymph nodes and myocardial deposition of mature auto-antibodies, provide allthe hallmark signs of an established autoimmune response in chronic heart failure.
Yakupoglu HY, De Robertis F, Prasad S, et al., 2020, Detection of multiple exercise-induced pathophysiological processes in concomitant coronary artery disease and hypertrophic cardiomyopathy by stress echocardiography, European Heart Journal - Case Reports, Vol: 4
Thaventhiran JED, Lango Allen H, Burren OS, et al., 2020, Whole-genome sequencing of a sporadic primary immunodeficiency cohort (vol 583, pg 90, 2020), Nature, Vol: 584, Pages: E2-E2, ISSN: 0028-0836
Thaventhiran JED, Lango Allen H, Burren OS, et al., 2020, Whole-genome sequencing of a sporadic primary immunodeficiency cohort, Nature, Vol: 583, Pages: 90-95, ISSN: 0028-0836
Primary immunodeficiency (PID) is characterized by recurrent and often life-threatening infections, autoimmunity and cancer, and it poses major diagnostic and therapeutic challenges. Although the most severe forms of PID are identified in early childhood, most patients present in adulthood, typically with no apparent family history and a variable clinical phenotype of widespread immune dysregulation: about 25% of patients have autoimmune disease, allergy is prevalent and up to 10% develop lymphoid malignancies1-3. Consequently, in sporadic (or non-familial) PID genetic diagnosis is difficult and the role of genetics is not well defined. Here we address these challenges by performing whole-genome sequencing in a large PID cohort of 1,318 participants. An analysis of the coding regions of the genome in 886 index cases of PID found that disease-causing mutations in known genes that are implicated in monogenic PID occurred in 10.3% of these patients, and a Bayesian approach (BeviMed4) identified multiple new candidate PID-associated genes, including IVNS1ABP. We also examined the noncoding genome, and found deletions in regulatory regions that contribute to disease causation. In addition, we used a genome-wide association study to identify loci that are associated with PID, and found evidence for the colocalization of-and interplay between-novel high-penetrance monogenic variants and common variants (at the PTPN2 and SOCS1 loci). This begins to explain the contribution of common variants to the variable penetrance and phenotypic complexity that are observed in PID. Thus, using a cohort-based whole-genome-sequencing approach in the diagnosis of PID can increase diagnostic yield and further our understanding of the key pathways that influence immune responsiveness in humans.
Tayal U, Wage R, Newsome S, et al., 2020, Predictors of left ventricular remodelling in patients with dilated cardiomyopathy - a cardiovascular magnetic resonance study, European Journal of Heart Failure, Vol: 22, Pages: 1160-1170, ISSN: 1388-9842
AimsThere is an important need for better biomarkers to predict left ventricular (LV) remodelling in dilated cardiomyopathy (DCM). We undertook a comprehensive assessment of cardiac structure and myocardial composition to determine predictors of remodelling.Methods and resultsProspective study of patients with recent‐onset DCM with cardiovascular magnetic resonance (CMR) assessment of ventricular structure and function, extracellular volume (T1 mapping), myocardial strain, myocardial scar (late gadolinium enhancement) and contractile reserve (dobutamine stress). Regression analyses were used to evaluate predictors of change in LV ejection fraction (LVEF) over 12 months. We evaluated 56 participants (34 DCM patients, median LVEF 43%; 22 controls). Absolute LV contractile reserve predicted change in LVEF (1% increase associated with 0.4% increase in LVEF at 12 months, P = 0.02). Baseline myocardial strain (P = 0.39 global longitudinal strain), interstitial myocardial fibrosis (P = 0.41), replacement myocardial fibrosis (P = 0.25), and right ventricular contractile reserve (P = 0.17) were not associated with LV reverse remodelling. There was a poor correlation between contractile reserve and either LV extracellular volume fraction (r = −0.22, P = 0.23) or baseline LVEF (r = 0.07, P = 0.62). Men were more likely to experience adverse LV remodelling (P = 0.01) but age (P = 0.88) and disease‐modifying heart failure medication (beta‐blocker, P = 0.28; angiotensin‐converting enzyme inhibitor, P = 0.92) did not predict follow‐up LVEF.ConclusionsSubstantial recovery of LV function occurs within 12 months in most patients with recent‐onset DCM. Women had the greatest improvement in LVEF. A low LV contractile reserve measured by dobutamine stress CMR appears to identify patients whose LVEF is less likely to recover.
Biffi C, Cerrolaza Martinez JJ, Tarroni G, et al., 2020, Explainable anatomical shape analysis through deep hierarchical generative models, IEEE Transactions on Medical Imaging, Vol: 39, Pages: 2088-2099, ISSN: 0278-0062
Quantification of anatomical shape changes currently relies on scalar global indexes which are largely insensitive to regional or asymmetric modifications. Accurate assessment of pathology-driven anatomical remodeling is a crucial step for the diagnosis and treatment of many conditions. Deep learning approaches have recently achieved wide success in the analysis of medical images, but they lack interpretability in the feature extraction and decision processes. In this work, we propose a new interpretable deep learning model for shape analysis. In particular, we exploit deep generative networks to model a population of anatomical segmentations through a hierarchy of conditional latent variables. At the highest level of this hierarchy, a two-dimensional latent space is simultaneously optimised to discriminate distinct clinical conditions, enabling the direct visualisation of the classification space. Moreover, the anatomical variability encoded by this discriminative latent space can be visualised in the segmentation space thanks to the generative properties of the model, making the classification task transparent. This approach yielded high accuracy in the categorisation of healthy and remodelled left ventricles when tested on unseen segmentations from our own multi-centre dataset as well as in an external validation set, and on hippocampi from healthy controls and patients with Alzheimer’s disease when tested on ADNI data. More importantly, it enabled the visualisation in three-dimensions of both global and regional anatomical features which better discriminate between the conditions under exam. The proposed approach scales effectively to large populations, facilitating highthroughput analysis of normal anatomy and pathology in largescale studies of volumetric imaging.
Kuk M, Newsome S, Alpendurada F, et al., 2020, A model based on clinical parameters to identify myocardial late gadolinium enhancement by magnetic resonance in patients with aortic stenosis: An observational study, JRSM Cardiovascular Disease, Vol: 9, Pages: 2048004020922400-2048004020922400, ISSN: 2048-0040
Objective: With increasing age, the prevalence of aortic stenosis grows exponentially, increasing left heart pressures and potentially leading to myocardial hypertrophy, myocardial fibrosis and adverse outcomes. To identify patients who are at greatest risk, an outpatient model for risk stratification would be of value to better direct patient imaging, frequency of monitoring and expeditious management of aortic stenosis with possible earlier surgical intervention. In this study, a relatively simple model is proposed to identify myocardial fibrosis in patients with a diagnosis of moderate or severe aortic stenosis. Design: Patients with moderate to severe aortic stenosis were enrolled into the study; patient characteristics, blood work, medications as well as transthoracic echocardiography and cardiovascular magnetic resonance were used to determine potential identifiers of myocardial fibrosis. Setting: The Royal Brompton Hospital, London, UK. Participants: One hundred and thirteen patients in derivation cohort and 26 patients in validation cohort. Main outcome measures: Identification of myocardial fibrosis. Results: Three blood biomarkers (serum platelets, serum urea, N-terminal pro-B-type natriuretic peptide) and left ventricular ejection fraction were shown to be capable of identifying myocardial fibrosis. The model was validated in a separate cohort of 26 patients. Conclusions: Although further external validation of the model is necessary prior to its use in clinical practice, the proposed clinical model may direct patient care with respect to earlier magnetic resonance imagining, frequency of monitoring and may help in risk stratification for surgical intervention for myocardial fibrosis in patients with aortic stenosis.
Copeland O, Messer A, Jabbour A, et al., 2020, Pressure Overload Is Associated With Low Levels of Troponin I and Myosin Binding Protein C Phosphorylation in the Hearts of Patients With Aortic Stenosis, FRONTIERS IN PHYSIOLOGY, Vol: 11, ISSN: 1664-042X
- Author Web Link
- Cite
- Citations: 2
Copeland O, Prasad S, Jabbour A, et al., 2020, Pressure overload is associated with low levels of troponin I and myosin binding protein C phosphorylation in the hearts of patients with aortic stenosis, Frontiers in Physiology, Vol: 11, ISSN: 1664-042X
In previous studies of septal heart muscle from HCM patients with hypertrophic obstructive cardiomyopathy (HOCM, LVOT gradient 50–120 mmHg) we found that the level of phosphorylation of troponin I (TnI) and myosin binding protein C (MyBP-C) was extremely low yet samples from hearts with HCM or DCM mutations that did not have pressure overload were similar to donor heart controls. We therefore investigated heart muscle samples taken from patients undergoing valve replacement for aortic stenosis, since they have pressure overload that is unrelated to inherited cardiomyopathy. Thirteen muscle samples from septum and from free wall were analyzed (LVOT gradients 30–100 mmHg) The levels of TnI and MyBP-C phosphorylation were determined in muscle myofibrils by separating phosphospecies using phosphate affinity SDS-PAGE and detecting with TnI and MyBP-C specific antibodies. TnI was predominantly monophosphorylated and total phosphorylation was 0.85 ± 0.03 molsPi/mol TnI. This phosphorylation level was significantly different (p < 0.0001) from both donor heart TnI (1.6 ± 0.06 molsPi/mol TnI) and HOCM heart TnI (0.19 ± 0.04 molsPi/mol TnI). MyBP-C is phosphorylated at up to four sites. In donor heart the 4P and 3P species predominate but in the pressure overload samples the 4P species was much reduced and 3P and 1P species predominated. Total phosphorylation was 2.0 ± 0.2 molsPi/mol MyBP-C (n = 8) compared with 3.4 ± 0.07 (n = 21) in donor heart and 1.1 ± 0.1 (n = 10) in HOCM heart. We conclude that pressure overload may be associated with substantial dephosphorylation of troponin I and MyBP-C.
Marrow BA, Cook SA, Prasad SK, et al., 2020, Emerging Techniques for Risk Stratification in Nonischemic Dilated Cardiomyopathy <i>JACC</i> Review Topic of the Week, JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, Vol: 75, Pages: 1196-1207, ISSN: 0735-1097
- Author Web Link
- Cite
- Citations: 21
Elming MB, Hammer-Hansen S, Voges I, et al., 2020, Myocardial fibrosis and the effect of primary prophylactic defibrillator implantation in patients with non-ischemic systolic heart failure-DANISH-MRI, AMERICAN HEART JOURNAL, Vol: 221, Pages: 165-176, ISSN: 0002-8703
- Author Web Link
- Cite
- Citations: 26
Esslinger U, Garnier S, Korniat A, et al., 2020, Correction: Exome-wide association study reveals novel susceptibility genes to sporadic dilated cardiomyopathy., PLoS One, Vol: 15, Pages: e0229472-e0229472, ISSN: 1932-6203
[This corrects the article DOI: 10.1371/journal.pone.0172995.].
Mazzarotto F, Tayal U, Buchan RJ, et al., 2020, Re-evaluating the genetic contribution of monogenic dilated cardiomyopathy, Circulation, Vol: 141, Pages: 387-398, ISSN: 0009-7322
Background: Dilated cardiomyopathy (DCM) is genetically heterogeneous, with >100 purported disease genes tested in clinical laboratories. However, many genes were originally identified based on candidate-gene studies that did not adequately account for background population variation. Here we define the frequency of rare variation in 2538 DCM patients across protein-coding regions of 56 commonly tested genes and compare this to both 912 confirmed healthy controls and a reference population of 60,706 individuals in order to identify clinically interpretable genes robustly associated with dominant monogenic DCM.Methods: We used the TruSight Cardio sequencing panel to evaluate the burden of rare variants in 56 putative DCM genes in 1040 DCM patients and 912 healthy volunteers processed with identical sequencing and bioinformatics pipelines. We further aggregated data from 1498 DCM patients sequenced in diagnostic laboratories and the ExAC database for replication and meta-analysis.Results: Truncating variants in TTN and DSP were associated with DCM in all comparisons. Variants in MYH7, LMNA, BAG3, TNNT2, TNNC1, PLN, ACTC1, NEXN, TPM1 and VCL were significantly enriched in specific patient subsets, with the last 2 genes potentially contributing primarily to early-onset forms of DCM. Overall, rare variants in these 12 genes potentially explained 17% of cases in the outpatient clinic cohort representing a broad range of adult DCM patients and 26% of cases in the diagnostic referral cohort enriched in familial and early-onset DCM. Whilst the absence of a significant excess in other genes cannot preclude a limited role in disease, such genes have limited diagnostic value since novel variants will be uninterpretable and their diagnostic yield is minimal.Conclusion: In the largest sequenced DCM cohort yet described, we observe robust disease association with 12 genes, highlighting their importance in DCM and translating into high interpretability in diagnostic testing. The
Prasad SK, Tayal U, 2020, The Value of Strain in Familial Dilated Cardiomyopathy Screening, JACC-CARDIOVASCULAR IMAGING, Vol: 13, Pages: 559-561, ISSN: 1936-878X
- Author Web Link
- Cite
- Citations: 2
Mazzarotto F, Hawley M, Beltrami M, et al., 2020, The genetic architecture of left ventricular non-compaction reveals both substantial overlap with other cardiomyopathies and a distinct aetiology in a subset of cases, Publisher: bioRxiv
Rationale: Left ventricular non-compaction (LVNC) is a condition characterised by trabeculations in the myocardial wall and is the subject of considerable conjecture as to whether it represents a distinct pathology or a secondary phenotype associated with other cardiac diseases, particularly cardiomyopathies. Objective: To investigate the genetic architecture of LVNC by identifying genes and variant classes robustly associated with disease and comparing these to other genetically characterised cardiomyopathies. Methods and Results: We performed rare variant association analysis using six different LVNC cohorts comprising 840 cases together with 125,748 gnomAD population controls and compared results to similar analyses with dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM) cases. We observed substantial overlap in genes and variant classes enriched in LVNC and DCM/HCM, indicating that in many cases LVNC belongs to a spectrum of more established cardiomyopathies, with non-compaction representing a phenotypic variation in patients with DCM- or HCM-causing variants. In contrast, five variant classes were uniquely enriched in LVNC cases, of which truncating variants in MYH7, ACTN2 and PRDM16 may represent a distinct LVNC aetiology. MYH7 truncating variants are generally considered as non-pathogenic but were detected in 2% of LVNC cases compared to 0.1% of controls, including a cluster of variants around a single splice region. Additionally, structural variants (exon deletions) in RYR2 and missense variants in the transmembrane region of HCN4 were enriched in LVNC cases, confirming prior reports regarding the association of these variant classes with combined LVNC and arrhythmia phenotypes. Conclusions: We demonstrated that genetic association analysis can clarify the relationship between LVNC and established cardiomyopathies, highlighted substantial overlap with DCM/HCM but also identified variant classes associated with distinct LVNC and with joint LVN
Biffi C, Doumou G, Duan J, et al., 2020, Explainable anatomical shape analysis through deep hierarchical generative models., Publisher: arXiv
Quantification of anatomical shape changes currently relies on scalar global indexes which are largely insensitive to regional or asymmetric modifications. Accurate assessment of pathology-driven anatomical remodeling is a crucial step for the diagnosis and treatment of many conditions. Deep learning approaches have recently achieved wide success in the analysis of medical images, but they lack interpretability in the feature extraction and decision processes. In this work, we propose a new interpretable deep learning model for shape analysis. In particular, we exploit deep generative networks to model a population of anatomical segmentations through a hierarchy of conditional latent variables. At the highest level of this hierarchy, a two-dimensional latent space is simultaneously optimised to discriminate distinct clinical conditions, enabling the direct visualisation of the classification space. Moreover, the anatomical variability encoded by this discriminative latent space can be visualised in the segmentation space thanks to the generative properties of the model, making the classification task transparent. This approach yielded high accuracy in the categorisation of healthy and remodelled left ventricles when tested on unseen segmentations from our own multi-centre dataset as well as in an external validation set, and on hippocampi from healthy controls and patients with Alzheimer's disease when tested on ADNI data. More importantly, it enabled the visualisation in three-dimensions of both global and regional anatomical features which better discriminate between the conditions under exam. The proposed approach scales effectively to large populations, facilitating highthroughput analysis of normal anatomy and pathology in largescale studies of volumetric imaging.
Singh A, Al Musa T, Treibel TA, et al., 2019, Sex differences in left ventricular remodelling, myocardial fibrosis and mortality after aortic valve replacement, HEART, Vol: 105, Pages: 1818-1824, ISSN: 1355-6037
- Author Web Link
- Cite
- Citations: 24
Papageorgiou V, Jones K, Mindham R, et al., 2019, ‘Do I really want to do this for the rest of my life?’: a qualitative exploration of participant and study staff perspectives from the Therapy withdrawal in Recovered Dilated cardiomyopathy - Heart Failure (TRED-HF) study, Chronic Living Conference 2020
Jones RE, Hammersley D, Karamasis GV, et al., 2019, Semi-Quantitative CMR Analysis of Left Anterior Descending Territory Ischaemia in Patients With a Right Coronary Artery Chronic Total Occlusion, Scientific Sessions of the American-Heart-Association, Publisher: LIPPINCOTT WILLIAMS & WILKINS, ISSN: 0009-7322
This data is extracted from the Web of Science and reproduced under a licence from Thomson Reuters. You may not copy or re-distribute this data in whole or in part without the written consent of the Science business of Thomson Reuters.