Imperial College London

DrAntonioSimoes Monteiro de Marvao

Faculty of MedicineInstitute of Clinical Sciences

Honorary Clinical Senior Lecturer
 
 
 
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Contact

 

+44 (0)20 3313 1510antonio.de-marvao

 
 
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Location

 

Robert Steiner MRI UnitHammersmith HospitalHammersmith Campus

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Summary

 

Publications

Publication Type
Year
to

131 results found

Hall M, de Marvao A, Schweitzer R, Cromb D, Colford K, Jandu P, O'Regan DP, Ho A, Price A, Chappell LC, Rutherford MA, Story L, Lamata P, Hutter Jet al., 2024, Preeclampsia associated differences in the placenta, fetal brain, and maternal heart can be demonstrated antenatally: an observational cohort study using MRI, Hypertension, Vol: 81, Pages: 836-847, ISSN: 0194-911X

BACKGROUND: Preeclampsia is a multiorgan disease of pregnancy that has short- and long-term implications for the woman and fetus, whose immediate impact is poorly understood. We present a novel multiorgan approach to magnetic resonance imaging (MRI) investigation of preeclampsia, with the acquisition of maternal cardiac, placental, and fetal brain anatomic and functional imaging. METHODS: An observational study was performed recruiting 3 groups of pregnant women: those with preeclampsia, chronic hypertension, or no medical complications. All women underwent a cardiac MRI, and pregnant women underwent a placental-fetal MRI. Cardiac analysis for structural, morphological, and flow data were undertaken; placenta and fetal brain volumetric and T2* (which describes relative tissue oxygenation) data were obtained. All results were corrected for gestational age. A nonpregnant cohort was identified for inclusion in the statistical shape analysis. RESULTS: Seventy-eight MRIs were obtained during pregnancy. Cardiac MRI analysis demonstrated higher left ventricular mass in preeclampsia with 3-dimensional modeling revealing additional specific characteristics of eccentricity and outflow track remodeling. Pregnancies affected by preeclampsia demonstrated lower placental and fetal brain T2*. Within the preeclampsia group, 23% placental T2* results were consistent with controls, these were the only cases with normal placental histopathology. Fetal brain T2* results were consistent with normal controls in 31% of cases. CONCLUSIONS: We present the first holistic assessment of the immediate implications of preeclampsia on maternal heart, placenta, and fetal brain. As well as having potential clinical implications for the risk stratification and management of women with preeclampsia, this gives an insight into the disease mechanism.

Journal article

Qiao M, Wang S, Qiu H, Marvao AD, O'Regan D, Rueckert D, Bai Wet al., 2024, CHeart: a conditional spatio-temporal generative model for cardiac anatomy, IEEE Transactions on Medical Imaging, Vol: 43, Pages: 1259-1269, ISSN: 0278-0062

Two key questions in cardiac image analysis are to assess the anatomy and motion of the heart from images; and to understand how they are associated with non-imaging clinical factors such as gender, age and diseases. While the first question can often be addressed by image segmentation and motion tracking algorithms, our capability to model and answer the second question is still limited. In this work, we propose a novel conditional generative model to describe the 4D spatio-temporal anatomy of the heart and its interaction with non-imaging clinical factors. The clinical factors are integrated as the conditions of the generative modelling, which allows us to investigate how these factors influence the cardiac anatomy. We evaluate the model performance in mainly two tasks, anatomical sequence completion and sequence generation. The model achieves high performance in anatomical sequence completion, comparable to or outperforming other state-of-the-art generative models. In terms of sequence generation, given clinical conditions, the model can generate realistic synthetic 4D sequential anatomies that share similar distributions with the real data. We will share the code and the trained generative model at https://github.com/MengyunQ/CHeart.

Journal article

Ardissino M, Morley A, Slob E, Schuermans A, Rayes B, Raisi-Estabragh Z, de Marvao A, Burgess S, Rogne T, Honigberg M, Ng FSet al., 2024, Birth weight influences cardiac structure, function, and disease risk: evidence of a causal association, European Heart Journal, Vol: 45, Pages: 443-454, ISSN: 0195-668X

Background and AimsLow birth weight is a common pregnancy complication, which has been associated with higher risk of cardiometabolic disease in later life. Prior Mendelian randomization (MR) studies exploring this question do not distinguish the mechanistic contributions of variants that directly influence birth weight through the foetal genome (direct foetal effects), vs. variants influencing birth weight indirectly by causing an adverse intrauterine environment (indirect maternal effects). In this study, MR was used to assess whether birth weight, independent of intrauterine influences, is associated with cardiovascular disease risk and measures of adverse cardiac structure and function.MethodsUncorrelated (r2 < .001), genome-wide significant (P < 5 × 10−8) single nucleotide polymorphisms were extracted from genome-wide association studies summary statistics for birth weight overall, and after isolating direct foetal effects only. Inverse-variance weighted MR was utilized for analyses on outcomes of atrial fibrillation, coronary artery disease, heart failure, ischaemic stroke, and 16 measures of cardiac structure and function. Multiple comparisons were accounted for by Benjamini–Hochberg correction.ResultsLower genetically-predicted birth weight, isolating direct foetal effects only, was associated with an increased risk of coronary artery disease (odds ratio 1.21, 95% confidence interval 1.06–1.37; P = .031), smaller chamber volumes, and lower stroke volume, but higher contractility.ConclusionsThe results of this study support a causal role of low birth weight in cardiovascular disease, even after accounting for the influence of the intrauterine environment. This suggests that individuals with a low birth weight may benefit from early targeted cardiovascular disease prevention strategies, independent of whether this was linked to an adverse intrauterine environment during gestation.

Journal article

Ng FS, Reddy R, Ardissino M, Morley A, Schuermans A, Hill P, Williamson C, Honigberg M, de Marvao Aet al., 2024, Genetically-proxied low-density lipoprotein cholesterol lowering via PCSK9-inhibitor drug targets and risk of congenital malformations, European Journal of Preventive Cardiology, ISSN: 2047-4873

Aims: Current guidelines advise against the use of lipid lowering drugs during pregnancy. This is based only on previous observational evidence demonstrating an association between statin use and congenital malformations, which is inceasingly controversial. In the absence of clinical trial data, we aimed to use drug-target Mendelian randomization to model the potential impact of fetal LDL lowering, overall and through PCSK9 drug targets, on congenital malformations.Methods: Instrumental variants influencing LDL levels overall and through PCSK9-inhibitor drug targets were extracted from genome-wide association study (GWAS) summary data for LDL on 1,320,016 individuals. Instrumental variants influencing circulating PCSK9 levels (pQTLs) and liver PCSK9 gene expression levels (eQTLs) were extracted respectively from a GWAS on 10,186 individuals and from the Genotype-Tissue Expression (GTEx) project. Gene-outcome association data was extracted from the 7th release of GWAS summary data on the FinnGen cohort (n=342,499) for eight categories of congenital malformations affecting multiple systems.Results: Genetically-proxied LDL-lowering through PCSK9 was associated with higher odds of malformations affecting multiple systems (OR 2.70, 95% CI 1.30-5.63, p=0.018), the skin (OR 2.23, 95% CI 1.33–3.75, p=0.007), and the vertebral, anorectal, cardiovascular, tracheo-esophageal, renal and limb association (VACTERL) (OR 1.51, 95% CI 1.16–1.96, p=0.007). An association was also found with obstructive defects of the renal pelvis and ureter, but this association was suggestive for horizontal pleiotropy. Lower PCSK9 pQTLs were associated with the same congenital malformations. Conclusion: These data provide genetic evidence supporting current manufacturer advice to avoid the use of PCSK9 inhibitors during pregnancy.

Journal article

Conti-Ramsden F, Bramham K, de Marvao A, 2024, Long-term cardiovascular disease after pre-eclampsia: time to move from epidemiology to action., Eur Heart J Qual Care Clin Outcomes, Vol: 10, Pages: 1-3

Journal article

Jones RE, Hammersley DJ, Zheng S, McGurk KA, de Marvao A, Theotokis PI, Owen R, Tayal U, Rea G, Hatipoglu S, Buchan RJ, Mach L, Curran L, Lota AS, Simard F, Reddy RK, Talukder S, Yoon WY, Vazir A, Pennell DJ, O'Regan DP, Baksi AJ, Halliday BP, Ware JS, Prasad SKet al., 2024, Assessing the association between genetic and phenotypic features of dilated cardiomyopathy and outcome in patients with coronary artery disease, European Journal of Heart Failure, Vol: 26, Pages: 46-55, ISSN: 1388-9842

AimsTo examine the relevance of genetic and cardiovascular magnetic resonance (CMR) features of dilated cardiomyopathy (DCM) in individuals with coronary artery disease (CAD).Methods and resultsThis study includes two cohorts. First, individuals with CAD recruited into the UK Biobank (UKB) were evaluated. Second, patients with CAD referred to a tertiary centre for evaluation with late gadolinium enhancement (LGE)-CMR were recruited (London cohort); patients underwent genetic sequencing as part of the research protocol and long-term follow-up. From 31 154 individuals with CAD recruited to UKB, rare pathogenic variants in DCM genes were associated with increased risk of death or major adverse cardiac events (hazard ratio 1.57, 95% confidence interval [CI] 1.22–2.01, p < 0.001). Of 1619 individuals with CAD included from the UKB CMR substudy, participants with a rare variant in a DCM-associated gene had lower left ventricular ejection fraction (LVEF) compared to genotype negative individuals (mean 47 ± 10% vs. 57 ± 8%, p < 0.001). Of 453 patients in the London cohort, 63 (14%) had non-infarct pattern LGE (NI-LGE) on CMR. Patients with NI-LGE had lower LVEF (mean 38 ± 18% vs. 48 ± 16%, p < 0.001) compared to patients without NI-LGE, with no significant difference in the burden of rare protein altering variants in DCM-associated genes between groups (9.5% vs. 6.7%, odds ratio 1.5, 95% CI 0.4–4.3, p = 0.4). NI-LGE was not independently associated with adverse clinical outcomes.ConclusionRare pathogenic variants in DCM-associated genes impact left ventricular remodelling and outcomes in stable CAD. NI-LGE is associated with adverse remodelling but is not an independent predictor of outcome and had no rare genetic basis in our study.

Journal article

Ardissino M, Halliday BP, de Marvao A, 2024, The global landscape of peripartum cardiomyopathy: Morbidity, mortality, recovery and inequity., Eur J Heart Fail, Vol: 26, Pages: 43-45

Journal article

Curran L, Simoes Monteiro de Marvao A, Inglese P, McGurk K, Schiratti P-R, Clement A, Zheng S, Li S, Pua CJ, Shah M, Jafari M, Theotokis P, Buchan R, Jurgens S, Raphael C, Baksi A, Pantazis A, Halliday B, Pennell D, Bai W, Chin C, Tadros R, Bezzina C, Watkins H, Cook S, Prasad S, Ware J, O'Regan Det al., 2023, Genotype-phenotype taxonomy of hypertrophic cardiomyopathy, Circulation: Genomic and Precision Medicine, Vol: 16, Pages: 559-570, ISSN: 2574-8300

Background:Hypertrophic cardiomyopathy (HCM) is an important cause of sudden cardiac death associated with heterogeneous phenotypes but there is no systematic framework for classifying morphology or assessing associated risks. Here we quantitatively survey genotype-phenotype associations in HCM to derive a data-driven taxonomy of disease expression.Methods:We enrolled 436 HCM patients (median age 60 years; 28.8% women) with clinical, genetic and imaging data. Anindependent cohort of 60 HCM patients from Singapore (median age 59 years; 11% women) and a reference population from UK Biobank (n = 16,691, mean age 55 years; 52.5% women) were also recruited. We used machine learning to analyse the three-dimensional structure of the left ventricle from cardiac magnetic resonance imaging and build a tree-based classification of HCM phenotypes. Genotype and mortality risk distributions were projected on the tree.Results:Carriers of pathogenic or likely pathogenic variants (P/LP) for HCM had lower left ventricular mass, but greater basalseptal hypertrophy, with reduced lifespan (mean follow-up 9.9 years) compared to genotype negative individuals(hazard ratio: 2.66; 95% confidence interval [CI]: 1.42-4.96; P < 0.002). Four main phenotypic branches were identified using unsupervised learning of three-dimensional shape: 1) non-sarcomeric hypertrophy with co-existing hypertension; 2) diffuse and basal asymmetric hypertrophy associated with outflow tract obstruction; 3) isolated basal hypertrophy; 4) milder non-obstructive hypertrophy enriched for familial sarcomeric HCM (odds ratio for P/LP variants: 2.18 [95% CI: 1.93-2.28, P = 0.0001]). Polygenic risk for HCM was also associated with different patterns and degrees of disease expression. The model was generalisable to an independent cohort (trustworthiness M1: 0.86-0.88).Conclusions:We report a data-driven taxonomy of HCM for identifying groups of patients with similar morphology while preserving a continuum of disease severi

Journal article

Bala R, Mehta S, Roy VC, Kaur G, de Marvao Aet al., 2023, Peripartum cardiomyopathy: a review, Revista Portuguesa de Cardiologia, Vol: 42, Pages: 917-924, ISSN: 0870-2551

Peripartum cardiomyopathy is a rare type of heart failure manifesting towards the end of pregnancy or in the months following delivery, in the absence of any other cause of heart failure. There is a wide range of incidence across countries reflecting different population demographics, uncertainty over definitions and under-reporting. Race, ethnicity, multiparity and advanced maternal age are considered important risk factors for the disease. Its etiopathogenesis is incompletely understood and is likely multifactorial, including hemodynamic stresses of pregnancy, vasculo-hormonal factors, inflammation, immunology and genetics. Affected women present with heart failure secondary to reduced left ventricular systolic function (LVEF <45%) and often with associated phenotypes such as LV dilatation, biatrial dilatation, reduced systolic function, impaired diastolic function, and increased pulmonary pressure. Electrocardiography, echocardiography, magnetic resonance imaging, endomyocardial biopsy, and certain blood biomarkers aid in diagnosis and management. Treatment for peripartum cardiomyopathy depends on the stage of pregnancy or postpartum, disease severity and whether the woman is breastfeeding. It includes standard pharmacological therapies for heart failure, within the safety restrictions for pregnancy and lactation. Targeted therapies such as bromocriptine have shown promise in early, small studies, with large definitive trials currently underway. Failure of medical interventions may require mechanical support and transplantation in severe cases. Peripartum cardiomyopathy carries a high mortality rate of up to 10% and a high risk of relapse in subsequent pregnancies, but over half of women present normalization of LV function within a year of diagnosis.

Journal article

Hammersley D, Jones R, Owen R, Mach L, Lota A, Khalique Z, de Marvao A, Androulakis E, Hatipoglu S, Gulati A, Reddy R, Yoon WY, Talukder S, Shah R, Baruah R, Guha K, Pantazis A, Baksi J, Gregson J, Cleland J, Tayal U, Pennell D, Ware J, Halliday B, Prasad Set al., 2023, Phenotype, outcomes and natural history of early-stage non-ischaemic cardiomyopathy, European Journal of Heart Failure, Vol: 25, Pages: 2050-2059, ISSN: 1388-9842

AimsTo characterize the phenotype, clinical outcomes and rate of disease progression in patients with early-stage non-ischaemic cardiomyopathy (early-NICM).Methods and resultsWe conducted a prospective observational cohort study of patients with early-NICM assessed by late gadolinium enhancement cardiovascular magnetic resonance (CMR). Cases were classified into the following subgroups: isolated left ventricular dilatation (early-NICM H−/D+), non-dilated left ventricular cardiomyopathy (early-NICM H+/D−), or early dilated cardiomyopathy (early-NICM H+/D+). Clinical follow-up for major adverse cardiovascular events (MACE) included non-fatal life-threatening arrhythmia, unplanned cardiovascular hospitalization or cardiovascular death. A subset of patients (n = 119) underwent a second CMR to assess changes in cardiac structure and function. Of 254 patients with early-NICM (median age 46 years [interquartile range 36–58], 94 [37%] women, median left ventricular ejection fraction [LVEF] 55% [52–59]), myocardial fibrosis was present in 65 (26%). There was no difference in the prevalence of fibrosis between subgroups (p = 0.90), however fibrosis mass was lowest in early-NICM H−/D+, higher in early-NICM H+/D− and highest in early-NICM H+/D+ (p = 0.03). Over a median follow-up of 7.9 (5.5–10.0) years, 28 patients (11%) experienced MACE. Non-sustained ventricular tachycardia (hazard ratio [HR] 5.1, 95% confidence interval [CI] 2.36–11.00, p < 0.001), myocardial fibrosis (HR 3.77, 95% CI 1.73–8.20, p < 0.001) and diabetes mellitus (HR 5.12, 95% CI 1.73–15.18, p = 0.003) were associated with MACE in a multivariable model. Only 8% of patients progressed from early-NICM to dilated cardiomyopathy with LVEF <50% over a median of 16 (11–34) months.ConclusionEarly-NICM is not benign. Fibrosis develops early in the phenot

Journal article

Shah M, Inacio M, Lu C, Schiratti P-R, Zheng S, Clement A, Simoes Monteiro de Marvao A, Bai W, King A, Ware J, Wilkins M, Mielke J, Elci E, Kryukov I, McGurk K, Bender C, Freitag D, O'Regan Det al., 2023, Environmental and genetic predictors of human cardiovascular ageing, Nature Communications, Vol: 14, Pages: 1-15, ISSN: 2041-1723

Cardiovascular ageing is a process that begins early in life and leads to a progressive change instructure and decline in function due to accumulated damage across diverse cell types, tissues andorgans contributing to multi-morbidity. Damaging biophysical, metabolic and immunological factors exceed endogenous repair mechanisms resulting in a pro-fibrotic state, cellular senescence andend-organ damage, however the genetic architecture of cardiovascular ageing is not known. Herewe use machine learning approaches to quantify cardiovascular age from image-derived traits ofvascular function, cardiac motion and myocardial fibrosis, as well as conduction traits from electrocardiograms, in 39,559 participants of UK Biobank. Cardiovascular ageing is found to be significantly associated with common or rare variants in genes regulating sarcomere homeostasis, myocardial immunomodulation, and tissue responses to biophysical stress. Ageing is accelerated bycardiometabolic risk factors and we also identify prescribed medications that are potential modifiersof ageing. Through large-scale modelling of ageing across multiple traits our results reveal insightsinto the mechanisms driving premature cardiovascular ageing and reveal potential molecular targetsto attenuate age-related processes.

Journal article

Ardissino M, Slob EAW, Reddy RK, Morley AP, Hill P, Williamson C, de Marvao A, Ng FSet al., 2023, GENETICALLY-PROXIED LOW DENSITY LIPOPROTEIN CHOLESTEROL LOWERING VIA PCSK9-INHIBITOR DRUG TARGETS AND RISK OF CONGENITAL MALFORMATIONS, Annual Conference of the British-Cardiovascular-Society (BCS), Publisher: BMJ PUBLISHING GROUP, Pages: A309-A310, ISSN: 1355-6037

Conference paper

Jones RE, Zaidi HA, Hammersley DJ, Hatipoglu S, Owen R, Balaban G, de Marvao A, Simard F, Lota AS, Mahon C, Almogheer B, Mach L, Musella F, Chen X, Gregson J, Lazzari L, Ravendren A, Leyva F, Zhao S, Vazir A, Lamata P, Halliday BP, Pennell DJ, Bishop MJ, Prasad SKet al., 2023, Comprehensive phenotypic characterization of late gadolinium enhancement predicts sudden cardiac death in coronary artery disease, JACC: Cardiovascular Imaging, Vol: 16, Pages: 628-638, ISSN: 1936-878X

BackgroundLate gadolinium enhancement (LGE) cardiac magnetic resonance (CMR) offers the potential to noninvasively characterize the phenotypic substrate for sudden cardiac death (SCD).ObjectivesThe authors assessed the utility of infarct characterization by CMR, including scar microstructure analysis, to predict SCD in patients with coronary artery disease (CAD).MethodsPatients with stable CAD were prospectively recruited into a CMR registry. LGE quantification of core infarction and the peri-infarct zone (PIZ) was performed alongside computational image analysis to extract morphologic and texture scar microstructure features. The primary outcome was SCD or aborted SCD.ResultsOf 437 patients (mean age: 64 years; mean left ventricular ejection fraction [LVEF]: 47%) followed for a median of 6.3 years, 49 patients (11.2%) experienced the primary outcome. On multivariable analysis, PIZ mass and core infarct mass were independently associated with the primary outcome (per gram: HR: 1.07 [95% CI: 1.02-1.12]; P = 0.002 and HR: 1.03 [95% CI: 1.01-1.05]; P = 0.01, respectively), and the addition of both parameters improved discrimination of the model (Harrell’s C-statistic: 0.64-0.79). PIZ mass, however, did not provide incremental prognostic value over core infarct mass based on Harrell’s C-statistic or risk reclassification analysis. Severely reduced LVEF did not predict the primary endpoint after adjustment for scar mass. On scar microstructure analysis, the number of LGE islands in addition to scar transmurality, radiality, interface area, and entropy were all associated with the primary outcome after adjustment for severely reduced LVEF and New York Heart Association functional class of >1. No scar microstructure feature remained associated with the primary endpoint when PIZ mass and core infarct mass were added to the regression models.ConclusionsComprehensive LGE characterization independently predicted SCD risk beyond conventional predictors used in im

Journal article

Hall M, de Marvao A, Schweitzer R, Cromb D, Colford K, Jandu P, O'Regan DP, Ho A, Price A, Chappell LC, Rutherford MA, Story L, Lamata P, Hutter Jet al., 2023, Characterisation of placental, fetal brain and maternal cardiac structure and function in pre-eclampsia using MRI., medRxiv

BACKGROUND: Pre-eclampsia is a multiorgan disease of pregnancy that has short- and long-term implications for the woman and fetus, whose immediate impact is poorly understood. We present a novel multi-system approach to MRI investigation of pre-eclampsia, with acquisition of maternal cardiac, placental, and fetal brain anatomical and functional imaging. METHODS: A prospective study was carried out recruiting pregnant women with pre-eclampsia, chronic hypertension, or no medical complications, and a non-pregnant female cohort. All women underwent a cardiac MRI, and pregnant women underwent a fetal-placental MRI. Cardiac analysis for structural, morphological and flow data was undertaken; placenta and fetal brain volumetric and T2* data were obtained. All results were corrected for gestational age. RESULTS: Seventy-eight MRIs were obtained during pregnancy. Pregnancies affected by pre-eclampsia demonstrated lower placental and fetal brain T2*. Within the pre-eclampsia group, three placental T2* results were within the normal range, these were the only cases with normal placental histopathology. Similarly, three fetal brain T2* results were within the normal range; these cases had no evidence of cerebral redistribution on fetal Dopplers. Cardiac MRI analysis demonstrated higher left ventricular mass in pre-eclampsia with 3D modelling revealing additional specific characteristics of eccentricity and outflow track remodelling. CONCLUSIONS: We present the first holistic assessment of the immediate implications of pre-eclampsia on the placenta, maternal heart, and fetal brain. As well as having potential clinical implications for the risk-stratification and management of women with pre-eclampsia, this gives an insight into disease mechanism.

Journal article

Tadros R, Zheng SL, Grace C, Jordà P, Francis C, Jurgens SJ, Thomson KL, Harper AR, Ormondroyd E, West DM, Xu X, Theotokis PI, Buchan RJ, McGurk KA, Mazzarotto F, Boschi B, Pelo E, Lee M, Noseda M, Varnava A, Vermeer AM, Walsh R, Amin AS, van Slegtenhorst MA, Roslin N, Strug LJ, Salvi E, Lanzani C, de Marvao A, Hypergenes InterOmics Collaborators, Roberts JD, Tremblay-Gravel M, Giraldeau G, Cadrin-Tourigny J, L'Allier PL, Garceau P, Talajic M, Pinto YM, Rakowski H, Pantazis A, Baksi J, Halliday BP, Prasad SK, Barton PJ, O'Regan DP, Cook SA, de Boer RA, Christiaans I, Michels M, Kramer CM, Ho CY, Neubauer S, HCMR Investigators, Matthews PM, Wilde AA, Tardif J-C, Olivotto I, Adler A, Goel A, Ware JS, Bezzina CR, Watkins Het al., 2023, Large scale genome-wide association analyses identify novel genetic loci and mechanisms in hypertrophic cardiomyopathy., medRxiv

Hypertrophic cardiomyopathy (HCM) is an important cause of morbidity and mortality with both monogenic and polygenic components. We here report results from the largest HCM genome-wide association study (GWAS) and multi-trait analysis (MTAG) including 5,900 HCM cases, 68,359 controls, and 36,083 UK Biobank (UKB) participants with cardiac magnetic resonance (CMR) imaging. We identified a total of 70 loci (50 novel) associated with HCM, and 62 loci (32 novel) associated with relevant left ventricular (LV) structural or functional traits. Amongst the common variant HCM loci, we identify a novel HCM disease gene, SVIL, which encodes the actin-binding protein supervillin, showing that rare truncating SVIL variants cause HCM. Mendelian randomization analyses support a causal role of increased LV contractility in both obstructive and non-obstructive forms of HCM, suggesting common disease mechanisms and anticipating shared response to therapy. Taken together, the findings significantly increase our understanding of the genetic basis and molecular mechanisms of HCM, with potential implications for disease management.

Journal article

Pillinger T, Osimo EF, de Marvao A, Shah M, Francis C, Huang J, D'Ambrosio E, Firth J, Nour MM, McCutcheon RA, Pardiñas AF, Matthews PM, O'Regan DP, Howes ODet al., 2023, Effect of polygenic risk for schizophrenia on cardiac structure and function: a UK Biobank observational study, The Lancet Psychiatry, Vol: 10, Pages: 98-107, ISSN: 2215-0366

BACKGROUND: Cardiovascular disease is a major cause of excess mortality in people with schizophrenia. Several factors are responsible, including lifestyle and metabolic effects of antipsychotics. However, variations in cardiac structure and function are seen in people with schizophrenia in the absence of cardiovascular disease risk factors and after accounting for lifestyle and medication. Therefore, we aimed to explore whether shared genetic causes contribute to these cardiac variations. METHODS: For this observational study, we used data from the UK Biobank and included White British or Irish individuals without diagnosed schizophrenia with variable polygenic risk scores for the condition. To test the association between polygenic risk score for schizophrenia and cardiac phenotype, we used principal component analysis and regression. Robust regression was then used to explore the association between the polygenic risk score for schizophrenia and individual cardiac phenotypes. We repeated analyses with fibro-inflammatory pathway-specific polygenic risk scores for schizophrenia. Last, we investigated genome-wide sharing of common variants between schizophrenia and cardiac phenotypes using linkage disequilibrium score regression. The primary outcome was principal component regression. FINDINGS: Of 33 353 individuals recruited, 32 279 participants had complete cardiac MRI data and were included in the analysis, of whom 16 625 (51·5%) were female and 15 654 (48·5%) were male. 1074 participants were excluded on the basis of incomplete cardiac MRI data (for all phenotypes). A model regressing polygenic risk scores for schizophrenia onto the first five cardiac principal components of the principal components analysis was significant (F=5·09; p=0·00012). Principal component 1 captured a pattern of increased cardiac volumes, increased absolute peak diastolic strain rates, and reduced ejection fractions; polygenic risk

Journal article

Hammersley DJ, Zaidi HA, Jones RE, Hatipoglu S, Androulakis E, Mach L, Lota AS, Tayal U, Khalique Z, De Marvao A, Baruah R, Guha K, Pennell DJ, Halliday BP, Bishop MJ, Prasad SKet al., 2023, 13 Myocardial fibrosis entropy is associated with life-threatening arrhythmia in non-ischaemic cardiomyopathy, Publisher: BMJ PUBLISHING GROUP, Pages: A10-A10, ISSN: 1355-6037

Conference paper

Hammersley DJ, Jones RE, Mach L, Owen R, Lota AS, Khalique Z, de Marvao A, Gulati A, Baruah R, Guha K, Ware JS, Cleland JG, Pennell DJ, Halliday BP, Tayal U, Prasad SKet al., 2022, Effect of Diabetes Mellitus on Clinical Phenotype and Cardiovascular Mortality in Non-Ischaemic Dilated Cardiomyopathy, Scientific Sessions of the American-Heart-Association / Resuscitation Science Symposium, Publisher: LIPPINCOTT WILLIAMS & WILKINS, ISSN: 0009-7322

Conference paper

Lota A, Hazebroek M, Theotokis P, Wassall R, Salmi S, Halliday B, Tayal U, Verdonschot J, Meena D, Owen R, de Marvao A, Iacob A, Yazdani M, Hammersley D, Jones R, Wage R, Buchan R, Vivian F, Hafouda Y, Noseda M, Gregson J, Mittal T, Wong J, Robertus JL, Baksi AJ, Vassiliou V, Tzoulaki I, Pantazis A, Cleland J, Barton P, Cook S, Pennell D, Cooper L, Garcia-Pavia P, Heymans S, Ware J, Prasad Set al., 2022, Genetic architecture of acute myocarditis and the overlap with inherited cardiomyopathy, Circulation, Vol: 146, Pages: 1123-1134, ISSN: 0009-7322

Background: Acute myocarditis is an inflammatory condition that may herald the onset of dilated (DCM) or arrhythmogenic cardiomyopathy (ACM). We investigated the frequency and clinical consequences of DCM and ACM genetic variants in a population-based cohort of patients with acute myocarditis. Methods: Population-based cohort of 336 consecutive patients with acute myocarditis enrolled in London and Maastricht. All participants underwent targeted DNA-sequencing for well-characterised cardiomyopathy-associated genes with comparison to healthy controls (n=1053) sequenced on the same platform. Case ascertainment in England was assessed against national hospital admission data. The primary outcome was all-cause mortality. Results: Variants that would be considered pathogenic if found in a patient with DCM or ACM were identified in 8% of myocarditis cases compared to <1% of healthy controls (p=0.0097). In the London cohort (n=230; median age 33years; 84% men), patients were representative of national myocarditis admissions (median age 32years; 71% men; 66% case ascertainment), and there was enrichment of rare truncating variants (tv) in ACM-associated genes (3.1% cases vs 0.4% controls; odds ratio 8.2; p=0.001). This was driven predominantly by desmoplakin (DSP)-tv in patients with normal LV ejection fraction and ventricular arrhythmia. In Maastricht (n=106; median age 54years; 61% men), there was enrichment of rare truncating variants in DCM-associated genes, particularly TTN-tv found in 7% (all with LVEF<50%) compared to 1% in controls (OR 3.6; p=0.0116). Across both cohorts over a median of 5.0 years (IQR 3.9-7.8), all-cause mortality was 5.4%. Two thirds of deaths were cardiovascular, due to worsening heart failure (92%) or sudden cardiac death (8%). The 5-year mortality risk was 3.3% in genotype negative patients versus 11.1% for genotype positive patients (Padjusted=0.08). Conclusions: We identified DCM- or ACM-associated genetic variants in 8% of patients wit

Journal article

Meng Q, Bai W, Liu T, Simoes Monteiro de Marvao A, O'Regan D, Rueckert Det al., 2022, MulViMotion: shape-aware 3D myocardial motion tracking from multi-view cardiac MRI, IEEE Transactions on Medical Imaging, Vol: 41, Pages: 1961-1974, ISSN: 0278-0062

Recovering the 3D motion of the heart from cine cardiac magnetic resonance (CMR) imaging enables the assessment of regional myocardial function and is important for understanding and analyzing cardiovascular disease. However, 3D cardiac motion estimation is challenging because the acquired cine CMR images are usually 2D slices which limit the accurate estimation of through-plane motion. To address this problem, we propose a novel multi-view motion estimation network (MulViMotion), which integrates 2D cine CMR images acquired in short-axis and long-axis planes to learn a consistent 3D motion field of the heart. In the proposed method, a hybrid 2D/3D network is built to generate dense 3D motion fields by learning fused representations from multi-view images. To ensure that the motion estimation is consistent in 3D, a shape regularization module is introduced during training, where shape information from multi-view images is exploited to provide weak supervision to 3D motion estimation. We extensively evaluate the proposed method on 2D cine CMR images from 580 subjects of the UK Biobank study for 3D motion tracking of the left ventricular myocardium. Experimental results show that the proposed method quantitatively and qualitatively outperforms competing methods.

Journal article

Bleakley C, de Marvao A, Morosin M, Androulakis E, Russell C, Athayde A, Cannata A, Passariello M, Ledot S, Singh S, Pepper J, Hill J, Cowie M, Price Set al., 2022, Utility of echocardiographic right ventricular subcostal strain in critical care, EUROPEAN HEART JOURNAL-CARDIOVASCULAR IMAGING, Vol: 23, Pages: 820-828, ISSN: 2047-2404

Journal article

Cheng HLH, Andreica E-C, Martin A, Teelucksingh S, De Marvao A, McMicking J, Banerjee Aet al., 2022, Improving management pathway for pregnant women with palpitations in a tertiary hospital, Publisher: WILEY, Pages: 164-165, ISSN: 1470-0328

Conference paper

Thanaj M, Mielke J, McGurk K, Bai W, Savioli N, Simoes Monteiro de Marvao A, Meyer H, Zeng L, Sohler F, Lumbers T, Wilkins M, Ware J, Bender C, Rueckert D, MacNamara A, Freitag D, O'Regan Det al., 2022, Genetic and environmental determinants of diastolic heart function, Nature Cardiovascular Research, Vol: 1, Pages: 361-371, ISSN: 2731-0590

Diastole is the sequence of physiological events that occur in the heart during ventricular filling and principally depends onmyocardial relaxation and chamber stiffness. Abnormal diastolic function is related to many cardiovascular disease processesand is predictive of health outcomes, but its genetic architecture is largely unknown. Here, we use machine learning cardiacmotion analysis to measure diastolic functional traits in 39,559 participants of the UK Biobank and perform a genome-wideassociation study. We identified 9 significant, independent loci near genes that are associated with maintaining sarcomericfunction under biomechanical stress and genes implicated in the development of cardiomyopathy. Age, sex and diabetes wereindependent predictors of diastolic function and we found a causal relationship between genetically-determined ventricularstiffness and incident heart failure. Our results provide insights into the genetic and environmental factors influencing diastolicfunction that are relevant for identifying causal relationships and potential tractable targets.

Journal article

Howard LSGE, He J, Watson GMJ, Huang L, Wharton J, Luo Q, Kiely DG, Condliffe R, Pepke-Zaba J, Morrell NW, Sheares KK, Ulrich A, Quan R, Zhao Z, Jing X, An C, Liu Z, Xiong C, Robbins PA, Dawes T, de MA, Rhodes CJ, Richter MJ, Gall H, Ghofrani HA, Zhao L, Huson L, Wilkins MRet al., 2022, Supplementation with Iron in Pulmonary Arterial Hypertension: Two Randomized Crossover Trials (vol 18, pg 981, 2021), ANNALS OF THE AMERICAN THORACIC SOCIETY, Vol: 19, Pages: 703-703, ISSN: 1546-3222

Journal article

McGurk KA, Zheng SL, Henry A, Josephs K, Edwards M, de Marvao A, Whiffin N, Roberts A, Lumbers TR, O'Regan DP, Ware JSet al., 2022, Correspondence on "ACMG SF v3.0 list for reporting of secondary findings in clinical exome and genome sequencing: a policy statement of the American College of Medical Genetics and Genomics (ACMG)" by Miller et al, Genetics in Medicine, Vol: 24, Pages: 744-746, ISSN: 1098-3600

Journal article

Jia X, Thorley A, Chen W, Qiu H, Shen L, Styles IB, Chang HJ, Leonardis A, de Marvao A, O'Regan DP, Rueckert D, Duan Jet al., 2022, Learning a Model-Driven Variational Network for Deformable Image Registration, IEEE TRANSACTIONS ON MEDICAL IMAGING, Vol: 41, Pages: 199-212, ISSN: 0278-0062

Journal article

Leo I, Nakou E, de Marvao A, Wong J, Bucciarelli-Ducci Cet al., 2022, Imaging in Women with Heart Failure: Sex-specific Characteristics and Current Challenges., Card Fail Rev, Vol: 8, ISSN: 2057-7540

Cardiovascular disease (CVD) represents a significant threat to women's health. Heart failure (HF) is one CVD that still has an increasing incidence and about half of all cases involve women. HF is characterised by strong sex-specific features in aetiology, clinical manifestation and outcomes. Women are more likely to have hypertensive heart disease and HF with preserved ejection fraction, they experience worse quality of life but have a better overall survival rate. Women's hearts also have unique morphological characteristics that should be considered during cardiovascular assessment. It is important to understand and highlight these sex-specific features to be able to provide a tailored diagnostic approach and therapeutic management. The aim of this article is to review these aspects together with the challenges and the unique characteristics of different imaging modalities used for the diagnosis and follow-up of women with HF.

Journal article

Osimo E, Sweeney M, De Marvao A, Berry A, Statton B, Perry BI, Pillinger T, Whitehurst T, Cook S, ORegan D, Thomas EL, Howes ODet al., 2021, Adipose tissue dysfunction, inflammation, and insulin resistance: alternative pathways to cardiac remodelling in schizophrenia. A multimodal, case-control study, Translational Psychiatry, Vol: 11, Pages: 1-9, ISSN: 2158-3188

Cardiovascular diseases are the leading cause of death in schizophrenia. Patients with schizophrenia show evidence of concentric cardiac remodelling (CCR), defined as an increase in left-ventricular mass over end-diastolic volumes. CCR is a predictor of cardiac disease, but the molecular pathways leading to this in schizophrenia are unknown. We aimed to explore the relevance of hypertensive and non-hypertensive pathways to CCR and their potential molecular underpinnings in schizophrenia. In this multimodal case–control study, we collected cardiac and whole-body fat magnetic resonance imaging (MRI), clinical measures, and blood levels of several cardiometabolic biomarkers known to potentially cause CCR from individuals with schizophrenia, alongside healthy controls (HCs) matched for age, sex, ethnicity, and body surface area. Of the 50 participants, 34 (68%) were male. Participants with schizophrenia showed increases in cardiac concentricity (d = 0.71, 95% CI: 0.12, 1.30; p = 0.01), indicative of CCR, but showed no differences in overall content or regional distribution of adipose tissue compared to HCs. Despite the cardiac changes, participants with schizophrenia did not demonstrate activation of the hypertensive CCR pathway; however, they showed evidence of adipose dysfunction: adiponectin was reduced (d = −0.69, 95% CI: −1.28, −0.10; p = 0.02), with evidence of activation of downstream pathways, including hypertriglyceridemia, elevated C-reactive protein, fasting glucose, and alkaline phosphatase. In conclusion, people with schizophrenia showed adipose tissue dysfunction compared to body mass-matched HCs. The presence of non-hypertensive CCR and a dysmetabolic phenotype may contribute to excess cardiovascular risk in schizophrenia. If our results are confirmed, acting on this pathway could reduce cardiovascular risk and resultant life-years lost in people with schizophrenia.

Journal article

Halliday BP, de Marvao A, Thilaganathan B, 2021, Peripartum cardiomyopathy and pre-eclampsia: two tips of the same iceberg, EUROPEAN JOURNAL OF HEART FAILURE, Vol: 23, Pages: 2070-2072, ISSN: 1388-9842

Journal article

Lota AS, Hazebroek M, Theotokis P, Wassall R, Salmi S, Halliday B, Tayal U, Verdonschot J, Meena D, de Marvao A, Iacob A, Hammersley D, Jones R, Wage R, Buchan R, Yazdani M, Noseda M, Mittal T, Wong J, Robertus JL, Baksi J, Vassiliou V, Tzoulaki Iet al., 2021, Genetic Overlap of Acute Myocarditis and Inherited Cardiomyopathy, Annual Scientific Sessions of the American-Heart-Association / Resuscitation Science Symposium, Publisher: LIPPINCOTT WILLIAMS & WILKINS, ISSN: 0009-7322

Conference paper

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