Imperial College London

DrBrianHalliday

Faculty of MedicineNational Heart & Lung Institute

Sr Lecturer Cardiomyopathy Cardiovascular Magnetic Resonance
 
 
 
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b.halliday

 
 
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Cardiovascular MR UnitRoyal Brompton Campus

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Summary

 

Publications

Publication Type
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115 results found

Hammersley DJ, Mukhopadhyay S, Chen X, Cheng L, Jones RE, Mach L, Curran L, Yazdani M, Iacob A, Lota AS, Khalique Z, De Marvao A, Baruah R, Guha K, Ware JS, Gregson J, Zhao S, Pennell DJ, Tayal U, Prasad SK, Halliday BPet al., 2024, Comparative prognostic importance of measures of left atrial structure and function in non-ischaemic dilated cardiomyopathy., Eur Heart J Cardiovasc Imaging

AIMS: To compare the association between measures of left atrial (LA) structure and function, derived from cardiovascular magnetic resonance (CMR), with cardiovascular (CV) death or non-fatal heart failure (HF) events in patients with non-ischaemic dilated cardiomyopathy (DCM). METHODS AND RESULTS: CMR studies of 580 prospectively recruited patients with DCM in sinus rhythm (median age 54 [interquartile range 44-64] years, 61% men, median LVEF 42% [30-51%]) were analysed for measures of LA structure (left atrial maximum volume index [LAVImax], left atrial minimum volume index [LAVImin]) and function (left atrial emptying fraction [LAEF], left atrial reservoir strain [LARS], left atrial conduit strain [LACS] and left atrial booster strain [LABS]). Over median follow-up of 7.4 years, 103 patients (18%) met the primary endpoint. Apart from LACS, each measure of LA structure and function was associated with the primary endpoint after adjusting for other important prognostic variables. The addition of each LA metric to a baseline model containing the same important prognostic covariates improved model discrimination, with LAVImin providing the greatest improvement (C-statistic improvement: 0.702 to 0.738; χ2 test comparing likelihood ratio p < 0.0001; categorical net reclassification index: 0.210 (95% CI 0.023-0.392)). Patients in the highest tercile of LAVImin had similar event rates to those with persistent atrial fibrillation. Measures of LA strain did not enhance model discrimination above LA volumetric measures. CONCLUSION: Measure of left atrial structure and function offer important prognostic information in patients with DCM and enhance prediction of adverse outcomes. LA strain was not incremental to volumetric analysis for risk prediction.

Journal article

Owen R, Buchan R, Frenneaux M, Jarman JWE, Baruah R, Lota AS, Halliday BP, Roberts AM, Izgi C, Van Spall H, Michos ED, McMurray J, Januzzi JL, Pennell DJ, Cook SA, Ware JS, Barton PJ, Gregson J, Prasad SK, Tayal Uet al., 2024, Sex differences in the clinical presentation and natural history of dilated cardiomyopathy, JACC: Heart Failure, Vol: 12, Pages: 352-363, ISSN: 2213-1787

Background: Biological sex has a diverse impact on the cardiovascular system. Its influence on dilated cardiomyopathy (DCM) remains unresolved.Objective: To investigate sex-specific differences in DCM presentation, natural history, and prognostic factors.Methods We conducted a prospective observational cohort study of DCM patients, assessing baseline characteristics, CMR-imaging, biomarkers and genotype. The composite outcome was cardiovascular mortality or major heart-failure (HF) events. Results: Overall, 206 females and 398 males with DCM were followed for a median of 3.9 years. At baseline female patients had higher left ventricular ejection fraction (LVEF), smaller left ventricular volumes, less prevalent mid-wall myocardial fibrosis (23% vs 42%) and lower high sensitivity cardiac troponin (hs-cTnI) than males (all p<0.05), with no difference in time from diagnosis, age at enrollment, NT-proBNP levels, pathogenic DCM genetic variants, myocardial fibrosis extent or medications used for HF. Despite a more favourable profile, the risk of the primary outcome at 2 years was higher in females than males (8.6% vs 4.4%, adjusted hazard ratio 3.14, 95% CI 1.55 to 6.35, p=0.001). Between 2-5 years, the effect of sex as a prognostic modifier attenuated. Age, mid-wall myocardial fibrosis, LVEF, left atrial volume, NT-proBNP, hs-cTnI, left bundle branch block and NYHA class were not sex specific prognostic factors. Conclusions: We identify a novel paradox in prognosis for females with DCM. Female DCM patients have a paradoxical early increase in major HF events despite less prevalent myocardial fibrosis and a milder phenotype at presentation. Future studies should interrogate the mechanistic basis for these sex differences.

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

Kasiakogias A, Ragavan A, Halliday BP, 2023, Your Heart Function Has Normalized-What Next After TRED-HF?, Curr Heart Fail Rep, Vol: 20, Pages: 542-554

PURPOSE OF REVIEW: With the widespread implementation of contemporary disease-modifying heart failure therapy, the rates of normalization of ejection fraction are continuously increasing. The TRED-HF trial confirmed that heart failure remission rather than complete recovery is typical in patients with dilated cardiomyopathy who respond to therapy. The present review outlines key points related to the management and knowledge gaps of this growing patient group, focusing on patients with non-ischaemic dilated cardiomyopathy. RECENT FINDINGS: There is substantial heterogeneity among patients with normalized ejection fraction. The specific etiology is likely to affect the outcome, although a multiple-hit phenotype is frequent and may not be identified without comprehensive characterization. A monogenic or polygenic genetic susceptibility is common. Ongoing pathophysiological processes may be unraveled with advanced cardiac imaging, biomarkers, multi-omics, and machine learning technologies. There are limited studies that have investigated the withdrawal of specific heart failure therapies in these patients. Diuretics may be safely withdrawn if there is no evidence of congestion, while continued therapy with at least some disease-modifying therapy is likely to be required to reduce myocardial workload and sustain remission for the vast majority. Understanding the underlying disease mechanisms of patients with normalized ejection fraction is crucial in identifying markers of myocardial relapse and guiding individualized therapy in the future. Ongoing clinical trials should inform personalized approaches to therapy.

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

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

Goh ZM, Javed W, Shabi M, Klassen JRL, Saunderson CED, Farley J, Spurr M, Dall'Armellina E, Levelt E, Greenwood J, Halliday B, Plein S, Swoboda Pet al., 2023, Early prediction of left ventricular function improvement in patients with new-onset heart failure and presumed non-ischaemic aetiology, Open Heart, Vol: 10, ISSN: 2053-3624

OBJECTIVES: To determine baseline characteristics predictive of left ventricular ejection fraction (LVEF) recovery in patients diagnosed with heart failure with reduced ejection fraction (HFrEF) and presumed non-ischaemic aetiology. METHODS: We prospectively recruited patients who were diagnosed with HFrEF (LVEF ≤40%) on echocardiography and subsequently underwent cardiac MRI. Patients were excluded if they had a known history of coronary artery disease (>70% on invasive coronary angiography), myocardial infarction, coronary revascularisation or anginal symptoms. At cardiac MRI assessment, patients were categorised as either ongoing HFrEF or heart failure with improved ejection fraction (HFimpEF, LVEF >40% with ≥10% of absolute improvement). Clinical characteristics were compared between the groups. Logistic regression was performed to identify variables that were associated with LVEF recovery. Optimal cut-offs in QRISK3 score and baseline LVEF for prediction of LVEF recovery were identified through receiver operating characteristic curve analysis. RESULTS: A total of 407 patients were diagnosed with HFrEF, and 139 (34%) attained HFimpEF at cardiac MRI assessment (median 63 days, IQR 41-119 days). Mean age of the patients was 63±12 years, and 260 (63.9%) were male. At multivariate logistic regression, both QRISK3 score (HR 0.978; 95% CI 0.963 to 0.993, p=0.004) and baseline LVEF (HR 1.044; 95% CI 1.015 to 1.073, p=0.002) were independent predictors of HFimpEF. Among patients with baseline LVEF ≤25%, only 22 (21.8%) recovered. In patients with baseline LVEF 25-40%, QRISK3 score >18% was associated with lack of recovery (HR 2.75; 95% CI 1.70 to 4.48, p<0.001). Additionally, QRISK3 score was associated with the presence of ischaemic late gadolinium enhancement (HR 1.035; 95% CI 1.018 to 1.053, p<0.001). CONCLUSIONS: The QRISK3 score helps identify patients with HFrEF with undiagnosed vascular dise

Journal article

Jones RE, Gruszczyk AV, Schmidt C, Hammersley DJ, Mach L, Lee M, Wong J, Yang M, Hatipoglu S, Lota AS, Barnett SN, Toscano-Rivalta R, Owen R, Raja S, De Robertis F, Smail H, De-Souza A, Stock U, Kellman P, Griffin J, Dumas M-E, Martin JL, Saeb-Parsy K, Vazir A, Cleland JGF, Pennell DJ, Bhudia SK, Halliday BP, Noseda M, Frezza C, Murphy MP, Prasad SKet al., 2023, Assessment of left ventricular tissue mitochondrial bioenergetics in patients with stable coronary artery disease, Nature Cardiovascular Research, Vol: 2, Pages: 733-745, ISSN: 2731-0590

Recurrent myocardial ischemia can lead to left ventricular (LV) dysfunction in patients with coronary artery disease (CAD). In this observational cohort study, we assessed for chronic metabolomic and transcriptomic adaptations within LV myocardium of patients undergoing coronary artery bypass grafting. During surgery, paired transmural LV biopsies were acquired on the beating heart from regions with and without evidence of inducible ischemia on preoperative stress perfusion cardiovascular magnetic resonance. From 33 patients, 63 biopsies were acquired, compared to analysis of LV samples from 11 donor hearts. The global myocardial adenosine triphosphate (ATP):adenosine diphosphate (ADP) ratio was reduced in patients with CAD as compared to donor LV tissue, with increased expression of oxidative phosphorylation (OXPHOS) genes encoding the electron transport chain complexes across multiple cell types. Paired analyses of biopsies obtained from LV segments with or without inducible ischemia revealed no significant difference in the ATP:ADP ratio, broader metabolic profile or expression of ventricular cardiomyocyte genes implicated in OXPHOS. Differential metabolite analysis suggested dysregulation of several intermediates in patients with reduced LV ejection fraction, including succinate. Overall, our results suggest that viable myocardium in patients with stable CAD has global alterations in bioenergetic and transcriptional profile without large regional differences between areas with or without inducible ischemia.

Journal article

Javed S, Halliday BP, 2023, Implantable cardioverter-defibrillator implantation in non-ischaemic cardiomyopathy: towards individualized risk stratification, EUROPEAN JOURNAL OF HEART FAILURE, Vol: 25, Pages: 751-753, ISSN: 1388-9842

Journal article

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

Zaidi HA, Jones RE, Hammersley DJ, Hatipoglu S, Balaban G, Mach L, Halliday BP, Lamata P, Prasad SK, Bishop MJet al., 2023, Machine learning analysis of complex late gadolinium enhancement patterns to improve risk prediction of major arrhythmic events, Frontiers in Cardiovascular Medicine, Vol: 10, ISSN: 2297-055X

Background: Machine learning analysis of complex myocardial scar patterns affords the potential to enhance risk prediction of life-threatening arrhythmia in stable coronary artery disease (CAD).Objective: To assess the utility of computational image analysis, alongside a machine learning (ML) approach, to identify scar microstructure features on late gadolinium enhancement cardiovascular magnetic resonance (LGE-CMR) that predict major arrhythmic events in patients with CAD.Methods: Patients with stable CAD were prospectively recruited into a CMR registry. Shape-based scar microstructure features characterizing heterogeneous (‘peri-infarct’) and homogeneous (‘core’) fibrosis were extracted. An ensemble of machine learning approaches were used for risk stratification, in addition to conventional analysis using Cox modeling.Results: Of 397 patients (mean LVEF 45.4 ± 16.0) followed for a median of 6 years, 55 patients (14%) experienced a major arrhythmic event. When applied within an ML model for binary classification, peri-infarct zone (PIZ) entropy, peri-infarct components and core interface area outperformed a model representative of the current standard of care (LVEF<35% and NYHA>Class I): AUROC (95%CI) 0.81 (0.81–0.82) vs. 0.64 (0.63–0.65), p = 0.002. In multivariate cox regression analysis, these features again remained significant after adjusting for LVEF<35% and NYHA>Class I: PIZ entropy hazard ratio (HR) 1.88, 95% confidence interval (CI) 1.38–2.56, p < 0.001; number of PIZ components HR 1.34, 95% CI 1.08–1.67, p = 0.009; core interface area HR 1.6, 95% CI 1.29–1.99, p = <0.001.Conclusion: Machine learning models using LGE-CMR scar microstructure improved arrhythmic risk stratification as compared to guideline-based clinical parameters; highlighting a potential novel approach to identifying candidates for implantab

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

Halliday BP, 2022, State of the art: multimodality imaging in dilated cardiomyopathy, HEART, Vol: 108, Pages: 1910-1917, ISSN: 1355-6037

Journal article

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

Amin R, Morris-Rosendahl D, Edwards M, Tayal U, Buchan R, Hammersley D, Jones R, Gati S, Khalique Z, Almogheer B, Pennell D, Baksi A, Pantazis A, Ware J, Prasad S, Halliday Bet al., 2022, The addition of genetic testing and cardiovascular magnetic resonance to routine clinical data for stratification of aetiology in dilated cardiomyopathy, Frontiers in Cardiovascular Medicine, Vol: 9, ISSN: 2297-055X

Background: Guidelines recommend genetic testing and cardiovascular magnetic resonance (CMR) for the investigation of dilated cardiomyopathy (DCM). However, the incremental value is unclear. We assessed the impact of these investigations in determining etiology.Methods: Sixty consecutive patients referred with DCM and recruited to our hospital biobank were selected. Six independent experts determined the etiology of each phenotype in a step-wise manner based on (1) routine clinical data, (2) clinical and genetic data and (3) clinical, genetic and CMR data. They indicated their confidence (1-3) in the classification and any changes to management at each step.Results: Six physicians adjudicated 60 cases. The addition of genetics and CMR resulted in 57 (15.8%) and 26 (7.2%) changes in the classification of etiology, including an increased number of genetic diagnoses and a reduction in idiopathic diagnoses. Diagnostic confidence improved at each step (p < 0.0005). The number of diagnoses made with low confidence reduced from 105 (29.2%) with routine clinical data to 71 (19.7%) following the addition of genetics and 37 (10.3%) with the addition of CMR. The addition of genetics and CMR led to 101 (28.1%) and 112 (31.1%) proposed changes to management, respectively. Interobserver variability showed moderate agreement with clinical data (κ = 0.44) which improved following the addition of genetics (κ = 0.65) and CMR (κ = 0.68).Conclusion: We demonstrate that genetics and CMR, frequently changed the classification of etiology in DCM, improved confidence and interobserver variability in determining the diagnosis and had an impact on proposed management.

Journal article

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

Balaban G, Halliday BP, Hammersley D, Rinaldi CA, Prasad SK, Bishop MJ, Lamata Pet al., 2022, Left ventricular shape predicts arrhythmic risk in fibrotic dilated cardiomyopathy, EUROPACE, Vol: 24, Pages: 1137-1147, ISSN: 1099-5129

Journal article

McGurk KA, Halliday BP, 2022, Dilated cardiomyopathy - details make the difference, European Journal of Heart Failure, Vol: 24, ISSN: 1388-9842

Journal article

Quinn EM, Mason S, Halliday B, 2022, Remote genetic counselling provision for heart failure patients at a UK transplant centre, Publisher: OXFORD UNIV PRESS, Pages: I124-I125, ISSN: 1474-5151

Conference paper

Ragavan A, Hogan J, Halliday BP, 2022, The spectrum of heart failure with improved ejection fraction: persistent congestion, to heart failure remission and perhaps recovery? COMMENT, EUROPEAN JOURNAL OF HEART FAILURE, Vol: 24, Pages: 1180-1182, ISSN: 1388-9842

Journal article

Tayal U, Verdonschot JAJ, Hazebroek MR, Howard J, Gregson J, Newsome S, Gulati A, Pua CJ, Halliday BP, Lota AS, Buchan RJ, Whiffin N, Kanapeckaite L, Baruah R, Jarman JWE, O'Regan DP, Barton PJR, Ware JS, Pennell DJ, Adriaans BP, Bekkers SCAM, Donovan J, Frenneaux M, Cooper LT, Januzzi JL, Cleland JGF, Cook SA, Deo RC, Heymans SRB, Prasad SKet al., 2022, Precision phenotyping of dilated cardiomyopathy using multidimensional data., Journal of the American College of Cardiology, Vol: 79, Pages: 2219-2232, ISSN: 0735-1097

BACKGROUND: Dilated cardiomyopathy (DCM) is a final common manifestation of heterogenous etiologies. Adverse outcomes highlight the need for disease stratification beyond ejection fraction. OBJECTIVES: The purpose of this study was to identify novel, reproducible subphenotypes of DCM using multiparametric data for improved patient stratification. METHODS: Longitudinal, observational UK-derivation (n = 426; median age 54 years; 67% men) and Dutch-validation (n = 239; median age 56 years; 64% men) cohorts of DCM patients (enrolled 2009-2016) with clinical, genetic, cardiovascular magnetic resonance, and proteomic assessments. Machine learning with profile regression identified novel disease subtypes. Penalized multinomial logistic regression was used for validation. Nested Cox models compared novel groupings to conventional risk measures. Primary composite outcome was cardiovascular death, heart failure, or arrhythmia events (median follow-up 4 years). RESULTS: In total, 3 novel DCM subtypes were identified: profibrotic metabolic, mild nonfibrotic, and biventricular impairment. Prognosis differed between subtypes in both the derivation (P < 0.0001) and validation cohorts. The novel profibrotic metabolic subtype had more diabetes, universal myocardial fibrosis, preserved right ventricular function, and elevated creatinine. For clinical application, 5 variables were sufficient for classification (left and right ventricular end-systolic volumes, left atrial volume, myocardial fibrosis, and creatinine). Adding the novel DCM subtype improved the C-statistic from 0.60 to 0.76. Interleukin-4 receptor-alpha was identified as a novel prognostic biomarker in derivation (HR: 3.6; 95% CI: 1.9-6.5; P = 0.00002) and validation cohorts (HR: 1.94; 95% CI: 1.3-2.8; P = 0.00005). CONCLUSIONS: Three reproducible, mechanistically distinct DCM subtypes were identified using widely available clinical and biological data, adding prognostic value to trad

Journal article

Mahmood A, Morris-Rosendahl D, Edwards M, Fleming A, Homfray T, Mason S, Quinn E, Ware J, Baksi J, Prasad S, Pantazis A, Halliday Bet al., 2022, DISEASE PENETRANCE IN ASYMPTOMATIC CARRIERS OF FAMILIAL CARDIOMYOPATHY VARIANTS, Annual Conference of the British-Cardiovascular-Society - 100 Years of Cardiology, Publisher: BMJ PUBLISHING GROUP, Pages: A9-A9, ISSN: 1355-6037

Conference paper

Tayal U, 2022, Exposure to elevated nitrogen dioxide concentrations and cardiac remodelling in patients with dilated cardiomyopathy, Journal of Cardiac Failure, Vol: 28, Pages: 924-934, ISSN: 1071-9164

Rationale: Empirical evidence suggests a strong link between exposure to air pollution and heart failure incidence, hospitalisations and mortality, but the biological basis of this remains unclear. Objective: To determine the relationship between differential air pollution levels and changes in cardiac structure and function in patients with dilated cardiomyopathy. Methods and Results: We undertook a prospective longitudinal observational cohort study of patients in England with dilated cardiomyopathy (enrollment 2009-2015; n=716, 66% male, 85% Caucasian) and conducted cross sectional analysis at the time of study enrollment. Annual average air pollution exposure estimates for nitrogen dioxide (NO2) and particulate matter with diameter ≤ 2.5µm (PM2.5) at enrolment were assigned to each residential postcode (on average 12 households). The relationship between air pollution and cardiac morphology was assessed using linear regression modelling. Greater ambient exposure to NO2 was associated with higher indexed left ventricular mass (4.3 g/m2 increase per interquartile range (IQR) increase in NO2, 95% CI 1.9 to 7.0 g/m2) and lower left ventricular ejection fraction (-1.5% decrease per IQR increase in NO2, 95% CI -2.7 to -0.2%), independent of age, sex, socio-economic status and clinical covariates. The associations were robust to adjustment for smoking status and geographical clustering by postcode area. The effect of air pollution on left ventricular mass was greatest in women. These effects were specific to NO2 exposure. Conclusion: Exposure to air pollution is associated with raised left ventricular mass and lower left ventricular ejection fraction, with the strongest effect in women. Whilst epidemiological associations between air pollution and heart failure have been established and supported by pre-clinical studies, our findings provide novel empirical evidence of cardiac remodelling and exposure to air pollution with important clinical and public health

Journal article

Halliday BP, Cleland JGF, 2022, Maintaining Success for Patients With Dilated Cardiomyopathy and Remission of Heart Failure, JACC-BASIC TO TRANSLATIONAL SCIENCE, Vol: 7, Pages: 500-503, ISSN: 2452-302X

Journal article

Tayal U, gregson J, Buchan R, Whiffin N, Halliday B, Lota A, Roberts A, Baksi A, Voges I, Jarman J, Baruah R, Frenneaux M, Cleland J, Barton P, Pennell D, Ware J, Cook S, Prasad Set al., 2022, Moderate excess alcohol consumption and adverse cardiac remodelling in dilated cardiomyopathy, Heart, Vol: 108, Pages: 619-625, ISSN: 1355-6037

Objective The effect of moderate excess alcohol consumption is widely debated and has not been well defined in dilated cardiomyopathy (DCM). There is need for a greater evidence base to help advise patients. We sought to evaluate the effect of moderate excess alcohol consumption on cardiovascular structure, function and outcomes in DCM. Methods Prospective longitudinal observational cohort study. Patients with DCM (n=604) were evaluated for a history of moderate excess alcohol consumption (UK government guidelines; >14 units/week for women, >21 units/week for men) at cohort enrollment, had cardiovascular magnetic resonance and were followed up for the composite endpoint of cardiovascular death, heart failure and arrhythmic events. Patients meeting criteria for alcoholic cardiomyopathy were not recruited. ResultsDCM patients with a history of moderate excess alcohol consumption (n=98, 16%) had lower biventricular function and increased chamber dilatation of the left ventricle, right ventricle and left atrium, as well as increased left ventricular hypertrophy compared to patients without moderate alcohol consumption. They were more likely to be male (alcohol excess group– n =92, 94% vs n =306, 61%, p=<0.001). After adjustment for biological sex, moderate excess alcohol was not associated with adverse cardiac structure. There was no difference in mid-wall myocardial fibrosis between groups. Prior moderate excess alcohol consumption did not affect prognosis (HR 1.29, 0.73 to 2.26, p=0.38) during median follow up of 3.9 years. ConclusionDilated cardiomyopathy patients with moderate excess alcohol consumption have adverse cardiac structure and function at presentation but this is largely due to biological sex. Alcohol may contribute to sex-specific phenotypic differences in DCM. These findings help to inform lifestyle discussions for patients with dilated cardiomyopathy.

Journal article

Halliday B, Owen R, Gregson J, Vazir A, Wassall R, Khalique Z, Lota A, Tayal U, Hammersley D, Jones R, Pennell D, Cowie M, Cleland J, Prasad Set al., 2022, Changes in clinical and imaging variables during withdrawal of heart failure therapy in recovered dilated cardiomyopathy, ESC Heart Failure, Vol: 9, ISSN: 2055-5822

Aims: To profile the changes in non-invasive clinical, biochemical and imaging markers during withdrawal of therapy in patients with recovered dilated cardiomyopathy, providing insights into the pathophysiology of relapse.Methods: Clinical, biochemical and imaging data from patients during phased withdrawal of therapy in the randomised or single-arm cross-over phases of TRED-HF were profiled. Clinical variables were measured at each study visit and imaging variables were measured at baseline, 16 weeks and 6 months. Results: Amongst the 49 patients (35% women, mean age 53.6 years [standard deviation 11.6]) who withdrew therapy, 20 relapsed. Increases in mean heart rate (7.6 beats per minute [95% CIs 4.5,10.7]), systolic blood pressure (6.6mmHg [95% CI 2.7,10.5]) and diastolic blood pressure (5.8mmHg [95% CI 3.1,8.5]) were observed within 4-8 weeks of starting to withdraw therapy. A rise in mean LV mass (5.1g/m2 [95%CI 2.8,7.3]) and LV end-diastolic volume (3.9ml/m2 [95% CI 1.1,6.7]) and a reduction in mean LV ejection fraction (-4.2 [95% CI -6.6, -1.8]) were seen by 16 weeks, the earliest imaging follow-up. Plasma NT-pro-BNP fell immediately after withdrawing beta-blockers and only tended to increase 6 months after beginning therapy withdrawal (mean change in log NT-pro-BNP at 6 months: 0.2, 95% CI -0.1,0.4). Conclusion: Changes in plasma NT-pro-BNP are a late feature of relapse, often months after a reduction in LV function. A rise in heart rate and blood pressure are observed soon after withdrawing therapy in recovered dilated cardiomyopathy, typically accompanied or closely followed by early changes in LV structure and function.

Journal article

Leyva F, Zegard A, Okafor O, Foley P, Umar F, Taylor RJ, Marshall H, Stegemann B, Moody W, Steeds RP, Halliday BP, Hammersley DJ, Jones RE, Prasad SK, Qiu Tet al., 2022, Myocardial Fibrosis Predicts Ventricular Arrhythmias and Sudden Death After Cardiac Electronic Device Implantation, JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, Vol: 79, Pages: 665-678, ISSN: 0735-1097

Journal article

Hammersley D, Buchan R, Lota A, Mach L, Jones R, Halliday B, Tayal U, Meena D, Dehghan A, Tzoulaki I, Baksi A, Pantazis A, Roberts A, Prasad S, Ware Jet al., 2022, Direct and indirect effect of the COVID-19 pandemic on patients with cardiomyopathy, Open Heart, Vol: 9, Pages: 1-9, ISSN: 2053-3624

Objectives: (i) To evaluate the prevalence and hospitalisation rate of COVID-19 infections amongst patients with dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM) in the Royal Brompton & Harefield Hospital Cardiovascular Research Centre (RBHH CRC) Biobank. (ii) To evaluate the indirect impact of the pandemic on patients with cardiomyopathy through the Heart Hive COVID-19 study. (iii) To assess the impact of the pandemic on national cardiomyopathy-related hospital admissions.Methods: (i) 1,236 patients (703 DCM, 533 HCM) in the RBHH CRC Biobank were assessed for COVID-19 infections and hospitalisations; ii) 207 subjects (131 cardiomyopathy, 76 without heart disease) in the Heart Hive COVID-19 study completed online surveys evaluating physical health, psychological wellbeing, and behavioural adaptations during the pandemic; (iii) 11,447 cardiomyopathy-related hospital admissions across NHS England were studied from NHS Digital Hospital Episode Statistics over 2019-2020. Results: A comparable proportion of patients with cardiomyopathy in the RBHH CRC Biobank had tested positive for COVID-19 compared with the UK population (1.1% vs 1.6%, p=0.14), but a higher proportion of those infected were hospitalised (53.8% vs 16.5%, p=0.002). In the Heart Hive COVID-19 study, more patients with cardiomyopathy felt their physical health had deteriorated due to the pandemic than subjects without heart disease (32.3% vs 13.2%, p=0.004) despite only 4.6% of the cardiomyopathy cohort reporting COVID-19 symptoms. A 17.9% year-on-year reduction in national cardiomyopathy-related hospital admissions was observed in 2020.Conclusion: Patients with cardiomyopathy had similar reported rates of testing positive for COVID-19 to the background population, but those with test-proven infection were hospitalised more frequently. Deterioration in physical health amongst patients could not be explained by COVID-19 symptoms, inferring a significant contribution of the indirect con

Journal article

Lota AS, Tsao A, Owen R, Halliday BP, Auger D, Vassiliou VS, Tayal U, Almogheer B, Vilches S, Al-Balah A, Patel A, Mouy F, Buchan R, Newsome S, Gregson J, Ware JS, Cook SA, Cleland JGF, Pennell DJ, Prasad SKet al., 2021, Prognostic significance of non-ischaemic patterns of myocardial fibrosis in patients with normal left ventricular volumes and ejection fraction – the FINALIZE study, JACC: Cardiovascular Imaging, Vol: 14, Pages: 2353-2365, ISSN: 1876-7591

Background: Non-ischaemic patterns of late gadolinium enhancement (LGE) with normal left ventricular volumes and ejection fraction are increasingly detected on cardiovascular magnetic resonance (CMR) but their prognostic significance, and consequently management, is uncertain. Objectives: To investigate the prognostic significance of LGE in patients without coronary artery disease and with normal range LV volumes and ejection fraction. Methods: Patients with mid-wall/subepicardial LGE and normal LV volumes, wall thickness and ejection fraction on CMR were enrolled and compared to a control group without LGE.57 The primary outcome was actual or aborted sudden cardiac death (SCD). Results: Of 748 patients enrolled, 401 had LGE and 347 did not. Median age was 50 years (IQR 38-61), LV ejection fraction 66% (IQR 62-70) and 287 (38%) were women. Scan indications included chest pain (40%), palpitation (33%) and breathlessness (13%). Nopatient experienced SCD and only one LGE+ patient (0.13%) had an aborted SCD in the 11th follow-up year. Over a median of 4.3years, thirty patients (4.0%) died. All-cause mortality was similar for LGE+/- patients (3.7% vs 4.3%; p=0.71) and was associated with age (H 2.04 per 10-years; 95%CI 1.46-2.79; p<0.001). Twenty-one LGE+ and 4 LGE- patients had an unplanned CV hospitalisation (HR 7.22; 95%CI 4.26-21.17; p<0.0001). Conclusion: There was a low SCD risk during long-term follow-up in patients with LGE but otherwise normal LV volumes and ejection fraction. Mortality was driven by age and not LGE presence, location or extent, although the latter was associated with greater CV hospitalisation for suspected myocarditis and symptomatic ventricular tachycardia.

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

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