Imperial College London

Dr Paz (Upasana) Tayal

Faculty of MedicineNational Heart & Lung Institute

Academic Clinical Lecturer
 
 
 
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Contact

 

u.tayal14

 
 
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Location

 

Cardiovascular BRUSydney StreetRoyal Brompton Campus

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Summary

 

Publications

Publication Type
Year
to

95 results found

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

Tayal U, 2022, The role of precision phenotyping in dilated cardiomyopathy: Defining novel disease subtypes using multidimensional data, Journal of the American College of Cardiology, 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: To identify novel, reproducible sub-phenotypes of DCM using multi-parametric data for improved patient-stratification. Methods: Longitudinal, observational UK-derivation (n=426, median age 54y, 67% men) and Dutch-validation (n=239, median age 56y, 64% men) cohorts of DCM patients (enrolled 2009-16) 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 4y). Results: Three novel DCM subtypes were identified: profibrotic metabolic; mild non-fibrotic; and biventricular impairment. Prognosis differed between subtypes in both 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, five variables were sufficient for classification (biventricular end-systolic and left atrial volumes, myocardial fibrosis, and creatinine). Adding the novel DCM subtype improved the C statistic from 0.6 to 0.76. Interleukin-4 receptor-alpha was identified as a novel prognostic biomarker in derivation (hazard ratio (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 traditional risk models. They may improve patient selection for novel interventions thereby enabling precis

Journal article

Lala A, Tayal U, Hamo CE, Youmans Q, Al-Khatib SM, Bozkurt B, Davis MB, Januzzi J, Mentz R, Sauer A, Walsh MN, Yancy C, Gulati Met al., 2022, Sex Differences in Heart Failure, JOURNAL OF CARDIAC FAILURE, Vol: 28, Pages: 477-498, ISSN: 1071-9164

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

Tayal U, 2021, Exposure to elevated nitrogen dioxide concentrations and cardiac remodelling in patients with dilated cardiomyopathy, Journal of Cardiac Failure, 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

Stroeks SLVM, Hellebrekers DMEI, Claes GRF, Tayal U, Krapels IPC, Vanhoutte EK, van den Wijngaard A, Henkens MTHM, Ware JS, Heymans SRB, Brunner HG, Verdonschot JAJet al., 2021, Clinical impact of re-evaluating genes and variants implicated in dilated cardiomyopathy, Genetics in Medicine, Vol: 23, Pages: 2186-2193, ISSN: 1098-3600

PurposeAccurate interpretation of variants detected in dilated cardiomyopathy (DCM) is crucial for patient care but has proven challenging. We applied a set of proposed refined American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) criteria for DCM, reclassified all detected variants in robust genes, and associated these results to patients' phenotype.MethodsThe study included 902 DCM probands from the Maastricht Cardiomyopathy Registry who underwent genetic testing. Two gene panel sizes (extended n = 48; and robust panel n = 14) and two standards of variant classification (standard versus the proposed refined ACMG/AMP criteria) were applied to compare genetic yield.ResultsA pathogenic or likely pathogenic (P/LP) variant was found in 17.8% of patients, and a variant of uncertain significance (VUS) was found in 32.8% of patients when using method 1 (extended panel (n = 48) + standard ACMG/AMP), compared to respectively 16.9% and 12.9% when using method 2 (robust panel (n = 14) + standard ACMG/AMP), and respectively 14% and 14.5% using method 3 (robust panel (n = 14) + refined ACMG/AMP). Patients with P/LP variants had significantly lower event-free survival compared to genotype-negative DCM patients.ConclusionStringent gene selection for DCM genetic testing reduced the number of VUS while retaining ability to detect similar P/LP variants. The number of genes on diagnostic panels should be limited to genes that have the highest signal to noise ratio.

Journal article

Simoes Monteiro de Marvao A, McGurk K, Zheng S, Thanaj M, Bai W, Duan J, Biffi C, Mazzarotto F, Statton B, Dawes T, Savioli N, Halliday B, Xu X, Buchan R, Baksi A, Quinlan M, Tokarczuk P, Tayal U, Francis C, Whiffin N, Theotokis A, Zhang X, Jang M, Berry A, Pantazis A, Barton P, Rueckert D, Prasad S, Walsh R, Ho C, Cook S, Ware J, O'Regan Det al., 2021, Phenotypic expression and outcomes in individuals with rare genetic variants of hypertrophic cardiomyopathy, Journal of the American College of Cardiology, Vol: 78, Pages: 1097-1110, ISSN: 0735-1097

Background: Hypertrophic cardiomyopathy (HCM) is caused by rare variants in sarcomereencoding genes, but little is known about the clinical significance of these variants in thegeneral population.Objectives: To compare lifetime outcomes and cardiovascular phenotypes according to thepresence of rare variants in sarcomere-encoding genes amongst middle-aged adults.Methods: We analysed whole exome sequencing and cardiac magnetic resonance (CMR)imaging in UK Biobank participants stratified by sarcomere-encoding variant status.Results: The prevalence of rare variants (allele frequency <0.00004) in HCM-associatedsarcomere-encoding genes in 200,584 participants was 2.9% (n=5,712; 1 in 35), and theprevalence of variants pathogenic or likely pathogenic for HCM (SARC-HCM-P/LP) was0.25% (n=493, 1 in 407). SARC-HCM-P/LP variants were associated with increased risk ofdeath or major adverse cardiac events compared to controls (HR 1.69, 95% CI 1.38 to 2.07,p<0.001), mainly due to heart failure endpoints (HR 4.23, 95% CI 3.07 to 5.83, p<0.001). In21,322 participants with CMR, SARC-HCM-P/LP were associated with asymmetric increasein left ventricular maximum wall thickness (10.9±2.7 vs 9.4±1.6 mm, p<0.001) buthypertrophy (≥13mm) was only present in 18.4% (n=9/49, 95% CI 9 to 32%). SARC-HCMP/LP were still associated with heart failure after adjustment for wall thickness (HR 6.74,95% CI 2.43 to 18.7, p<0.001).Conclusions: In this population of middle-aged adults, SARC-HCM-P/LP variants have lowaggregate penetrance for overt HCM but are associated with increased risk of adversecardiovascular outcomes and an attenuated cardiomyopathic phenotype. Although absoluteevent rates are low, identification of these variants may enhance risk stratification beyondfamilial disease.

Journal article

Halliday B, Vazir A, Owen R, Gregson J, Wassall R, Lota A, Khalique Z, Tayal U, Jones R, Hammersley D, Pantazis A, Baksi A, Rosen S, Pennell D, Cowie M, Cleland J, Prasad Set al., 2021, Heart rate as a marker of relapse during withdrawal of therapy in recovered dilated cardiomyopathy, JACC: Heart Failure, Vol: 9, Pages: 509-517, ISSN: 2213-1779

Objective: To determine the relationship between heart rate and relapse amongst patients in the TRED-HF trial. Background: Understanding markers and mechanisms of relapse amongst patients with recovered dilated cardiomyopathy (DCM) might enable personalised management.Methods: The relationship between serial heart rate measurements and relapse was examined amongst patients TRED-HF, a randomised trial which examined the safety and feasibility of withdrawing heart failure therapy amongst 51 patients with recovered DCM over 6 months. In total, 25 patients were randomised to therapy withdrawal and 26 to continue therapy, of whom 25 subsequently began therapy withdrawal in a single arm crossover phase.Results: The mean heart rate (standard deviation) for those who had therapy withdrawn and did not relapse was 64.6bpm (10.7) at baseline and 74.7bpm (10.4) at follow-up compared to 68.3bpm (11.3) and 86.1bpm (11.8) for those who relapsed. After adjusting for baseline heart rate, patients who had therapy withdrawn and relapsed had a 10.4bpm (95% confidence intervals [CIs] 4.0-16.8) greater rise in heart rate compared to patients who had therapy withdrawn and did not relapse (p=0.002). After adjusting for age, log NT-pro-BNP and LVEF, heart rate (per 10bpm - hazard ratio: 1.65, 95%CI 1.10-2.57, p=0.01) and change in heart rate from baseline (per 10bpm - hazard ratio: 1.70, 95%CI 1.12-2.57, p=0.01) were associated with relapse. The results remained qualitatively the same after adjusting for beta-blocker dose.Conclusion: For patients with DCM and improved LVEF, the rise in heart rate after withdrawing treatment identifies patients who are more likely to relapse. Whether the increase in heart rate is a marker or mediator of relapse requires investigation.

Journal article

Tayal U, Ware JS, Lakdawala NK, Heymans S, Prasad SKet al., 2021, Understanding the genetics of adult-onset dilated cardiomyopathy: what a clinician needs to know., European Heart Journal, Vol: 42, Pages: 2384-2396, ISSN: 0195-668X

There is increasing understanding of the genetic basis to dilated cardiomyopathy and in this review, we offer a practical primer for the practising clinician. We aim to help all clinicians involved in the care of patients with dilated cardiomyopathy to understand the clinical relevance of the genetic basis of dilated cardiomyopathy, introduce key genetic concepts, explain which patients and families may benefit from genetic testing, which genetic tests are commonly performed, how to interpret genetic results, and the clinical applications of results. We conclude by reviewing areas for future research in this dynamic field.

Journal article

Tayal U, Verdonschot J, Hazebroek M, Pua CJ, Lota A, Halliday B, Donovan J, Frenneaux MP, Cleland J, Cook S, Heymans S, Deo R, Prasad Set al., 2021, MULTI-PARAMETRIC PHENOMAPPING USING MACHINE LEARNING IDENTIFIES A NOVEL SUBTYPE OF DILATED CARDIOMYOPATHY AND HIGHLIGHTS IL4R AS A NOVEL PROGNOSTIC BIOMARKER, 70th Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC), Publisher: ELSEVIER SCIENCE INC, Pages: 3408-3408, ISSN: 0735-1097

Conference paper

Tayal U, Fecht D, Chadeau-Hyam M, Owen R, Gregson J, Halliday B, Lota A, Gulliver J, Ware J, Pennell D, Kelly F, Shah A, Miller M, Newby D, Prasad Set al., 2021, AIR POLLUTION AND ADVERSE CARDIAC REMODELLING IN PATIENTS WITH DILATED CARDIOMYOPATHY, 70th Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC), Publisher: ELSEVIER SCIENCE INC, Pages: 600-600, ISSN: 0735-1097

Conference paper

Halliday B, Owen R, Gregson J, Vassiliou V, Chen X, Wage R, Lota A, Khalique Z, Tayal U, Hammersley D, Jones R, Baksi A, Cowie M, Cleland J, Pennell D, Prasad Set al., 2021, Myocardial remodelling after withdrawing therapy for heart failure in patients with recovered dilated cardiomyopathy: insights from TRED-HF, European Journal of Heart Failure, Vol: 23, Pages: 293-301, ISSN: 1388-9842

Aims: To characterize adverse ventricular remodelling after withdrawing therapy in recovered dilated cardiomyopathy (DCM). Methods and results: TRED-HF was a randomized controlled trial with a follow-on single-arm cross-over phase that examined the safety and feasibility of therapy withdrawal in patients with recovered DCM over 6 months. The primary endpoint was relapse of heart failure defined by (i) a reduction in left ventricular (LV) ejection fraction >10% and to <50%, (ii) >10% increase in LV end-diastolic volume and to above the normal range, (iii) a twofold rise in N-terminal pro-B-type natriuretic peptide and to >400 ng/L, or (iv) evidence of heart failure. LV mass, LV and right ventricular (RV) global longitudinal strain (GLS) and extracellular volume were measured using cardiovascular magnetic resonance at baseline and follow-up (6 months or relapse) for 48 patients. LV cell and extracellular matrix masses were derived. The effect of withdrawing therapy, stratified by relapse and genotype, was investigated in the randomized and follow-on phases. In the randomized comparison, withdrawing therapy led to an increase in mean LV mass [5.4 g/m2; 95% confidence interval (CI) 1.3–9.5] and cell mass (4.2 g/m2; 95% CI 0.5–8.0) and a reduction in LV (3.5; 95% CI 1.6–5.5) and RV (2.4; 95% CI 0.1–4.7) GLS. In a non-randomized comparison of all patients (n = 47) who had therapy withdrawn in either phase, there was an increase in LV mass (6.2 g/m2; 95% CI 3.6–8.9; P = 0.0001), cell mass (4.0 g/m2; 95% CI 1.8–6.2; P = 0.0007) and matrix mass (1.7 g/m2; 95% CI 0.7–2.6; P = 0.001) and a reduction in LV GLS (2.7; 95% CI 1.5–4.0; P = 0.0001). Amongst those who had therapy withdrawn and did not relapse, similar changes were observed (n = 28; LV mass: 5.1 g/m2, 95% CI 1.5–8.8, P = 0.007; cell mass: 3.7 g/m2, 95% CI 0.3–7.0, P = 0.03; matrix mass: 1.7 g/m2, 95% CI 0.4–3.0, P = 0.02; LV GLS: 1.7, 95% CI

Journal article

Sweeney M, Cole GD, Pabari P, Hadjiphilippou S, Tayal U, Mayet J, Chapman N, Plymen CMet al., 2021, Urinary drug metabolite testing in chronic heart failure patients indicates high levels of adherence with life-prolonging therapies, ESC HEART FAILURE, Vol: 8, Pages: 2334-2337, ISSN: 2055-5822

Journal article

Balaban G, Halliday B, Bradley P, Bai W, Nygaard S, Owen R, Hatipoglu S, Ferreira ND, Izgi C, Tayal U, Corden B, Ware J, Pennell D, Rueckert D, Plank G, Rinaldi CA, Prasad SK, Bishop Met 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.

Journal article

de Marvao A, McGurk KA, Zheng SL, Thanaj M, Bai W, Duan J, Biffi C, Mazzarotto F, Statton B, Dawes TJW, Savioli N, Halliday BP, Xu X, Buchan RJ, Baksi AJ, Quinlan M, Tokarczuk P, Tayal U, Francis C, Whiffin N, Theotokis PI, Zhang X, Jang M, Berry A, Pantazis A, Barton PJR, Rueckert D, Prasad SK, Walsh R, Ho CY, Cook SA, Ware JS, ORegan DPet al., 2021, Outcomes and phenotypic expression of rare variants in hypertrophic cardiomyopathy genes amongst UK Biobank participants, Publisher: Cold Spring Harbor Laboratory

<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>Hypertrophic cardiomyopathy (HCM) is caused by rare variants in sarcomere-encoding genes, but little is known about the clinical significance of these variants in the general population.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>We compared outcomes and cardiovascular phenotypes in UK Biobank participants with whole exome sequencing stratified by sarcomere-encoding variant status.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>The prevalence of rare variants (allele frequency &lt;0.00004) in HCM-associated sarcomere-encoding genes in 200,584 participants was 2.9% (n=5,727; 1 in 35), of which 0.24% (n=474, 1 in 423) were pathogenic or likely pathogenic variants (SARC-P/LP). SARC-P/LP variants were associated with increased risk of death or major adverse cardiac events compared to controls (HR 1.68, 95% CI 1.37-2.06, p&lt;0.001), mainly due to heart failure (HR 4.40, 95% CI 3.22-6.02, p&lt;0.001) and arrhythmia (HR 1.55, 95% CI 1.18-2.03, p=0.002). In 21,322 participants with cardiac magnetic resonance imaging, SARC-P/LP were associated with increased left ventricular maximum wall thickness (10.9±2.7 vs 9.4±1.6 mm, p&lt;0.001) and concentric remodelling (mass/volume ratio: 0.63±0.12 vs 0.58±0.09 g/mL, p&lt;0.001), but hypertrophy (≥13mm) was only present in 16% (n=7/43, 95% CI 7-31%). Other rare sarcomere-encoding variants had a weak effect on wall thickness (9.5±1.7 vs 9.4±1.6 mm, p=0.002) with no combined excess cardiovascular risk (HR 1.00 95% CI 0.92-1.08, p=0.9).</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>In the general population, SARC-P/LP variants have low aggregate penetrance for overt HCM bu

Working paper

Tayal U, Wage R, Newsome S, Manivarmane R, Izgi C, Muthumala A, Dungu JN, Assomull R, Hatipoglu S, Halliday BP, Lota AS, Ware JS, Gregson J, Frenneaux M, Cook SA, Pennell DJ, Scott AD, Cleland JGF, Prasad SKet 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.

Journal article

Tayal U, Fecht D, Chadeau M, Gulliver J, Ware J, Cook S, Prasad Set al., 2020, RESIDENTIAL EXPOSURE TO FINE PARTICULATE MATTER AIR POLLUTION IS ASSOCIATED WITH IMPAIRED CARDIAC PHENOTYPES IN DILATED CARDIOMYOPATHY, Publisher: BMJ PUBLISHING GROUP, Pages: A2-A3, ISSN: 1355-6037

Conference paper

Mazzarotto F, Tayal U, Buchan RJ, Midwinter W, Wilk A, Whiffin N, Govind R, Mazaika E, de Marvao A, Dawes T, Felkin LE, Ahmad M, Theotokis PI, Edwards E, Ing AI, Thomson KL, Chan LLH, Sim D, Baksi AJ, Pantazis A, Roberts AM, Watkins H, Funke B, O'Regan D, Olivotto I, Barton PJR, Prasad SK, Cook SA, Ware JS, Walsh Ret 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

Journal article

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

Journal article

Tayal U, Verdonschot J, Hazebroek M, Newsome S, Adriaans B, Bekkers S, Gulati A, Pua CJ, Halliday B, Lota AS, Whiffin N, Kanapeckaite L, Baruah R, Jarman J, Barton PJ, Ware JS, Pennell DJ, Donovan J, Frenneaux M, Cleland J, Cook S, Heymans S, Deo RC, Prasad SKet al., 2019, The Application of Machine Learning Tools in an Extensively Phenotyped Cohort of Patients With Dilated Cardiomyopathy Provides Novel Insights Into Disease Pathobiology and Prognosis, Scientific Sessions of the American-Heart-Association, Publisher: LIPPINCOTT WILLIAMS & WILKINS, ISSN: 0009-7322

Conference paper

Halliday B, Vassiliou V, Wassall R, Lota A, Khalique Z, Wage R, Smith G, Tayal U, Hammersley D, Jones R, Baksi J, Pennell DJ, Cleland JG, Prasad SKet al., 2019, Myocardial Remodelling Following Heart Failure Therapy Withdrawal in Patients With Dilated Cardiomyopathy and Improved Left Ventricular Ejection Fraction Results From TRED-HF, Scientific Sessions of the American-Heart-Association, Publisher: LIPPINCOTT WILLIAMS & WILKINS, ISSN: 0009-7322

Conference paper

Halliday BP, Balaban G, Costa CM, Bai W, Porter B, Hatipoglu S, Fereira ND, Izgi C, Corden B, Tayal U, Ware JS, Plank G, Rinaldi CA, Rueckert D, Prasad SK, Bishop Met al., 2019, Improving Arrhythmic Risk Stratification in Non-Ischemic Dilated Cardiomyopathy Through the Evaluation of Novel Scar Characteristics Using CMR, Scientific Sessions of the American-Heart-Association, Publisher: LIPPINCOTT WILLIAMS & WILKINS, ISSN: 0009-7322

Conference paper

Hammersley D, Halliday B, Gulati A, Ismail TF, Ali A, Hsu L-Y, Jones R, Tayal U, Lota A, Wage R, Gatehouse P, Firmin D, Auger D, Owen R, Pennell DJ, Arai AE, Prasad SKet al., 2019, Impaired myocardial perfusion reserve is associated with adverse cardiovascular events in patients with dilated cardiomyopathy, Scientific Sessions of the American-Heart-Association, Publisher: American Heart Association, ISSN: 0009-7322

Conference paper

Lota AS, Halliday B, Tayal U, Salmi S, Shakur R, Hammersley D, Jones R, Daubeney P, Ware JS, Cleland JG, Cook SA, Pennell DJ, Prasad SKet al., 2019, Epidemiological Trends and Outcomes of Acute Myocarditis in the National Health Service of England, Scientific Sessions of the American-Heart-Association, Publisher: LIPPINCOTT WILLIAMS & WILKINS, ISSN: 0009-7322

Conference paper

Halliday BP, Baksi AJ, Gulati A, Ali A, Newsome S, Izgi C, Arzanauskaite M, Lota A, Tayal U, Vassiliou V, Gregson J, Alpendurada F, Frenneaux M, Cook S, Cleland J, Pennell D, Prasad Set al., 2019, Outcome in dilated cardiomyopathy related to the extent, location and pattern of late gadolinium enhancement, JACC: Cardiovascular Imaging, Vol: 12, Pages: 1645-1655, ISSN: 1936-878X

ObjectivesThis study sought to investigate the association between the extent, location, and pattern of late gadolinium enhancement (LGE) and outcome in a large dilated cardiomyopathy (DCM) cohort.BackgroundThe relationship between LGE and prognosis in DCM is incompletely understood.MethodsWe examined the association between LGE and all-cause mortality and a sudden cardiac death (SCD) composite based on the extent, location, and pattern of LGE in DCM.ResultsOf 874 patients (588 men, median age 52 years) followed for a median of 4.9 years, 300 (34.3%) had nonischemic LGE. Estimated adjusted hazard ratios for patients with an LGE extent of 0 to 2.55%, 2.55% to 5.10%, and >5.10%, respectively, were 1.59 (95% confidence interval [CI]: 0.99 to 2.55), 1.56 (95% CI: 0.96 to 2.54), and 2.31 (95% CI: 1.50 to 3.55) for all-cause mortality, and 2.79 (95% CI: 1.42 to 5.49), 3.86 (95% CI: 2.09 to 7.13), and 4.87 (95% CI: 2.78 to 8.53) for the SCD end-point. There was a marked nonlinear relationship between LGE extent and outcome such that even small amounts of LGE predicted a substantial increase in risk. The presence of septal LGE was associated with increased mortality, but SCD was most associated with the combined presence of septal and free-wall LGE. Predictive models using LGE presence and location were superior to models based on LGE extent or pattern.ConclusionsIn DCM, the presence of septal LGE is associated with a large increase in the risk of death and SCD events, even when the extent is small. SCD risk is greatest with concomitant septal and free-wall LGE. The incremental value of LGE extent beyond small amounts and LGE pattern is limited.

Journal article

Garcia-Pavia P, Kim Y, Restrepo-Cordoba MA, Lunde IG, Wakimoto H, Smith AM, Toepfer CN, Getz K, Gorham J, Patel P, Ito K, Willcox JA, Arany Z, Li J, Owens AT, Govind R, Nuñez B, Mazaika E, Bayes-Genis A, Walsh R, Finkelman B, Lupon J, Whiffin N, Serrano I, Midwinter W, Wilk A, Bardaji A, Ingold N, Buchan R, Tayal U, Pascual-Figal DA, de Marvao A, Ahmad M, Garcia-Pinilla JM, Pantazis A, Dominguez F, John Baksi A, O'Regan DP, Rosen SD, Prasad SK, Lara-Pezzi E, Provencio M, Lyon AR, Alonso-Pulpon L, Cook SA, DePalma SR, Barton PJR, Aplenc R, Seidman JG, Ky B, Ware JS, Seidman CEet al., 2019, Genetic variants associated with cancer therapy-induced cardiomyopathy, Circulation, Vol: 140, Pages: 31-41, ISSN: 0009-7322

BackgroundCancer therapy-induced cardiomyopathy (CCM) is associated with cumulative drug exposures and pre-existing cardiovascular disorders. These parametersincompletely account for substantial inter-individual susceptibility to CCM. We hypothesized that rare variants in cardiomyopathy genes contribute to CCM.MethodsWe studied 213 CCM patients from three cohorts: retrospectively recruited adults with diverse cancers (n=99), prospectively phenotyped breast cancer adults (n=73) and prospectively phenotyped children with acute myeloid leukemia (n=41). Cardiomyopathy genes, including nine pre-specified genes were sequenced. The prevalence of rare variants was compared between CCM cohorts and The Cancer Genome Atlas (TCGA) participants(n=2053), healthy volunteers(n=445), and ancestry-matchedreference population. Clinical characteristics and outcomes were assessed, stratified by genotypes. A prevalent CCM genotype was modeled in anthracycline-treated mice.ResultsCCM was diagnosed 0.4-9 years after chemotherapy; 90% of these patients received anthracyclines. Adult CCM patients had cardiovascular risk factors similar to the U.S. population. Among nine prioritized genes CCM patients had more rare protein-altering variants than comparative cohorts (p≤1.98e-04). Titin-truncating variants (TTNtv) predominated, occurring in 7.5% CCM patients versus 1.1% TCGA participants (p=7.36e-08), 0.7% healthy volunteers (p=3.42e-06), and 0.6% reference population (p=5.87e-14). Adult CCM patients with TTNtv experienced more heart failure and atrial fibrillation (p=0.003)and impaired myocardial recovery (p=0.03) than those without.Consistent with human data, anthracycline-treated TTNtv mice and isolated TTNtv cardiomyocytes showed sustained contractile dysfunction unlike wildtype (p=0.0004 and p<0.002, respectively).ConclusionsUnrecognized rare variants in cardiomyopathy-associated genes, particularly TTNtv, increased the risk for CCM in children and adults, and adverse cardiac events

Journal article

Corden B, Jarman J, Whiffin N, Tayal U, Buchan R, Sehmi J, Harper A, Midwinter W, Lascelles K, Mason M, Baksi J, Pantazis A, Pennell D, Barton P, Prasad S, Wong T, Cook S, Ware Jet al., 2019, Association between titin truncating variants and life-threatening cardiac arrhythmias in patients with dilated cardiomyopathy and implantable defibrillator, JAMA Network Open, Vol: 2, Pages: 1-12, ISSN: 2574-3805

Importance There is a need for better arrhythmic risk stratification in nonischemic dilated cardiomyopathy (DCM). Titin-truncating variants (TTNtvs) in the TTN gene are the most common genetic cause of DCM and may be associated with higher risk of arrhythmias in patients with DCM.Objective To determine if TTNtv status is associated with the development of life-threatening ventricular arrhythmia and new persistent atrial fibrillation in patients with DCM and implanted cardioverter defibrillator (ICD) or cardiac resynchronization therapy defibrillator (CRT-D) devices.Design, Setting, and Participants This retrospective, multicenter cohort study recruited 148 patients with or without TTNtvs who had nonischemic DCM and ICD or CRT-D devices from secondary and tertiary cardiology clinics in the United Kingdom from February 1, 2011, to June 30, 2016, with a median (interquartile range) follow-up of 4.2 (2.1-6.5) years. Exclusion criteria were ischemic cardiomyopathy, primary valve disease, congenital heart disease, or a known or likely pathogenic variant in the lamin A/C gene. Analyses were performed February 1, 2017, to May 31, 2017.Main Outcome and Measures The primary outcome was time to first device-treated ventricular tachycardia of more than 200 beats/min or first device-treated ventricular fibrillation. Secondary outcome measures included time to first development of persistent atrial fibrillation.Results Of 148 patients recruited, 117 adult patients with nonischemic DCM and an ICD or CRT-D device (mean [SD] age, 56.9 [12.5] years; 76 [65.0%] men; 106 patients [90.6%] with primary prevention indications) were included. Having a TTNtv was associated with a higher risk of receiving appropriate ICD therapy (shock or antitachycardia pacing) for ventricular tachycardia or fibrillation (hazard ratio [HR], 4.9; 95% CI, 2.2-10.7; P < .001). This association was independent of all covariates, including midwall fibrosis measured by late gadolinium enhanc

Journal article

Tayal U, Wage R, Ferreira P, Nielles-Vallespin S, Epstein F, Auger D, Zhong X, Pennell D, Firmin D, Scott A, Prasad Set al., 2019, The feasibility of a novel limited field of view spiral cine DENSE sequence to assess myocardial strain in dilated cardiomyopathy, Magnetic Resonance Materials in Physics, Biology and Medicine, Vol: 32, Pages: 317-329, ISSN: 0968-5243

ObjectiveDevelop an accelerated cine displacement encoding with stimulated echoes (DENSE) cardiovascular magnetic resonance (CMR) sequence to enable clinically feasible myocardial strain evaluation in patients with dilated cardiomyopathy (DCM).Materials and methodsA spiral cine DENSE sequence was modified by limiting the field of view in two dimensions using in-plane slice-selective pulses in the stimulated echo. This reduced breath hold duration from 20RR to 14RR intervals. Following phantom and pilot studies, the feasibility of the sequence to assess peak radial, circumferential, and longitudinal strain was tested in control subjects (n = 18) and then applied in DCM patients (n = 29).ResultsDENSE acquisition was possible in all participants. Elements of the data were not analysable in 1 control (6%) and 4 DCM r(14%) subjects due to off-resonance or susceptibility artefacts and low signal-to-noise ratio. Peak radial, circumferential, short-axis contour strain and longitudinal strain was reduced in DCM patients (p < 0.001 vs. controls) and strain measurements correlated with left ventricular ejection fraction (with circumferential strain r = − 0.79, p < 0.0001; with vertical long-axis strain r = − 0.76, p < 0.0001). All strain measurements had good inter-observer agreement (ICC > 0.80), except peak radial strain.DiscussionWe demonstrate the feasibility of CMR strain assessment in healthy controls and DCM patients using an accelerated cine DENSE technique. This may facilitate integration of strain assessment into routine CMR studies.

Journal article

Lota AS, Halliday BP, Hatipoglu S, Owen R, Tayal U, Vassiliou V, Hammersley D, Jones R, Newsome S, Gulati A, Ware JS, Cook SA, Cleland J, Pennell DJ, Prasad SKet al., 2019, Risk prediction in patients with mild dilated cardiomyopathy by cardiovascular magnetic resonance: integrating assessment of myocardial mechanics with tissue characterisation, Publisher: WILEY, Pages: 406-407, ISSN: 1388-9842

Conference paper

Tayal U, King L, Schofield R, Castellano I, Stirrup J, Pontana F, Earls J, Nicol Eet al., 2019, Image reconstruction in cardiovascular CT: Part 2-Iterative reconstruction; potential and pitfalls, Journal of Cardiovascular Computed Tomography, Vol: 13, Pages: 3-10, ISSN: 1876-861X

The use of IR in CT previously has been prohibitively complicated and time consuming, however improvements in computer processing power now make it possible on almost all CT scanners. Due to its potential to allow scanning at lower doses, IR has received a lot of attention in the medical literature and has become a successful commercial product. Its use in cardiovascular CT has been driven in part due to concerns about radiation dose and image quality. This manuscript discusses the various vendor permutations of iterative reconstruction (IR) in detail and critically appraises the current clinical research available on the various IR techniques used in cardiovascular CT.

Journal article

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