Publications
115 results found
Tayal U, Newsome S, Buchan R, et al., 2017, Phenotype and clinical outcomes of titin cardiomyopathy, Journal of the American College of Cardiology, Vol: 70, Pages: 2264-2274, ISSN: 0735-1097
Background Improved understanding of dilated cardiomyopathy (DCM) due to titin truncation (TTNtv) may help guide patient stratification.Objectives The purpose of this study was to establish relationships among TTNtv genotype, cardiac phenotype, and outcomes in DCM.Methods In this prospective, observational cohort study, DCM patients underwent clinical evaluation, late gadolinium enhancement cardiovascular magnetic resonance, TTN sequencing, and adjudicated follow-up blinded to genotype for the primary composite endpoint of cardiovascular death, and major arrhythmic and major heart failure events.Results Of 716 subjects recruited (mean age 53.5 ± 14.3 years; 469 men [65.5%]; 577 [80.6%] New York Heart Association function class I/II), 83 (11.6%) had TTNtv. Patients with TTNtv were younger at enrollment (49.0 years vs. 54.1 years; p = 0.002) and had lower indexed left ventricular mass (5.1 g/m2 reduction; padjusted = 0.03) compared with patients without TTNtv. There was no difference in biventricular ejection fraction between TTNtv+/− groups. Overall, 78 of 604 patients (12.9%) met the primary endpoint (median follow-up 3.9 years; interquartile range: 2.0 to 5.8 years), including 9 of 71 patients with TTNtv (12.7%) and 69 of 533 (12.9%) without. There was no difference in the composite primary outcome of cardiovascular death, heart failure, or arrhythmic events, for patients with or without TTNtv (hazard ratio adjusted for primary endpoint: 0.92 [95% confidence interval: 0.45 to 1.87]; p = 0.82).Conclusions In this large, prospective, genotype-phenotype study of ambulatory DCM patients, we show that prognostic factors for all-cause DCM also predict outcome in TTNtv DCM, and that TTNtv DCM does not appear to be associated with worse medium-term prognosis.
Tayal U, Prasad SK, 2017, Myocardial remodelling and recovery in dilated cardiomyopathy, JRSM Cardiovascular Disease, Vol: 6, Pages: 1-7, ISSN: 2048-0040
Myocardial reverse remodeling has been reported to occur in 25–70% of patients with dilated cardiomyopathy. It is not yet fully understood whether remodeling represents disease remission or cure and which hearts retain this capacity to recover. In this review article we discuss the capacity for recovery in DCM, the prognostic implications of this recovery and potential clinical and imaging predictors for myocardial remodeling.
Tayal U, Newsome S, Walsh R, et al., 2017, Defining the genetic architecture of dilated cardiomyopathy- insights from population genetic variation and the role of titin, Publisher: OXFORD UNIV PRESS, Pages: 821-822, ISSN: 0195-668X
Tayal U, Buchan R, Whiffin N, et al., 2017, EVALUATION OF TITIN CARDIOMYOPATHY IN PATIENTS WITH DILATED CARDIOMYOPATHY REVEALS A BLUNTED HYPERTROPHIC RESPONSE, AN EARLY ARRHYTHMIC RISK AND A SIGNIFICANT INTERACTION WITH ALCOHOL, Annual Conference of the British-Cardiovascular-Society (BCS), Publisher: BMJ PUBLISHING GROUP, Pages: A95-A95, ISSN: 1355-6037
Halliday BP, Gulati A, Ali A, et al., 2017, Association between mid-wall late gadolinium enhancement and sudden cardiac death in patients with dilated cardiomyopathy and mild and moderate left ventricular systolic dysfunction, Circulation, Vol: 135, Pages: 2106-2115, ISSN: 0009-7322
Background—Current guidelines only recommend the use of an implantable cardioverter defibrillator (ICD) in patients with dilated cardiomyopathy (DCM) for the primary prevention of sudden cardiac death (SCD) in those with a left ventricular ejection fraction (LVEF)<35%. However, registries of out-of-hospital cardiac arrests demonstrate that 70-80% of such patients have a LVEF>35%. Patients with a LVEF>35% also have low competing risks of death from non-sudden causes. Therefore, those at high-risk of SCD may gain longevity from successful ICD therapy. We investigated whether late gadolinium enhancement cardiovascular magnetic resonance (LGE-CMR) identified patients with DCM without severe LV systolic dysfunction at high-risk of SCD.Methods—We prospectively investigated the association between mid-wall late gadolinium enhancement (LGE) and the pre-specified primary composite outcome of SCD or aborted SCD amongst consecutive referrals with DCM and a LVEF≥40% to our center between January 2000 and December 2011, who did not have a pre-existing indication for ICD implantation.Results—Of 399 patients (145 women, median age 50 years, median LVEF 50%, 25.3% with LGE) followed for a median of 4.6 years, 18 of 101 (17.8%) patients with LGE reached the pre-specified end-point, compared to 7 of 298 (2.3%) without (HR 9.2; 95% CI 3.9-21.8; p<0.0001). Nine patients (8.9%) with LGE compared to 6 (2.0%) without (HR 4.9; 95% CI 1.8-13.5; p=0.002) died suddenly, whilst 10 patients (9.9%) with LGE compared to 1 patient (0.3%) without (HR 34.8; 95% CI 4.6-266.6; p<0.001) had aborted SCD. Following adjustment, LGE predicted the composite end-point (HR 9.3; 95% CI 3.9-22.3; p<0.0001), SCD (HR 4.8; 95% CI 1.7-13.8; p=0.003) and aborted SCD (HR 35.9; 95% CI 4.8-271.4; p<0.001). Estimated hazard ratios for the primary end-point for patients with a LGE extent of 0-2.5%, 2.5-5% and >5% compared to those without LGE were 10.6 (95%CI 3.9-29.4), 4.9 (9
Tayal U, Newsome S, Buchan R, et al., 2017, Truncating variants in titin independently predict early arrhythmias in patients with dilated cardiomyopathy, Journal of the American College of Cardiology, Vol: 69, Pages: 2466-2468, ISSN: 1558-3597
Halliday BP, Chiew K, Newsome S, et al., 2017, Incremental prognostic value of cardiopulmonary exercise testing in non-ischemic dilated cardiomyopathy, EUROPEAN JOURNAL OF HEART FAILURE, Vol: 19, Pages: 435-435, ISSN: 1388-9842
Lota AS, Wassall R, Scott AD, et al., 2017, T2 MAPPING IN ACUTE AND RECOVERED MYOCARDITIS: POTENTIAL ROLE IN CLINICAL SURVEILLANCE, 12th Annual Meeting of the British-Society-of-Cardiovascular-Magnetic-Resonance (BSCMR), Publisher: BMJ PUBLISHING GROUP, Pages: A22-A24, ISSN: 1355-6037
Tayal U, Newsome S, Voges I, et al., 2017, MULTIMODALITY ASSESSMENT OF RISK IN DILATED CARDIOMYOPATHY-THE IMPORTANCE OF CMR, 12th Annual Meeting of the British-Society-of-Cardiovascular-Magnetic-Resonance (BSCMR), Publisher: BMJ PUBLISHING GROUP, Pages: A4-A4, ISSN: 1355-6037
Halliday BP, Gulati A, Ali A, et al., 2017, SUDDEN CARDIAC DEATH RISK STRATIFICATION IN PATIENTS WITH MILD DILATED CARDIOMYOPATHY, 12th Annual Meeting of the British-Society-of-Cardiovascular-Magnetic-Resonance (BSCMR), Publisher: BMJ PUBLISHING GROUP, Pages: A2-A2, ISSN: 1355-6037
Tayal U, Newsome S, Whiffin N, et al., 2017, PRECISE PHENOTYPING WITH CMR IDENTIFIES MODERATE ALCOHOL CONSUMPTION AS AN IMPORTANT PHENOTYPIC MODIFIER OF TITIN CARDIOMYOPATHY, 12th Annual Meeting of the British-Society-of-Cardiovascular-Magnetic-Resonance (BSCMR), Publisher: BMJ PUBLISHING GROUP, Pages: A2-A3, ISSN: 1355-6037
Lota A, Baksi J, Tsao A, et al., 2017, Cardiovascular magnetic resonance in survivors of sudden cardiac arrest: 14 year experience from a tertiary referral centre in the United Kingdom, JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, Vol: 69, Pages: 491-491, ISSN: 0735-1097
Tayal U, Buchan R, Whiffin N, et al., 2017, INTEGRATED ANALYSIS OF THE CLINICAL MANIFESTATIONS AND PHENOTYPIC DRIVERS OF TITIN CARDIOMYOPATHY, 66th Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC), Publisher: ELSEVIER SCIENCE INC, Pages: 2563-2563, ISSN: 0735-1097
Tayal U, Prasad S, Cook SA, 2017, Genetics and genomics of dilated cardiomyopathy and systolic heart failure, GENOME MEDICINE, Vol: 9, ISSN: 1756-994X
Heart failure is a major health burden, affecting 40 million people globally. One of the main causes of systolic heart failure is dilated cardiomyopathy (DCM), the leading global indication for heart transplantation. Our understanding of the genetic basis of both DCM and systolic heart failure has improved in recent years with the application of next-generation sequencing and genome-wide association studies (GWAS). This has enabled rapid sequencing at scale, leading to the discovery of many novel rare variants in DCM and of common variants in both systolic heart failure and DCM. Identifying rare and common genetic variants contributing to systolic heart failure has been challenging given its diverse and multiple etiologies. DCM, however, although rarer, is a reasonably specific and well-defined condition, leading to the identification of many rare genetic variants. Truncating variants in titin represent the single largest genetic cause of DCM. Here, we review the progress and challenges in the detection of rare and common variants in DCM and systolic heart failure, and the particular challenges in accurate and informed variant interpretation, and in understanding the effects of these variants. We also discuss how our increasing genetic knowledge is changing clinical management. Harnessing genetic data and translating it to improve risk stratification and the development of novel therapeutics represents a major challenge and unmet critical need for patients with heart failure and their families.
Tayal U, Gulati A, Prasad SK, 2017, Myocarditis and Dilated Cardiomyopathy, Diagnosis and Management of Adult Congenital Heart Disease, Pages: 606-614, ISBN: 9780702069321
Schafer S, de Marvao A, Adami E, et al., 2017, Titin-truncating variants affect heart function in disease cohorts and the general population, Nature Genetics, Vol: 49, Pages: 46-53, ISSN: 1546-1718
Titin-truncating variants (TTNtv) commonly cause dilated cardiomyopathy (DCM). TTNtv are also encountered in ~1% of the general population, where they may be silent, perhaps reflecting allelic factors. To better understand TTNtv, we integrated TTN allelic series, cardiac imaging and genomic data in humans and studied rat models with disparate TTNtv. In patients with DCM, TTNtv throughout titin were significantly associated with DCM. Ribosomal profiling in rat showed the translational footprint of premature stop codons in Ttn, TTNtv-position-independent nonsense-mediated degradation of the mutant allele and a signature of perturbed cardiac metabolism. Heart physiology in rats with TTNtv was unremarkable at baseline but became impaired during cardiac stress. In healthy humans, machine-learning-based analysis of high-resolution cardiac imaging showed TTNtv to be associated with eccentric cardiac remodeling. These data show that TTNtv have molecular and physiological effects on the heart across species, with a continuum of expressivity in health and disease.
Tayal U, Cook SA, 2016, Truncating variants in filamin C: the challenges of genotype-phenotype correlations in cardiomyopathies, Journal of the American College of Cardiology, Vol: 68, Pages: 2452-2453, ISSN: 1558-3597
Tayal U, Newsome S, Buchan R, et al., 2016, Genetic determinants of arrhythmia in dilated cardiomyopathy, Congress of the European-Society-of-Cardiology (ESC), Publisher: OXFORD UNIV PRESS, Pages: 206-206, ISSN: 0195-668X
Halliday BP, Ali A, Gulati A, et al., 2016, The natural history of non-ischaemic dilated cardiomyopathy diagnosed after the age of 65 years of age, Congress of the European-Society-of-Cardiology (ESC), Publisher: OXFORD UNIV PRESS, Pages: 1324-1324, ISSN: 0195-668X
Halliday BP, Ali A, Gulati A, et al., 2016, Gender differences in the natural history and outcome of dilated cardiomyopathy, Congress of the European-Society-of-Cardiology (ESC), Publisher: OXFORD UNIV PRESS, Pages: 325-326, ISSN: 0195-668X
Tayal U, Newsome S, Buchan R, et al., 2016, Defining titin cardiomyopathy: genotype- phenotype correlations in a large prospective cohort of dilated cardiomyopathy patients, Congress of the European-Society-of-Cardiology (ESC), Publisher: OXFORD UNIV PRESS, Pages: 365-365, ISSN: 0195-668X
Halliday BP, Gulati A, Ali A, et al., 2016, Risk stratification of mild-to-moderate phenotypes of dilated cardiomyopathy - the role of mid-wall fibrosis, Congress of the European-Society-of-Cardiology (ESC), Publisher: OXFORD UNIV PRESS, Pages: 198-199, ISSN: 0195-668X
Lota A, Wassall R, Tsao A, et al., 2016, Prevalence and prognostic significance of right ventricular systolic function assessed by CMR in patients with suspected acute myocarditis, Congress of the European-Society-of-Cardiology (ESC), Publisher: OXFORD UNIV PRESS, Pages: 1365-1366, ISSN: 0195-668X
Tayal U, Buchan RJ, Whiffin N, et al., 2016, Clinical and Genetic Characteristics of Familial Dilated Cardiomyopathy in a Large UK Prospective Cohort, Annual Conference of the British Cardiovascular Society (BCS) on Prediction and Prevention, Publisher: BMJ Publishing Group, Pages: A103-A103, ISSN: 1355-6037
Tayal U, Buchan RJ, Whiffin N, et al., 2016, Effects of Truncating Variants in Titin on Cardiac Phenotype and Left Ventricular Remodelling in Dilated Cardiomyopathy, Annual Conference of the British Cardiovascular Society (BCS) on Prediction and Prevention, Publisher: BMJ Publishing Group, Pages: A102-A103, ISSN: 1355-6037
Tayal U, Newsome S, Buchan R, et al., 2016, The presence of a truncating mutation in titin independently associates with arrhythmic burden in patients with dilated cardiomyopathy, Heart Failure 2016 Conference, Publisher: Wiley, Pages: 156-156, ISSN: 1879-0844
Vassiliou V, Anita S, Malley T, et al., 2016, Systolic T1 mapping for estimation of myocardial diffuse fibrosis, Journal of Cardiovascular Magnetic Resonance, Vol: 18, Pages: 1-2, ISSN: 1097-6647
Scott AD, Tayal U, Nielles-Vallespin S, et al., 2016, Accelerating cine DENSE using a zonal excitation, Journal of Cardiovascular Magnetic Resonance, Vol: 18, Pages: 1-3, ISSN: 1097-6647
- Cite
- Citations: 7
Mazzarotto F, Walsh R, Buchan RJ, et al., 2015, Comprehensive sequencing of dilated cardiomyopathy genes reveals additive effects of multiple genes on disease risk and severity, Congress of the European-Society-of-Cardiology (ESC), Publisher: OXFORD UNIV PRESS, Pages: 523-523, ISSN: 0195-668X
Tayal U, Mazzarotto F, Buchan R, et al., 2015, Comprehensive Assessment of Rare Genetic Variation in Dilated Cardiomyopathy Genes in Patients and Controls (vol 101, pg A41, 2015), HEART, Vol: 101, ISSN: 1355-6037
This data is extracted from the Web of Science and reproduced under a licence from Thomson Reuters. You may not copy or re-distribute this data in whole or in part without the written consent of the Science business of Thomson Reuters.