Imperial College London

ProfessorDudleyPennell

Faculty of MedicineNational Heart & Lung Institute

Professor of Cardiology
 
 
 
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Contact

 

+44 (0)20 7351 8810d.pennell

 
 
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Location

 

CMR UnitRoyal BromptonRoyal Brompton Campus

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Summary

 

Publications

Publication Type
Year
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896 results found

Ferreira PF, Martin RR, Scott AD, Khalique Z, Yang G, Nielles-Vallespin S, Pennell DJ, Firmin DNet al., 2020, Automating in vivo cardiac diffusion tensor postprocessing with deep learning-based segmentation, Magnetic Resonance in Medicine, Vol: 84, Pages: 2801-2814, ISSN: 0740-3194

PurposeIn this work we develop and validate a fully automated postprocessing framework for in vivo diffusion tensor cardiac magnetic resonance (DT‐CMR) data powered by deep learning.MethodsA U‐Net based convolutional neural network was developed and trained to segment the heart in short‐axis DT‐CMR images. This was used as the basis to automate and enhance several stages of the DT‐CMR tensor calculation workflow, including image registration and removal of data corrupted with artifacts, and to segment the left ventricle. Previously collected and analyzed scans (348 healthy scans and 144 cardiomyopathy patient scans) were used to train and validate the U‐Net. All data were acquired at 3 T with a STEAM‐EPI sequence. The DT‐CMR postprocessing and U‐Net training/testing were performed with MATLAB and Python TensorFlow, respectively.ResultsThe U‐Net achieved a median Dice coefficient of 0.93 [0.92, 0.94] for the segmentation of the left‐ventricular myocardial region. The image registration of diffusion images improved with the U‐Net segmentation (P < .0001), and the identification of corrupted images achieved an F1 score of 0.70 when compared with an experienced user. Finally, the resulting tensor measures showed good agreement between an experienced user and the fully automated method.ConclusionThe trained U‐Net successfully automated the DT‐CMR postprocessing, supporting real‐time results and reducing human workload. The automatic segmentation of the heart improved image registration, resulting in improvements of the calculated DT parameters.

Journal article

Raphael CE, Liew AC, Mitchell F, Kanaganayagam GS, Pietro ED, Newsome S, Owen R, Gregson J, Cooper R, Amin FR, Gatehouse P, Vassiliou V, Ernst S, O'Hanlon R, Frenneaux M, Pennell DJ, Prasad SKet al., 2020, Predictors and Mechanisms of Atrial Fibrillation in Patients with Hypertrophic Cardiomyopathy., Am J Cardiol

Atrial fibrillation (AF) in hypertrophic cardiomyopathy (HC) is associated with significant symptomatic deterioration, heart failure and thromboembolic disease. There is a need for better mechanistic insight and improved identification of at risk patients. We used CMR to assess predictors of AF in HC, in particular the role of myocardial fibrosis. Consecutive patients with HC referred for CMR 2003-2013 were prospectively enrolled. CMR parameters including left ventricular volumes, presence and percentage of late gadolinium enhancement in the left ventricle (%LGE) and left atrial volume index (LAVi) were measured. Overall, 377 patients were recruited (age 62 ±14 years, 73% men). Sixty-two patients (16%) developed new-onset AF during a median follow up of 4.5 (IQR 2.9 - 6.0) years. Multivariable analysis revealed %LGE [hazard ratio (HR) 1.3 per 10% (CI: 1.0-1.5; p=0.02), LAVi [HR 1.4 per 10mL/m2 (1.2-1.5; p<0.001)], age at HC diagnosis, non-sustained ventricular tachycardia and diabetes to be independent predictors of AF. We constructed a simple risk prediction score for future AF based on the multivariable model with a Harrell's C-statistic of 0.73. In conclusion, the extent of ventricular fibrosis and LA volume independently predicted AF in patients with HC. This finding suggests a mechanistic relation between fibrosis and future AF in HC. CMR with quantification of fibrosis has incremental value over LV and LA measurements in risk stratification for AF. A risk prediction score may be used to identify patients at high risk of future AF who may benefit from more intensive rhythm monitoring and a lower threshold for oral anticoagulation.

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., Late-gadolinium enhancement interface area and electrophysiological simulations predict arrhythmic events in non-ischemic dilated cardiomyopathy patients, JACC: Clinical Electrophysiology, 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

Nielles-Vallespin S, Scott A, Ferreira P, Khalique Z, Pennell D, Firmin Det al., 2020, Cardiac Diffusion: Technique and Practical Applications, JOURNAL OF MAGNETIC RESONANCE IMAGING, Vol: 52, Pages: 348-368, ISSN: 1053-1807

Journal article

Halliday B, Senior R, Pennell D, Assessing left ventricular systolic function – from ejection fraction to strain analysis, European Heart Journal, ISSN: 0195-668X

The measurement of left ventricular ejection fraction (LVEF) is a ubiquitous component of imaging studies used to evaluate patients with cardiac conditions and acts as an arbiter for many management decisions. This follows early trials investigating heart failure therapies which used a binary LVEF cut-off to select patients with the worst prognosis, who may gain the most benefit. Forty years on, the cardiac disease landscape has changed. LVEF is now a poor indicator of prognosis for many heart failure patients; specifically, for the half of patients with heart failure and truly preserved ejection fraction (HF-PEF). It is also recognised that LVEF may remain normal amongst patients with valvular heart disease who have significant myocardial dysfunction. This emphasises the importance of the interaction between LVEF and left ventricular geometry. Guidelines based on LVEF may therefore miss a proportion of patients who would benefit from early intervention to prevent further myocardial decompensation and future adverse outcomes. The assessment of myocardial strain, or intrinsic deformation, holds promise to improve these issues. The measurement of global longitudinal strain (GLS) has consistently been shown to improve the risk stratification of patients with heart failure and identify patients with valvular heart disease who have myocardial decompensation despite preserved LVEF and an increased risk of adverse outcomes. To complete the integration of GLS into routine clinical practice, further studies are required to confirm that such approaches improve therapy selection and accordingly, the outcome for patients.

Journal article

Daar S, Al Khabori M, Al Rahbi S, Hassan M, El Tigani A, Pennell DJet al., 2020, Cardiac T2*MR in patients with thalassemia major: a 10-year long-term follow-up, ANNALS OF HEMATOLOGY, Vol: 99, Pages: 2009-2017, ISSN: 0939-5555

Journal article

Khalique Z, Ferreira P, Scott A, Nielles-Vallespin S, Firmin D, Pennell Det al., 2020, Diffusion tensor cardiovascular magnetic resonance: a clinical perspective, JACC: Cardiovascular Imaging, Vol: 13, Pages: 1235-1255, ISSN: 1936-878X

Imaging the heart is central to cardiac phenotyping but in clinical practice this has been restricted to macroscopic interrogation. Diffusion tensor cardiovascular magnetic resonance (DT-CMR) is a novel, non-invasive technique which is beginning to unlock details of this microstructure in humans in-vivo. DT-CMR demonstrates the helical cardiomyocyte arrangement that drives rotation and torsion. Sheetlets (functional units of cardiomyocytes, separated by shear layers) have been shown to reorientate between diastole and systole, revealing how microstructural function facilitates cardiac thickening. Measures of tissue diffusion can also be made; fractional anisotropy (a measure of myocyte organisation) and mean diffusivity (a measure of myocyte packing). Abnormal myocyte orientation and sheetlet function has been demonstrated in congenital heart disease, cardiomyopathy and after myocardial infarction. It is too early to predict the clinical importance of DT-CMR, but such unique in-vivo information will likely prove valuable in early diagnosis and risk prediction of cardiac dysfunction and arrhythmias.

Journal article

Khalique Z, Ferreira PF, Scott AD, Nielles-Vallespin S, Martinez-Naharro A, Fontana M, Hawkins P, Firmin DN, Pennell DJet al., 2020, Diffusion tensor cardiovascular magnetic resonance in cardiac amyloidosis, Circulation: Cardiovascular Imaging, Vol: 13, ISSN: 1941-9651

Background Cardiac amyloidosis (CA) is a disease of interstitial myocardial infiltration, usually by light chains or transthyretin. We used diffusion tensor cardiovascular magnetic resonance (DT-CMR) to noninvasively assess the effects of amyloid infiltration on the cardiac microstructure. Methods DT-CMR was performed at diastole and systole in 20 CA, 11 hypertrophic cardiomyopathy, and 10 control subjects with calculation of mean diffusivity, fractional anisotropy, and sheetlet orientation (secondary eigenvector angle). Results Mean diffusivity was elevated and fractional anisotropy reduced in CA compared with both controls and hypertrophic cardiomyopathy (P<0.001). In CA, mean diffusivity was correlated with extracellular volume (r=0.68, P=0.004), and fractional anisotropy was inversely correlated with circumferential strain (r=-0.65, P=0.02). In CA, diastolic secondary eigenvector angle was elevated, and secondary eigenvector angle mobility was reduced compared with controls (both P<0.001). Diastolic secondary eigenvector angle was correlated with amyloid burden measured by extracellular volume in transthyretin, but not light chain amyloidosis. Conclusions DT-CMR can characterize the microstructural effects of amyloid infiltration and is a contrast-free method to identify the location and extent of the expanded disorganized myocardium. The diffusion biomarkers mean diffusivity and fractional anisotropy effectively discriminate CA from hypertrophic cardiomyopathy. DT-CMR demonstrated that failure of sheetlet relaxation in diastole correlated with extracellular volume in transthyretin, but not light chain amyloidosis. This indicates that different mechanisms may be responsible for impaired contractility in CA, with an amyloid burden effect in transthyretin, but an idiosyncratic effect in light chain amyloidosis. Consequently, DT-CMR offers a contrast-free tool to identify novel pathophysiology, improve diagnostics, and monitor disease through noninvasive micr

Journal article

Kuk M, Newsome S, Alpendurada F, Dweck M, Pennell DJ, Vassiliou VS, Prasad SKet al., 2020, A model based on clinical parameters to identify myocardial late gadolinium enhancement by magnetic resonance in patients with aortic stenosis: An observational study, JRSM Cardiovascular Disease, Vol: 9, Pages: 2048004020922400-2048004020922400, ISSN: 2048-0040

Objective: With increasing age, the prevalence of aortic stenosis grows exponentially, increasing left heart pressures and potentially leading to myocardial hypertrophy, myocardial fibrosis and adverse outcomes. To identify patients who are at greatest risk, an outpatient model for risk stratification would be of value to better direct patient imaging, frequency of monitoring and expeditious management of aortic stenosis with possible earlier surgical intervention. In this study, a relatively simple model is proposed to identify myocardial fibrosis in patients with a diagnosis of moderate or severe aortic stenosis. Design: Patients with moderate to severe aortic stenosis were enrolled into the study; patient characteristics, blood work, medications as well as transthoracic echocardiography and cardiovascular magnetic resonance were used to determine potential identifiers of myocardial fibrosis. Setting: The Royal Brompton Hospital, London, UK. Participants: One hundred and thirteen patients in derivation cohort and 26 patients in validation cohort. Main outcome measures: Identification of myocardial fibrosis. Results: Three blood biomarkers (serum platelets, serum urea, N-terminal pro-B-type natriuretic peptide) and left ventricular ejection fraction were shown to be capable of identifying myocardial fibrosis. The model was validated in a separate cohort of 26 patients. Conclusions: Although further external validation of the model is necessary prior to its use in clinical practice, the proposed clinical model may direct patient care with respect to earlier magnetic resonance imagining, frequency of monitoring and may help in risk stratification for surgical intervention for myocardial fibrosis in patients with aortic stenosis.

Journal article

Killick S, Jackson A, Coulthard HC, Yap C, Das-Gupta E, Pennell DJ, Porter J, Bowen D, Culligan Det al., 2020, De-Iron: a phase 2 trial of the activity and safety of Deferasirox administered at early iron loading in patients with transfusion-dependent myelodysplastic syndromes, BRITISH JOURNAL OF HAEMATOLOGY, Vol: 189, Pages: E237-E240, ISSN: 0007-1048

Journal article

Schulz-Menger J, Bluemke DA, Bremerich J, Flamm SD, Fogel MA, Friedrich MG, Kim RJ, von Knobelsdorff-Brenkenhoff F, Kramer CM, Pennell DJ, Plein S, Nagel Eet al., 2020, Standardized image interpretation and post-processing in cardiovascular magnetic resonance-2020 update Society for Cardiovascular Magnetic Resonance (SCMR): Board of Trustees Task Force on Standardized Post-Processing, JOURNAL OF CARDIOVASCULAR MAGNETIC RESONANCE, Vol: 22, ISSN: 1097-6647

Journal article

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, 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

Pennell D, Delgado V, Knuuti J, Maurovich-Horvat P, Bax JJet al., 2020, The year in cardiology: imaging: The year in cardiology 2019, EUROPEAN HEART JOURNAL, Vol: 41, Pages: 739-+, ISSN: 0195-668X

Journal article

Halliday BP, Pennell DJ, 2019, Cardiovascular Magnetic Resonance to Guide and Monitor the Myocardial Response to Treatment, CIRCULATION-CARDIOVASCULAR IMAGING, Vol: 12, ISSN: 1941-9651

Journal article

Khalique Z, Scott AD, Ferreira PF, Nielles-Vallespin S, Firmin DN, Pennell DJet al., 2019, Diffusion tensor cardiovascular magnetic resonance in hypertrophic cardiomyopathy: a comparison of motion-compensated spin echo and stimulated echo techniques, Magnetic Resonance Materials in Physics, Biology and Medicine, Vol: 33, Pages: 331-342, ISSN: 0968-5243

ObjectivesDiffusion tensor cardiovascular magnetic resonance (DT-CMR) interrogates myocardial microstructure. Two frequently used in vivo DT-CMR techniques are motion-compensated spin echo (M2-SE) and stimulated echo acquisition mode (STEAM). Whilst M2-SE is strain-insensitive and signal to noise ratio efficient, STEAM has a longer diffusion time and motion compensation is unnecessary. Here we compare STEAM and M2-SE DT-CMR in patients.Materials and methodsBiphasic DT-CMR using STEAM and M2-SE, late gadolinium imaging and pre/post gadolinium T1-mapping were performed in a mid-ventricular short-axis slice, in ten hypertrophic cardiomyopathy (HCM) patients at 3 T.ResultsAdequate quality data were obtained from all STEAM, but only 7/10 (systole) and 4/10 (diastole) M2-SE acquisitions. Compared with STEAM, M2-SE yielded higher systolic mean diffusivity (MD) (p = 0.02) and lower fractional anisotropy (FA) (p = 0.02, systole). Compared with segments with neither hypertrophy nor late gadolinium, segments with both had lower systolic FA using M2-SE (p = 0.02) and trend toward higher MD (p = 0.1). The negative correlation between FA and extracellular volume fraction was stronger with STEAM than M2-SE (r2 = 0.29, p < 0.001 STEAM vs. r2 = 0.10, p = 0.003 M2-SE).DiscussionIn HCM, only STEAM reliably assesses biphasic myocardial microstructure. Higher MD and lower FA from M2-SE reflect the shorter diffusion times. Further work will relate DT-CMR parameters and microstructural changes in disease.

Journal article

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

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

Bhatti YJ, O'hanlon R, Ismail TF, Pennell D, Vassiliou V, Prasad Set al., 2019, The effect of eplerenone on fibrosis in hypertrophic cardiomyopathy. A randomised controlled trial assessed using cardiopulmonary exercise testing and cardiovascular magnetic resonance, Congress of the European-Society-of-Cardiology (ESC) / World Congress of Cardiology, Publisher: OXFORD UNIV PRESS, Pages: 737-737, ISSN: 0195-668X

Conference paper

Ghonim S, Gatzoulis MA, Smith GC, Heng E, Ernst S, Li W, Keegan J, Diller GP, Dimpoulos K, Moon JC, Pennell DJ, Babu-Narayan SVet al., 2019, LGE CMR predicts sudden death and VT in adults with repaired tetralogy of Fallot - a prospective study with 3500 patient follow up years, Congress of the European-Society-of-Cardiology (ESC) / World Congress of Cardiology, Publisher: OXFORD UNIV PRESS, Pages: 1367-1367, ISSN: 0195-668X

Conference paper

Khan TZ, Gorog DA, Arachchillage DJ, Ahnström J, Rhodes S, Donovan J, Banya W, Pottle A, Barbir M, Pennell DJet al., 2019, Impact of lipoprotein apheresis on thrombotic parameters in patients with refractory angina and raised lipoprotein(a): Findings from a randomized controlled cross-over trial, Journal of Clinical Lipidology, Vol: 13, Pages: 788-796, ISSN: 1876-4789

BACKGROUND: Raised lipoprotein(a) [Lp(a)] is a cardiovascular risk factor common in patients with refractory angina. The apolipoprotein(a) component of Lp(a) exhibits structural homology with plasminogen and can enhance thrombosis and impair fibrinolysis. OBJECTIVES: The objective of the study was to assess the effect of lipoprotein apheresis on markers of thrombosis and fibrinolysis in patients with high Lp(a). METHODS: In a prospective, single-blind, crossover trial, 20 patients with refractory angina and raised Lp(a) > 50 mg/dL were randomized to three months of weekly lipoprotein apheresis or sham. Blood taken before and after apheresis/sham was assessed using the Global Thrombosis Test, to assess time taken for in vitro thrombus formation (occlusion time) and endogenous fibrinolysis (lysis time), as well as von Willebrand Factor, fibrinogen, D-dimer, thrombin/anti-thrombin III complex, prothrombin fragments 1 + 2, and thrombin generation assays. RESULTS: Lp(a) was significantly reduced by apheresis (100.2 [interquartile range {IQR}, 69.6143.0] vs 24.8 [17.2,34.0] mg/dL, P = .0001) but not by sham (P = .0001 between treatment arms). Apheresis prolonged occlusion time (576 ± 116 s vs 723 ± 142 s, P < .0001) reflecting reduced platelet reactivity and reduced lysis time (1340 [1128, 1682] s vs 847 [685,1302] s, P = .0006) reflecting enhanced fibrinolysis, without corresponding changes with sham. Apheresis, but not sham, reduced von Willebrand Factor (149 [89.0, 164] vs 64.2 [48.5, 89.8] IU/dL, P = .0001), and fibrinogen (3.12 ± 0.68 vs 2.20 ± 0.53 g/L, P < .0001), and increased prothrombin fragments 1 + 2 (158.16 [128.77, 232.09] vs 795.12 [272.55, 1201.00] pmol/L, P = .0006). There was no change in D-dimer, thrombin/anti-thrombin III complex, or thrombin generation assay with

Journal article

Gulati A, Ismail TF, Ali A, Hsu L-Y, Goncalves C, Ismail NA, Krishnathasan K, Davendralingam N, Ferreira P, Halliday BP, Jones DA, Wage R, Newsome S, Gatehouse P, Firmin D, Jabbour A, Assomull RG, Mathur A, Pennell DJ, Arai AE, Prasad SKet al., 2019, Microvascular Dysfunction in Dilated Cardiomyopathy A Quantitative Stress Perfusion Cardiovascular Magnetic Resonance Study, JACC-CARDIOVASCULAR IMAGING, Vol: 12, Pages: 1699-1708, ISSN: 1936-878X

Journal article

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

Khalique Z, Pennell D, 2019, Diffusion tensor cardiovascular magnetic resonance., Postgraduate Medical Journal, Vol: 95, Pages: 433-438, ISSN: 0032-5473

Cardiac structure and function are complex and inter-related. Current in vivo techniques assess the heart on a macroscopic scale, but a novel technique called diffusion tensor cardiovascular magnetic resonance (DT-CMR) can now assess the cardiac microstructure non-invasively. It provides information on the helical arrangement of cardiomyocytes that drives torsion and offers dynamic assessment of the sheetlets (aggregated cardiomyocytes) that rotate through the cardiac cycle to facilitate wall thickening. Through diffusion biomarkers, the expansion and organisation of the underlying myocardium can be described. DT-CMR has already identified novel microstructural abnormalities in cardiomyopathy, and ischaemic and congenital heart disease. This new knowledge supports the potential of DT-CMR to improve diagnostics and prognostication in various cardiac diseases.

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

Ghonim S, Gatehouse PD, Giblin G, Keegan J, Smith GC, Mathews GC, Jenkins S, Alpendurada F, Dimopoulos K, Pennell DJ, Li W, Moon JC, Gatzoulis M, Babu-Narayan Set al., 2019, Can RV optimised native T1 mapping and ECV add clinical value in repaired tetralogy of Fallot?, Publisher: OXFORD UNIV PRESS, Pages: 204-205, ISSN: 2047-2404

Conference paper

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

Khalique Z, Ferreira PF, Scott AD, Nielles-Vallespin S, Wage R, Martinez-Naharro A, Fontana M, Hawkins PN, Firmin DN, Pennell DJet al., 2019, DIFFUSION TENSOR CARDIOVASCULAR MAGNETIC RESONANCE IN CARDIAC AMYLOIDOSIS, Annual Meeting of the British-Society-of-Cardiovascular-Magnetic-Resonance (BSCMR), Publisher: BMJ PUBLISHING GROUP, Pages: A6-A7, ISSN: 1355-6037

Conference paper

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