Publications
463 results found
Vassiliou VS, Chin CWL, Malley T, et al., 2019, Left ventricular fibrosis in patients with aortic stenosis, Surgical Management of Aortic Pathology: Current Fundamentals for the Clinical Management of Aortic Disease, Pages: 127-139, ISBN: 9783709148723
Aortic valve stenosis is the commonest form of valvular heart disease in the Western world, currently affecting about 7% of the population over the age of 60, while 3% of people over the age of 75 have severe stenosis. With an aging population, its prevalence is expected to increase dramatically in the next few decades with major financial implications for global healthcare systems. Aortic stenosis is characterized by progressive valve narrowing that leads to a high-pressure load on the left ventricle (LV), triggering hypertrophy of cardiac myocytes, and increase in LV wall thickness and mass. At present there is no effective medical therapy capable of altering disease progression so that the only treatment is aortic valve replacement (AVR), usually with either surgical or percutaneous techniques. Current international guidelines recommended AVR in patients with severe stenosis and evidence of LV decompensation (either on the basis of symptoms or a reduced ejection fraction). Following AVR patients demonstrate a variable degree of regression of the ventricular hypertrophy with favorable prognosis demonstrated in the cohort of patients with the highest level of regression. Myocardial fibrosis is often seen in patients before intervention, and its presence is associated with worse perioperative and long-term outcome. In this chapter we review the literature pertaining to the importance of myocardial fibrosis in patients with aortic stenosis and evaluate the mechanisms, detection, and clinical significance.
Halliday BP, Wassail R, Lota AS, et al., 2019, Brief Comment Video to the Recommended Article of the Month, REVISTA PORTUGUESA DE CARDIOLOGIA, Vol: 38, Pages: 71-71, ISSN: 0870-2551
Cui C, Yin G, Lu M, et al., 2019, Retrospective Electrocardiography-Gated Real Time Cardiac Cine MRI at 3T: Comparison with Conventional Segmented Cine MRI, KOREAN JOURNAL OF RADIOLOGY, Vol: 20, Pages: 114-125, ISSN: 1229-6929
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- Citations: 9
Balaban G, Halliday BP, Costa CM, et al., 2018, Fibrosis Microstructure Modulates Reentry in Non-ischemic Dilated Cardiomyopathy: Insights From Imaged Guided 2D Computational Modeling, Frontiers in Physiology, Vol: 9, ISSN: 1664-042X
Aims: Patients who present with non-ischemic dilated cardiomyopathy (NIDCM) andenhancement on late gadolinium magnetic resonance imaging (LGE-CMR), are at highrisk of sudden cardiac death (SCD). Further risk stratification of these patients basedon LGE-CMR may be improved through better understanding of fibrosis microstructure.Our aim is to examine variations in fibrosis microstructure based on LGE imaging, andquantify the effect on reentry inducibility and mechanism. Furthermore, we examine therelationship between transmural activation time differences and reentry.Methods and Results: 2D Computational models were created from a single short axisLGE-CMR image, with 401 variations in fibrosis type (interstitial, replacement) and density,as well as presence or absence of reduced conductivity (RC). Transmural activationtimes (TAT) were measured, as well as reentry incidence and mechanism. Reentrieswere inducible above specific density thresholds (0.8, 0.6 for interstitial, replacementfibrosis). RC reduced these thresholds (0.3, 0.4 for interstitial, replacement fibrosis) andincreased reentry incidence (48 no RC vs. 133 with RC). Reentries were classified as rotor,micro-reentry, or macro-reentry and depended on fibrosis micro-structure. Differencesin TAT at coupling intervals 210 and 500ms predicted reentry in the models (sensitivity89%, specificity 93%). A sensitivity analysis of TAT and reentry incidence showed thatthese quantities were robust to small changes in the pacing location.Conclusion: Computational models of fibrosis micro-structure underlying areas ofLGE in NIDCM provide insight into the mechanisms and inducibility of reentry, andtheir dependence upon the type and density of fibrosis. Transmural activation times,measured at the central extent of the scar, can potentially differentiate microstructureswhich support reentry.
Halliday BP, Wassall R, Lota A, et al., 2018, Withdrawal of Pharmacological Heart Failure Therapy in Recovered Dilated Cardiomyopathy - A Randomised Controlled Trial (TRED-HF), Scientific Sessions of the American-Heart-Association (AHA) / Resuscitation Science Symposium, Publisher: LIPPINCOTT WILLIAMS & WILKINS, Pages: E761-E761, ISSN: 0009-7322
Halliday BP, Lota AS, Prasad SK, 2018, Sudden death risk markers for patients with left ventricular ejection fractions greater than 40, Trends in Cardiovascular Medicine, Vol: 28, Pages: 516-521, ISSN: 1050-1738
The major burden of sudden cardiac death (SCD) in patients with heart disease occurs in those with a left ventricular ejection fraction > 40%. Although the annual risk of SCD may be lower in these patients compared to those with lower LVEF, their lifetime cumulative risk of SCD may be greater due to a better overall prognosis. It is plausible that those with LVEF > 40% who are at highest risk of life-threatening arrhythmia will benefit from implantable cardioverter defibrillators. Features that identify patients with a LVEF > 40% at high risk of SCD are urgently needed. We review existing studies examining SCD markers in this sub-group and discuss gaps in the current evidence base.
Cheng S, Fang M, Cui C, et al., 2018, LGE-CMR-derived texture features reflect poor prognosis in hypertrophic cardiomyopathy patients with systolic dysfunction: preliminary results, EUROPEAN RADIOLOGY, Vol: 28, Pages: 4615-4624, ISSN: 0938-7994
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- Citations: 48
Musa TA, Treibel TA, Vassiliou VS, et al., 2018, Myocardial Scar and Mortality in Severe Aortic Stenosis: Data From the BSCMR Valve Consortium, CIRCULATION, Vol: 138, Pages: 1935-1947, ISSN: 0009-7322
Halliday BP, Gulati A, Ali A, et al., 2018, Sex and age-based differences in the natural history and outcome of dilated cardiomyopathy, European Journal of Heart Failure, Vol: 20, Pages: 1392-1400, ISSN: 1388-9842
Aims: To evaluate the relationship between sex, age and outcome in dilated cardiomyopathy (DCM). Methods & Results: We used proportional hazard modelling to examine the association between sex, age and all-cause mortality in consecutive patients with DCM. Overall, 881 patients (290 women, median age 52 years) were followed for a median of 4.9 years. Women were more likely to present with heart failure (64.0% vs 54.5%; p=0.007) and had more severe symptoms (p<0.001) compared to men. Women had smaller left ventricular end-diastolic volume (125ml/m2 vs 135ml/m2, p<0.001), higher left ventricular ejection fraction (40.2% vs 37.9%, p=0.019) and were less likely to have mid-wall late gadolinium enhancement (23.0% vs 38.9%, p<0.0001). During follow-up 149 (16.9%) patients died, including 41 (4.7%) who died suddenly. After adjustment, all-cause mortality (HR 0.61; 95%CI 0.41:0.92; p=0.018) was lower in women, with similar trends for cardiovascular (HR 0.60; 95%CI 0.35-1.05; p=0.07), non-sudden (HR 0.63; 95%CI 0.39-1.02; p=0.06) and sudden death (HR 0.70, 95%CI 0.30:1.63; p=0.41). All-cause mortality (per 10 yrs: HR 1.36, 95%CI 1.20-1.55; p<0.00001) and non-sudden death (per 10 yrs: HR 1.51, 95%CI 1.26 – 1.82; p<0.00001) increased with age. Cumulative incidence curves confirmed favourable outcomes, particularly in women and those <60 years. Increased all-cause mortality in patients >60 years of age was driven by non-sudden death. Conclusion: Women with DCM have better survival compared to men, which may partly be due to less severe left ventricular dysfunction and a smaller scar burden. There is increased mortality driven by non-sudden death in patients >60 years of age that is less marked in women. Outcomes with contemporary treatment were favourable, with a low incidence of sudden death.
Prasad SK, Lota AS, 2018, Improving Risk Stratification by Cardiac Magnetic Resonance Imaging in Heart Failure Is Strain the Missing Link?, JACC-CARDIOVASCULAR IMAGING, Vol: 11, Pages: 1430-1432, ISSN: 1936-878X
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- Citations: 1
Loudon B, Ntatsaki E, Newsome S, et al., 2018, Osteoprotegerin and myocardial fibrosis in patients with aortic stenosis, Scientific Reports, Vol: 8, ISSN: 2045-2322
Left ventricular myocardial fibrosis in patients with aortic stenosis (AS) confers worse prognosis. Plasma osteoprotegerin (OPG), a cytokine from the TNF receptor family, correlates with the degree of valve calcification in AS, reflecting the activity of the tissue RANKL/RANK/OPG (receptor activator of nuclear factor κΒ ligand/RANK/osteoprotegerin) axis, and is associated with poorer outcomes in AS. Its association with myocardial fibrosis is unknown. We hypothesised that OPG levels would reflect the extent of myocardial fibrosis in AS. We included 110 consecutive patients with AS who had undergone late-gadolinium contrast enhanced cardiovascular magnetic resonance (LGE-CMR). Patients were characterised according to pattern of fibrosis (no fibrosis, midwall fibrosis, or chronic myocardial infarction fibrosis). Serum OPG was measured with ELISA and compared between groups defined by valve stenosis severity. Some 36 patients had no fibrosis, 38 had midwall fibrosis, and 36 had chronic infarction. Patients with midwall fibrosis did not have higher levels of OPG compared to those without fibrosis (6.78 vs. 5.25 pmol/L, p = 0.12). There was no difference between those with midwall or chronic myocardial infarction fibrosis (6.78 vs. 6.97 pmol/L, p = 0.27). However, OPG levels in patients with chronic myocardial infarction fibrosis were significantly higher than those without fibrosis (p = 0.005).
Puntmann VO, Valbuena S, Hinojar R, et al., 2018, Society for Cardiovascular Magnetic Resonance (SCMR) expert consensus for CMR imaging endpoints in clinical research: Part i - Analytical validation and clinical qualification, Journal of Cardiovascular Magnetic Resonance, Vol: 20, ISSN: 1097-6647
Cardiovascular disease remains a leading cause of morbidity and mortality globally. Changing natural history of the disease due to improved care of acute conditions and ageing population necessitates new strategies to tackle conditions which have more chronic and indolent course. These include an increased deployment of safe screening methods, life-long surveillance, and monitoring of both disease activity and tailored-treatment, by way of increasingly personalized medical care. Cardiovascular magnetic resonance (CMR) is a non-invasive, ionising radiation-free method, which can support a significant number of clinically relevant measurements and offers new opportunities to advance the state of art of diagnosis, prognosis and treatment. The objective of the SCMR Clinical Trial Taskforce was to summarizes the evidence to emphasize where currently CMR-guided clinical care can indeed translate into meaningful use and efficient deployment of resources results in meaningful and efficient use. The objective of the present initiative was to provide an appraisal of evidence on analytical validation, including the accuracy and precision, and clinical qualification of parameters in disease context, clarifying the strengths and weaknesses of the state of art, as well as the gaps in the current evidence This paper is complementary to the existing position papers on standardized acquisition and post-processing ensuring robustness and transferability for widespread use. Themed imaging-endpoint guidance on trial design to support drug-discovery or change in clinical practice (part II), will be presented in a follow-up paper in due course. As CMR continues to undergo rapid development, regular updates of the present recommendations are foreseen.
Gulati A, Japp AG, Raza S, et al., 2018, Absence of myocardial fibrosis predicts favorable long-term survival in new-onset heart failure a cardiovascular magnetic resonance study, Circulation: Cardiovascular Imaging, Vol: 11, ISSN: 1941-9651
Background:Myocardial fibrosis, identified by late gadolinium enhancement cardiovascular magnetic resonance, predicts outcomes in chronic heart failure (HF). Its prognostic significance in new-onset HF and reduced left ventricular ejection fraction (LVEF) is unclear. We investigated whether the pattern and extent of fibrosis predict survival in new-onset HF and reduced LVEF of initially uncertain pathogenesis.Methods and Results:Of 120 consecutive patients with new-onset (<6 months) HF and reduced LVEF, 31 (26%) had infarct fibrosis, 25 (21%) had midwall fibrosis, and 64 (53%) had no fibrosis. During median follow-up of 8.9 years, 33 (28%) patients died. Patients with infarct fibrosis (hazard ratios [HR], 3.32; 95% CI, 1.46–7.58; P=0.004) or midwall fibrosis (HR, 2.99; 95% CI, 1.24–7.19; P=0.014) were more likely to die compared with those without fibrosis. On multivariable analysis, the pattern and extent of fibrosis were both associated with all-cause mortality (by fibrosis pattern: infarct: HR, 2.60; 95% CI, 1.08–6.27; P=0.033; midwall: HR, 2.64; 95% CI, 1.08–6.47; P=0.034; by fibrosis extent per 1%: HR, 1.07; 95% CI, 1.03–1.12; P<0.001). Fibrosis pattern also predicted composites of cardiovascular mortality or aborted sudden cardiac death (infarct: HR, 3.45; 95% CI, 1.20–9.90; P=0.022; midwall: HR, 6.59; 95% CI, 2.26–19.22; P<0.001), and all-cause mortality, HF hospitalization, or aborted sudden cardiac death (infarct: HR, 2.69; 95% CI, 1.26–5.76; P=0.011; midwall fibrosis: HR, 2.97; 95% CI, 1.37–6.45; P=0.006). Addition of fibrosis pattern to LVEF improved risk prediction for all-cause mortality (LVEF versus LVEF+fibrosis C statistic: 0.66 versus 0.71; P=0.033). Importantly, the absence of fibrosis heralded a favorable prognosis with an 85% survival rate over the duration of follow-up.Conclusions:The pattern and extent of myocardial fibrosis predict adverse outcomes in new-onset HF and reduced LVEF.
Biffi C, Oktay O, Tarroni G, et al., 2018, Learning interpretable anatomical features through deep generative models: Application to cardiac remodeling, International Conference On Medical Image Computing & Computer Assisted Intervention, Publisher: Springer, Pages: 464-471, ISSN: 0302-9743
Alterations in the geometry and function of the heart define well-established causes of cardiovascular disease. However, current approaches to the diagnosis of cardiovascular diseases often rely on subjective human assessment as well as manual analysis of medical images. Both factors limit the sensitivity in quantifying complex structural and functional phenotypes. Deep learning approaches have recently achieved success for tasks such as classification or segmentation of medical images, but lack interpretability in the feature extraction and decision processes, limiting their value in clinical diagnosis. In this work, we propose a 3D convolutional generative model for automatic classification of images from patients with cardiac diseases associated with structural remodeling. The model leverages interpretable task-specific anatomic patterns learned from 3D segmentations. It further allows to visualise and quantify the learned pathology-specific remodeling patterns in the original input space of the images. This approach yields high accuracy in the categorization of healthy and hypertrophic cardiomyopathy subjects when tested on unseen MR images from our own multi-centre dataset (100%) as well on the ACDC MICCAI 2017 dataset (90%). We believe that the proposed deep learning approach is a promising step towards the development of interpretable classifiers for the medical imaging domain, which may help clinicians to improve diagnostic accuracy and enhance patient risk-stratification.
Stephenson E, Coe D, Nadkarni S, et al., 2018, c-Met as a novel T-cell marker in patients with acute myocarditis and dilated cardiomyopathy, European-Society-of-Cardiology Congress, Publisher: OXFORD UNIV PRESS, Pages: 921-921, ISSN: 0195-668X
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- Citations: 1
Tayal U, Halliday B, Prasad S, 2018, Role of CMR in Dilated Cardiomyopathy, Cardiovascular Magnetic Resonance A Companion to Braunwald's Heart Disease, Publisher: Churchill Livingstone, ISBN: 9780323415613
Complemented by: Braunwald's heart disease / edited by Douglas P. Zipes, Peter Libby, Robert O. Bonow, Douglas L. Mann, and Gordon F. Tomaselli. 11th ed. 2018.
Selvadurai MBBS, BSc BSN, 2018, Definition of Left Ventricular Segments for Cardiac Magnetic Resonance Imaging, JACC: Cardiovascular Imaging, Vol: 11, Pages: 926-928, ISSN: 1936-878X
Everett RJ, Tastet L, Clavel M-A, et al., 2018, Progression of Hypertrophy and Myocardial Fibrosis in Aortic Stenosis A Multicenter Cardiac Magnetic Resonance Study, CIRCULATION-CARDIOVASCULAR IMAGING, Vol: 11, ISSN: 1941-9651
Background:Aortic stenosis is accompanied by progressive left ventricular hypertrophy and fibrosis. We investigated the natural history of these processes in asymptomatic patients and their potential reversal post-aortic valve replacement (AVR).Methods:Asymptomatic and symptomatic patients with aortic stenosis underwent repeat echocardiography and magnetic resonance imaging. Changes in peak aortic-jet velocity, left ventricular mass index, diffuse fibrosis (indexed extracellular volume), and replacement fibrosis (late gadolinium enhancement [LGE]) were quantified.RESULTS:In 61 asymptomatic patients (43% mild, 34% moderate, and 23% severe aortic stenosis), significant increases in peak aortic-jet velocity, left ventricular mass index, indexed extracellular volume, and LGE mass were observed after 2.1±0.7 years, with the most rapid progression observed in patients with most severe stenosis. Patients with baseline midwall LGE (n=16 [26%]; LGE mass, 2.5 g [0.8–4.8 g]) demonstrated particularly rapid increases in scar burden (78% [50%–158%] increase in LGE mass per year). In 38 symptomatic patients (age, 66±8 years; 76% men) who underwent AVR, there was a 19% (11%–25%) reduction in left ventricular mass index (P<0.0001) and an 11% (4%–16%) reduction in indexed extracellular volume (P=0.003) 0.9±0.3 years after surgery. By contrast midwall LGE (n=10 [26%]; mass, 3.3 g [2.6–8.0 g]) did not change post-AVR (n=10; 3.5 g [2.1–8.0 g]; P=0.23), with no evidence of regression even out to 2 years.Conclusions:In patients with aortic stenosis, cellular hypertrophy and diffuse fibrosis progress in a rapid and balanced manner but are reversible after AVR. Once established, midwall LGE also accumulates rapidly but is irreversible post valve replacement. Given its adverse long-term prognosis, prompt AVR when midwall LGE is first identified may improve clinical outcomes.
Raphael CE, Cooper R, Mitchell F, et al., 2018, PERFUSION ABNORMALITIES IN HYPERTROPHIC CARDIOMYOPATHY: MECHANISMS AND PROGNOSTIC IMPORTANCE, Annual Conference of the British-Cardiovascular-Society on High Performing Teams, Publisher: BMJ PUBLISHING GROUP, Pages: A112-A113, ISSN: 1355-6037
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Vassiliou VS, Cameron D, Prasad SK, et al., 2018, Magnetic resonance imaging: Physics basics for the cardiologist, JRSM CARDIOVASCULAR DISEASE, Vol: 7, ISSN: 2048-0040
Magnetic resonance imaging physics can be a complex and challenging topic for the practising cardiologist. Its evolving nature and the increasing number of novel sequences used in clinical scanning have been topics of excellent reviews; however, the basic understanding of physics underlying the creation of images remains difficult for many cardiologists. In this review, we go back to the basic physics theories underpinning magnetic resonance and explain their application and use in achieving good quality cardiac imaging, whilst describing established and novel magnetic resonance sequences. By understanding these basic principles, it is anticipated that cardiologists and other health professionals will then appreciate more advanced physics manuscripts on cardiac scanning and novel sequences.
Ware JS, Amor-Salamanca A, Tayal U, et al., 2018, A genetic etiology for alcohol-induced cardiac toxicity, Journal of the American College of Cardiology, Vol: 71, Pages: 2293-2302, ISSN: 0735-1097
Background: Alcoholic cardiomyopathy (ACM) is defined by a dilated and impaired left ventricle due to chronic excess alcohol consumption. It is largely unknown what factors determine cardiac toxicity on exposure to alcohol.Objectives: We sought to evaluate the role of variation in cardiomyopathy-associated genes in the pathophysiology of ACM, and to examine the effects of alcohol intake and genotype on DCM severity.Methods: We characterized 141 ACM cases, 716 dilated cardiomyopathy (DCM) cases and 445 healthy volunteers. We compared the prevalence of rare, protein-altering variants in 9 genes associated with inherited DCM. We evaluated the effect of genotype and alcohol-consumption on phenotype in DCM.Results: Variants in well-characterized DCM-causing genes were more prevalent in patients with ACM than controls (13.5% vs 2.9%; P=1.2e-05), but similar between patients with ACM and DCM (19.4%; P=0.12) and with a predominant burden of Titin-truncating variants (TTNtv, 9.9%). Separately, we identified an interaction between TTN genotype and excess alcohol consumption in a cohort of DCM patients not meeting ACM criteria. On multivariate analysis, DCM patients with a TTNtv who consumed excess alcohol had an 8.7% absolute reduction in ejection fraction (95% CI -2.3 to -15.1, P<0.007) compared with those without TTNtv and excess alcohol consumption. The presence of TTNtv did not predict phenotype, outcome or functional recovery on treatment in ACM patients. Conclusions: TTNtv represent a prevalent genetic predisposition for ACM, and are also associated with a worse LVEF in DCM patients who consume alcohol above recommended levels. Familial evaluation and genetic testing should be considered in patients presenting with ACM.
Cui C, Wang S, Lu M, et al., 2018, Detection of recent myocardial infarction using native T1 Mapping in a swine model: a validation study, Sci Rep, Vol: 8
Late gadolinium enhancement (LGE) imaging is the currently the gold standard for in-vivo detection of myocardial infarction. However, gadolinium contrast administration is contraindicated in patients with renal insufficiency. We aim to evaluate the diagnostic sensitivity and specificity of this contrast-free MRI technique, native T1 mapping, in detecting recent myocardial infarction versus a reference histological gold standard. Ten pigs underwent CMR at 2 weeks after induced MI. The infarct size and transmural extent of MI was calculated using native T1 maps and LGE images. Histological validation was performed using triphenyl tetrazolium chloride (TTC) staining in the corresponding ex-vivo slices. The infarct size and transmural extent of myocardial infarction assessed by T1 mapping correlated well with that assessed by LGE and TTC images. Using TTC staining as the reference, T1 mapping demonstrated underestimation of infarct size and transmural extent of infarction. Additionally, there was a slight but not significant difference found in the diagnostic performance between the native T1 maps and LGE images for the location of MI. Our study shows that native T1 mapping is feasible alternative method to the LGE technique for the assessment of the size, transmural extent, and location of MI in patients who cannot receive gadolinium contrast.
Halliday BP, Baksi AJ, Izgi C, et al., 2018, Improving risk stratification for sudden cardiac death in dilated cardiomyopathy using late gadolinium enhancement cardiovascular magnetic resonance, Heart Failure 2018, Publisher: WILEY, Pages: 184-184, ISSN: 1388-9842
Halliday BP, Wassall R, Khalique Z, et al., 2018, Comprehensive phenoptyping of patients with dilated cardiomyopathy and recovered ejection fraction, Heart Failure 2018, Publisher: WILEY, Pages: 185-185, ISSN: 1388-9842
Cheng S, Choe YH, Ota H, et al., 2018, CMR assessment and clinical outcomes of hypertrophic cardiomyopathy with or without ventricular remodeling in the end-stage phase, INTERNATIONAL JOURNAL OF CARDIOVASCULAR IMAGING, Vol: 34, Pages: 597-605, ISSN: 1569-5794
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- Citations: 11
Bhalodiya JM, Palit A, Tiwari MK, et al., 2018, A Novel Hierarchical Template Matching Model for Cardiac Motion Estimation, SCIENTIFIC REPORTS, Vol: 8, ISSN: 2045-2322
Cardiovascular disease diagnosis and prognosis can be improved by measuring patient-specific in-vivo local myocardial strain using Magnetic Resonance Imaging. Local myocardial strain can be determined by tracking the movement of sample muscles points during cardiac cycle using cardiac motion estimation model. The tracking accuracy of the benchmark Free Form Deformation (FFD) model is greatly affected due to its dependency on tunable parameters and regularisation function. Therefore, Hierarchical Template Matching (HTM) model, which is independent of tunable parameters, regularisation function, and image-specific features, is proposed in this article. HTM has dense and uniform points correspondence that provides HTM with the ability to estimate local muscular deformation with a promising accuracy of less than half a millimetre of cardiac wall muscle. As a result, the muscles tracking accuracy has been significantly (p < 0.001) improved (30%) compared to the benchmark model. Such merits of HTM provide reliably calculated clinical measures which can be incorporated into the decision-making process of cardiac disease diagnosis and prognosis.
Tayal U, Prasad SK, 2018, Titin cardiomyopathy: why we need to go big to understand the giant, EUROPEAN HEART JOURNAL, Vol: 39, Pages: 874-875, ISSN: 0195-668X
Stirrat CG, Alam SR, MacGillivray TJ, et al., 2018, Ferumoxytol-enhanced magnetic resonance imaging in acute myocarditis, Heart, Vol: 104, Pages: 300-305, ISSN: 1355-6037
Objectives Ultrasmall superparamagnetic particles of iron oxide (USPIO)-enhanced MRI can detect tissue-resident macrophage activity and identify cellular inflammation within tissues. We hypothesised that USPIO-enhanced MRI would provide a non-invasive imaging technique that would improve the diagnosis and management of patients with acute myocarditis.Methods Ten volunteers and 14 patients with suspected acute myocarditis underwent T2, T2* and late gadolinium enhancement (LGE) 3T MRI, with further T2* imaging at 24 hours after USPIO (ferumoxytol, 4 mg/kg) infusion, at baseline and 3 months. Myocardial oedema and USPIO enhancement were determined within areas of LGE as well as throughout the myocardium.Results Myocarditis was confirmed in nine of the 14 suspected cases of myocarditis. There was greater myocardial oedema in regions of LGE in patients with myocarditis when compared with healthy volunteer myocardium (T2 value, 57.1±5.3 vs 46.7±1.6 ms, p<0.0001). There was no demonstrable difference in USPIO enhancement between patients and volunteers even within regions displaying LGE (change in R2*, 35.0±15.0 vs 37.2±9.6 s−1, p>0.05). Imaging after 3 months in patients with myocarditis revealed a reduction in volume of LGE, a reduction in oedema measures within regions displaying LGE and improvement in ejection fraction (mean −19.7 mL, 95% CI (−0.5 to −40.0)), −5.8 ms (−0.9 to −10.7) and +6% (0.5% to 11.5%), respectively, p<0.05 for all).Conclusion In patients with acute myocarditis, USPIO-enhanced MRI does not provide additional clinically relevant information to LGE and T2 mapping MRI. This suggests that tissue-resident macrophages do not provide a substantial contribution to the myocardial inflammation in this condition.Clinical trial registration NCT02319278; Results.
Whiffin N, walsh R, Govind R, et al., 2018, CardioClassifier: disease- and gene-specific computational decision support for clinical genome interpretation, Genetics in Medicine, Vol: 20, Pages: 1246-1254, ISSN: 1098-3600
PurposeInternationally adopted variant interpretation guidelines from the American College of Medical Genetics and Genomics (ACMG) are generic and require disease-specific refinement. Here we developed CardioClassifier (http://www.cardioclassifier.org), a semiautomated decision-support tool for inherited cardiac conditions (ICCs).MethodsCardioClassifier integrates data retrieved from multiple sources with user-input case-specific information, through an interactive interface, to support variant interpretation. Combining disease- and gene-specific knowledge with variant observations in large cohorts of cases and controls, we refined 14 computational ACMG criteria and created three ICC-specific rules.ResultsWe benchmarked CardioClassifier on 57 expertly curated variants and show full retrieval of all computational data, concordantly activating 87.3% of rules. A generic annotation tool identified fewer than half as many clinically actionable variants (64/219 vs. 156/219, Fisher’s P = 1.1 × 10−18), with important false positives, illustrating the critical importance of disease and gene-specific annotations. CardioClassifier identified putatively disease-causing variants in 33.7% of 327 cardiomyopathy cases, comparable with leading ICC laboratories. Through addition of manually curated data, variants found in over 40% of cardiomyopathy cases are fully annotated, without requiring additional user-input data.ConclusionCardioClassifier is an ICC-specific decision-support tool that integrates expertly curated computational annotations with case-specific data to generate fast, reproducible, and interactive variant pathogenicity reports, according to best practice guidelines.
Tayal U, Gulati A, Prasad SK, 2018, Myocarditis and dilated cardiomyopathy, Diagnosis and Management of Adult Congenital Heart Disease: Third Edition, Pages: 606-614, ISBN: 9780702069291
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