Michael Roughton

Novartis, Bâle, Basel-City, Switzerland

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Publications (102)587.21 Total impact

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    ABSTRACT: Microvascular dysfunction in HCM has been associated with adverse clinical outcomes. Advances in quantitative cardiovascular magnetic resonance (CMR) perfusion imaging now allow myocardial blood flow to be quantified at the pixel level. We applied these techniques to investigate the spectrum of microvascular dysfunction in hypertrophic cardiomyopathy (HCM) and to explore its relationship with fibrosis and wall thickness.
    Journal of cardiovascular magnetic resonance : official journal of the Society for Cardiovascular Magnetic Resonance. 08/2014; 16(1):49.
  • Journal of Cardiovascular Magnetic Resonance 08/2014; · 4.44 Impact Factor
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    ABSTRACT: Background Heart failure activates neurohormones, and elevated levels of brain natriuretic peptide (BNP) are associated with adverse outcomes. The SENIORS trial showed that nebivolol, a highly selective beta-1 antagonist with vasodilating properties, reduced the composite outcome of all cause mortality or cardiovascular hospital admissions in older patients with heart failure. We explored the effects of nebivolol on a range of neurohormones, cytokines and markers of nitric oxide activity in heart failure. Methods In a subset of patients in SENIORS we measured N-terminal pro-brain natriuretic peptide (NT-BNP), pro atrial natriuretic peptide (Pro-ANP), endothelin-1 (ET-1), peripheral norepinephrine (PNE), soluble Fas (sFas), soluble Fas-ligand (sFas-L), tumour necrosis factor-alpha (TNF-α), serum uric acid (SUA), symmetrical dimethyl arginine (SDMA), arginine, citrulline and asymmetrical dimethyl arginine (ADMA) at baseline (before study drug), at 6 months and 12 months in a prespecified substudy. Results One hundred and six patients were enrolled and 75 had a baseline and at least one follow-up sample. There were no significant differences in neurohormone cytokines or nitric oxide markers measured between the two groups at six or twelve months. NT-ProBNP showed a numerical increase in the nebivolol group compared to placebo (P = 0.08) and sFas showed a numerical increase in patients on placebo (P = 0.08). Mean baseline LVEF was 35% in both groups and at 12 months was 43% on nebivolol group and 34% on placebo group (P = 0.01). Conclusion There were trends but no clear changes associated with nebivolol in neurohormones, cytokines or markers of nitric oxide activity in this study of elderly patients with heart failure. Further studies are needed to understand the mechanistic effects of beta blockers on biomarkers in heart failure.
    International Journal of Cardiology. 08/2014; 175(2):253–260.
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    ABSTRACT: AimsThere is limited information about the effects of beta-blockers in heart failure (HF) stratified by blood pressure, especially in the elderly and those with preserved EF. We evaluate the effects of nebivolol on outcomes in elderly patients with HF stratified by baseline systolic blood pressure (SBP) and EF.Methods and resultsThe SENIORS trial evaluated the effects of nebivolol and enrolled 2128 patients ≥70 years of age with HF. Patients were divided into three baseline pre-treatment SBP categories (<110, 110–130, and >130 mmHg). In addition, we evaluated the influence of SBP (≤130 and >130 mmHg) on patients with LVEF <40% vs. ≥40%. Low baseline SBP was associated with worse clinical outcomes irrespective of treatment group, both in patients with reduced EF and in those with preserved EF. Nebivolol had similar benefits irrespective of baseline SBP: the hazard ratio (HR) for primary outcome of all-cause mortality or cardiovascular hospitalization in the three SBP categories for nebivolol vs. placebo was 0.85 [95% confidence interval (CI) 0.50–1.45], 0.79 (95% CI 0.61–1.01), and 0.88 (95% CI 0.72–1.07), respectively (P for interaction = 0.61). Similar results were obtained for the secondary endpoint of all-cause mortality. There was no significant interaction for the effects of nebivolol by baseline SBP stratified by LVEF.Conclusions Elderly HF patients with lower SBP have a worse outcome than those with higher SBP, but nebivolol appears to be safe and well tolerated, with similar benefits on the composite outcome of death or cardiovascular hospital admission irrespective of baseline SBP and LVEF.
    European Journal of Heart Failure 07/2014; · 5.25 Impact Factor
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    ABSTRACT: Myocardial fibrosis identified by late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) in patients with hypertrophic cardiomyopathy (HCM) is associated with adverse cardiovascular events, but its value as an independent risk factor for sudden cardiac death (SCD) is unknown. We investigated the role of LGE-CMR in the risk stratification of HCM.
    Heart (British Cardiac Society) 06/2014; · 5.01 Impact Factor
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    ABSTRACT: There is a need to standardise non-invasive measurements of liver iron concentrations (LIC) so clear inferences can be drawn about body iron levels that are associated with hepatic and extra-hepatic complications of iron overload. Since the first demonstration of an inverse relationship between biopsy LIC and liver magnetic resonance (MR) using a proof-of-concept T2* sequence, MR technology has advanced dramatically with a shorter minimum echo-time, closer inter-echo spacing and constant repetition time. These important advances allow more accurate calculation of liver T2* especially in patients with high LIC.
    Journal of cardiovascular magnetic resonance : official journal of the Society for Cardiovascular Magnetic Resonance. 06/2014; 16(1):40.
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    ABSTRACT: Objectives Multicentre registries facilitate studies of rarer conditions, but may introduce unidentified confounders. Fetal aortic valvuloplasty may prevent progression of aortic stenosis to hypoplastic left heart syndrome and allow biventricular rather than univentricular postnatal treatment. We investigate whether a blinded, simulated multidisciplinary team (MDT) approach aids interpretation of multicentre data to uncover institutional bias in postnatal decision-making following fetal cardiac intervention (FCI).Methods The MDT, blinded to FCI, institutional location and postnatal treatment assigned a surgical pathway to 109 neonates diagnosed prenatally with aortic stenosis in 13 European countries, where 32 had undergone FCI. MDT decisions were the numerical consensus of silent voting with case review where a decision was split. Funnel plots showing concordance between MDT and local team's surgical choice (first pathway) and with outcome (final pathway) were created.Results105 had biventricular or univentricular decision with 4 undecided. Blinded MDT consensus for first pathway matched surgical centre decisions in 93/105 (89%) with no difference in agreement in those undergoing FCI (n = 32) and no (74) or unsuccessful (3) valvuloplasty (no-FCI) (Kappa 0.73, 95% CI 0.38-1.00 vs 0.74, 95% CI 0.51-0.96). However funnel plots comparing MDT individual decisions with local teams’ display more discordance (meaning biventricular – univentricular conversion) for final surgical pathway following FCI than no-FCI (36/74 vs 34/130), p = 0.002 and identified one outlying centre. The important difference was a deficiency of their integrated surgical programme.Conclusions This method may improve interpretation of outcomes in multicentre studies by identifying and investigating outliers identified in funnel plots.
    Ultrasound in Obstetrics and Gynecology 06/2014; · 3.56 Impact Factor
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    ABSTRACT: BACKGROUND:The assessment of myocardial iron using T2* cardiovascular magnetic resonance (CMR) has been validated and calibrated, and is in clinical use. However, there is very limited data assessing the relaxation parameters T1 and T2 for measurement of human myocardial iron.METHODS:Twelve hearts were examined from transfusion-dependent patients: 11 with end-stage heart failure, either following death (n=7) or cardiac transplantation (n=4), and 1 heart from a patient who died from a stroke with no cardiac iron loading. Ex-vivo R1 and R2 measurements (R1=1/T1 and R2=1/T2) at 1.5 Tesla were compared with myocardial iron concentration measured using inductively coupled plasma atomic emission spectroscopy.RESULTS:From a single myocardial slice in formalin which was repeatedly examined, a modest decrease in T2 was observed with time, from mean (+/-SD) 23.7+/-0.93ms at baseline (13days after death and formalin fixation) to 18.5+/-1.41ms at day 566 (p<0.001). Raw T2 values were therefore adjusted to correct for this fall over time. Myocardial R2 was correlated with iron concentration [Fe] (R2 0.566, p<0.001), but the correlation was stronger between LnR2 and Ln[Fe] (R2 0.790, p<0.001). The relation was [Fe]=5081 *(T2)-2.22 between T2 (ms) and myocardial iron (mg/g dry weight). Analysis of T1 proved challenging with a dichotomous distribution of T1, with very short T1 (mean 72.3+/-25.8ms) that was independent of iron concentration in all hearts stored in formalin for greater than 12months. In the remaining hearts stored for <10weeks prior to scanning, LnR1 and iron concentration were correlated but with marked scatter (R2 0.517, p<0.001). A linear relationship was present between T1 and T2 in the hearts stored for a short period (R2 0.657, p<0.001).CONCLUSION:Myocardial T2 correlates well with myocardial iron concentration, which raises the possibility that T2 may provide additive information to T2* for patients with myocardial siderosis. However, ex-vivo T1 measurements are less reliable due to the severe chemical effects of formalin on T1 shortening, and therefore T1 calibration may only be practical from in-vivo human studies.
    Journal of Cardiovascular Magnetic Resonance 01/2014; 16(1):62. · 4.44 Impact Factor
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    ABSTRACT: Compare cardiac function at ten years in three groups of monochorionic twin pairs (MCDA): uncomplicated MCDA (n = 6), Twin-Twin Transfusion Syndrome (TTTS) managed by amnioreduction (TTTS-amnio, n = 9) or laser photocoagulation (TTTS-laser, n = 10).and dichorionic (DCDA, n = 6) controls. Echocardiograms optimising apical 4-chamber and short axis left ventricular views were stored for off-line speckle-tracking analysis, blinded to twin type. Myocardial long axis shortening (S') and lengthening (E' and A') velocities were measured using pulsed Doppler at the cardiac base. M-mode measurements of fractional shortening (short axis) and maximal displacement of the atrioventricular annulus (4-chamber) were recorded. Syngo Vector Velocity Imaging software tracked left ventricular myocardial motion off-line to produce free wall Strain, Strain Rate and Rotation. Inter-twin pair and group differences were investigated using ANOVA. Cardiac measurements lay within normal ranges for 10 year olds. No significant within twin-pair and inter-group differences were found in current size, heart rates, Strain or Strain Rate. Compared to DCDA controls, TTTS showed lower cardiac rotation (TTTS-laser, p < 0.001 and TTTS-amnio, p = 0.054) with significant inter-twin pair reduction in ex-Recipient, TTTS-amnio (p = 0.006) and larger MCDA twins (p = 0.027) compared to their co-twins. A similar pattern was seen in left ventricular early relaxation velocities (MVE') in all monochorionic groups only achieving significance in TTTS-amnio (p = 0.037). Intra-pair differences in rotation and MVE' were significantly different following treatment at Quintero stages 3 or 4. Within twin-pair patterns of left ventricular rotation and diastolic function differ at 10 years in ex-Recipients of TTTS-amnio compared with TTTS-laser and controls.
    Ultrasound in Obstetrics and Gynecology 12/2013; · 3.56 Impact Factor
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    ABSTRACT: Cardiovascular Magnetic Resonance (CMR) is the gold-standard technique for assessment of ventricular function. Although left ventricular (LV) volumes and ejection fraction are strong predictors of outcome in dilated cardiomyopathy (DCM), there are limited data regarding the prognostic significance of right ventricular (RV) systolic dysfunction (RVSD). We investigated whether CMR assessment of RV function has prognostic value in DCM. We prospectively studied 250 consecutive DCM patients using CMR. RVSD, defined by RV ejection fraction ≤45%, was present in 86 (34%) patients. During a median follow-up period of 6.8 years, there were 52 deaths and 7 patients underwent cardiac transplantation . The primary end point of all-cause mortality or cardiac transplantation was reached by 42 of 86 patients with RVSD and 17 of 164 patients without RVSD (49% vs. 10%; hazard ratio [HR], 5.90; 95% confidence interval [CI], 3.35 to 10.37; P<0.001). On multivariable analysis, RVSD remained a significant independent predictor of the primary end point (HR, 3.90; 95% CI, 2.16 to 7.04; P<0.001), as well as secondary outcomes of cardiovascular mortality or cardiac transplantation (HR, 3.35; 95% CI, 1.76 to 6.39; P<0.001), and heart failure (HF) death, HF hospitalization or cardiac transplantation (HR, 2.70; 95% CI, 1.32 to 5.51; P=0.006). Assessment of RVSD improved risk stratification for all-cause mortality or cardiac transplantation (net reclassification improvement, 0.31; 95% CI 0.10 to 0.53; P=0.001). RVSD is a powerful, independent predictor of transplant-free survival and adverse HF outcomes in DCM. CMR assessment of RV function is important in the evaluation and risk stratification of DCM patients.
    Circulation 08/2013; · 15.20 Impact Factor
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    ABSTRACT: ABSTRACT Accumulation of myocardial iron is the cause of heart failure and early death in most transfused thalassemia major patients. T2* cardiovascular magnetic resonance provides calibrated, reproducible measurements of myocardial iron. However, there is little data regarding myocardial iron loading and its relation to outcome across the world. A survey is reported of 3,095 patients in 27 worldwide centres using T2* cardiovascular magnetic resonance. Data on baseline T2* and numbers of patients with symptoms of heart failure at first scan (defined as symptoms and signs of heart failure with objective evidence of left ventricular dysfunction) were requested together with more detailed information about patients who subsequently developed heart failure or died. At first scan, 20.6% had severe myocardial iron (T2*≤10ms), 22.8% had moderate myocardial iron (T2* 10-20ms) and 56.6% of patients had no iron loading (T2*>20ms). There was significant geographic variation in myocardial iron loading (24.8-52.6%, p<0.001). At first scan, 85 (2.9%) of 2,915 patients were reported to have heart failure (81.2% had T2* <10ms; 98.8% had T2* <20ms). During follow-up, 108 (3.8%) of 2,830 patients developed new heart failure. Of these, T2* at first scan had been <10ms in 96.3% and <20ms in 100%. There were 35 (1.1%) cardiac deaths. Of these patients, myocardial T2* at first scan had been <10ms in 85.7% and <20ms in 97.1%. Therefore, in this worldwide cohort of thalassemia major patients, >43% had moderate/severe myocardial iron loading with significant geographic differences, and myocardial T2* values <10ms were strongly associated with heart failure and death.
    Haematologica 06/2013; 98(9):1368-1374. · 5.94 Impact Factor
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    ABSTRACT: BACKGROUND: Early recognition and accurate risk stratification are important in the management of arrhythmogenic right ventricular cardiomyopathy (ARVC). Identification of predictors of outcome by cardiovascular magnetic resonance (CMR) in patients undergoing evaluation for ARVC is limited. We investigated the predictive value of morphological abnormalities detected by CMR for major clinical events in patients with suspected ARVC. METHODS: We performed a longitudinal study on 369 consecutive patients with at least one criterion for ARVC. Abnormal CMR was defined by the presence of one of the following: increased right ventricular (RV) volumes, reduced RV ejection fraction, RV regional wall motion abnormalities, myocardial fatty infiltration, and myocardial fibrosis. The end-point was a composite of cardiac death, sustained ventricular tachycardia, ventricular fibrillation, and appropriate ICD discharge. RESULTS: Twenty patients met the composite end-point over a mean follow-up of 4.3±1.5years. An abnormal CMR was an independent predictor of outcomes (p<0.001). The presence of multiple abnormalities heralded a particular high risk of events (HR 23.0, 95% CI 5.7-93.2, p<0.001 for 2 abnormalities; HR 35.8, 95% CI 9.7-132.6, p<0.001 for 3 or more abnormalities). The positive predictive value of an abnormal CMR study was 21.0% for an adverse event, whilst the negative predictive value of a normal CMR study was 98.8% over the follow-up period. CONCLUSIONS: CMR provides important prognostic information in patients under evaluation for ARVC. A normal study portends a good prognosis. Conversely, the presence of multiple abnormalities identifies a high risk group of patients who may benefit from ICD implantation.
    International journal of cardiology 05/2013; · 6.18 Impact Factor
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    ABSTRACT: BACKGROUND: Cardiovascular magnetic resonance (CMR) steady state free precession (SSFP) cine sequences with high temporal resolution and improved post-processing can accurately measure RA dimensions. We used this technique to define ranges for normal RA volumes and dimensions normalized, when necessary, to the influence of gender, body surface area (BSA) and age, and also to define the best 2D images-derived predictors of RA enlargement. METHODS: For definition of normal ranges of RA volume we studied 120 healthy subjects (60 men, 60 women; 20 subjects per age decile from 20 to 80 years), after careful exclusion of cardiovascular abnormality. We also studied 120 patients (60 men, 60 women; age range 20 to 80 years) with a clinical indication for CMR in order to define the best 1D and 2D predictors of RA enlargement. Data were generated from SSFP cine CMR, with 3-dimensional modeling, including tracking of the atrioventricular ring motion and time-volume curves analysis. RESULTS: In the group of healthy individuals, age influenced RA 2-chamber area and transverse diameter. Gender influenced most absolute RA dimensions and volume. Interestingly, right atrial volumes did not change with age and gender when indexed to body surface area. New CMR normal ranges for RA dimensions were modeled and displayed for clinical use with normalization for BSA and gender and display of parameter variation with age. Finally, the best 2D images-derived independent predictors of RA enlargement were indexed area and indexed longitudinal diameter in the 2-chamber view. CONCLUSION: Reference RA dimensions and predictors of RA enlargement are provided using state-of-the-art CMR techniques.
    Journal of Cardiovascular Magnetic Resonance 04/2013; 15(1):29. · 4.44 Impact Factor
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    ABSTRACT: AIMS: Echocardiographic studies have shown that left atrial volume (LAV) predicts adverse outcome in small heart failure (HF) cohorts of mixed aetiology. However, the prognostic value of LAV in non-ischaemic dilated cardiomyopathy (DCM) is unknown. Cardiovascular magnetic resonance (CMR) allows accurate and reproducible measurement of LAV. We sought to determine the long-term prognostic significance of LAV assessed by CMR in DCM. METHODS AND RESULTS: We measured LAV indexed to body surface area (LAVi) in 483 consecutive DCM patients referred for CMR. Patients were prospectively followed up for a primary endpoint of all-cause mortality or cardiac transplantation. During a median follow-up of 5.3 years, 75 patients died and 9 underwent cardiac transplantation. After adjustment for established risk factors, LAVi was an independent predictor of the primary endpoint [hazard ratio (HR) per 10 mL/m2 1.08; 95% confidence interval (CI) 1.01-1.15; P = 0.022]. LAVi was also independently associated with the secondary composite endpoints of cardiovascular mortality or cardiac transplantation (HR per 10 mL/m2 1.11; 95% CI 1.04-1.19; P = 0.003), and HF death, HF hospitalization, or cardiac transplantation (HR per 10 mL/m2 1.11; 95% CI 1.04-1.18; P = 0.001). The optimal LAVi cut-off value for predicting the primary endpoint was 72 mL/m2. Patients with LAVi >72 mL/m2 had a three-fold elevated risk of death or transplantation (HR 3.00; 95% CI 1.92-4.70; P < 0.001). LAVi provided incremental prognostic value for the prediction of transplant-free survival (net reclassification improvement 0.17; 95% CI 0.05-0.29; P = 0.002). CONCLUSIONS: LAVi is a powerful independent predictor of transplant-free survival and HF outcomes in DCM. Assessment of LAV improves risk stratification in DCM and should be incorporated into routine CMR examination.
    European Journal of Heart Failure 03/2013; · 5.25 Impact Factor
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    ABSTRACT: BACKGROUND: and Objective Predicting the development and progression of twin-twin transfusion syndrome (TTTS) in genetically identical monochorionic diamniotic (MCDA) twins remains difficult. Attempts to find improved methods of characterizing and risk stratifying in TTTS have turned to measures of cardiac dysfunction. To date the ability of cardiovascular parameters to predict the need for or response to treatment is unsatisfactory, with only a weak correlation with Quintero staging and wide variation at each stage. Vector velocity imaging (VVI) is a non-Doppler ultrasound technology that tracks myocardial speckles frame by frame to produce measures of myocardial deformation, including strain. Strain signifies the fractional change in ventricular wall length and allows quantification of myocardial performance offline. Although strain, like the myocardial performance index (MPI), is load dependent, the assessment of cardiac wall deformation provides a more direct reflection of intrinsic cardiomyocyte function. Many studies of VVI speckle tracking in the fetus have been limited by measurement at low frame rates, resulting in falsely low measures of strain, particularly in the left ventricle, or the use of software calculated "global" or "natural" strain rather than Lagrangian strain. We assess the feasibility of using VVI speckle tracking to measure Lagrangian strain in twin pregnancies, including those complicated by TTTS. We investigate whether ventricular strain measurement might aid risk stratification of TTTS, specifically whether within-pair differences in ventricular strain exist in early TTTS. Finally, we assess whether VVI measurements can reflect functional recovery following fetal laser therapy for TTTS. MATERIALS AND METHODS: This was a prospective case-control study enrolling consecutive women with MCDA pregnancies referred for ultrasound assessment from local maternity units. Fetal echocardiograms were performed using dummy ECG gating to ensure optimal transfer of frame rates to the Syngo software to perform offline speckle tracking. Subjects included 27 women with TTTS pregnancies and 28 controls that did not develop TTTS. Single scans were performed for each control. Of the 27 TTTS pregnancies, 18 underwent serial scans. Data from 50 TTTS scans (200 ventricles) were available for analysis. The fetal heart rate was determined by mitral valve closure and a single heartbeat was selected for analysis. The endocardial border was tracked manually in end-diastole and tracking curves were created automatically in subsequent frames. The 2 orthogonal X,Y tracking coordinates stored by the software's database were used to calculate peak negative systolic strain along the whole length of right and left free wall (Lagrangian strain). Strain is defined as a relative change in length and is represented in this paper as a positive percentage change. RESULTS: VVI tracking was suitable for analysis in 96/112 (86%) non-TTTS control scans and in 182/200 (91%) TTTS scans. Reproducibility was good, with an intraclass correlation for RV and LV strain of 0.894 and 0.928, respectively. Non-TTTS control twins were described as "heavy" or "light" controls. Recipient and donor twins were generally lighter than heavy and light twins, respectively. Mean estimated fetal weight discordance was greater in the TTTS group compared to the non-TTTS group, as expected; however, Kendall's Tau showed no significant relationship between estimated weight discordance and strain discordance for either left or right ventricles.
    American journal of obstetrics and gynecology 03/2013; · 3.28 Impact Factor
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    ABSTRACT: Risk stratification of patients with nonischemic dilated cardiomyopathy is primarily based on left ventricular ejection fraction (LVEF). Superior prognostic factors may improve patient selection for implantable cardioverter-defibrillators (ICDs) and other management decisions. To determine whether myocardial fibrosis (detected by late gadolinium enhancement cardiovascular magnetic resonance [LGE-CMR] imaging) is an independent and incremental predictor of mortality and sudden cardiac death (SCD) in dilated cardiomyopathy. Prospective, longitudinal study of 472 patients with dilated cardiomyopathy referred to a UK center for CMR imaging between November 2000 and December 2008 after presence and extent of midwall replacement fibrosis were determined. Patients were followed up through December 2011. Primary end point was all-cause mortality. Secondary end points included cardiovascular mortality or cardiac transplantation; an arrhythmic composite of SCD or aborted SCD (appropriate ICD shock, nonfatal ventricular fibrillation, or sustained ventricular tachycardia); and a composite of HF death, HF hospitalization, or cardiac transplantation. Among the 142 patients with midwall fibrosis, there were 38 deaths (26.8%) vs 35 deaths (10.6%) among the 330 patients without fibrosis (hazard ratio [HR], 2.96 [95% CI, 1.87-4.69]; absolute risk difference, 16.2% [95% CI, 8.2%-24.2%]; P < .001) during a median follow-up of 5.3 years (2557 patient-years of follow-up). The arrhythmic composite was reached by 42 patients with fibrosis (29.6%) and 23 patients without fibrosis (7.0%) (HR, 5.24 [95% CI, 3.15-8.72]; absolute risk difference, 22.6% [95% CI, 14.6%-30.6%]; P < .001). After adjustment for LVEF and other conventional prognostic factors, both the presence of fibrosis (HR, 2.43 [95% CI, 1.50-3.92]; P < .001) and the extent (HR, 1.11 [95% CI, 1.06-1.16]; P < .001) were independently and incrementally associated with all-cause mortality. Fibrosis was also independently associated with cardiovascular mortality or cardiac transplantation (by fibrosis presence: HR, 3.22 [95% CI, 1.95-5.31], P < .001; and by fibrosis extent: HR, 1.15 [95% CI, 1.10-1.20], P < .001), SCD or aborted SCD (by fibrosis presence: HR, 4.61 [95% CI, 2.75-7.74], P < .001; and by fibrosis extent: HR, 1.10 [95% CI, 1.05-1.16], P < .001), and the HF composite (by fibrosis presence: HR, 1.62 [95% CI, 1.00-2.61], P = .049; and by fibrosis extent: HR, 1.08 [95% CI, 1.04-1.13], P < .001). Addition of fibrosis to LVEF significantly improved risk reclassification for all-cause mortality and the SCD composite (net reclassification improvement: 0.26 [95% CI, 0.11-0.41]; P = .001 and 0.29 [95% CI, 0.11-0.48]; P = .002, respectively). Assessment of midwall fibrosis with LGE-CMR imaging provided independent prognostic information beyond LVEF in patients with nonischemic dilated cardiomyopathy. The role of LGE-CMR in the risk stratification of dilated cardiomyopathy requires further investigation.
    JAMA The Journal of the American Medical Association 03/2013; 309(9):896-908. · 29.98 Impact Factor
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    ABSTRACT: Correction to McGill LA, Ismail T, Nielles-Vallespin S, Ferreira P, Scott AD, Roughton M, Kilner PJ, Ho SY, McCarthy KP, Gatehouse PD, de Silva R, Speier P, Feiweier T, Mekkaoui C, Sosnovik DE, Prasad SK, Firmin DN, Pennell DJ. Reproducibility of in-vivo diffusion tensor cardiovascular magnetic resonance in hypertrophic cardiomyopathy. Journal of Cardiovascular Magnetic Resonance 2012, 14:86.
    Journal of Cardiovascular Magnetic Resonance 02/2013; 15(1):22. · 4.44 Impact Factor
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    Journal of Cardiovascular Magnetic Resonance 01/2013; 15(1). · 4.44 Impact Factor
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    Journal of Cardiovascular Magnetic Resonance 01/2013; 15(1). · 4.44 Impact Factor
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    ABSTRACT: BACKGROUND: Myocardial disarray is an important histological feature of hypertrophic cardiomyopathy (HCM) which has been studied post-mortem, but its in-vivo prevalence and extent is unknown. Cardiac Diffusion Tensor Imaging (cDTI) provides information on mean intravoxel myocyte orientation and potentially myocardial disarray. Recent technical advances have improved in-vivo cDTI, and the aim of this study was to assess the interstudy reproducibility of quantitative in-vivo cDTI in patients with HCM. Methods and results A stimulated-echo single-shot-EPI sequence with zonal excitation and parallel imaging was implemented. Ten patients with HCM were each scanned on 2 different days. For each scan 3 short axis mid-ventricular slices were acquired with cDTI at end systole. Fractional anisotropy (FA), mean diffusivity (MD), and helix angle (HA) maps were created using a cDTI post-processing platform developed in-house. The mean +/- SD global FA was 0.613 +/-0.044, MD was 0.750 +/-0.154 x 10-3 mm2/s and HA was epicardium 34.3 +/-7.6degrees, mesocardium 3.5 +/-6.9degrees and endocardium 38.9 +/-8.1degrees. Comparison of initial and repeat studies showed global interstudy reproducibility for FA (SD = +/-0.045, Coefficient of Variation (CoV) = 7.2%), MD (SD = +/-0.135 x 10-3 mm2/s, CoV = 18.6%) and HA (epicardium SD = +/-4.8degrees; mesocardium SD = +/-3.4degrees; endocardium SD = +/-2.9degrees). Reproducibility of FA was superior to MD (p = 0.003). Global MD was significantly higher in the septum than the reference lateral wall (0.784 +/-0.188 vs 0.750 +/-0.154 x10-3 mm2/s, p < 0.001). Septal HA was significantly lower than the reference lateral wall in all 3 transmural layers (from 8.3degrees to 10.4degrees, all p < 0.001). CONCLUSIONS: To the best of our knowledge, this is the first study to assess the interstudy reproducibility of DTI in the human HCM heart in-vivo and the largest cDTI study in HCM to date. Our results show good reproducibility of FA, MD and HA which indicates that current technology yields robust in-vivo measurements that have potential clinical value. The interpretation of regional differences in the septum requires further investigation.
    Journal of Cardiovascular Magnetic Resonance 12/2012; 14(1):86. · 4.44 Impact Factor

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2k Citations
587.21 Total Impact Points


  • 2014
    • Novartis
      Bâle, Basel-City, Switzerland
  • 2013
    • Royal College of Physicians
      Londinium, England, United Kingdom
  • 2008–2013
    • Centre for Statistics in Medicine
      Oxford, England, United Kingdom
    • Hospital Arnau de Vilanova
      Valenza, Valencia, Spain
    • University College London
      Londinium, England, United Kingdom
  • 2007–2013
    • Royal Brompton and Harefield NHS Foundation Trust
      Harefield, England, United Kingdom
  • 2006–2013
    • Imperial College London
      • • Centre for Pathology
      • • Division of Diabetes, Endocrinology and Metabolism
      • • Institute of Reproductive and Developmental Biology
      Londinium, England, United Kingdom
  • 2011
    • University of Alcalá
      Cómpluto, Madrid, Spain
  • 2009
    • University of Groningen
      • Department of Cardiology
      Groningen, Province of Groningen, Netherlands