Showing papers by "David E. Newby published in 2018"
TL;DR: In this article, the authors determine the association between non-communicable illnesses and HIV-related deaths in people with HIV and cardiovascular diseases, and show that most deaths in persons with HIV are now attributable to noncommunicable diseases, especially cardiovascular diseases.
Abstract: Background: With advances in antiretroviral therapy, most deaths in people with HIV are now attributable to noncommunicable illnesses, especially cardiovascular disease. We determine the associatio...
477 citations
TL;DR: The implementation of an hs-cTnI assay was evaluated in consecutive patients who had been admitted to the hospitals' emergency departments with suspected acute coronary syndrome and its findings question whether the diagnostic threshold for myocardial infarction should be based on the 99th centile derived from a normal reference population.
240 citations
TL;DR: Optimal CT-AVC thresholds for diagnosing severe AS were determined in patients with concordant echocardiographic assessments, before being used to arbitrate disease severity in those with discordant measurements.
Abstract: Background— Computed tomography aortic valve calcium scoring (CT-AVC) holds promise for the assessment of patients with aortic stenosis (AS). We sought to establish the clinical utility of CT-AVC in an international multicenter cohort of patients. Methods and Results— Patients with AS who underwent ECG-gated CT-AVC within 3 months of echocardiography were entered into an international, multicenter, observational registry. Optimal CT-AVC thresholds for diagnosing severe AS were determined in patients with concordant echocardiographic assessments, before being used to arbitrate disease severity in those with discordant measurements. In patients with long-term follow-up, we assessed whether CT-AVC thresholds predicted aortic valve replacement and death. In 918 patients from 8 centers (age, 77±10 years; 60% men; peak velocity, 3.88±0.90 m/s), 708 (77%) patients had concordant echocardiographic assessments, in whom CT-AVC provided excellent discrimination for severe AS (C statistic: women 0.92, men 0.89). Our optimal sex-specific CT-AVC thresholds (women 1377 Agatston unit and men 2062 Agatston unit) were nearly identical to those previously reported (women 1274 Agatston unit and men 2065 Agatston unit). Clinical outcomes were available in 215 patients (follow-up 1029 [126–2251] days). Sex-specific CT-AVC thresholds independently predicted aortic valve replacement and death (hazard ratio, 3.90 [95% confidence interval, 2.19–6.78]; P P =0.010). Conclusions— Sex-specific CT-AVC thresholds accurately identify severe AS and provide powerful prognostic information. These findings support their integration into routine clinical practice. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifiers: NCT01358513, NCT02132026, NCT00338676, NCT00647088, NCT01679431.
224 citations
TL;DR: In patients with COPD with CVD or risk factors for CVD, exacerbations confer an increased risk of subsequent CVD events, especially in hospitalized patients and within the first 30 days after exacerbation.
Abstract: Rationale: Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are common, associated with acute inflammation, and may increase subsequent cardiovascular disease (CVD) risk.Object...
159 citations
TL;DR: An updated overview of recent major studies regarding the impact of PM2.5 on cardiometabolic health is provided and key remaining scientific questions are outlined to allow for the promulgation of formal evidence-base recommendations regarding their appropriate usage in the global battle against air pollution.
121 citations
TL;DR: 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.
Abstract: 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 potenti...
119 citations
TL;DR: F fluorine-18-NaF PET-CT is a novel and promising approach to the identification of disease activity in patients with abdominal aortic aneurysm and is an additive predictor of aneurYSm growth and future clinical events.
115 citations
TL;DR: Clinical risk scores significantly improved the safety of the European Society of Cardiology 3-hour pathway, which relies on a single cardiac troponin threshold at the 99th percentile to rule in and rule out myocardial infarction.
Abstract: Background: High-sensitivity cardiac troponin assays can help to identify patients who are at low risk of myocardial infarction in the emergency department. We aimed to determine whether the additi...
83 citations
TL;DR: A novel high-sensitivity cardiac troponin I assay can safely identify patients at low risk of myocardial infarction or cardiac death and miss fewer events than those that rely on the 99th centile to rule out my Cardiac Infarction.
Abstract: Background High-sensitivity cardiac troponin assays enable the early risk stratification of patients with suspected acute coronary syndrome to identify those at low risk of myocardial infarction or cardiac death. We evaluated the performance of a novel high-sensitivity cardiac troponin I assay in early rule out pathways. Methods In 1920 patients with suspected acute coronary syndrome, cardiac troponin was measured using the Siemens Atellica high-sensitivity cardiac troponin I assay (99th centile: 34 ng/L women, 53 ng/L men). We evaluated three pathways which use either low risk-stratification thresholds of cardiac troponin ( High-S ensitivity T roponin in the E valuation of patients with A cute C oronary S yndrome (High-STEACS) and the European Society of Cardiology (ESC) 1 hour pathway) or the 99th centile diagnostic threshold (ESC 3 hour pathway) to rule out myocardial infarction. Results The primary outcome of myocardial infarction or cardiac death at 30 days occurred in 14.4% (277/1920). The High-STEACS pathway ruled out 63% of patients (1218/1920), with five missed events for a negative predictive value (NPV) of 99.5% (95% CI (CI) 99.1% to 99.8%). Similar performance was observed for the ESC 1 hour pathway with an NPV of 99.0% (97.6% to 99.8%). In contrast, the ESC 3 hour pathway ruled out 65% of patients (1248/1920), but missed 25 events for an NPV of 98.0% (97.1% to 98.7%). Conclusions A novel high-sensitivity cardiac troponin I assay can safely identify patients at low risk of myocardial infarction or cardiac death. Diagnostic pathways that use low cardiac troponin concentrations for risk stratification miss fewer events than those that rely on the 99th centile to rule out myocardial infarction. Trial registration NCT1852123.
65 citations
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TL;DR: A two-stage modified Unet framework that simultaneously learns to detect a ROI within the full volume and to classify voxels without losing the original resolution is developed.
Abstract: Deep convolutional neural networks (CNNs) have been intensively used for multi-class segmentation of data from different modalities and achieved state-of-the-art performances. However, a common problem when dealing with large, high resolution 3D data is that the volumes input into the deep CNNs has to be either cropped or downsampled due to limited memory capacity of computing devices. These operations lead to loss of resolution and increment of class imbalance in the input data batches, which can downgrade the performances of segmentation algorithms. Inspired by the architecture of image super-resolution CNN (SRCNN) and self-normalization network (SNN), we developed a two-stage modified Unet framework that simultaneously learns to detect a ROI within the full volume and to classify voxels without losing the original resolution. Experiments on a variety of multi-modal volumes demonstrated that, when trained with a simply weighted dice coefficients and our customized learning procedure, this framework shows better segmentation performances than state-of-the-art Deep CNNs with advanced similarity metrics.
64 citations
TL;DR: Compared with risk-based guidelines, symptom-focused assessment identifies a larger group of low-risk chest pain patients potentially deriving limited benefit from noninvasive testing.
Abstract: Objectives This study sought to compare the performance of major guidelines for the assessment of stable chest pain including risk-based (American College of Cardiology/American Heart Association and European Society of Cardiology) and symptom-focused (National Institute for Health and Care Excellence) strategies. Background Although noninvasive testing is not recommended in low-risk individuals with stable chest pain, guidelines recommend differing approaches to defining low-risk patients. Methods Patient-level data were obtained from the PROMISE (Prospective Multicenter Imaging Study for Evaluation of Chest Pain) and SCOT-HEART (Scottish Computed Tomography of the Heart) trials. Pre-test probability was determined and patients dichotomized into low-risk and intermediate-high–risk groups according to each guideline’s definitions. The primary endpoint was obstructive coronary artery disease on coronary computed tomography angiography. Secondary endpoints were coronary revascularization at 90 days and cardiovascular death or nonfatal myocardial infarction up to 3 years. Results In total, 13,773 patients were included of whom 6,160 had coronary computed tomography angiography. The proportions of patients identified as low risk by the American College of Cardiology/American Heart Association, European Society of Cardiology, and National Institute for Health and Care Excellence guidelines, respectively, were 2.5%, 2.5%, and 10.0% within PROMISE, and 14.0%, 19.8%, and 38.4% within SCOT-HEART. All guidelines identified lower rates of obstructive coronary artery disease in low- versus intermediate-high–risk patients with a negative predictive value of ≥0.90. Compared with low-risk groups, all intermediate-high–risk groups had greater risks of coronary revascularization (odds ratio [OR]: 2.2 to 24.1) and clinical outcomes (OR: 1.84 to 5.8). Conclusions Compared with risk-based guidelines, symptom-focused assessment identifies a larger group of low-risk chest pain patients potentially deriving limited benefit from noninvasive testing. (Scottish Computed Tomography of the Heart Trial [SCOT-HEART]; NCT01149590; Prospective Multicenter Imaging Study for Evaluation of Chest Pain [PROMISE]; NCT01174550)
TL;DR: The current understanding of the mechanism and function of ncRNA is reviewed, focusing on miRNAs and lncRNAs in vascular disease and atherosclerosis and existing therapies and current delivery methods.
Abstract: Only recently have we begun to appreciate the importance and complexity of the non-coding genome, owing in some part to truly significant advances in genomic technology such as RNA sequencing and genome-wide profiling studies. Previously thought to be non-functional transcriptional “noise”, non-coding RNAs are now known to play important roles in many diverse biological pathways, not least in vascular disease. Whilst micro RNAs (miRNA) are known to regulate protein-coding gene expression principally through mRNA degradation, long non-coding RNAs (lncRNAs) can activate and repress genes by a variety of mechanisms at both transcriptional and translational levels. These versatile molecules, with complex secondary structures, may interact with chromatin, proteins and other RNA to form complexes with an array of functional consequences. A body of emerging evidence indicates that both classes of non-coding RNAs regulate multiple physiological and pathological processes in vascular physiology and disease. Whilst dozens of miRNAs are now implicated and described in relative mechanistic depth, relatively fewer lncRNAs are well described. However, notable examples include ANRIL, SMILR and SENCR in vascular smooth muscle cells; MALAT1 and GATA-6S in endothelial cells; and mitochondrial lncRNA LIPCAR as a powerful biomarker. Due to such ubiquitous involvement in pathology and well-known biogenesis and functional genetics, novel microRNA-based therapies and delivery methods are now in development, including some early stage clinical trials. Although lncRNAs may hold similar potential, much more needs to be understood about their relatively complex molecular behaviours before realistic translation into novel therapies. Here, we review the current understanding of the mechanism and function of non-coding RNA, focusing on microRNAs and long non-coding RNAs in vascular disease and atherosclerosis. We discuss existing therapies and current delivery methods, emphasising the importance of miRNAs and lncRNAs as effectors and biomarkers in vascular pathology.
TL;DR: A GMP-compatible hESC-ECP is demonstrated that improved ischemic limb perfusion and increased local angiogenesis without engraftment, paving the way for translation of this therapy.
TL;DR: In patients with moderate COPD and heightened cardiovascular risk, FF alone or in combination with VI appears to reduce the rate of FEV1 decline.
Abstract: Rationale: Many patients with chronic obstructive pulmonary disease (COPD) have an accelerated loss of lung function. It is unclear whether drug treatment can modify this in patients with moderately severe disease.Objectives: In a prespecified analysis of the key secondary outcome in SUMMIT (Study to Understand Mortality and Morbidity), we investigated whether the inhaled corticosteroid fluticasone furoate (FF; 100 μg), the long-acting β-agonist vilanterol (VI; 25 μg), or their combination (FF/VI) modified the rate of decline in FEV1 compared with placebo. We also investigated how baseline covariates affected this decline.Methods: Spirometry was measured every 12 weeks in this event-driven, randomized, placebo-controlled trial of 16,485 patients with moderate COPD and heightened cardiovascular risk. An average of seven spirometric assessments per subject among the 15,457 patients with at least one on-treatment measurement were used in the analysis of rate of FEV1 decline. All statistical comparisons are c...
TL;DR: NICE-guided patient selection maximises the benefits of CTCA on diagnostic certainty, use of invasive coronary angiography and reductions in fatal and non-fatal myocardial infarction.
Abstract: Objectives To evaluate the diagnostic and prognostic benefits of CT coronary angiography (CTCA) using the 2016 National Institute for Health and Care Excellence (NICE) guidelines for the assessment of suspected stable angina. Methods Post hoc analysis of the Scottish COmputed Tomography of the HEART (SCOT-HEART) trial of 4146 participants with suspected angina randomised to CTCA. Patients were dichotomised into NICE guideline-defined possible angina and non-anginal presentations. Primary (diagnostic) endpoint was diagnostic certainty of angina at 6 weeks and prognostic endpoint comprised fatal and non-fatal myocardial infarction (MI). Results In 3770 eligible participants, CTCA increased diagnostic certainty more in those with possible angina (relative risk (RR) 2.22 (95% CI 1.91 to 2.60), p interaction Conclusions NICE-guided patient selection maximises the benefits of CTCA on diagnostic certainty, use of invasive coronary angiography and reductions in fatal and non-fatal myocardial infarction. Patients with non-anginal chest pain derive minimal benefit from CTCA and increase the rates of invasive investigation. Trial registration number ClinicalTrials.gov: NCT01149590;post results.
TL;DR: In patients with COPD and heightened cardiovascular risk, plasma cardiac troponin I concentrations are a specific and major indicator of future cardiovascular events and cardiovascular death.
16 Sep 2018
TL;DR: This work proposes a two-stage modified U-Net framework that simultaneously learns to detect a ROI within the full volume and to classify voxels without losing the original resolution.
Abstract: Deep convolutional neural networks (CNNs) have achieved state-of-the-art performances for multi-class segmentation of medical images. However, a common problem when dealing with large, high resolution 3D data is that the volumes input into the deep CNNs has to be either cropped or downsampled due to limited memory capacity of computing devices. These operations can lead to loss of resolution and class imbalance in the input data batches, thus downgrade the performances of segmentation algorithms. Inspired by the architecture of image super-resolution CNN (SRCNN), we propose a two-stage modified U-Net framework that simultaneously learns to detect a ROI within the full volume and to classify voxels without losing the original resolution. Experiments on a variety of multi-modal 3D cardiac images have demonstrated that this framework shows better segmentation performances than state-of-the-art Deep CNNs with trained with the same similarity metrics.
TL;DR: Coronary CTA/PET protocol with CTA first followed by PET-only allows for reliable and reproducible quantification of 18F-NaF coronary uptake and may facilitate selection of high-risk patients for PET- only imaging based on results from prior CTA, providing a practical workflow for clinical application.
Abstract: Background: We assessed the feasibility of utilizing previously acquired computed tomography angiography (CTA) with subsequent positron-emission tomography (PET)-only scan for the quantitative eval...
TL;DR: In this article, the effects of apelin on pulmonary hemodynamics in patients with PAH are unknown, however, it was shown that apelin infusion caused a significant reduction in pulmonary vascular resistance and increase in cardiac output without a change in heart rate or systemic vascular resistance.
TL;DR: It is hypothesized that former smokers with COPD would have greater short- and long-term changes in lung function, respiratory-related quality of life, and exacerbation risk, in response to ICS than continuing and intermittent smokers.
Abstract: Current smokers have a blunted FEV1 response and exacerbation reduction with inhaled corticosteroidshttp://ow.ly/PBIW30hcISK
TL;DR: Clinically significant noncardiac findings occur in 10% of patients undergoing CCTA, which means application of new lung nodule guidelines will reduce the cost of surveillance, without the risk of missing malignancy.
Abstract: Noncardiac findings are common on coronary computed tomography angiography (CCTA). We assessed the clinical impact of noncardiac findings, and potential changes to surveillance scans with the application of new lung nodule guidelines. This substudy of the SCOT-HEART randomized controlled trial assessed noncardiac findings identified on CCTA. Clinically significant noncardiac findings were those causing symptoms or requiring further investigation, follow-up or treatment. Lung nodule follow-up was undertaken following the 2005 Fleischner guidelines. The potential impact of the 2015 British Thoracic Society (BTS) and the 2017 Fleischner guidelines was assessed. CCTA was performed in 1,778 patients and noncardiac findings were identified in 677 (38%). In 173 patients (10%) the abnormal findings were clinically significant and in 55 patients (3%) the findings were the cause of symptoms. Follow-up imaging was recommended in 136 patients (7.6%) and additional clinic consultations were organized in 46 patients (2.6%). Malignancy was diagnosed in 7 patients (0.4%). Application of the new lung nodule guidelines would have reduced the number of patients undergoing a follow-up CT scan: 68 fewer with the 2015 BTS guidelines and 78 fewer with the 2017 Fleischner guidelines; none of these patients subsequently developed malignancy. Clinically significant noncardiac findings are identified in 10% of patients undergoing CCTA. Application of new lung nodule guidelines will reduce the cost of surveillance, without the risk of missing malignancy. • Clinically significant noncardiac findings occur in 10% of patients undergoing CCTA.
• Noncardiac findings may be an important treatable cause of chest pain
• Further imaging investigations for noncardiac findings were recommended in 8% of patients after CCTA.
• New lung nodule follow-up guidelines will result in cost savings.
TL;DR: Despite overestimating the probability of minimal- risk, the PROMISE minimal-risk tool outperforms the CADC model with regards to prognostic discrimination in patients with suspected stable angina, and may assist clinicians in decisions regarding non-invasive testing.
TL;DR: A linear relationship exists between heart rate and all-cause mortality and cardiovascular events in patients with COPD and heightened cardiovascular risk in this population of patients, extending the prognostic importance of BP to this growing group of patients and raising concerns that both high and low BP may pose health risks.
Abstract: Aims To characterize the relationship between blood pressure (BP) or heart rate and mortality and morbidity in chronic obstructive pulmonary disease (COPD). Methods and results We performed post hoc analysis of baseline BP or heart rate and all-cause mortality and cardiovascular events in the SUMMIT trial. SUMMIT was a randomized double-blind outcome trial of 16 485 participants (65 ± 8 years, 75% male, and 47% active smokers) enrolled at 1368 sites in 43 countries. Participants with moderate COPD with or at risk for cardiovascular disease (CVD) were randomized to placebo, long-acting beta agonist, inhaled corticosteroid, or their combination. All-cause mortality increased in relation to high systolic [≥140 mmHg; hazard ratio (HR) 1.27, 95% confidence interval (CI) 1.12-1.45] or diastolic (≥90 mmHg; HR 1.35, 95% CI 1.14-1.59) BP and low systolic (<120 mmHg; HR 1.36, 95% CI 1.13-1.63) or diastolic (<80 mmHg; HR 1.15, 95% CI 1.00-1.32) BP. Higher heart rates (≥80 per minute; HR 1.39, 95% CI 1.21-1.60) and pulse pressures (≥80 mmHg; HR 1.39, 95% CI 1.07-1.80) were more linearly related to increases in all-cause mortality. The risks of cardiovascular events followed similar patterns to all-cause mortality. Similar findings were observed in subgroups of patients without established CVD. Conclusion A 'U-shaped' relationship between BP and all-cause mortality and cardiovascular events exists in patients with COPD and heightened cardiovascular risk. A linear relationship exists between heart rate and all-cause mortality and cardiovascular events in this population. These findings extend the prognostic importance of BP to this growing group of patients and raise concerns that both high and low BP may pose health risks.
TL;DR: In patients with acute myocarditis, USPIO-enhanced MRI does not provide additional clinically relevant information to LGE and T2 mapping MRI, suggesting that tissue-resident macrophages do not provide a substantial contribution to the myocardial inflammation in this condition.
Abstract: 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 0.05). 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 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.
TL;DR: The REstart or STop Antithrombotics Randomised Trial (RESTART) is an investigator-led, randomisation, open, assessor-blind, parallel-group, randomised trial comparing starting versus avoiding antiplatelet drugs for adults surviving antithrombotic-associated ICH at 122 hospital sites in the United Kingdom.
Abstract: For adults surviving stroke due to spontaneous (non-traumatic) intracerebral haemorrhage (ICH) who had taken an antithrombotic (i.e. anticoagulant or antiplatelet) drug for the prevention of vaso-occlusive disease before the ICH, it is unclear whether starting antiplatelet drugs results in an increase in the risk of recurrent ICH or a beneficial net reduction of all serious vascular events compared to avoiding antiplatelet drugs. The REstart or STop Antithrombotics Randomised Trial (RESTART) is an investigator-led, randomised, open, assessor-blind, parallel-group, randomised trial comparing starting versus avoiding antiplatelet drugs for adults surviving antithrombotic-associated ICH at 122 hospital sites in the United Kingdom. RESTART uses a central, web-based randomisation system using a minimisation algorithm, with 1:1 treatment allocation to which central research staff are masked. Central follow-up includes annual postal or telephone questionnaires to participants and their general (family) practitioners, with local provision of information about adverse events and outcome events. The primary outcome is recurrent symptomatic ICH. The secondary outcomes are: symptomatic haemorrhagic events; symptomatic vaso-occlusive events; symptomatic stroke of uncertain type; other fatal events; modified Rankin Scale score; adherence to antiplatelet drug(s). The magnetic resonance imaging (MRI) sub-study involves the conduct of brain MRI according to a standardised imaging protocol before randomisation to investigate heterogeneity of treatment effect according to the presence of brain microbleeds. Recruitment began on 22 May 2013. The target sample size is at least 720 participants in the main trial (at least 550 in the MRI sub-study). Final results of RESTART will be analysed and disseminated in 2019. ISRCTN71907627 (
www.isrctn.com/ISRCTN71907627
). Prospectively registered on 25 April 2013.
TL;DR: Asymmetric wall thickening is common in aortic stenosis and is associated with increased myocardial injury, left ventricular decompenzation, and adverse events, and its presence may help identify patients likely to proceed quickly towards AVR.
Abstract: Aims Asymmetric wall thickening has been described in patients with aortic stenosis. However, it remains poorly characterized and its prognostic implications are unclear. We hypothesized this pattern of adaptation is associated with advanced remodelling, left ventricular decompenzation, and a poor prognosis. Methods and results In a prospective observational cohort study, 166 patients with aortic stenosis (age 69, 69% males, mean aortic valve area 1.0 ± 0.4 cm2) and 37 age and sex-matched healthy volunteers underwent phenotypic characterization with comprehensive clinical, imaging, and biomarker evaluation. Asymmetric wall thickening on both echocardiography and cardiovascular magnetic resonance was defined as regional wall thickening ≥ 13 mm and > 1.5-fold the thickness of the opposing myocardial segment. Although no control subject had asymmetric wall thickening, it was observed in 26% (n = 43) of patients with aortic stenosis using magnetic resonance and 17% (n = 29) using echocardiography. Despite similar demographics, co-morbidities, valve narrowing, myocardial hypertrophy, and fibrosis, patients with asymmetric wall thickening had increased cardiac troponin I and brain natriuretic peptide concentrations (both P < 0.001). Over 28 [22, 33] months of follow-up, asymmetric wall thickening was an independent predictor of aortic valve replacement (AVR) or death whether detected by magnetic resonance [hazard ratio (HR) = 2.15; 95% confidence interval (CI) 1.29-3.59; P = 0.003] or echocardiography (HR = 1.79; 95% CI 1.08-3.69; P = 0.021). Conclusion Asymmetric wall thickening is common in aortic stenosis and is associated with increased myocardial injury, left ventricular decompenzation, and adverse events. Its presence may help identify patients likely to proceed quickly towards AVR. Clinical Trial Registration https://clinicaltrials.gov/show/NCT01755936: NCT01755936.
TL;DR: In healthy volunteers and patients with symptomatic carotid artery stenosis, transcranial Doppler generates reproducible data regarding the middle cerebral artery velocities, however, larger studies are needed to validate its clinical applicability.
Abstract: Transcranial Doppler ultrasound remains the only imaging modality that is capable of real-time measurements of blood flow velocity and microembolic signals in the cerebral circulation. We here assessed the repeatability and reproducibility of transcranial Doppler ultrasound in healthy volunteers and patients with symptomatic carotid artery stenosis. Between March and August 2017, we recruited 20 healthy volunteers and 20 patients with symptomatic carotid artery stenosis. In a quiet temperature-controlled room, two 1-h transcranial Doppler measurements of blood flow velocities and microembolic signals were performed sequentially on the same day (within-day repeatability) and a third 7–14 days later (between-day reproducibility). Levels of agreement were assessed by interclass correlation co-efficient. In healthy volunteers (31±9 years, 11 male), within-day repeatability of Doppler measurements were 0.880 (95% CI 0.726–0.950) for peak velocity, 0.867 (95% CI 0.700–0.945) for mean velocity, and 0.887 (95% CI 0.741–0.953) for end-diastolic velocity. Between-day reproducibility was similar but lower: 0.777 (95% CI 0.526–0.905), 0.795 (95% CI 0.558–0.913), and 0.674 (95% CI 0.349–0.856) respectively. In patients (72±11 years, 11 male), within-day repeatability of Doppler measurements were higher: 0.926 (95% CI 0.826–0.970) for peak velocity, 0.922 (95% CI 0.817–0.968) for mean velocity, and 0.868 (95% CI 0.701–0.945) for end-diastolic velocity. Similarly, between-day reproducibility revealed lower values: 0.800 (95% CI 0.567–0.915), 0.786 (95% CI 0.542–0.909), and 0.778 (95% CI 0.527–0.905) respectively. In both cohorts, the intra-observer Bland Altman analysis demonstrated acceptable mean measurement differences and limits of agreement between series of middle cerebral artery velocity measurements with very few outliers. In patients, the carotid stenoses were 30–40% (n = 9), 40–50% (n = 6), 50–70% (n = 3) and > 70% (n = 2). No spontaneous embolisation was detected in either of the groups. Transcranial Doppler generates reproducible data regarding the middle cerebral artery velocities. However, larger studies are needed to validate its clinical applicability. ClinicalTrial.gov
(ID NCT 03050567), retrospectively registered on 15/05/2017.
16 Sep 2018
TL;DR: This paper presents a deformation-invariant CycleGAN (DicycleGAN) method using deformable convolutional layers and new cycle-consistency losses that has displayed its ability to generate synthesized data that is aligned with the source while maintaining a proper quality of signal compared to CycleGAN-generated data.
Abstract: Recently, the cycle-consistent generative adversarial networks (CycleGAN) has been widely used for synthesis of multi-domain medical images. The domain-specific nonlinear deformations captured by CycleGAN make the synthesized images difficult to be used for some applications, for example, generating pseudo-CT for PET-MR attenuation correction. This paper presents a deformation-invariant CycleGAN (DicycleGAN) method using deformable convolutional layers and new cycle-consistency losses. Its robustness dealing with data that suffer from domain-specific nonlinear deformations has been evaluated through comparison experiments performed on a multi-sequence brain MR dataset and a multi-modality abdominal dataset. Our method has displayed its ability to generate synthesized data that is aligned with the source while maintaining a proper quality of signal compared to CycleGAN-generated data. The proposed model also obtained comparable performance with CycleGAN when data from the source and target domains are alignable through simple affine transformations.
TL;DR: There is no evidence to suggest that baseline &bgr;‐blocker therapy reduces the respiratory benefits or increases the cardiovascular risk of inhaled long‐acting &b gr;‐agonists in patients with chronic obstructive pulmonary disease and heightened cardiovascular risk.
Abstract: Rationale: Cardiovascular disease is a common comorbidity in patients with chronic obstructive pulmonary disease. Although β-blockers can be used safely in patients with chronic obstructive pulmona...
TL;DR: MEMRI with T1 mapping provides an accurate assessment of infarct size and can also identify changes in calcium handling in the remote myocardium, and induced concentration-dependent shortening of myocardial T1 values.
Abstract: Background. Manganese-enhanced MRI (MEMRI) has the potential to identify viable myocardium and quantify calcium influx and handling. Two distinct manganese contrast media have been developed for clinical application, mangafodipir and EVP1001-1, employing different strategies to mitigate against adverse effects resulting from calcium-channel agonism. Mangafodipir delivers manganese ions as a chelate, and EVP1001-1 coadministers calcium gluconate. Using myocardial T1 mapping, we aimed to explore chelated and nonchelated manganese contrast agents, their mechanism of myocardial uptake, and their application to infarcted hearts. Methods. T1 mapping was performed in healthy adult male Sprague-Dawley rats using a 7T MRI scanner before and after nonchelated (EVP1001-1 or MnCl2 (22 μmol/kg)) or chelated (mangafodipir (22–44 μmol/kg)) manganese-based contrast media in the presence of calcium channel blockade (diltiazem (100–200 μmol/kg/min)) or sodium chloride (0.9%). A second cohort of rats underwent surgery to induce anterior myocardial infarction by permanent coronary artery ligation or sham surgery. Infarcted rats were imaged with standard gadolinium delayed enhancement MRI (DEMRI) with inversion recovery techniques (DEMRI inversion recovery) as well as DEMRI T1 mapping. A subsequent MEMRI scan was performed 48 h later using either nonchelated or chelated manganese and T1 mapping. Finally, animals were culled at 12 weeks, and infarct size was quantified histologically with Masson’s trichrome (MTC). Results. Both manganese agents induced concentration-dependent shortening of myocardial T1 values. This was greatest with nonchelated manganese, and could be inhibited by 30–43% with calcium-channel blockade. Manganese imaging successfully delineated the area of myocardial infarction. Indeed, irrespective of the manganese agent, there was good agreement between infarct size on MEMRI T1 mapping and histology (bias 1.4%, 95% CI −14.8 to 17.1 ). In contrast, DEMRI inversion recovery overestimated infarct size (bias 11.4%, 95% CI −9.1 to 31.8 ), as did DEMRI T1 mapping (bias 8.2%, 95% CI −10.7 to 27.2 ). Increased manganese uptake was also observed in the remote myocardium, with remote myocardial ∆T1 inversely correlating with left ventricular ejection fraction after myocardial infarction ( , ). Conclusions. MEMRI causes concentration and calcium channel-dependent myocardial T1 shortening. MEMRI with T1 mapping provides an accurate assessment of infarct size and can also identify changes in calcium handling in the remote myocardium. This technique has potential applications for the assessment of myocardial viability, remodelling, and regeneration.