Showing papers by "David E. Newby published in 2021"
TL;DR: In this paper, the effects of COVID-19-related hospitalisation on health and employment, to identify factors associated with recovery, and to describe recovery phenotypes were determined.
313 citations
Icahn School of Medicine at Mount Sinai1, University of Minnesota2, University of Texas Southwestern Medical Center3, Cedars-Sinai Medical Center4, Brigham and Women's Hospital5, University of British Columbia6, British Heart Foundation7, National Institutes of Health8, Stanford University9, NewYork–Presbyterian Hospital10, University of Virginia Health System11
111 citations
Cornell University1, Brigham and Women's Hospital2, Leiden University3, Oregon Health & Science University4, University of São Paulo5, Cedars-Sinai Medical Center6, University of British Columbia7, University of Virginia8, University of Edinburgh9, University of Pennsylvania10, Beth Israel Deaconess Medical Center11, Baptist Hospital of Miami12, Leiden University Medical Center13, University of California, Los Angeles14, Yonsei University15, Icahn School of Medicine at Mount Sinai16, Innsbruck Medical University17, Harvard University18, University of Minnesota19
TL;DR: Standardized definitions for high-risk plaque (HRP) features are provided and the evidence on the effectiveness of risk stratification into usable practice points are distilled.
86 citations
TL;DR: A review of cardiac-specific SGLT2 inhibitor-mediated mechanisms is provided in this paper, where the authors highlight studies currently underway investigating some of the proposed mechanisms of action in cardiovascular health and disease.
Abstract: Patients with type 2 diabetes mellitus are at a higher risk of developing heart failure compared with the healthy population. In recent landmark clinical trials, sodium-glucose co-transporter 2 (SGLT2) inhibitor therapies improve blood glucose control and also reduce cardiovascular events and heart failure hospitalisations in patients with type 2 diabetes. Intriguingly, such clinical benefits have also been seen in patients with heart failure in the absence of type 2 diabetes although the underlying mechanisms are not clearly understood. Potential pathways include improved glycaemic control, diuresis, weight reduction and reduction in blood pressure, but none fully explain the observed improvements in clinical outcomes. More recently, novel mechanisms have been proposed to explain these benefits that include improved cardiomyocyte calcium handling, enhanced myocardial energetics, induced autophagy and reduced epicardial fat. We provide an up-to-date review of cardiac-specific SGLT2 inhibitor-mediated mechanisms and highlight studies currently underway investigating some of the proposed mechanisms of action in cardiovascular health and disease.
69 citations
TL;DR: A deformation invariant cycle-consistency model is presented that can achieve better alignment between the source and target data while maintaining superior image quality of signal compared to several state-of-the-art CycleGAN-based methods.
59 citations
TL;DR: In this paper, high-sensitivity cardiac troponin assays enable myocardial infarction to be ruled out earlier, but the safety and efficacy of this approach is uncertain.
Abstract: Background: High-sensitivity cardiac troponin assays enable myocardial infarction to be ruled out earlier, but the safety and efficacy of this approach is uncertain. We investigated whether an earl...
58 citations
TL;DR: In this article, Valvular calcification is central to the pathogenesis and progression of aortic stenosis, with preclinical and observational studies suggesting that bone turnover and osteoblastic diffe...
Abstract: Background: Valvular calcification is central to the pathogenesis and progression of aortic stenosis, with preclinical and observational studies suggesting that bone turnover and osteoblastic diffe...
50 citations
TL;DR: The start or stop anticoagulation randomized trial (SoSTART) as mentioned in this paper was designed to investigate whether starting anticagulation is not not better than avoiding oral anticaagulation for patients with atrial fibrillation.
Abstract: Summary Background Oral anticoagulation reduces the rate of systemic embolism for patients with atrial fibrillation by two-thirds, but its benefits for patients with previous intracranial haemorrhage are uncertain. In the Start or STop Anticoagulants Randomised Trial (SoSTART), we aimed to establish whether starting is non-inferior to avoiding oral anticoagulation for survivors of intracranial haemorrhage who have atrial fibrillation. Methods SoSTART was a prospective, randomised, open-label, assessor-masked, parallel-group, pilot phase trial done at 67 hospitals in the UK. We recruited adults (aged ≥18 years) who had survived at least 24 h after symptomatic spontaneous intracranial haemorrhage, had atrial fibrillation, and had a CHA2DS2-VASc score of at least 2. Web-based computerised randomisation incorporating a minimisation algorithm allocated participants (1:1) to start or avoid long-term (≥1 year) full treatment dose open-label oral anticoagulation. The participants assigned to start oral anticoagulation received either a direct oral anticoagulant or vitamin K antagonist, and the group assigned to avoid oral anticoagulation received standard clinical practice (antiplatelet agent or no antithrombotic agent). The primary outcome was recurrent symptomatic spontaneous intracranial haemorrhage, and was adjudicated by an individual masked to treatment allocation. All outcomes were ascertained for at least 1 year after randomisation and assessed in the intention-to-treat population of all randomly assigned participants, using Cox proportional hazards regression adjusted for minimisation covariates. We planned a sample size of 190 participants (one-sided p=0·025, power 90%, allowing for non-adherence) based on a non-inferiority margin of 12% (or adjusted hazard ratio [HR] of 3·2). This trial is registered with ClinicalTrials.gov (NCT03153150) and is complete. Findings Between March 29, 2018, and Feb 27, 2020, consent was obtained at 61 sites for 218 participants, of whom 203 were randomly assigned at a median of 115 days (IQR 49–265) after intracranial haemorrhage onset. 101 were assigned to start and 102 to avoid oral anticoagulation. Participants were followed up for median of 1·2 years (IQR 0·97–1·95; completeness 97·2%). Starting oral anticoagulation was not non-inferior to avoiding oral anticoagulation: eight (8%) of 101 in the start group versus four (4%) of 102 in the avoid group had intracranial haemorrhage recurrences (adjusted HR 2·42 [95% CI 0·72–8·09]; p=0·152). Serious adverse events occurred in 17 (17%) participants in the start group and 15 (15%) in the avoid group. 22 (22%) patients in the start group and 11 (11%) patients in the avoid group died during the study. Interpretation Whether starting oral anticoagulation was non-inferior to avoiding it for people with atrial fibrillation after intracranial haemorrhage was inconclusive, although rates of recurrent intracranial haemorrhage were lower than expected. In view of weak evidence from analyses of three composite secondary outcomes, the possibility that oral anticoagulation might be superior for preventing symptomatic major vascular events should be investigated in adequately powered randomised trials. Funding British Heart Foundation, Medical Research Council, Chest Heart & Stroke Scotland.
41 citations
TL;DR: Early CT coronary angiography was associated with a slightly longer time in hospital (median increase 0.21 (95% confidence interval 0.05 to 0.40) days from a median hospital stay of 2.0 to 2.6) hours.
Abstract: Objectives To establish if the use of early computed tomography (CT) coronary angiography improves one year clinical outcomes in patients presenting to the emergency department with acute chest pain and at intermediate risk of acute coronary syndrome and subsequent clinical events. Design Randomised controlled trial. Setting 37 hospitals in the UK. Participants Adults with suspected or a provisional diagnosis of acute coronary syndrome and one or more of previous coronary heart disease, raised levels of cardiac troponin, or abnormal electrocardiogram. Interventions Early CT coronary angiography and standard of care compared with standard of care only. Main outcome measures Primary endpoint was all cause death or subsequent type 1 or 4b myocardial infarction at one year. Results Between 23 March 2015 and 27 June 2019, 1748 participants (mean age 62 years (standard deviation 13), 64% men, mean global registry of acute coronary events (GRACE) score 115 (standard deviation 35)) were randomised to receive early CT coronary angiography (n=877) or standard of care only (n=871). Median time from randomisation to CT coronary angiography was 4.2 (interquartile range 1.6-21.6) hours. The primary endpoint occurred in 51 (5.8%) participants randomised to CT coronary angiography and 53 (6.1%) participants who received standard of care only (adjusted hazard ratio 0.91 (95% confidence interval 0.62 to 1.35), P=0.65). Invasive coronary angiography was performed in 474 (54.0%) participants randomised to CT coronary angiography and 530 (60.8%) participants who received standard of care only (adjusted hazard ratio 0.81 (0.72 to 0.92), P=0.001). There were no overall differences in coronary revascularisation, use of drug treatment for acute coronary syndrome, or subsequent preventive treatments between the two groups. Early CT coronary angiography was associated with a slightly longer time in hospital (median increase 0.21 (95% confidence interval 0.05 to 0.40) days from a median hospital stay of 2.0 to 2.2 days). Conclusions In intermediate risk patients with acute chest pain and suspected acute coronary syndrome, early CT coronary angiography did not alter overall coronary therapeutic interventions or one year clinical outcomes, but reduced rates of invasive angiography while modestly increasing length of hospital stay. These findings do not support the routine use of early CT coronary angiography in intermediate risk patients with acute chest pain and suspected acute coronary syndrome. Trial registration ISRCTN19102565, NCT02284191.
35 citations
TL;DR: In this paper, the role of CARMN lncRNA in the development of atherosclerosis in vivo was investigated using a CRISPR-Cas9 knock-out approach, which revealed that CARMN and associated miRNAs were downregulated in advanced versus early atherosclerotic lesions.
Abstract: Rationale: In the microenvironment of atherosclerotic lesions, vascular smooth muscle cells (vSMCs) switch to a dedifferentiated state but the underlying molecular mechanisms driving this switch are not fully understood. Long noncoding RNAs (lncRNAs) are dysregulated during vascular pathology, but relatively little is known about their involvement in controlling vSMCs function. CARMN is a lncRNA located immediately upstream of the microRNAs (miRNAs) miR-143 and miR-145, both involved in vSMCs function. Objective: We investigated the role of the lncRNA CARMN, independent from miR-143 and miR-145, as potential a regulator of vSMC phenotypes in vitro and the consequences of its loss during the development of atherosclerosis in vivo. We hypothesized that loss of CARMN is a primary event controlling the functional switch towards pro-atherogenic vSMC phenotype and accelerates the development of the plaques in vivo. Methods and Results: Expression of CARMN lncRNA was silenced using GapmeRs in human coronary arterial smooth muscle cells (hCASMCs), revealing that GapmeR-mediated loss of CARMN negatively affects miR-143 and miR-145 miRNA expression. RNA sequencing of CARMN-depleted hCASMCs revealed large transcriptomic changes, associated with vSMC proliferation, migration, inflammation, lipid metabolism and dedifferentiation. The use of miR-143 and miR-145 mimics revealed that CARMN regulates hCASMC proliferation in a miRNA-independent manner. In human and mouse, CARMN and associated miRNAs were downregulated in advanced versus early atherosclerotic lesions. Using a CRISPR-Cas9 knock-out approach, we explored the implications of CARMN depletion during atherosclerosis in vivo. Consistent with in vitro results, the knock-out of CARMN impaired the expression of miR-143 and miR-145 under homeostatic conditions. Importantly, when atherosclerosis was induced in these mice, CARMN knock-out increased the volume, size, pro-inflammatory LGALS3-expressing cells content and altered plaque composition, yielding an advanced phenotype. Conclusions: We identified the early loss of CARMN lncRNA as critical event which primes vSMCs towards a pro-atherogenic phenotype in vitro and accelerates the development of atherosclerosis in vivo.
32 citations
Seoul National University Hospital1, British Heart Foundation2, Barts Health NHS Trust3, Core Laboratories4, University of Leeds5, University of Oxford6, University of Leicester7, Laval University8, Charité9, Royal Free Hospital10, University of Ulsan11, University of Pittsburgh12, Samsung Medical Center13, Université catholique de Louvain14
TL;DR: In this article, the authors used machine learning to identify prognostically important CMR markers in AS and their thresholds of mortality, including extracellular volume fraction, late gadolinium enhancement, indexed left ventricular end-diastolic volume (LVEDVi), and right ventricular ejection fraction.
TL;DR: In this article, an optimal machine-learning model for the future risk of myocardial infarction in patients with stable coronary disease was developed by combining clinical data with these approaches in a machine learning model.
Abstract: Coronary 18F-sodium fluoride (18F-NaF) positron emission tomography (PET) and computed tomography (CT) angiography-based quantitative plaque analysis have shown promise in refining risk stratification in patients with coronary artery disease. We combined both of these novel imaging approaches to develop an optimal machine-learning model for the future risk of myocardial infarction in patients with stable coronary disease. Methods: Patients with known coronary artery disease underwent coronary 18F-NaF PET and CT angiography on a hybrid PET/CT scanner. Machine-learning by extreme gradient boosting was trained using clinical data, CT quantitative plaque analysis measures and 18F-NaF PET, and it was tested using repeated 10-fold hold-out testing. Results: Among 293 study participants (65±9 years; 84% male), 22 subjects experienced a myocardial infarction over the 53 [40-59] months of follow-up. On univariable receiver-operator-curve analysis, only 18F-NaF coronary uptake emerged as a predictor of myocardial infarction (c-statistic 0.76, 95% confidence interval [CI] 0.68-0.83). When incorporated into machine-learning models, clinical characteristics showed limited predictive performance (c-statistic 0.64, 95% CI 0.53-0.76;) and were outperformed by a quantitative plaque analysis-based machine-learning model (c-statistic 0.72, 95% CI 0.60-0.84). After inclusion of all available data (clinical, quantitative plaque and 18F-NaF PET), we achieved a substantial improvement (P = 0.008 versus 18F-NaF PET alone) in the model performance (c-statistic 0.85, 95% CI 0.79-0.91). Conclusion: Both 18F-NaF uptake and quantitative plaque analysis measures are additive and strong predictors of outcome in patients with established coronary artery disease. Optimal risk stratification can be achieved by combining clinical data with these approaches in a machine-learning model.
TL;DR: In this article, major uncertainties remain regarding disease activity within the retained native aortic valve, and regarding bioprosthetic valve durability, after transcatheter aortric valve implantatio...
Abstract: Background: Major uncertainties remain regarding disease activity within the retained native aortic valve, and regarding bioprosthetic valve durability, after transcatheter aortic valve implantatio...
TL;DR: 18F-LW223 is not susceptible to the rs6971 genetic polymorphism in in vitro assays, has favorable in vivo characteristics, and is able to accurately map macrophage-driven inflammation after MI.
Abstract: Myocardial infarction (MI) is one of the leading causes of death worldwide, and inflammation is central to tissue response and patient outcomes. The 18-kDa translocator protein (TSPO) has been used in PET as an inflammatory biomarker. The aims of this study were to screen novel, fluorinated, TSPO radiotracers for susceptibility to the rs6971 genetic polymorphism using in vitro competition binding assays in human brain and heart; assess whether the in vivo characteristics of our lead radiotracer, 18F-LW223, are suitable for clinical translation; and validate whether 18F-LW223 can detect macrophage-driven inflammation in a rat MI model. Methods: Fifty-one human brain and 29 human heart tissue samples were screened for the rs6971 polymorphism. Competition binding assays were conducted with 3H-PK11195 and the following ligands: PK11195, PBR28, and our novel compounds (AB5186 and LW223). Naive rats and mice were used for in vivo PET kinetic studies, radiometabolite studies, and dosimetry experiments. Rats underwent permanent coronary artery ligation and were scanned using PET/CT with an invasive input function at 7 d after MI. For quantification of PET signal in the hypoperfused myocardium, K1 (rate constant for transfer from arterial plasma to tissues) was used as a surrogate marker of perfusion to correct the binding potential for impaired radiotracer transfer from plasma to tissue (BPTC). Results: LW223 binding to TSPO was not susceptible to the rs6971 genetic polymorphism in human brain and heart samples. In rodents, 18F-LW223 displayed a specific uptake consistent with TSPO expression, a slow metabolism in blood (69% of parent at 120 min), a high plasma free fraction of 38.5%, and a suitable dosimetry profile (effective dose of 20.5–24.5 μSv/MBq). 18F-LW223 BPTC was significantly higher in the MI cohort within the infarct territory of the anterior wall relative to the anterior wall of naive animals (32.7 ± 5.0 vs. 10.0 ± 2.4 cm3/mL/min, P ≤ 0.001). Ex vivo immunofluorescent staining for TSPO and CD68 (macrophage marker) resulted in the same pattern seen with in vivo BPTC analysis. Conclusion:18F-LW223 is not susceptible to the rs6971 genetic polymorphism in in vitro assays, has favorable in vivo characteristics, and is able to accurately map macrophage-driven inflammation after MI.
TL;DR: In this paper, the authors explored the development and validation of machine-learning models for augmenting the echocardiographic grading of aortic stenosis (AS) severity.
Abstract: Objectives The authors explored the development and validation of machine-learning models for augmenting the echocardiographic grading of aortic stenosis (AS) severity. Background In AS, symptoms and adverse events develop secondarily to valvular obstruction and left ventricular decompensation. The current echocardiographic grading of AS severity focuses on the valve and is limited by diagnostic uncertainty. Methods Using echocardiography (ECHO) measurements (ECHO cohort, n = 1,052), we performed patient similarity analysis to derive high-severity and low-severity phenogroups of AS. We subsequently developed a supervised machine-learning classifier and validated its performance with independent markers of disease severity obtained using computed tomography (CT) (CT cohort, n = 752) and cardiovascular magnetic resonance (CMR) imaging (CMR cohort, n = 160). The classifier’s prognostic value was further validated using clinical outcomes (aortic valve replacement [AVR] and death) observed in the ECHO and CMR cohorts. Results In 1,964 patients from the 3 multi-institutional cohorts, 1,346 (68%) subjects had either nonsevere or discordant AS severity. Machine learning identified 1,117 (57%) patients as having high-severity and 847 (43%) as having low-severity AS. High-severity patients in CT and CMR cohorts had higher valve calcium scores and left ventricular mass and fibrosis, respectively than the low-severity group. In the ECHO cohort, progression to AVR and progression to death in patients who did not receive AVR was faster in the high-severity group. Compared with the conventional classification of disease severity, machine-learning–based severity classification improved discrimination (integrated discrimination improvement: 0.07; 95% confidence interval: 0.02 to 0.12) and reclassification (net reclassification improvement: 0.17; 95% confidence interval: 0.11 to 0.23) for the outcome of AVR at 5 years. For both ECHO and CMR cohorts, we observed prognostic value of the machine-learning classifications for subgroups with asymptomatic, nonsevere or discordant AS. Conclusions Machine learning can integrate ECHO measurements to augment the classification of disease severity in most patients with AS, with major potential to optimize the timing of AVR.
TL;DR: In this paper, the authors investigated whether coronary computed tomography angiography assessments of coronary plaque might explain differences in the prognosis of men and women presenting with chest pain compared to men.
Abstract: Objectives This study was designed to investigate whether coronary computed tomography angiography assessments of coronary plaque might explain differences in the prognosis of men and women presenting with chest pain. Background Important sex differences exist in coronary artery disease. Women presenting with chest pain have different risk factors, symptoms, prevalence of coronary artery disease and prognosis compared to men. Methods Within a multicenter randomized controlled trial, we explored sex differences in stenosis, adverse plaque characteristics (positive remodeling, low-attenuation plaque, spotty calcification, or napkin ring sign) and quantitative assessment of total, calcified, noncalcified and low-attenuation plaque burden. Results Of the 1,769 participants who underwent coronary computed tomography angiography, 772 (43%) were female. Women were more likely to have normal coronary arteries and less likely to have adverse plaque characteristics (p 4% (41% vs. 59%; p Conclusions Women presenting with stable chest pain have less atherosclerotic plaque of all subtypes compared to men and a lower risk of subsequent MI. However, quantitative low-attenuation plaque is as strong a predictor of subsequent MI in women as in men. (Scottish Computed Tomography of the HEART Trial [SCOT-HEART]; NCT01149590 )
TL;DR: In this article, a review briefly discusses the pathobiology and most promising pharmacologic targets, screening, diagnosis and progression of calcific aortic stenosis, identification of subgroups that should be targeted in clinical trials, and the need to elicit the patient voice earlier rather than later in clinical trial design and implementation.
TL;DR: In a prospective two-centre observational study, patients hospitalised with confirmed COVID-19 underwent gadolinium and manganese-enhanced MRI and CT coronary angiography (CTCA) and compared with healthy and comorbidity-matched volunteers after blinded analysis as discussed by the authors.
Abstract: Objectives To determine the contribution of comorbidities on the reported widespread myocardial abnormalities in patients with recent COVID-19. Methods In a prospective two-centre observational study, patients hospitalised with confirmed COVID-19 underwent gadolinium and manganese-enhanced MRI and CT coronary angiography (CTCA). They were compared with healthy and comorbidity-matched volunteers after blinded analysis. Results In 52 patients (median age: 54 (IQR 51–57) years, 39 males) who recovered from COVID-19, one-third (n=15, 29%) were admitted to intensive care and a fifth (n=11, 21%) were ventilated. Twenty-three patients underwent CTCA, with one-third having underlying coronary artery disease (n=8, 35%). Compared with younger healthy volunteers (n=10), patients demonstrated reduced left (ejection fraction (EF): 57.4±11.1 (95% CI 54.0 to 60.1) versus 66.3±5 (95 CI 62.4 to 69.8)%; p=0.02) and right (EF: 51.7±9.1 (95% CI 53.9 to 60.1) vs 60.5±4.9 (95% CI 57.1 to 63.2)%; p≤0.0001) ventricular systolic function with elevated native T1 values (1225±46 (95% CI 1205 to 1240) vs 1197±30 (95% CI 1178 to 1216) ms;p=0.04) and extracellular volume fraction (ECV) (31±4 (95% CI 29.6 to 32.1) vs 24±3 (95% CI 22.4 to 26.4)%; p Conclusions Patients demonstrate right but not left ventricular dysfunction. Previous reports of left ventricular myocardial abnormalities following COVID-19 may reflect pre-existing comorbidities. Trial registration number NCT04625075.
TL;DR: In the presence of advanced coronary disease, semi-automated plaque quantification provides excellent reproducibility, particularly for total and non-calcified plaque volumes as mentioned in this paper.
TL;DR: In this article, the authors assessed aortic valve calcific and non-calcific disease using contrast-enhanced CT using a post hoc analysis of 164 patients (median age 71 (IQR 66-77) years, 78% male) with aortric stenosis (41 mild, 89 moderate, 34 severe; 7% bicuspid).
Abstract: Objectives Non-contrast CT aortic valve calcium scoring ignores the contribution of valvular fibrosis in aortic stenosis. We assessed aortic valve calcific and non-calcific disease using contrast-enhanced CT. Methods This was a post hoc analysis of 164 patients (median age 71 (IQR 66–77) years, 78% male) with aortic stenosis (41 mild, 89 moderate, 34 severe; 7% bicuspid) who underwent echocardiography and contrast-enhanced CT as part of imaging studies. Calcific and non-calcific (fibrosis) valve tissue volumes were quantified and indexed to annulus area, using Hounsfield unit thresholds calibrated against blood pool radiodensity. The fibrocalcific ratio assessed the relative contributions of valve fibrosis and calcification. The fibrocalcific volume (sum of indexed non-calcific and calcific volumes) was compared with aortic valve peak velocity and, in a subgroup, histology and valve weight. Results Contrast-enhanced CT calcium volumes correlated with CT calcium score (r=0.80, p Conclusions Contrast-enhanced CT assessment of aortic valve calcific and non-calcific volumes correlates with aortic stenosis severity and may be preferable to non-contrast CT when fibrosis is a significant contributor to valve obstruction.
University of Oxford1, University of Cape Town2, Cleveland Clinic3, Johns Hopkins University4, Houston Methodist Hospital5, Icahn School of Medicine at Mount Sinai6, Duke University7, Yale University8, University of Calgary9, University of Leicester10, St Bartholomew's Hospital11, Guy's and St Thomas' NHS Foundation Trust12, University of Edinburgh13, National Institutes of Health14, University of Glasgow15, University of Aberdeen16, Charité17, Bosch18, Sapienza University of Rome19, Vita-Salute San Raffaele University20, University of Florence21, Erasmus University Rotterdam22, Vanderbilt University Medical Center23, St George's, University of London24, Oregon Health & Science University25, Mount Sinai Hospital26, University of Bristol27, Siemens28, Philips29, University of Leeds30, Montreal Heart Institute31, University Hospitals of Leicester NHS Trust32, University of Virginia33, Brigham and Women's Hospital34
TL;DR: In this article, a quality assurance (QA) program was developed to ensure standardized T1 measurements for clinical use, including ShMOLLI T1-mapping and reference T1 and T2 protocols.
TL;DR: In this paper, the potential metabolic benefits of SGLT-2 inhibition in patients with type 2 diabetes or heart failure were discussed. But, they did not consider the effect of co-transporter inhibition on free fatty acid oxidation and impaired glucose uptake.
Abstract: The Authors’ reply
We would like to thank Yalta et al 1 for their interest in our review. We share their enthusiasm for the potential metabolic benefits of sodium-glucose co-transporter 2 (SGLT-2) inhibition.
We agree with Yalta et al that in patients with type 2 diabetes or heart failure, there is dysregulated fatty acid oxidation and impaired glucose uptake causing myocardial dysfunction. In this setting of restricted fuel selection and low energetic reserve, ketone bodies are a super-fuel producing Adenosine triphosphate (ATP) more efficiently than free fatty acids or glucose, which usually serve as fuels for …
TL;DR: Cardiovascular PET/MR demonstrates good visual and quantitative agreement with PET/CT, but is hampered by stent-related artifacts currently limiting clinical application.
TL;DR: In this article, aortic microcalcification activity (AMA) was used to quantify the uptake of 18F-sodium fluoride (18F-NaF) in the thoracic aorta.
TL;DR: USPIO-enhanced CMR can provide valuable additional information regarding the cellular inflammatory component of myocardial and vascular diseases, and some of their future potential are highlighted.
Abstract: Cardiac magnetic resonance (CMR) is at the forefront of noninvasive methods for the assessment of myocardial anatomy, function, and most importantly tissue characterization. The role of CMR is becoming even more significant with an increasing recognition that inflammation plays a major role for various myocardial diseases such as myocardial infarction, myocarditis, and takotsubo cardiomyopathy. Ultrasmall superparamagnetic particles of iron oxide (USPIO) are nanoparticles that are taken up by monocytes and macrophages accumulating at sites of inflammation. In this context, USPIO-enhanced CMR can provide valuable additional information regarding the cellular inflammatory component of myocardial and vascular diseases. Here, we will review the recent diagnostic applications of USPIO in terms of imaging myocardial and vascular inflammation, and highlight some of their future potential.
TL;DR: Aortic and mitral valve calcification occurs in one in six patients with stable chest pain undergoing CCTA and is associated with concomitant coronary atherosclerosis.
Abstract: AIMS Valvular heart disease can be identified by calcification on coronary computed tomography angiography (CCTA) and has been associated with adverse clinical outcomes. We assessed aortic and mitral valve calcification in patients presenting with stable chest pain and their association with cardiovascular risk factors, coronary artery disease, and cardiovascular outcomes. METHODS AND RESULTS In 1769 patients (58 ± 9 years, 56% male) undergoing CCTA for stable chest pain, aortic and mitral valve calcification were quantified using Agatston score. Aortic valve calcification was present in 241 (14%) and mitral calcification in 64 (4%). Independent predictors of aortic valve calcification were age, male sex, hypertension, diabetes mellitus, and cerebrovascular disease, whereas the only predictor of mitral valve calcification was age. Patients with aortic and mitral valve calcification had higher coronary artery calcium scores and more obstructive coronary artery disease. The composite endpoint of cardiovascular mortality, non-fatal myocardial infarction, or non-fatal stroke was higher in those with aortic [hazard ratio (HR) 2.87; 95% confidence interval (CI) 1.60-5.17; P < 0.001] or mitral (HR 3.50; 95% CI 1.47-8.07; P = 0.004) valve calcification, but this was not independent of coronary artery calcification or obstructive coronary artery disease. CONCLUSION Aortic and mitral valve calcification occurs in one in six patients with stable chest pain undergoing CCTA and is associated with concomitant coronary atherosclerosis. Whilst valvular calcification is associated with a higher risk of cardiovascular events, this was not independent of the burden of coronary artery disease.
TL;DR: In this paper, the authors developed a molecular imaging probe targeting three characteristic signatures of neutrophil activation: pinocytosis, phagosomal alkalinisation, and human neutrophIL elastase (HNE) activity.
Abstract: Neutrophil activation is an integral process to acute inflammation and is associated with adverse clinical sequelae. Identification of neutrophil activation in real time in the lungs of patients may permit biological stratification of patients in otherwise heterogenous cohorts typically defined by clinical criteria. No methods for identifying neutrophil activation in real time in the lungs of patients currently exist. We developed a bespoke molecular imaging probe targeting three characteristic signatures of neutrophil activation: pinocytosis, phagosomal alkalinisation, and human neutrophil elastase (HNE) activity. The probe functioned as designed in vitro and ex vivo. We evaluated optical endomicroscopy imaging of neutrophil activity using the probe in real-time at the bedside of healthy volunteers, patients with bronchiectasis, and critically unwell mechanically ventilated patients. We detected a range of imaging responses in vivo reflecting heterogeneity of condition and severity. We corroborated optical signal was due to probe function and neutrophil activation.
01 Aug 2021
TL;DR: Over the last 25 years, substantial reductions in myocardial infarction and ischemic stroke incidence are attributable to major shifts in risk factor levels.
Abstract: Background: Understanding trends in the incidence and outcomes of myocardial infarction and stroke, and how these are influenced by changes in cardiovascular risk factors can inform health policy and healthcare provision. Methods: We identified all patients 30 years or older with myocardial infarction or stroke in Scotland. Risk factor levels were determined from national health surveys. Incidence, potential impact fractions and burden attributable to risk factor changes were calculated. Risk of subsequent fatal and non-fatal events (myocardial infarction, stroke, bleeding and heart failure hospitalization) were calculated with multi-state models. Findings: From 1990 to 2014, there were 372,873 (71±13 years) myocardial infarctions and 290,927 (74±13 years) ischemic or hemorrhagic strokes. Age-standardized incidence per 100,000 fell from 1,069 (95% confidence interval, 1,024-1,116) to 276 (263-290) for myocardial infarction and from 608 (581-636) to 188 (178-197) for ischemic stroke. Systolic blood pressure, smoking and cholesterol decreased, but body-mass index increased, and diabetes prevalence doubled. Changes in risk factors accounted for a 74% (57-91%) reduction in myocardial infarction and 68% (55-83%) reduction in ischemic stroke. Following myocardial infarction, the risk of death decreased (30% to 20%), but non-fatal events increased (20% to 24%) whereas the risk of both death (47% to 34%) and non-fatal events (22% to 17%) decreased following stroke. Interpretation: Over the last 25 years, substantial reductions in myocardial infarction and ischemic stroke incidence are attributable to major shifts in risk factor levels. Deaths following the index event decreased for both myocardial infarction and stroke, but rates remained substantially higher for stroke. Funding: British heart foundation.
TL;DR: In this article, a post-hoc analysis, computed tomography (CT) images and 5-year clinical outcomes were assessed in SCOT-HEART trial participants, and adverse plaques were investigated by qualitative (visual categorization of positive remodelling, low-attenuation plaque, spotty calcification, and napkin ring sign) and quantitative (calcified, non-calcification, low attenuation, lowattenuation, and total plaque burden; Autoplaque) assessments.
Abstract: AIMS Coronary artery calcification is a marker of cardiovascular risk, but its association with qualitatively and quantitatively assessed plaque subtypes is unknown. METHODS AND RESULTS In this post-hoc analysis, computed tomography (CT) images and 5-year clinical outcomes were assessed in SCOT-HEART trial participants. Agatston coronary artery calcium score (CACS) was measured on non-contrast CT and was stratified as zero (0 Agatston units, AU), minimal (1-9 AU), low (10-99 AU), moderate (100-399 AU), high (400-999 AU), and very high (≥1000 AU). Adverse plaques were investigated by qualitative (visual categorization of positive remodelling, low-attenuation plaque, spotty calcification, and napkin ring sign) and quantitative (calcified, non-calcified, low-attenuation, and total plaque burden; Autoplaque) assessments. Of 1769 patients, 36% had a zero, 9% minimal, 20% low, 17% moderate, 10% high, and 8% very high CACS. Amongst patients with a zero CACS, 14% had non-obstructive disease, 2% had obstructive disease, 2% had visually assessed adverse plaques, and 13% had low-attenuation plaque burden >4%. Non-calcified and low-attenuation plaque burden increased between patients with zero, minimal, and low CACS (P 1000 AU and low-attenuation plaque burden were the only predictors of myocardial infarction, independent of obstructive disease, and 10-year cardiovascular risk score. CONCLUSION In patients with stable chest pain, zero CACS is associated with a good but not perfect prognosis, and CACS cannot rule out obstructive coronary artery disease, non-obstructive plaque, or adverse plaque phenotypes, including low-attenuation plaque.
TL;DR: A review of the current understanding of myocardial infarction with non-obstructive coronary arteries (MINOCA) can be found in this article, where the authors highlight important issues relating to the diagnosis, investigation and management of patients with MINOCA.
Abstract: Myocardial infarction with non-obstructive coronary arteries (MINOCA) was first described over 80 years ago. The term has been widely and inconsistently used in clinical practice, influencing various aspects of disease classification, investigation and management. MINOCA encompasses a heterogenous group of conditions that include both atherosclerotic and non-atherosclerotic disease resulting in myocardial damage that is not due to obstructive coronary artery disease. In many ways, it is a term that describes a moment in the diagnostic pathway of the patient and is arguably not a diagnosis. Central to the definition is also the distinction between myocardial infarction and injury. The universal definition of myocardial infarction distinguishes acute myocardial infarction, including those with MINOCA, from other causes of myocardial injury by the presence of clinical evidence of ischaemia. However, these ischaemic features are often non-specific causing diagnostic confusion, and can create difficulties for patient management and follow-up. The purpose of this review is to summarise our current understanding of MINOCA and highlight important issues relating to the diagnosis, investigation and management of patients with MINOCA.