ORCID Profile
0000-0001-9847-5917
Current Organisations
The University of Edinburgh
,
American College of Cardiology
,
Royal College of Physicians
,
British Heart Foundation
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Publications
Aortic Wall Inflammation Predicts Abdominal Aortic Aneurysm Expansion, Rupture, and Need for Surgical Repair
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 29-08-2017
DOI: 10.1161/CIRCULATIONAHA.117.028433
Abstract: Ultrasmall superparamagnetic particles of iron oxide (USPIO) detect cellular inflammation on magnetic resonance imaging (MRI). In patients with abdominal aortic aneurysm, we assessed whether USPIO-enhanced MRI can predict aneurysm growth rates and clinical outcomes. In a prospective multicenter open-label cohort study, 342 patients with abdominal aortic aneurysm (diameter ≥40 mm) were classified by the presence of USPIO enhancement and were monitored with serial ultrasound and clinical follow-up for ≥2 years. The primary end point was the composite of aneurysm rupture or repair. Participants (85% male, 73.1±7.2 years) had a baseline aneurysm diameter of 49.6±7.7 mm, and USPIO enhancement was identified in 146 (42.7%) participants, absent in 191 (55.8%), and indeterminant in 5 (1.5%). During follow-up (1005±280 days), 17 (5.0%) abdominal aortic aneurysm ruptures, 126 (36.8%) abdominal aortic aneurysm repairs, and 48 (14.0%) deaths occurred. Compared with those without uptake, patients with USPIO enhancement have increased rates of aneurysm expansion (3.1±2.5 versus 2.5±2.4 mm/year, P =0.0424), although this was not independent of current smoking habit ( P =0.1993). Patients with USPIO enhancement had higher rates of aneurysm rupture or repair (47.3% versus 35.6% 95% confidence intervals, 1.1–22.2 P =0.0308). This finding was similar for each component of rupture (6.8% versus 3.7%, P =0.1857) or repair (41.8% versus 32.5%, P =0.0782). USPIO enhancement was associated with reduced event-free survival for aneurysm rupture or repair ( P =0.0275), all-cause mortality ( P =0.0635), and aneurysm-related mortality ( P =0.0590). Baseline abdominal aortic aneurysm diameter ( P .0001) and current smoking habit ( P =0.0446) also predicted the primary outcome, and the addition of USPIO enhancement to the multivariate model did not improve event prediction (c-statistic, 0.7935–0.7936). USPIO-enhanced MRI is a novel approach to the identification of aortic wall cellular inflammation in patients with abdominal aortic aneurysms and predicts the rate of aneurysm growth and clinical outcome. However, it does not provide independent prediction of aneurysm expansion or clinical outcomes in a model incorporating known clinical risk factors. URL: www.isrctn.com . Unique identifier: ISRCTN76413758.
Wall Stress and Geometry of the Thoracic Aorta in Patients With Aortic Valve Disease
Publisher: Elsevier BV
Date: 04-2018
DOI: 10.1016/J.ATHORACSUR.2017.11.061
Abstract: Aortic valve disease increases velocity and changes the way blood enters the aorta. Over time, the biomechanical environment can cause aortic remodelling. We hypothesized that aortic geometry and wall stress would be different in patients with aortic valve disease compared with controls. We examined 40 patients with aortic sclerosis (n = 10) or mild (n = 10), moderate (n = 10), and severe (n = 10) aortic stenosis, and also 10 control in iduals. The thoracic aorta of each in idual was reconstructed into a three-dimensional model from computed tomography. We measured geometric variables and used finite element analysis to compute aortic wall stress. Statistical analyses were performed to test our hypothesis. Aortic wall stress was significantly associated with tortuosity of the descending aorta (r = 0.35, p = 0.01), arch radius (r = 0.49, p < 0.01), ascending aortic diameter (r = 0.59, p < 0.01), and aortic centerline length (r = 0.39, p < 0.01). Wall stress was highest in patients with severe stenosis (p = 0.02), although elevations in wall stress were also noted in those with mild stenosis (p = 0.02), and aortic sclerosis (p = 0.02) compared with controls. Similar trends were observed when we corrected for difference in blood pressure. Total centerline tortuosity was higher in patients with severe aortic stenosis than in controls (p = 0.04), as was descending aorta tortuosity (p = 0.04). Aortic geometry is associated with aortic wall stress. Patients with aortic valve disease have higher aortic wall stress than controls, and those with severe aortic stenosis have more tortuous aortas. However, increases in geometric measures and wall stress are not stepwise with increasing disease severity.
Ablation of the androgen receptor from vascular smooth muscle cells demonstrates a role for testosterone in vascular calcification
Publisher: Springer Science and Business Media LLC
Date: 20-04-2016
DOI: 10.1038/SREP24807
Abstract: Vascular calcification powerfully predicts mortality and morbidity from cardiovascular disease. Men have a greater risk of cardiovascular disease, compared to women of a similar age. These gender disparities suggest an influence of sex hormones. Testosterone is the primary and most well-recognised androgen in men. Therefore, we addressed the hypothesis that exogenous androgen treatment induces vascular calcification. Immunohistochemical analysis revealed expression of androgen receptor (AR) in the calcified media of human femoral artery tissue and calcified human valves. Furthermore, in vitro studies revealed increased phosphate (Pi)-induced mouse vascular smooth muscle cell (VSMC) calcification following either testosterone or dihydrotestosterone (DHT) treatment for 9 days. Testosterone and DHT treatment increased tissue non-specific alkaline phosphatase ( Alpl ) mRNA expression. Testosterone-induced calcification was blunted in VSMC-specific AR-ablated (SM-ARKO) VSMCs compared to WT. Consistent with these data, SM-ARKO VSMCs showed a reduction in Osterix mRNA expression. However, intriguingly, a counter-intuitive increase in Alpl was observed. These novel data demonstrate that androgens play a role in inducing vascular calcification through the AR. Androgen signalling may represent a novel potential therapeutic target for clinical intervention.
Atorvastatin lowers 68Ga-DOTATATE uptake in coronary arteries, bone marrow and spleen in individuals with type 2 diabetes
Publisher: Springer Science and Business Media LLC
Date: 15-08-2023
DOI: 10.1007/S00125-023-05990-9
Abstract: Inflammation is a core component of residual cardiovascular risk in type 2 diabetes. With new anti-inflammatory therapeutics entering the field, accurate markers to evaluate their effectiveness in reducing cardiovascular disease are paramount. Gallium-68-labelled DOTATATE ( 68 Ga-DOTATATE) has recently been proposed as a more specific marker of arterial wall inflammation than 18 F-fluorodeoxyglucose ( 18 F-FDG). This study set out to investigate whether 68 Ga-DOTATATE uptake is amenable to therapeutic intervention in in iduals with type 2 diabetes. In iduals aged years with type 2 diabetes underwent 68 Ga-DOTATATE positron emission tomography (PET)/computed tomography (CT) at baseline and after 3 months treatment with atorvastatin 40 mg once daily. Primary outcome was the difference in coronary 68 Ga-DOTATATE uptake, expressed as target-to-background ratio (TBR). The secondary outcome was difference in bone marrow and splenic uptake, expressed as the standardised uptake value (SUV). Twenty-two in iduals with type 2 diabetes (mean age 63.2±6.4 years, 82% male, LDL-cholesterol 3.42±0.81 mmol/l, HbA 1c 55±12 mmol/mol [7.2%±3.2%]) completed both 68 Ga-DOTATATE PET/CT scans. The maximum TBR was −31% (95% CI −50, −12) lower in the coronary arteries, and bone marrow and splenic 68 Ga-DOTATATE uptake was also significantly lower post statin treatment, with a mean percentage reduction of −15% (95% CI −27, −4) and −17% (95% CI −32, −2), respectively. 68 Ga-DOTATATE uptake across the cardio–haematopoietic axis was lower after statin therapy in in iduals with type 2 diabetes. Therefore, 68 Ga-DOTATATE is promising as a metric for vascular and haematopoietic inflammation in intervention studies using anti-inflammatory therapeutics in in iduals with type 2 diabetes. ClinicalTrials.gov NCT05730634
Tricuspid Valve-in-Valve and Bioprosthetic Surgical Tricuspid and Pulmonic Valve Degeneration
Publisher: Elsevier BV
Date: 12-2020
Computed tomographic angiography in coronary artery disease
Publisher: Europa Digital & Publishing
Date: 04-2023
Society for Cardiovascular Magnetic Resonance (SCMR) expert consensus for CMR imaging endpoints in clinical research: part I - analytical validation and clinical qualification
Publisher: Springer Science and Business Media LLC
Date: 20-09-2018
18 F-Fluoride and 18 F-Fluorodeoxyglucose Positron Emission Tomography After Transient Ischemic Attack or Minor Ischemic Stroke
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-2017
DOI: 10.1161/CIRCIMAGING.116.004976
Abstract: Combined positron emission tomography (PET) and computed tomography (CT) can assess both anatomy and biology of carotid atherosclerosis. We sought to assess whether 18 F-fluoride or 18 F-fluorodeoxyglucose can identify culprit and high-risk carotid plaque. We performed 18 F-fluoride and 18 F-fluorodeoxyglucose PET/CT in 26 patients after recent transient ischemic attack or minor ischemic stroke: 18 patients with culprit carotid stenosis awaiting carotid endarterectomy and 8 controls without culprit carotid atheroma. We compared standardized uptake values in the clinically adjudicated culprit to the contralateral asymptomatic artery, and assessed the relationship between radiotracer uptake and plaque phenotype or predicted cardiovascular risk (ASSIGN score [Assessing Cardiovascular Risk Using SIGN Guidelines to Assign Preventive Treatment]). We also performed micro PET/CT and histological analysis of excised plaque. On histological and micro PET/CT analysis, 18 F-fluoride selectively highlighted microcalcification. Carotid 18 F-fluoride uptake was increased in clinically adjudicated culprit plaques compared with asymptomatic contralateral plaques (log 10 standardized uptake value mean 0.29±0.10 versus 0.23±0.11, P =0.001) and compared with control patients (log 10 standardized uptake value mean 0.29±0.10 versus 0.12±0.11, P =0.001). 18 F-Fluoride uptake correlated with high-risk plaque features (remodeling index [ r =0.53, P =0.003], plaque burden [ r =0.51, P =0.004]), and predicted cardiovascular risk [ r =0.65, P =0.002]). Carotid 18 F-fluorodeoxyglucose uptake appeared to be increased in 7 of 16 culprit plaques, but no overall differences in uptake were observed in culprit versus contralateral plaques or control patients. However, 18 F-fluorodeoxyglucose did correlate with predicted cardiovascular risk ( r =0.53, P =0.019), but not with plaque phenotype. 18 F-Fluoride PET/CT highlights culprit and phenotypically high-risk carotid plaque. This has the potential to improve risk stratification and selection of patients who may benefit from intervention.
Transcatheter Aortic Heart Valves
Publisher: Elsevier BV
Date: 2019
DOI: 10.1016/J.JCMG.2018.06.028
Abstract: This study investigated processes causing leaflet thickening and structural valve degeneration (SVD). Although transcatheter aortic valve replacement (TAVR) has changed the treatment of aortic stenosis, concerns remain regarding SVD, potentially related to valve thrombosis and thickening, based on studies using computed tomography (CT). Detailed histological analyses are provided to help attain insights into these processes. Explanted transcatheter heart valves (THVs) were evaluated for thrombosis, fibrosis, and calcification for quantification of leaflet thickness. Immunohistochemical and microscopy approaches were used to investigate SVD-associated mechanisms. THVs (n = 23) were obtained from 22 patients (median 81 years of age 50% male) from 0 to 2,583 days post TAVR. Maximal leaflet thickness increased relative to implant duration (ρ = 0.427 p = 0.027). THVs explanted after >2 years were thicker than those explanted after <2 years (p = 0.007). All THVs had adherent thrombus on both aortic and ventricular sides, which beyond 60 days was seen in combination with fibrosis and beyond 4 years had calcification. Early thrombus formation (<60 days) occurred despite rapid endothelialization with an abnormal hyperplastic phenotype. Fibrosis was observed in 6 patients on both the aortic and the ventricular THV surfaces, remodeled over time, and was associated with matrix metalloproteinase-1 expression. Five THVs showed overt calcification associated with adherent thrombus and fibrosis. There is a time-dependent degeneration of THVs consisting of thrombus formation, endothelial hyperplasia, fibrosis, tissue remodeling, proteinase expression, and calcification. Future investigation is needed to further understand these mechanisms contributing to leaflet thickening and SVD.
Related Organisations
The University Of Edinburgh
Location: United Kingdom of Great Britain and Northern Ireland
Royal College Of Physicians
Location: United Kingdom of Great Britain and Northern Ireland
British Heart Foundation
Location: United Kingdom of Great Britain and Northern Ireland
Related Funding Activities
No related grants have been discovered for marc dweck.