Early detection of vascular inflammation would allow deployment of targeted strategies for the prevention or treatment of multiple disease states. Because vascular inflammation is not detectable with ...commonly used imaging modalities, we hypothesized that phenotypic changes in perivascular adipose tissue (PVAT) induced by vascular inflammation could be quantified using a new computerized tomography (CT) angiography methodology. We show that inflamed human vessels release cytokines that prevent lipid accumulation in PVAT-derived preadipocytes in vitro, ex vivo, and in vivo. We developed a three-dimensional PVAT analysis method and studied CT images of human adipose tissue explants from 453 patients undergoing cardiac surgery, relating the ex vivo images with in vivo CT scan information on the biology of the explants. We developed an imaging metric, the CT fat attenuation index (FAI), that describes adipocyte lipid content and size. The FAI has excellent sensitivity and specificity for detecting tissue inflammation as assessed by tissue uptake of 18F-fluorodeoxyglucose in positron emission tomography. In a validation cohort of 273 subjects, the FAI gradient around human coronary arteries identified early subclinical coronary artery disease in vivo, as well as detected dynamic changes of PVAT in response to variations of vascular inflammation, and inflamed, vulnerable atherosclerotic plaques during acute coronary syndromes. Our study revealed that human vessels exert paracrine effects on the surrounding PVAT, affecting local intracellular lipid accumulation in preadipocytes, which can be monitored using a CT imaging approach. This methodology can be implemented in clinical practice to noninvasively detect plaque instability in the human coronary vasculature.
Summary Background Despite recent studies, the optimum duration of dual antiplatelet therapy (DAPT) after coronary drug-eluting stent placement remains uncertain. We performed a meta-analysis with ...several analytical approaches to investigate mortality and other clinical outcomes with different DAPT strategies. Methods We searched Medline, Embase, Cochrane databases, and proceedings of international meetings on Nov 20, 2014, for randomised controlled trials comparing different DAPT durations after drug-eluting stent implantation. We extracted study design, inclusion and exclusion criteria, sample characteristics, and clinical outcomes. DAPT duration was categorised in each study as shorter versus longer, and as 6 months or shorter versus 1 year versus longer than 1 year. Analyses were done by both frequentist and Bayesian approaches. Findings We identified ten trials published between Dec 16, 2011, and Nov 16, 2014, including 31 666 randomly assigned patients. By frequentist pairwise meta-analysis, shorter DAPT was associated with significantly lower all-cause mortality compared with longer DAPT (HR 0·82, 95% CI 0·69–0·98; p=0·02; number needed to treat NNT=325), with no significant heterogeneity apparent across trials. The reduced mortality with shorter compared with longer DAPT was attributable to lower non-cardiac mortality (0·67, 0·51–0·89; p=0·006; NNT=347), with similar cardiac mortality (0·93, 0·73–1·17; p=0.52). Shorter DAPT was also associated with a lower risk of major bleeding, but a higher risk of myocardial infarction and stent thrombosis. We noted similar results in a Bayesian framework with non-informative priors. By network meta-analysis, patients treated with 6-month or shorter DAPT and 1-year DAPT had higher risk of myocardial infarction and stent thrombosis but lower risk of mortality compared with patients treated with DAPT for longer than 1 year. Patients treated with DAPT for 6 months or shorter had similar rates of mortality, myocardial infarction, and stent thrombosis, but lower rates of major bleeding than did patients treated with 1-year DAPT. Interpretation Although treatment with DAPT beyond 1 year after drug-eluting stent implantation reduces myocardial infarction and stent thrombosis, it is associated with increased mortality because of an increased risk of non-cardiovascular mortality not offset by a reduction in cardiac mortality. Funding None.
Oxidative stress plays a critical role in the vascular complications of type 2 diabetes. We examined the effect of type 2 diabetes on NADPH oxidase in human vessels and explored the mechanisms of ...this interaction. Segments of internal mammary arteries (IMAs) with their perivascular adipose tissue (PVAT) and thoracic adipose tissue were obtained from 386 patients undergoing coronary bypass surgery (127 with type 2 diabetes). Type 2 diabetes was strongly correlated with hypoadiponectinemia and increased vascular NADPH oxidase-derived superoxide anions (O2˙(-)). The genetic variability of the ADIPOQ gene and circulating adiponectin (but not interleukin-6) were independent predictors of NADPH oxidase-derived O2˙(-). However, adiponectin expression in PVAT was positively correlated with vascular NADPH oxidase-derived O2˙(-). Recombinant adiponectin directly inhibited NADPH oxidase in human arteries ex vivo by preventing the activation/membrane translocation of Rac1 and downregulating p22(phox) through a phosphoinositide 3-kinase/Akt-mediated mechanism. In ex vivo coincubation models of IMA/PVAT, the activation of arterial NADPH oxidase triggered a peroxisome proliferator-activated receptor-γ-mediated upregulation of the adiponectin gene in the neighboring PVAT via the release of vascular oxidation products. We demonstrate for the first time in humans that reduced adiponectin levels in individuals with type 2 diabetes stimulates vascular NADPH oxidase, while PVAT "senses" the increased NADPH oxidase activity in the underlying vessel and responds by upregulating adiponectin gene expression. This PVAT-vessel interaction is identified as a novel therapeutic target for the prevention of vascular complications of type 2 diabetes.
Adiponectin is an adipokine with potentially important roles in human cardiovascular disease states. We studied the role of adiponectin in the cross-talk between adipose tissue and vascular redox ...state in patients with atherosclerosis.
The study included 677 patients undergoing coronary artery bypass graft surgery. Endothelial function was evaluated by flow-mediated dilation of the brachial artery in vivo and by vasomotor studies in saphenous vein segments ex vivo. Vascular superoxide (O2(-)) and endothelial nitric oxide synthase (eNOS) uncoupling were quantified in saphenous vein and internal mammary artery segments. Local adiponectin gene expression and ex vivo release were quantified in perivascular (saphenous vein and internal mammary artery) subcutaneous and mesothoracic adipose tissue from 248 patients. Circulating adiponectin was independently associated with nitric oxide bioavailability and O2(-) production/eNOS uncoupling in both arteries and veins. These findings were supported by a similar association between functional polymorphisms in the adiponectin gene and vascular redox state. In contrast, local adiponectin gene expression/release in perivascular adipose tissue was positively correlated with O2(-) and eNOS uncoupling in the underlying vessels. In ex vivo experiments with human saphenous veins and internal mammary arteries, adiponectin induced Akt-mediated eNOS phosphorylation and increased tetrahydrobiopterin bioavailability, improving eNOS coupling. In ex vivo experiments with human saphenous veins/internal mammary arteries and adipose tissue, we demonstrated that peroxidation products produced in the vascular wall (ie, 4-hydroxynonenal) upregulate adiponectin gene expression in perivascular adipose tissue via a peroxisome proliferator-activated receptor-γ-dependent mechanism.
We demonstrate for the first time that adiponectin improves the redox state in human vessels by restoring eNOS coupling, and we identify a novel role of vascular oxidative stress in the regulation of adiponectin expression in human perivascular adipose tissue.
Personalized external aortic root support (PEARS) is an emerging technology. It is a pre-emptive operation to halt aortic root expansion and maintain aortic valve function in Marfan syndrome and is ...also applicable to aortic root aneurysms of other aetiologies. To fully evaluate PEARS, awareness of all those who advise these patients is necessary to ensure that patients are fully informed of the alternative operations, to carefully build experience, to ensure safety and quality and to monitor outcomes. Herein, we present a summary of published methods and outcomes and the arrangements in place for fuller evaluation.
Obesity is associated with changes in the secretome of adipose tissue (AT), which affects the vasculature through endocrine and paracrine mechanisms. Wingless-related integration site 5A (WNT5A) and ...secreted frizzled-related protein 5 (SFRP5), adipokines that regulate noncanonical Wnt signaling, are dysregulated in obesity. We hypothesized that WNT5A released from AT exerts endocrine and paracrine effects on the arterial wall through noncanonical RAC1-mediated Wnt signaling. In a cohort of 1004 humans with atherosclerosis, obesity was associated with increased WNT5A bioavailability in the circulation and the AT, higher expression of WNT5A receptors Frizzled 2 and Frizzled 5 in the human arterial wall, and increased vascular oxidative stress due to activation of NADPH oxidases. Plasma concentration of WNT5A was elevated in patients with coronary artery disease compared to matched controls and was independently associated with calcified coronary plaque progression. We further demonstrated that WNT5A induces arterial oxidative stress and redox-sensitive migration of vascular smooth muscle cells via Frizzled 2-mediated activation of a previously uncharacterized pathway involving the deubiquitinating enzyme ubiquitin-specific protease 17 (USP17) and the GTPase RAC1. Our study identifies WNT5A and its downstream vascular signaling as a link between obesity and vascular disease pathogenesis, with translational implications in humans.
We sought to identify the histologic basis of myocardial late gadolinium enhancement cardiovascular magnetic resonance (CMR) in hypertrophic cardiomyopathy (HCM).
The histologic basis of late ...gadolinium CMR in patients with HCM is unknown.
A 28-year-old male patient with HCM and heart failure underwent late gadolinium enhancement CMR and, 49 days later, heart transplantation. The explanted heart was examined histologically for the extent of collagen and disarray, and the results were compared with a previous in vivo CMR scan.
Overall, 19% of the myocardium was collagen, but the amount per segment varied widely (SD ± 19, range 0% to 71%). Both disarray and collagen were more likely to be found in the mesocardium than in the endo- or epicardium. There was a significant relationship between the extent of late gadolinium enhancement and collagen (r = 0.7, p < 0.0001) but not myocardial disarray (p = 0.58). Segments containing >15% collagen were more likely to have late gadolinium enhancement. Regional wall motion was inversely related to the extent of myocardial collagen and late gadolinium enhancement but not disarray (p = 0.0003, 0.04, and NS, respectively).
In this patient with HCM and heart failure, regions of myocardial late gadolinium enhancement by CMR represented regions of increased myocardial collagen but not disarray.
IntroductionBeing on a waiting list for elective (planned) cardiac surgery can be physically and psychologically challenging for patients. Research suggests that stress associated with waiting for ...surgery is dependent on different individual and contextual factors. However, most data on patients’ experiences of waiting for surgery and preferences for waiting list management derives from non-cardiac clinical populations. The aim of the current study is to explore patients’ experiences of being on a waiting list for elective cardiac surgery, and their views on how the waiting experience could be improved in the future. This work will inform the patient management strategy during the waiting period for surgery across the four major hospitals in London directly involved in this study, and potentially beyond by transferring learning to other services.Methods and analysisThis is a mixed-methods study that will collect quantitative and qualitative data using a cross-sectional online survey. Patients who are on waiting lists for elective surgery across four major cardiac surgery departments in London hospitals, and are at least 18 years old, will be invited by their healthcare team via text message or letter to complete the survey. The target sample size of non-randomly selected participants will be 268. Bivariable and multivariable regression models will be used to assess associations between survey items measuring the impact of the cardiac condition on specific life domains (eg, daily activities, social and family relationships, hobbies, sexual life), anxiety and depression symptoms as measured by the Patient Health Questionnaire-4 and survey items evaluating experiences of health services. Data on experience and preferences for improvements to the waiting experience will be analysed with qualitative content analysis using an inductive approach.Ethics and disseminationThis study was reviewed and granted ethical approval by the East of England—East Cambridge Research Ethics Committee. Findings from this study will be disseminated through peer-reviewed journals, a research website and social media and with an online event engaging patients, members of the public, healthcare professionals and other relevant stakeholders.Trial registration numbNCT05996640
Thorough reanalysis of available data found that the strong links between the splenic signal intensity change and delta spleen T1, and the ability of delta spleen T1 to predict the splenic switch-off ...sign, could not be independently reproduced, although the general observations reported in Table 2 (that the spleen T1 decreases significantly in response to Adenosine) and inter-observer reproducibility of delta spleen T1 could be reproduced. ...of the information available, the Editor-in-Chief advises readers to interpret the results of this publication with due caution. Rights and permissions Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. Thorough reanalysis of available data found that the strong links between the splenic signal intensity change and delta spleen T1, and the ability of delta spleen T1 to predict the splenic switch-off sign, could not be independently reproduced, although the general observations reported in Table 2 (that the spleen T1 decreases significantly in response to Adenosine) and inter-observer reproducibility of delta spleen T1 could be reproduced. ...of the information available, the Editor-in-Chief advises readers to interpret the results of this publication with due caution.
Abstract
Background
The coronavirus-disease 2019 (COVID-19) pandemic imposed an unprecedented burden on the provision of cardiac surgical services. The reallocation of workforce and resources ...necessitated the postponement of elective operations in this cohort of high-risk patients. We investigated the impact of this outbreak on the aortic valve surgery activity at a single two-site centre in the United Kingdom.
Methods
Data were extracted from the local surgical database, including the demographics, clinical characteristics, and outcomes of patients operated on from March 2020 to May 2020 with only one of the two sites resuming operative activity and compared with the respective 2019 period. A similar comparison was conducted with the period between June 2020 and August 2020, when operative activity was restored at both institutional sites. The experience of centres world-wide was invoked to assess the efficiency of our services.
Results
There was an initial 38.2% reduction in the total number of operations with a 70% reduction in elective cases, compared with a 159% increase in urgent and emergency operations. The attendant surgical risk was significantly higher median Euroscore II was 2.7 1.9–5.2 in 2020 versus 2.1 0.9–3.7 in 2019 (
p
= 0.005) but neither 30-day survival nor freedom from major post-operative complications (re-sternotomy for bleeding/tamponade, transient ischemic attack/stroke, renal replacement therapy) was compromised (
p
> 0.05 for all comparisons). Recommencement of activity at both institutional sites conferred a surgical volume within 17% of the pre-COVID-19 era.
Conclusions
Our institution managed to offer a considerable volume of aortic valve surgical activity over the first COVID-19 outbreak to a cohort of higher-risk patients, without compromising post-operative outcomes. A backlog of elective cases is expected to develop, the accommodation of which after surgical activity normalisation will be crucial to monitor.
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