•Factorisation decomposes input into spatial anatomical and imaging factors.•Factors offer unique opportunity to interpret imaging data for many learning tasks.•Achieve semi-supervised segmentation ...using a fraction of labelled images needed.•Supervision can be obtained by combining multimodal data sources or auxiliary tasks.•Extensive results using four different cardiovascular MR and CT datasets.
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Typically, a medical image offers spatial information on the anatomy (and pathology) modulated by imaging specific characteristics. Many imaging modalities including Magnetic Resonance Imaging (MRI) and Computed Tomography (CT) can be interpreted in this way. We can venture further and consider that a medical image naturally factors into some spatial factors depicting anatomy and factors that denote the imaging characteristics. Here, we explicitly learn this decomposed (disentangled) representation of imaging data, focusing in particular on cardiac images. We propose Spatial Decomposition Network (SDNet), which factorises 2D medical images into spatial anatomical factors and non-spatial modality factors. We demonstrate that this high-level representation is ideally suited for several medical image analysis tasks, such as semi-supervised segmentation, multi-task segmentation and regression, and image-to-image synthesis. Specifically, we show that our model can match the performance of fully supervised segmentation models, using only a fraction of the labelled images. Critically, we show that our factorised representation also benefits from supervision obtained either when we use auxiliary tasks to train the model in a multi-task setting (e.g. regressing to known cardiac indices), or when aggregating multimodal data from different sources (e.g. pooling together MRI and CT data). To explore the properties of the learned factorisation, we perform latent-space arithmetic and show that we can synthesise CT from MR and vice versa, by swapping the modality factors. We also demonstrate that the factor holding image specific information can be used to predict the input modality with high accuracy. Code will be made available at https://github.com/agis85/anatomy_modality_decomposition.
Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are common, associated with acute inflammation, and may increase subsequent cardiovascular disease (CVD) risk.
Determine whether ...AECOPD events are associated with increased risk of subsequent CVD.
We performed a secondary cohort analysis of the SUMMIT (Study to Understand Mortality and Morbidity) trial, a convenience sample of current/former smokers with moderate COPD from 1,368 centers in 43 countries. All had CVD or increased CVD risk. AECOPD was defined as an increase in respiratory symptoms requiring treatment with antibiotics, systemic corticosteroids, and/or hospitalization. CVD events were a composite outcome of cardiovascular death, myocardial infarction, stroke, unstable angina, and transient ischemic attack. All CVD events were adjudicated. Cox proportional hazards models compared the hazard for a CVD event before AECOPD versus after AECOPD.
Among 16,485 participants in SUMMIT, 4,704 participants had at least one AECOPD and 688 had at least one CVD event. The hazard ratio (HR) for CVD events after AECOPD was increased, particularly in the first 30 days after AECOPD (HR, 3.8; 95% confidence interval, 2.7-5.5) and was elevated up to 1 year after AECOPD. The 30-day HR after hospitalized AECOPD was more than twofold greater (HR, 9.9; 95% confidence interval, 6.6-14.9).
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. Patients and clinicians should have heightened vigilance for early CVD events after AECOPD. Clinical trial registered with www.clinicaltrials.gov (NCT 01313676).
Abstract Background Lowering the diagnostic threshold for troponin is controversial because it may disproportionately increase the diagnosis of myocardial infarction in patients without acute ...coronary syndrome. We assessed the impact of lowering the diagnostic threshold of troponin on the incidence, management, and outcome of patients with type 2 myocardial infarction or myocardial injury. Methods Consecutive patients with elevated plasma troponin I concentrations (≥50 ng/L; n = 2929) were classified with type 1 (50%) myocardial infarction, type 2 myocardial infarction or myocardial injury (48%), and type 3 to 5 myocardial infarction (2%) before and after lowering the diagnostic threshold from 200 to 50 ng/L with a sensitive assay. Event-free survival from death and recurrent myocardial infarction was recorded at 1 year. Results Lowering the threshold increased the diagnosis of type 2 myocardial infarction or myocardial injury more than type 1 myocardial infarction (672 vs 257 additional patients, P < .001). Patients with myocardial injury or type 2 myocardial infarction were at higher risk of death compared with those with type 1 myocardial infarction (37% vs 16%; relative risk RR, 2.31; 95% confidence interval CI, 1.98-2.69) but had fewer recurrent myocardial infarctions (4% vs 12%; RR, 0.35; 95% CI, 0.26-0.49). In patients with troponin concentrations 50 to 199 ng/L, lowering the diagnostic threshold was associated with increased healthcare resource use ( P < .05) that reduced recurrent myocardial infarction and death for patients with type 1 myocardial infarction (31% vs 20%; RR, 0.64; 95% CI, 0.41-0.99), but not type 2 myocardial infarction or myocardial injury (36% vs 33%; RR, 0.93; 95% CI, 0.75-1.15). Conclusions After implementation of a sensitive troponin assay, the incidence of type 2 myocardial infarction or myocardial injury disproportionately increased and is now as frequent as type 1 myocardial infarction. Outcomes of patients with type 2 myocardial infarction or myocardial injury are poor and do not seem to be modifiable after reclassification despite substantial increases in healthcare resource use.
Background Smoking and COPD are risk factors for cardiovascular disease, and the pathogenesis may involve endothelial dysfunction. We tested the hypothesis that endothelium-derived ...epoxyeicosatrienoic acid (EET)-mediated endothelial function is impaired in patients with COPD and that a novel soluble epoxide hydrolase inhibitor, GSK2256294, attenuates EET-mediated endothelial dysfunction in human resistance vessels both in vitro and in vivo. Methods Endogenous and stimulated endothelial release of EETs was assessed in 12 patients with COPD, 11 overweight smokers, and two matched control groups, using forearm plethysmography with intraarterial infusions of fluconazole, bradykinin, and the combination. The effects of GSK2256294 on EET-mediated vasodilation in human resistance arteries were assessed in vitro and in vivo in a phase I clinical trial in healthy overweight smokers. Results Compared with control groups, there was reduced vasodilation with bradykinin ( P = .005), a blunted effect of fluconazole on bradykinin-induced vasodilation ( P = .03), and a trend toward reduced basal EET/dihydroxyepoxyeicosatrienoic acid ratio in patients with COPD ( P = .08). A similar pattern was observed in overweight smokers. In vitro, 10 μM GSK2256294 increased 11,12-EET-mediated vasodilation compared with vehicle (90% ± 4.2% vs 72.6% ± 6.2% maximal dilatation) and shifted the bradykinin half-maximal effective concentration (EC50) (–8.33 ± 0.172 logM vs –8.10 ± 0.118 logM; P = .001 for EC50). In vivo, 18 mg GSK2256294 improved the maximum bradykinin response from 338% ± 46% before a dose to 566% ± 110% after a single dose ( P = .02) and to 503% ± 123% after a chronic dose ( P = .003). Conclusions GSK2256294 attenuates smoking-related EET-mediated endothelial dysfunction, suggesting potential therapeutic benefits in patients with COPD. Trial Registry ClinicalTrials.gov; No.: NCT01762774 ; URL: www.clinicaltrials.gov
Objective To evaluate the diagnosis of myocardial infarction using a high sensitivity troponin I assay and sex specific diagnostic thresholds in men and women with suspected acute coronary ...syndrome.Design Prospective cohort study.Setting Regional cardiac centre, United Kingdom.Participants Consecutive patients with suspected acute coronary syndrome (n=1126, 46% women). Two cardiologists independently adjudicated the diagnosis of myocardial infarction by using a high sensitivity troponin I assay with sex specific diagnostic thresholds (men 34 ng/L, women 16 ng/L) and compared with current practice where a contemporary assay (50 ng/L, single threshold) was used to guide care.Main outcome measure Diagnosis of myocardial infarction.Results The high sensitivity troponin I assay noticeably increased the diagnosis of myocardial infarction in women (from 11% to 22%; P<0.001) but had a minimal effect in men (from 19% to 21%, P=0.002). Women were less likely than men to be referred to a cardiologist or undergo coronary revascularisation (P<0.05 for both). At 12 months, women with undisclosed increases in troponin concentration (17-49 ng/L) and those with myocardial infarction (≥50 ng/L) had the highest rate of death or reinfarction compared with women without (≤16 ng/L) myocardial infarction (25%, 24%, and 4%, respectively; P<0.001).Conclusions Although having little effect in men, a high sensitivity troponin assay with sex specific diagnostic thresholds may double the diagnosis of myocardial infarction in women and identify those at high risk of reinfarction and death. Whether use of sex specific diagnostic thresholds will improve outcomes and tackle inequalities in the treatment of women with suspected acute coronary syndrome requires urgent attention.
Abstract Ischemic heart disease is a complex disease process caused by the development of coronary atherosclerosis, with downstream effects on the left ventricular myocardium. It is characterized by ...a long preclinical phase, abrupt development of myocardial infarction, and more chronic disease states such as stable angina and ischemic cardiomyopathy. Recent advances in computed tomography (CT) and cardiac magnetic resonance (CMR) now allow detailed imaging of each of these different phases of the disease, potentially allowing ischemic heart disease to be tracked during a patient’s lifetime. In particular, CT has emerged as the noninvasive modality of choice for imaging the coronary arteries, whereas CMR offers detailed assessments of myocardial perfusion, viability, and function. The clinical utility of these techniques is increasingly being supported by robust randomized controlled trial data, although the widespread adoption of cardiac CT and CMR will require further evidence of clinical efficacy and cost effectiveness.
The incidence of hypertension and cardiovascular disease (CVD) correlates with latitude and rises in winter. The molecular basis for this remains obscure. As nitric oxide (NO) metabolites are ...abundant in human skin, we hypothesized that exposure to UVA may mobilize NO bioactivity into the circulation to exert beneficial cardiovascular effects independently of vitamin D. In 24 healthy volunteers, irradiation of the skin with two standard erythemal doses of UVA lowered blood pressure (BP), with concomitant decreases in circulating nitrate and rises in nitrite concentrations. Unexpectedly, acute dietary intervention aimed at modulating systemic nitrate availability had no effect on UV-induced hemodynamic changes, indicating that cardiovascular effects were not mediated via direct utilization of circulating nitrate. UVA irradiation of the forearm caused increased blood flow independently of NO synthase (NOS) activity, suggesting involvement of pre-formed cutaneous NO stores. Confocal fluorescence microscopy studies of human skin pre-labeled with the NO-imaging probe diaminofluorescein 2 diacetate revealed that UVA-induced NO release occurs in a NOS-independent, dose-dependent manner, with the majority of the light-sensitive NO pool in the upper epidermis. Collectively, our data provide mechanistic insights into an important function of the skin in modulating systemic NO bioavailability, which may account for the latitudinal and seasonal variations of BP and CVD.
BACKGROUND:With advances in antiretroviral therapy, most deaths in people with HIV are now attributable to noncommunicable illnesses, especially cardiovascular disease. We determine the association ...between HIV and cardiovascular disease, and estimate the national, regional, and global burden of cardiovascular disease attributable to HIV.
METHODS:We conducted a systematic review across 5 databases from inception to August 2016 for longitudinal studies of cardiovascular disease in HIV infection. A random-effects meta-analysis across 80 studies was used to derive the pooled rate and risk of cardiovascular disease in people living with HIV. We then estimated the temporal changes in the population-attributable fraction and disability-adjusted life-years (DALYs) from HIV-associated cardiovascular disease from 1990 to 2015 at a regional and global level. National cardiovascular DALYs associated with HIV for 2015 were derived for 154 of the 193 United Nations member states. The main outcome measure was the pooled estimate of the rate and risk of cardiovascular disease in people living with HIV and the national, regional, and global estimates of DALYs from cardiovascular disease associated with HIV.
RESULTS:In 793 635 people living with HIV and a total follow-up of 3.5 million person-years, the crude rate of cardiovascular disease was 61.8 (95% CI, 45.8–83.4) per 10 000 person-years. In comparison with individuals without HIV, the risk ratio for cardiovascular disease was 2.16 (95% CI, 1.68–2.77). Over the past 26 years, the global population–attributable fraction from cardiovascular disease attributable to HIV increased from 0.36% (95% CI, 0.21%–0.56%) to 0.92% (95% CI, 0.55%–1.41%), and DALYs increased from 0.74 (95% CI, 0.44–1.16) to 2.57 (95% CI, 1.53–3.92) million. There was marked regional variation with most DALYs lost in sub-Saharan Africa (0.87 million, 95% CI, 0.43–1.70) and the Asia Pacific (0.39 million, 95% CI, 0.23–0.62) regions. The highest population-attributable fraction and burden were observed in Swaziland, Botswana, and Lesotho.
CONCLUSIONS:People living with HIV are twice as likely to develop cardiovascular disease. The global burden of HIV-associated cardiovascular disease has tripled over the past 2 decades and is now responsible for 2.6 million DALYs per annum with the greatest impact in sub-Saharan Africa and the Asia Pacific regions.
CLINICAL TRIAL REGISTRATION:URLhttps://www.crd.york.ac.uk/prospero. Unique identifierCRD42016048257.
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