Deep-Learning for Epicardial Adipose Tissue Assessment with Computed Tomography: Implications for Cardiovascular Risk Prediction

Background: Epicardial adipose tissue (EAT) volume is a marker of visceral obesity that can be measured in coronary computed tomography angiograms (CCTA). The clinical value of integrating this measurement in routine CCTA interpretation has not been documented./ Objectives: This study sought to develop a deep-learning network for automated quantification of EAT volume from CCTA, test it in patients who are technically challenging, and validate its prognostic value in routine clinical care./ Methods: The deep-learning network was trained and validated to autosegment EAT volume in 3,720 CCTA scans from the ORFAN (Oxford Risk Factors and Noninvasive Imaging Study) cohort. The model was tested in patients with challenging anatomy and scan artifacts and applied to a longitudinal cohort of 253 patients post-cardiac surgery and 1,558 patients from the SCOT-HEART (Scottish Computed Tomography of the Heart) Trial, to investigate its prognostic value./ Results: External validation of the deep-learning network yielded a concordance correlation coefficient of 0.970 for machine vs human. EAT volume was associated with coronary artery disease (odds ratio [OR] per SD increase in EAT volume: 1.13 [95% CI: 1.04-1.30]; P = 0.01), and atrial fibrillation (OR: 1.25 [95% CI:1.08-1.40]; P = 0.03), after correction for risk factors (including body mass index). EAT volume predicted all-cause mortality (HR per SD: 1.28 [95% CI: 1.10-1.37]; P = 0.02), myocardial infarction (HR: 1.26 [95% CI:1.09-1.38]; P = 0.001), and stroke (HR: 1.20 [95% CI: 1.09-1.38]; P = 0.02) independently of risk factors in SCOT-HEART (5-year follow-up). It also predicted in-hospital (HR: 2.67 [95% CI: 1.26-3.73]; P ≤ 0.01) and long-term post–cardiac surgery atrial fibrillation (7-year follow-up; HR: 2.14 [95% CI: 1.19-2.97]; P ≤ 0.01). Conclusions: Automated assessment of EAT volume is possible in CCTA, including in patients who are technically challenging; it forms a powerful marker of metabolically unhealthy visceral obesity, which could be used for cardiovascular risk stratification

‘Super Rehab’: can we achieve coronary artery disease regression? A feasibility study protocol

Introduction Patients diagnosed with coronary artery disease (CAD) are currently treated with medications and lifestyle advice to reduce the likelihood of disease progression and risk of future major adverse cardiovascular events (MACE). Where obstructive disease is diagnosed, revascularisation may be considered to treat refractory symptoms. However, many patients with coexistent cardiovascular risk factors, particularly those with metabolic syndrome (MetS), remain at heightened risk of future MACE despite current management.Cardiac rehabilitation is offered to patients post-revascularisation, however, there is no definitive evidence demonstrating its benefit in a primary prevention setting. We propose that an intensive lifestyle intervention (Super Rehab, SR) incorporating high-intensity exercise, diet and behavioural change techniques may improve symptoms, outcomes, and enable CAD regression.This study aims to examine the feasibility of delivering a multicentre randomised controlled trial (RCT) testing SR for patients with CAD, in a primary prevention setting.Methods and analysis This is a multicentre randomised controlled feasibility study of SR versus usual care in patients with CAD. The study aims to recruit 50 participants aged 18–75 across two centres. Feasibility will be assessed against rates of recruitment, retention and, in the intervention arm, attendance and adherence to SR. Qualitative interviews will explore trial experiences of study participants and practitioners. Variance of change in CAD across both arms of the study (assessed with serial CT coronary angiography) will inform the design and power of a future, multi-centre RCT.Ethics and dissemination Ethics approval was granted by South West—Frenchay Research Ethics Committee (reference: 21/SW/0153, 18 January 2022). Study findings will be disseminated via presentations to relevant stakeholders, national and international conferences and open-access peer-reviewed research publications.Trial registration number ISRCTN14603929

Safety and Feasibility of a 16-Week Progressive Exercise Intervention in Treatment Naïve Chronic Lymphocytic Leukaemia

A growing body of evidence from preclinical and human epidemiology studies of multiple cancer types indicate that physical activity can delay or avert the outgrowth of cancer, in a mechanistic process that may involve exercise-induced alterations to anti-cancer immunity. Many Chronic Lymphocytic leukaemia (CLL) patients present with asymptomatic, early-stage disease that is monitored until disease progression. Thus, exercise may be an effective way to manage disease burden and delay progression in treatment naïve CLL. The primary objective of this pilot study was to investigate the safety and feasibility of an exercise programme in people with treatment naïve CLL, and preliminarily explore the effects of exercise training on CLL counts, body composition, cardiorespiratory fitness, and immune cell phenotypes including T-cells. We approached N = 100 treatment naïve CLL patients (Binet stage A and B) (Figure 1). Trial uptake was 40%, thus n = 40 participants with treatment naïve CLL were screened. After assessing suitability for exercise (e.g., resting electrocardiogram and other safety tests), n = 11 participants were excluded - the majority of these, n = 9, were due to the presence of cardiac abnormalities. Consequently, n = 28 participants were randomised into a 16-week, home-based, supervised, personalised, progressive exercise intervention ( n = 14: mean ± SD: age = 62 ± 12 years) or 16-weeks of usual care, control group ( n = 14: mean ± SD: age = 61 ± 10 years). The overall retention rate was 86%, with 79% of the exercise group and 93% of the control group completing the trial. Adherence to the exercise intervention was 92 ± 8%. One serious adverse event was reported (hospitalisation for pneumonia) that was unrelated to the trial and one adverse event was reported (syncope following exercise) that was related to the trial. Together, this evidence indicates that exercise training is both safe and feasible in people with treatment naïve CLL who passed pre-trial screening. The exercise intervention elicited a 2% increase in DEXA-derived lean mass in the exercise group compared to a 0.4% decrease in the control group ( p = .01) (Table 1). DEXA-derived total body fat percentage decreased by 4% and 1% and fat mass decreased by 3% and 2% ( p 0.05). Resting systolic and diastolic blood pressure was lower at post-intervention in both groups ( p 0.05) suggesting the observed changes could be the result of “white coat hypertension” pre-intervention. Additionally, no changes were observed for whole-body mass, BMI, bone mineral density, resting heart rate, or measures of cardiorespiratory fitness (all p>0.05). This trial provided a unique opportunity to investigate the effects of regular exercise on neoplastic activity in humans (i.e., CLL counts) without the confounding presence of anti-cancer therapy. Resting blood samples collected pre- and post-intervention were analysed by flow cytometry to enumerate CD5 +CD19 + CLL cells clonally restricted to kappa or lambda. No differences were observed for clonal CLL cells over time or between conditions ( p>0.05) (Table 1). We also analysed resting blood samples collected pre- and post-intervention by flow cytometry to enumerate T cell subsets. No statistically significant changes were observed between conditions pre-intervention to post-intervention for CD4 + or CD8 + T-cell subsets including, naïve (CD27 +CD45RA +), stem cell-like memory (CD27 +CD45RA +CD127 +CD95 +), central memory (CD27 +CD45RA -), effector memory (CD27 -CD45RA -), EMRAs (CD27 -CD45RA +) or exhausted T-cells (PD1 +, Tim3 +) or FoxP3 T-regulatory cells (CD4 +CD127 lowCD25 +FoxP3 +) (all p>0.05). Our results show that exercise is safe and feasible in people with treatment naïve CLL who passed pre-trial screening. In addition, exercise training increased lean mass. No changes were observed to CLL cells. The latter finding is unsurprising given the poorly immunogenic profile of CLL