Association of epicardial adipose tissue with early structural and functional cardiac changes in Type 2 diabetes.

BACKGROUND: Dysregulated epicardial adipose tissue (EAT) may contribute to the development of heart failure in Type 2 diabetes (T2D). This study aimed to evaluate the associations between EAT volume and composition with imaging markers of subclinical cardiac dysfunction in people with T2D and no prevalent cardiovascular disease. METHODS: Prospective case-control study enrolling participants with and without T2D and no known cardiovascular disease. Two hundred and fifteen people with T2D (median age 63 years, 60 % male) and thirty-nine non-diabetics (median age 59 years, 62 % male) were included. Using computed tomography (CT), total EAT volume and mean CT attenuation, as well as, low attenuation (Hounsfield unit range -190 to -90) EAT volume were quantified by a deep learning method and volumes indexed to body surface area. Associations with cardiac magnetic resonance-derived left ventricular (LV) volumes and strain indices were assessed using linear regression. RESULTS: T2D participants had higher LV mass/volume ratio (median 0.89 g/mL [0.82-0.99] vs 0.79 g/mL [0.75-0.89]) and lower global longitudinal strain (GLS; 16.1 ± 2.3 % vs 17.2 ± 2.2 %). Total indexed EAT volume correlated inversely with mean CT attenuation. Low attenuation indexed EAT volume was 2-fold higher (18.8 cm3/m2 vs. 9.4 cm3/m2, p < 0.001) in T2D and independently associated with LV mass/volume ratio (ß = 0.002, p = 0.01) and GLS (ß = -0.03, p = 0.03). CONCLUSIONS: Higher EAT volumes seen in T2D are associated with a lower mean CT attenuation. Low attenuation indexed EAT volume is independently, but only weakly, associated with markers of subclinical cardiac dysfunction in T2D.

The development and internal pilot trial of a digital physical activity and emotional well-being intervention (Kidney BEAM) for people with chronic kidney disease.

This trial assessed the feasibility and acceptability of Kidney BEAM, a physical activity and emotional well-being self-management digital health intervention (DHI) for people with chronic kidney disease (CKD), which offers live and on-demand physical activity sessions, educational blogs and videos, and peer support. In this mixed-methods, multicentre randomised waitlist-controlled internal pilot, adults with established CKD were recruited from five NHS hospitals and randomised 1:1 to Kidney BEAM or waitlist control. Feasibility outcomes were based upon a priori progression criteria. Acceptability was primarily explored via individual semi-structured interviews (n = 15). Of 763 individuals screened, n = 519 (68%, 95% CI 65 to 71%) were eligible. Of those eligible, n = 303 (58%, 95% CI 54-63%) did not respond to an invitation to participate by the end of the pilot period. Of the 216 responders, 50 (23%, 95% CI 18-29%) consented. Of the 42 randomised, n = 22 (10 (45%) male; 49 ± 16 years; 14 (64%) White British) were allocated to Kidney BEAM and n = 20 (12 (55%) male; 56 ± 11 years; 15 (68%) White British) to the waitlist control group. Overall, n = 15 (30%, 95% CI 18-45%) withdrew during the pilot phase. Participants completed a median of 14 (IQR 5-21) sessions. At baseline, 90-100% of outcome data (patient reported outcome measures and a remotely conducted physical function test) were completed and 62-83% completed at 12 weeks follow-up. Interview data revealed that remote trial procedures were acceptable. Participants' reported that Kidney BEAM increased their opportunity and motivation to be physically active, however, lack of time remained an ongoing barrier to engagement with the DHI. An randomised controlled trial of Kidney BEAM is feasible and acceptable, with adaptations to increase recruitment, retention and engagement.Trial registration NCT04872933. Date of first registration 05/05/2021.

Circulating sphingolipids and relationship to cardiac remodelling before and following a low-energy diet in asymptomatic Type 2 Diabetes.

BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) is a heterogenous multi-system syndrome with limited efficacious treatment options. The prevalence of Type 2 diabetes (T2D) continues to rise and predisposes patients to HFpEF, and HFpEF remains one of the biggest challenges in cardiovascular medicine today. Novel therapeutic targets are required to meet this important clinical need. Deep phenotyping studies including -OMIC analyses can provide important pathogenic information to aid the identification of such targets. The aims of this study were to determine; 1) the impact of a low-energy diet on plasma sphingolipid/ceramide profiles in people with T2D compared to healthy controls and, 2) if the change in sphingolipid/ceramide profile is associated with reverse cardiovascular remodelling. METHODS: Post-hoc analysis of a randomised controlled trial (NCT02590822) including adults with T2D with no cardiovascular disease who completed a 12-week low-energy (∼810 kcal/day) meal-replacement plan (MRP) and matched healthy controls (HC). Echocardiography, cardiac MRI and a fasting blood for lipidomics were undertaken pre/post-intervention. Candidate biomarkers were identified from case-control comparison (fold change > 1.5 and statistical significance p < 0.05) and their response to the MRP reported. Association between change in biomarkers and change indices of cardiac remodelling were explored. RESULTS: Twenty-four people with T2D (15 males, age 51.1 ± 5.7 years), and 25 HC (15 male, 48.3 ± 6.6 years) were included. Subjects with T2D had increased left ventricular (LV) mass:volume ratio (0.84 ± 0.13 vs. 0.70 ± 0.08, p < 0.001), increased systolic function but impaired diastolic function compared to HC. Twelve long-chain polyunsaturated sphingolipids, including four ceramides, were downregulated in subjects with T2D at baseline. Three sphingomyelin species and all ceramides were inversely associated with LV mass:volume. There was a significant increase in all species and shift towards HC following the MRP, however, none of these changes were associated with reverse cardiac remodelling. CONCLUSION: The lack of association between change in sphingolipids/ceramides and reverse cardiac remodelling following the MRP casts doubt on a causative role of sphingolipids/ceramides in the progression of heart failure in T2D. TRIAL REGISTRATION: NCT02590822.

Improving self-management behaviour through a digital lifestyle intervention: An internal pilot study.

BACKGROUND: Self-management is a key component of successful chronic kidney disease (CKD) management. Here, we present the findings from the internal pilot of a multicentre randomised controlled trial (RCT) aimed to test the effect of a digital self-management programme ('My Kidneys & Me' (MK&M)). METHODS: Participants (aged ≥18 years and CKD stages 3-4) were recruited from hospital kidney services across England. Study processes were completed virtually. Participants were randomised 2:1 to either intervention (MK&M) or control group. The first 60 participants recruited were included in a 10-week internal pilot which assessed study feasibility and acceptability against pre-specified progression criteria: 1) eligibility and recruitment, acceptability of 2) randomisation and 3) outcomes, 4) MK&M activation, and 5) retention and attrition rates. Semi-structured interviews further explored views on trial participation. RESULTS: Of the 60 participants recruited, 41 were randomised to MK&M and 19 to control. All participants completed baseline measures and 62% (n=37) completed post-intervention outcome measures. All progression criteria met the minimum thresholds to proceed. Nine participants were interviewed. The themes identified were satisfaction with study recruitment processes (openness to participate, reading and agreeing to "terms and conditions"), acceptability of study design (remote study participation, acceptability of randomisation, completion of online assessment(s)), and methods to improve recruitment and retention (personalised approach, follow-up communication). CONCLUSION: This internal pilot demonstrated the feasibility and acceptability of a virtually run RCT. Progression criteria thresholds to proceed to the definitive RCT were met. Areas for improvement were identified and protocol amendments were made to improve trial delivery.

Ethnic differences in cardiac structure and function assessed by MRI in healthy South Asian and White European people: A UK Biobank Study.

BACKGROUND: Echocardiographic studies indicate South Asian people have smaller ventricular volumes, lower mass and more concentric remodelling than White European people, but there are no data using cardiac MRI (CMR). We aimed to compare CMR quantified cardiac structure and function in White European and South Asian people. METHODS: Healthy White European and South Asian participants in the UK Biobank Imaging CMR sub-study were identified by excluding those with a history of cardiovascular disease, hypertension, obesity or diabetes. Ethnic groups were matched by age and sex. Cardiac volumes, mass and feature tracking strain were compared. RESULTS: 121 matched pairs (77 male/44 female, mean age 58 ± 8 years) of South Asian and White European participants were included. South Asian males and females had smaller absolute but not indexed left ventricular (LV) volumes, and smaller absolute and indexed right ventricular volumes, with lower absolute and indexed LV mass and lower LV mass:volume than White European participants. Although there were no differences in ventricular or atrial ejection fractions, LV global longitudinal strain was higher in South Asian females than White European females but not males, and global circumferential strain was higher in both male and South Asian females than White European females. Peak early diastolic strain rates were higher in South Asian versus White European males, but not different between South Asian and White European females. CONCLUSIONS: Contrary to echocardiographic studies, South Asian participants in the UK Biobank study had less concentric remodelling and higher global circumferential strain than White European subjects. These findings emphasise the importance of sex- and ethnic- specific normal ranges for cardiac volumes and function.

Evaluating the effect of a digital health intervention to enhance physical activity in people with chronic kidney disease (Kidney BEAM): a multicentre, randomised controlled trial in the UK.

BACKGROUND: Remote digital health interventions to enhance physical activity provide a potential solution to improve the sedentary behaviour, physical inactivity, and poor health-related quality of life that are typical of chronic conditions, particularly for people with chronic kidney disease. However, there is a need for high-quality evidence to support implementation in clinical practice. The Kidney BEAM trial evaluated the clinical effect of a 12-week physical activity digital health intervention on health-related quality of life. METHODS: In a single-blind, randomised controlled trial conducted at 11 centres in the UK, adult participants (aged ≥18 years) with chronic kidney disease were recruited and randomly assigned (1:1) to the Kidney BEAM physical activity digital health intervention or a waiting list control group. Randomisation was performed with a web-based system, in randomly permuted blocks of six. Outcome assessors were masked to treatment allocation. The primary outcome was the difference in the Kidney Disease Quality of Life Short Form version 1.3 Mental Component Summary (KDQoL-SF1.3 MCS) between baseline and 12 weeks. The trial was powered to detect a clinically meaningful difference of 3 arbitrary units (AU) in KDQoL-SF1.3 MCS. Outcomes were analysed by an intention-to-treat approach using an analysis of covariance model, with baseline measures and age as covariates. The trial was registered with ClinicalTrials.gov, NCT04872933. FINDINGS: Between May 6, 2021, and Oct 30, 2022, 1102 individuals were assessed for eligibility, of whom 340 participants were enrolled and randomly assigned to the Kidney BEAM intervention group (n=173) or the waiting list control group (n=167). 268 participants completed the trial (112 in the Kidney BEAM group and 156 in the waiting list control group). All 340 randomly assigned participants were included in the intention-to treat population. At 12 weeks, there was a significant improvement in KDQoL-SF.13 MCS score in the Kidney BEAM group (from mean 44·6 AU [SD 10·8] at baseline to 47·0 AU [10·6] at 12 weeks) compared with the waiting list control group (from 46·1 AU [10·5] to 45·0 AU [10·1]; between-group difference of 3·1 AU [95% CI 1·8-4·4]; p<0·0001). INTERPRETATION: The Kidney BEAM physical activity platform is an efficacious digital health intervention to improve mental health-related quality of life in patients with chronic kidney disease. These findings could facilitate the incorporation of remote digital health interventions into clinical practice and offer a potential intervention worthy of investigation in other chronic conditions. FUNDING: Kidney Research UK.

Resource efficient aortic distensibility calculation by end to end spatiotemporal learning of aortic lumen from multicentre multivendor multidisease CMR images.

Aortic distensibility (AD) is important for the prognosis of multiple cardiovascular diseases. We propose a novel resource-efficient deep learning (DL) model, inspired by the bi-directional ConvLSTM U-Net with densely connected convolutions, to perform end-to-end hierarchical learning of the aorta from cine cardiovascular MRI towards streamlining AD quantification. Unlike current DL aortic segmentation approaches, our pipeline: (i) performs simultaneous spatio-temporal learning of the video input, (ii) combines the feature maps from the encoder and decoder using non-linear functions, and (iii) takes into account the high class imbalance. By using multi-centre multi-vendor data from a highly heterogeneous patient cohort, we demonstrate that the proposed method outperforms the state-of-the-art method in terms of accuracy and at the same time it consumes [Formula: see text] 3.9 times less fuel and generates [Formula: see text] 2.8 less carbon emissions. Our model could provide a valuable tool for exploring genome-wide associations of the AD with the cognitive performance in large-scale biomedical databases. By making energy usage and carbon emissions explicit, the presented work aligns with efforts to keep DL's energy requirements and carbon cost in check. The improved resource efficiency of our pipeline might open up the more systematic DL-powered evaluation of the MRI-derived aortic stiffness.

Exercise as a therapeutic intervention in chronic kidney disease: are we nearly there yet?

PURPOSE OF REVIEW: The opportunity to review the more recent evidence for prescribing exercise-based physical rehabilitation for people living with chronic kidney disease (CKD) is timely. There has been a recent global focus evaluating how physical activity interventions might improve health-related quality of life and outcomes for people living with chronic health conditions in a post-COVID era. There is finally a long overdue commitment from the kidney research and clinical community to deliver pragmatic interventions to help people living with CKD to be able to live well with their condition. RECENT FINDINGS: This article reviews recent research, and discusses the challenges and potential solutions, for providing exercise-based therapeutic options for people living with CKD; including predialysis self-management interventions, options for both prehabilitation and posttransplant rehabilitation, pragmatic considerations for delivery of exercise therapy for people receiving haemodialysis treatment and the role of virtual kidney-specific rehabilitation. SUMMARY: Whilst there remains a need for further research in this area of patient care, there is now a body of evidence and kidney-specific guidelines that firmly support a rollout of pragmatic and scalable exercise-based interventions for people living with CKD. We are indeed nearly there now.

The NightLife study - the clinical and cost-effectiveness of thrice-weekly, extended, in-centre nocturnal haemodialysis versus daytime haemodialysis using a mixed methods approach: study protocol for a randomised controlled trial.

BACKGROUND: In-centre nocturnal haemodialysis (INHD) offers extended-hours haemodialysis, 6 to 8 h thrice-weekly overnight, with the support of dialysis specialist nurses. There is increasing observational data demonstrating potential benefits of INHD on health-related quality of life (HRQoL). There is a lack of randomised controlled trial (RCT) data to confirm these benefits and assess safety. METHODS: The NightLife study is a pragmatic, two-arm, multicentre RCT comparing the impact of 6 months INHD to conventional haemodialysis (thrice-weekly daytime in-centre haemodialysis, 3.5-5 h per session). The primary outcome is the total score from the Kidney Disease Quality of Life tool at 6 months. Secondary outcomes include sleep and cognitive function, measures of safety, adherence to dialysis and impact on clinical parameters. There is an embedded Process Evaluation to assess implementation, health economic modelling and a QuinteT Recruitment Intervention to understand factors that influence recruitment and retention. Adults (≥ 18 years old) who have been established on haemodialysis for > 3 months are eligible to participate. DISCUSSION: There are 68,000 adults in the UK that need kidney replacement therapy (KRT), with in-centre haemodialysis the treatment modality for over a third of cases. HRQoL is an independent predictor of hospitalisation and mortality in individuals on maintenance dialysis. Haemodialysis is associated with poor HRQoL in comparison to the general population. INHD has the potential to improve HRQoL. Vigorous RCT evidence of effectiveness is lacking. The NightLife study is an essential step in the understanding of dialysis therapies and will guide patient-centred decisions regarding KRT in the future. TRIAL REGISTRATION: Trial registration number: ISRCTN87042063. Registered: 14/07/2020.

Digital health interventions in chronic kidney disease: levelling the playing field?

Digital health interventions (DHIs) have long been thought of as a convenient way to deliver aspects of healthcare and broaden access to services. For patients with chronic kidney disease (CKD), DHIs designed to improve health literacy, self-efficacy and health-related behaviours such as physical activity, diet and adherence have been developed and are being tested, but their translation into clinical practice will be challenging. While DHIs potentially have broad reach, it is increasingly clear that patients from lower socio-economic and educational backgrounds, minority ethnic groups, elderly patients and those who face digital poverty are the least likely to access and benefit from DHIs, when they are precisely the patients who stand to gain the most. This article discusses the potential for DHIs to level the playing field for patients with CKD as well as the steps researchers, clinicians and developers should consider ensuring DHIs are developed, in collaboration with patients, to be inclusive and effective, as well as strategies that should be considered during development to support translation into practice.

The AFLETES Study: Atrial Fibrillation in Veteran Athletes and the Risk of Stroke.

OBJECTIVES: Endurance athletes are at an increased risk of atrial fibrillation (AF) when compared with the general population. However, the risk of stroke in athletes with AF is unknown. DESIGN AND SETTING: We aimed to assess this risk using an international online survey. PATIENTS: Individuals that had competed in ≥1 competitive events and were ≥40 years old were included. INTERVENTIONS: Self-reported demographic, medical history, and training history data were collected, and a CHA 2 DS 2 -VASc was calculated. MAIN OUTCOME MEASURES: Binary logistic regression was used to assess variables associated with AF and stroke. RESULTS: There were 1002 responses from participants in 41 countries across Africa, Asia, Australasia, Europe, and North and South America, and 942 were included in the final analysis. The average age was 52.4 ± 8.5 years, and 84% were male. The most common sports were cycling (n = 677, 72%), running (n = 558, 59%), and triathlon (n = 245, 26%). There were 190 (20%) individuals who reported AF and 26 individuals (3%) who reported stroke; of which, 14 (54%) had AF. Lifetime exercise dose [odds ratio (OR), 1.02, 95% confidence interval (95% CI),1.00-1.03, P = 0.02] and swimming (OR, 1.56, 95% CI, 1.02-2.39, P = 0.04) were associated with AF in multivariable analysis, independent of other risk factors. Atrial fibrillation was associated with stroke (OR, 4.18, 95% CI, 1.80-9.72, P < 0.01), even in individuals with a low (0/1) CHA 2 DS 2 -VASc score (OR, 4.20, 95% CI, 1.83-9.66, P < 0.01). CONCLUSIONS: This survey provides early evidence that veteran endurance athletes who develop AF may be at an increased risk of developing stroke, even in those deemed to be at low risk by CHA 2 DS 2 -VASc score.

Associations of health literacy with self-management behaviours and health outcomes in chronic kidney disease: a systematic review.

INTRODUCTION: Low health literacy is widely reported in people with chronic kidney disease (CKD) and has been associated with reduced disease self-management, poor health outcomes, increased mortality and poorer quality of life. However, these associations are still not well understood. METHODS: Electronic-based systematic searches were performed to identify studies examining associations between health literacy and self-management behaviours and/or health outcomes in patients with CKD. A tabular and narrative synthesis of the data was performed. Meta-analysis was not appropriate due to the heterogeneity of study designs and methods. RESULTS: Searches identified 48 studies that met the inclusion criteria. A total of 41 published articles, six conference abstracts, and one thesis were included. Of the 48 studies, 11 were cohort and 37 were cross-sectional. In total there were 25,671 patients; 16,952 from cohort studies. Median study sample size was 159 (IQR 92-275). Study quality was high (5), moderate (24) and poor (19). Thirteen measures of health literacy were used. Despite the limitations of the available evidence, there appear to be consistent relationships between higher health literacy and favourable self-management behaviours for patients with CKD. Definitive relationships between health literacy and patient outcomes are far less clear and remain incompletely understood. DISCUSSION: Conclusive evidence describing a causal link between health literacy and patient outcomes remains limited, but for many outcomes, a consistent association is described. In addition to associations with mortality, hospitalisation and clinical events, there were consistent associations between health literacy and favourable self-management behaviours which could support the development of patient education aimed at improving health literacy.

Exercise and chronic kidney disease: potential mechanisms underlying the physiological benefits.

Increasing evidence indicates that exercise has beneficial effects on chronic inflammation, cardiorespiratory function, muscle and bone strength and metabolic markers in adults with chronic kidney disease (CKD), kidney failure or kidney transplants. However, the mechanisms that underlie these benefits have received little attention, and the available clinical evidence is mainly from small, short-duration (<12 weeks) exercise intervention studies. The available data, mainly from patients with CKD or on dialysis, suggest that exercise-mediated shifts towards a less inflammatory immune cell profile, enhanced activity of the NRF2 pathway and reduced monocyte infiltration into adipose tissue may underlie improvements in inflammatory biomarkers. Exercise-mediated increases in nitric oxide release and bioavailability, reduced angiotensin II accumulation in the heart, left ventricular remodelling and reductions in myocardial fibrosis may contribute to improvements in left ventricular hypertrophy. Exercise stimulates an anabolic response in skeletal muscle in CKD, but increases in mitochondrial mass and satellite cell activation seem to be impaired in this population. Exercise-mediated activation of the canonical wnt pathway may lead to bone formation and improvements in the levels of the bone-derived hormones klotho and fibroblast growth factor 23 (FGF23). Longer duration studies with larger sample sizes are needed to confirm these mechanisms in CKD, kidney failure and kidney transplant populations and provide evidence for targeted exercise interventions.

The Interfield Strength Agreement of Left Ventricular Strain Measurements at 1.5 T and 3 T Using Cardiac MRI Feature Tracking.

BACKGROUND: Left ventricular (LV) strain measurements can be derived using cardiac MRI from routinely acquired balanced steady-state free precession (bSSFP) cine images. PURPOSE: To compare the interfield strength agreement of global systolic strain, peak strain rates and artificial intelligence (AI) landmark-based global longitudinal shortening at 1.5 T and 3 T. STUDY TYPE: Prospective. SUBJECTS: A total of 22 healthy individuals (mean age 36 ± 12 years; 45% male) completed two cardiac MRI scans at 1.5 T and 3 T in a randomized order within 30 minutes. FIELD STRENGTH/SEQUENCE: bSSFP cine images at 1.5 T and 3 T. ASSESSMENT: Two software packages, Tissue Tracking (cvi42, Circle Cardiovascular Imaging) and QStrain (Medis Suite, Medis Medical Imaging Systems), were used to derive LV global systolic strain in the longitudinal, circumferential and radial directions and peak (systolic, early diastolic, and late diastolic) strain rates. Global longitudinal shortening and mitral annular plane systolic excursion (MAPSE) were measured using an AI deep neural network model. STATISTICAL TESTS: Comparisons between field strengths were performed using Wilcoxon signed-rank test (P value < 0.05 considered statistically significant). Agreement was determined using intraclass correlation coefficients (ICCs) and Bland-Altman plots. RESULTS: Minimal bias was seen in all strain and strain rate measurements between field strengths. Using Tissue Tracking, strain and strain rate values derived from long-axis images showed poor to fair agreement (ICC range 0.39-0.71), whereas global longitudinal shortening and MAPSE showed good agreement (ICC = 0.81 and 0.80, respectively). Measures derived from short-axis images showed good to excellent agreement (ICC range 0.78-0.91). Similar results for the agreement of strain and strain rate measurements were observed with QStrain. CONCLUSION: The interfield strength agreement of short-axis derived LV strain and strain rate measurements at 1.5 T and 3 T was better than those derived from long-axis images; however, the agreement of global longitudinal shortening and MAPSE was good. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.

Association of ambulatory blood pressure with coronary microvascular and cardiac dysfunction in asymptomatic type 2 diabetes.

BACKGROUND: Type 2 diabetes (T2D) and hypertension commonly coexist and are associated with subclinical myocardial structural and functional changes. We sought to determine the association between blood pressure (BP) and left ventricular (LV) remodeling, systolic/diastolic function, and coronary microvascular function, among individuals with T2D without prevalent cardiovascular disease. METHODS: Participants with T2D and age-, sex-, and ethnicity-matched controls underwent comprehensive cardiovascular phenotyping including fasting bloods, transthoracic echocardiography, cardiovascular magnetic resonance imaging with quantitative adenosine stress/rest perfusion, and office and 24-h ambulatory BP monitoring. Multivariable linear regression was performed to determine independent associations between BP and imaging markers of remodeling and function in T2D. RESULTS: Individuals with T2D (n = 205, mean age 63 ± 7 years) and controls (n = 40, mean age 61 ± 8 years) were recruited. Mean 24-h systolic BP, but not office BP, was significantly greater among those with T2D compared to controls (128.8 ± 11.7 vs 123.0 ± 13.1 mmHg, p = 0.006). Those with T2D had concentric LV remodeling (mass/volume 0.91 ± 0.15 vs 0.82 ± 0.11 g/mL, p < 0.001), decreased myocardial perfusion reserve (2.82 ± 0.83 vs 3.18 ± 0.82, p = 0.020), systolic dysfunction (global longitudinal strain 16.0 ± 2.3 vs 17.2 ± 2.1%, p = 0.004) and diastolic dysfunction (E/e' 9.30 ± 2.43 vs 8.47 ± 1.53, p = 0.044) compared to controls. In multivariable regression models adjusted for 14 clinical variables, mean 24-h systolic BP was independently associated with concentric LV remodeling (ß = 0.165, p = 0.031), diastolic dysfunction (ß = 0.273, p < 0.001) and myocardial perfusion reserve (ß = - 0.218, p = 0.016). Mean 24-h diastolic BP was associated with LV concentric remodeling (ß = 0.201, p = 0.016). CONCLUSION: 24-h ambulatory systolic BP, but not office BP, is independently associated with cardiac remodeling, coronary microvascular dysfunction, and diastolic dysfunction among asymptomatic individuals with T2D. (Clinical trial registration. URL: https://clinicaltrials.gov/ct2/show/NCT03132129 Unique identifier: NCT03132129).

The Effect of Non-Pharmacological and Pharmacological Interventions on Measures Associated with Sarcopenia in End-Stage Kidney Disease: A Systematic Review and Meta-Analysis.

This systematic review and meta-analysis provides a synthesis of the available evidence for the effects of interventions on outcome measures associated with sarcopenia in end-stage kidney disease (ESKD). Thirteen databases were searched, supplemented with internet and hand searching. Randomised controlled trials of non-pharmacological or pharmacological interventions in adults with ESKD were eligible. Trials were restricted to those which had reported measures of sarcopenia. Primary outcome measures were hand grip strength and sit-to-stand tests. Sixty-four trials were eligible (with nineteen being included in meta-analyses). Synthesised data indicated that intradialytic exercise increased hand grip strength (standardised mean difference, 0.58; 0.24 to 0.91; p = 0.0007; I2 = 40%), and sit-to-stand (STS) 60 score (mean difference, 3.74 repetitions; 2.35 to 5.14; p < 0.001; I2 = 0%). Intradialytic exercise alone, and protein supplementation alone, resulted in no statistically significant change in STS5 (−0.78 s; −1.86 to 0.30; p = 0.16; I2 = 0%), and STS30 (MD, 0.97 repetitions; −0.16 to 2.10; p = 0.09; I2 = 0%) performance, respectively. For secondary outcomes, L-carnitine and nandrolone-decanoate resulted in significant increases in muscle quantity in the dialysis population. Intradialytic exercise modifies measures of sarcopenia in the haemodialysis population; however, the majority of trials were low in quality. There is limited evidence for efficacious interventions in the peritoneal dialysis and transplant recipient populations.

Feasibility and acceptability of high-intensity interval training and moderate-intensity continuous training in kidney transplant recipients: the PACE-KD study.

BACKGROUND: Kidney transplant recipients (KTRs) exhibit unique elevated inflammation, impaired immune function, and increased cardiovascular risk. Although exercise reduces cardiovascular risk, there is limited research on this population, particularly surrounding novel high-intensity interval training (HIIT). The purpose of this pilot study was to determine the feasibility and acceptability of HIIT in KTRs. METHODS: Twenty KTRs (male 14; eGFR 58±19 mL/min/1.73 m2; age 49±11 years) were randomised and completed one of three trials: HIIT A (4-, 2-, and 1-min intervals; 80-90% watts at V̇O2peak), HIITB (4×4 min intervals; 80-90% V̇O2peak) or MICT (~40 min; 50-60% V̇O2peak) for 24 supervised sessions on a stationary bike (approx. 3x/week over 8 weeks) and followed up for 3 months. Feasibility was assessed by recruitment, retention, and intervention acceptability and adherence. RESULTS: Twenty participants completed the intervention, and 8 of whom achieved the required intensity based on power output (HIIT A, 0/6 [0%]; HIITB, 3/8 [38%]; MICT, 5/6 [83%]). Participants completed 92% of the 24 sessions with 105 cancelled and rescheduled sessions and an average of 10 weeks to complete the intervention. Pre-intervention versus post-intervention V̇O2peak (mL/kg-1/min-1) was 24.28±4.91 versus 27.06±4.82 in HIITA, 24.65±7.67 versus 27.48±8.23 in HIIT B, and 29.33±9.04 versus 33.05±9.90 in MICT. No adverse events were reported. CONCLUSIONS: This is the first study to report the feasibility of HIIT in KTRs. Although participants struggled to achieve the required intensity (power), this study highlights the potential that exercise has to reduce cardiovascular risk in KTRs. HIIT and MICT performed on a cycle, with some modification, could be considered safe and feasible in KTRs. Larger scale trials are required to assess the efficacy of HIIT in KTRs and in particular identify the most appropriate intensities, recovery periods, and session duration. Some flexibility in delivery, such as incorporating home-based sessions, may need to be considered to improve recruitment and retention. TRIAL REGISTRATION: ISRCTN, ISRCTN17122775 . Registered on 30 January 2017.

Fibro-inflammatory recovery and type 2 diabetes remission following a low calorie diet but not exercise training: A secondary analysis of the DIASTOLIC randomised controlled trial.

AIMS: To investigate the relationship between fibro-inflammatory biomarkers and cardiovascular structure/function in people with Type 2 Diabetes (T2D) compared to healthy controls and the effect of two lifestyle interventions in T2D. METHODS: Data were derived from the DIASTOLIC randomised controlled trial (RCT) and includes a comparison between those with T2D and the matched healthy volunteers recruited at baseline. Adults with T2D without cardiovascular disease (CVD) were randomized to a 12-week intervention either: (1) exercise training, (2) a low-energy (∼810 kcal/day) meal-replacement plan (MRP) or (3) standard care. Principal Component and Fisher's linear discriminant analysis were used to investigate the relationships between MRI acquired cardiovascular outcomes and fibro-inflammatory biomarkers in cases versus controls and pre- and post-intervention in T2D. RESULTS: At baseline, 83 people with T2D (mean age 50.5 ± 6.4; 58% male) and 36 healthy controls (mean age 48.6 ± 6.2; 53% male) were compared and 76 people with T2D completed the RCT for pre- post-analysis. Compared to healthy controls, subjects with T2D had adverse cardiovascular remodelling and a fibro-inflammatory profile (20 differentially expressed biomarkers). The 3D data visualisations showed almost complete separation between healthy controls and those with T2D, and a marked shift towards healthy controls following the MRP (15 biomarkers significantly changed) but not exercise training. CONCLUSIONS: Fibro-inflammatory pathways and cardiovascular structure/function are adversely altered before the onset of symptomatic CVD in middle-aged adults with T2D. The MRP improved the fibro-inflammatory profile of people with T2D towards a more healthy status. Long-term studies are required to assess whether these changes lead to continued reverse cardiac remodelling and prevent CVD.

Primary skeletal muscle cells from chronic kidney disease patients retain hallmarks of cachexia in vitro.

BACKGROUND: Skeletal muscle wasting and dysfunction are common characteristics noted in people who suffer from chronic kidney disease (CKD). The mechanisms by which this occurs are complex, and although progress has been made, the key underpinning mechanisms are not yet fully elucidated. With work to date primarily conducted in nephrectomy-based animal models, translational capacity to our patient population has been challenging. This could be overcome if rationale developing work could be conducted in human based models with greater translational capacity. This could be achieved using cells derived from patient biopsies, if they retain phenotypic traits noted in vivo. METHODS: Here, we performed a systematic characterization of CKD derived muscle cells (CKD; n = 10; age: 54.40 ± 15.53 years; eGFR: 22.25 ± 13.22 ml/min/1.73 m2 ) in comparison with matched controls (CON; n = 10; age: 58.66 ± 14.74 years; eGFR: 85.81 ± 8.09 ml/min/1.73 m2 ). Harvested human derived muscle cells (HDMCs) were taken through proliferative and differentiation phases and investigated in the context of myogenic progression, inflammation, protein synthesis, and protein breakdown. Follow up investigations exposed HDMC myotubes from each donor type to 0, 0.4, and 100 nM of IGF-1 in order to investigate any differences in anabolic resistance. RESULTS: Harvested human derived muscle cells isolated from CKD patients displayed higher rates of protein degradation (P = 0.044) alongside elevated expression of both TRIM63 (2.28-fold higher, P = 0.054) and fbox32 (6.4-fold higher, P < 0.001) in comparison with CONs. No differences were noted in rates of protein synthesis under basal conditions (P > 0.05); however, CKD derived cells displayed a significant degree of anabolic resistance in response to IGF-1 stimulation (both doses) in comparison with matched CONs (0.4 nm: P < 0.001; 100 nM: P < 0.001). CONCLUSIONS: In summary, we report for the first time that HDMCs isolated from people suffering from CKD display key hallmarks of the well documented in vivo phenotype. Not only do these findings provide further mechanistic insight into CKD specific cachexia, but they also demonstrate this is a reliable and suitable model in which to perform targeted experiments to begin to develop novel therapeutic strategies targeting the CKD associated decline in skeletal muscle mass and function.