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.

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.

Skeletal Muscle Texture Assessment Using Ultrasonography: Comparison with Magnetic Resonance Imaging in Chronic Kidney Disease.

Skeletal muscle dysfunction is common in chronic kidney disease (CKD). Of interest is the concept of "muscle quality," of which measures include ultrasound-derived echo intensity (EI). Alternative parameters of muscle texture, for example, gray level of co-occurrence matrix (GCLM), are available and may circumvent limitations in EI. The validity of EI is limited in humans, particularly in chronic diseases. This study aimed to investigate the associations between ultrasound-derived parameters of muscle texture with MRI. Images of the thigh were acquired using a 3 Tesla MRI scanner. Quantification of muscle (contractile), fat (non-contractile), and miscellaneous (connective tissue, fascia) components were estimated. Anatomical rectus femoris cross-sectional area was measured using B-mode 2D ultrasonography. To assess muscle texture, first (i.e., EI)- and second (i.e., GLCM)-order statistical analyses were performed. Fourteen participants with CKD were included (age: 58.0 ± 11.9 years, 50% male, eGFR: 27.0 ± 7.4 ml/min/1.73m2, 55% Stage 4). Higher EI was associated with lower muscle % (quadriceps: ß = -.568, p = .034; hamstrings: ß = -.644, p = .010). Higher EI was associated with a higher fat % in the hamstrings (ß = -.626, p = .017). A higher angular second moment from GLCM analysis was associated with greater muscle % (ß = .570, p = .033) and lower fat % (ß = -.534, p = .049). A higher inverse difference moment was associated with greater muscle % (ß = .610, p = .021 and lower fat % (ß = -.599, p = .024). This is the first study to investigate the associations between ultrasound-derived parameters of muscle texture with MRI. Our preliminary findings suggest ultrasound-derived texture analysis provides a novel indicator of reduced skeletal muscle % and thus increased intramuscular fat.

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 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.

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.

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).

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.

Inflammation and physical dysfunction: responses to moderate intensity exercise in chronic kidney disease.

BACKGROUND: People with chronic kidney disease (CKD) experience skeletal muscle wasting, reduced levels of physical function and performance, and chronic systemic inflammation. While it is known that a relationship exists between inflammation and muscle wasting, the association between inflammation and physical function or performance in CKD has not been well studied. Exercise has anti-inflammatory effects, but little is known regarding the effect of moderate intensity exercise. This study aimed to (i) compare systemic and intramuscular inflammation between CKD stage G3b-5 and non-CKD controls; (ii) establish whether a relationship exists between physical performance, exercise capacity and inflammation in CKD; (iii) determine changes in systemic and intramuscular inflammation following 12 weeks of exercise; and (iv) investigate whether improving inflammatory status via training contributes to improvements in physical performance and muscle mass. METHODS: This is a secondary analysis of previously collected data. CKD patients stages G3b-5 (n = 84, n = 43 males) and non-CKD controls (n = 26, n = 17 males) underwent tests of physical performance, exercise capacity, muscle strength and muscle size. In addition, a subgroup of CKD participants underwent 12 weeks of exercise training, randomized to aerobic (AE, n = 21) or combined (CE, n = 20) training. Plasma and intramuscular inflammation and myostatin were measured at rest and following exercise. RESULTS: Tumour necrosis factor-α was negatively associated with lower $^{^{^{.}}}{\rm V}$O2Peak (P = 0.01), Rectus femoris-cross sectional area (P = 0.002) and incremental shuttle walk test performance (P < 0.001). Interleukin-6 was negatively associated with sit-to-stand 60 performances (P = 0.006) and hand grip strength (P = 0.001). Unaccustomed exercise created an intramuscular inflammatory response that was attenuated following 12 weeks of training. Exercise training did not reduce systemic inflammation, but AE training did significantly reduce mature myostatin levels (P = 0.02). Changes in inflammation were not associated with changes in physical performance. CONCLUSIONS: Systemic inflammation may contribute to reduced physical function in CKD. Twelve weeks of exercise training was unable to reduce the level of chronic systemic inflammation in these patients, but did reduce plasma myostatin concentrations. Further research is required to further investigate this.

Circulating endotoxin and inflammation: associations with fitness, physical activity and the effect of a 6-month programme of cycling exercise during haemodialysis.

BACKGROUND: Intradialytic cycling (IDC) may provide cardiovascular benefits to individuals receiving haemodialysis, but the exact mechanism behind these improvements remains unclear. The primary aim of this study was to investigate the effect of a 6-month programme of IDC on circulating endotoxin (secondary analysis from the CYCLE-HD trial). Secondary aims were to investigate changes in circulating cytokines [interleukin-6 (IL-6), IL-10, tumour necrosis factor-α, C-reactive protein (CRP) and the IL-6:IL-10 ratio] and their associations with physical activity, fitness and cardiovascular outcomes. METHODS: Participants were randomized to either a 6-month programme of IDC (thrice weekly, moderate intensity cycling at a rating of perceived exertion of 12-14) in addition to usual care (n = 46) or usual care only (control group; n = 46). Outcome measures were obtained at baseline and then again at 6 months. RESULTS: There was no significant (P = 0.137) difference in circulating endotoxin between groups at 6 months (IDC group: 0.34 ± 0.08 EU/mL; control group: 0.37 ± 0.07 EU/mL). There were no significant between-group differences in any circulating cytokine following the 6-month programme of IDC. Higher levels of physical activity and fitness were associated with lower levels of endotoxin, IL-6, CRP and IL-6:IL-10 ratio. CONCLUSIONS: Our data show no change in circulating endotoxin or cytokines following a 6-month programme of IDC. However, higher levels of physical activity outside of haemodialysis were associated with lower levels of inflammation.

Exercise, inflammation and acute cardiovascular events.

Individuals who participate in regular exercise over time have a markedly reduced risk of cardiovascular disease. Paradoxically, in susceptible individuals with underlying, often undiagnosed, disease states, exercise may acutely increase an individual's risk of cardiovascular events during and immediately following physical exertion. Exercise is thought to evoke conditions that trigger atheromatous plaque rupture or trigger life threatening arrhythmias in individuals with pre-existing, vulnerable coronary artery and inherited cardiovascular disease respectively. This transient increased risk may be driven by the inflammatory trigger provided by physical exertion where exercise is associated with an upregulation of inflammatory mediators in the acute phase. Conversely, habitual exercise can lead to a modulation of the inflammatory response over time. This review explores: exercise related inflammation; acute cardiovascular events related to exercise and strategies to mitigate these risks.

Perceived barriers and facilitators to exercise in kidney transplant recipients: A qualitative study.

BACKGROUND: Exercise has the potential to attenuate the high levels of cardiovascular morbidity and mortality present in kidney transplant recipients (KTRs). Despite this, activity levels in KTRs remain low. The aim of this qualitative study was to explore the barriers and facilitators of exercise in KTRs. METHODS: Thirteen KTRs (eight males; mean ± SD; age 53 ± 13 years; estimated glomerular filtration rate 53 ± 21 ml/min/1.73 m2 ) were recruited and completed semistructured one-to-one interviews at University Hospitals of Leicester NHS Trust. All KTRs were eligible if their kidney transplant was completed >12 weeks before interview and their consultant considered them to have no major contraindications to exercise. All interviews were audio recorded, transcribed verbatim and subject to framework analysis to identify and report themes. RESULTS: Themes were organized into personal, behavioural and environmental factors based on social cognitive theory. Facilitators of exercise were largely internal: enjoyment, exercise for general health and health of the transplanted kidney and desire to maintain normality. Social interaction, support and guidance of healthcare professionals and goal setting were perceived as motivational. Harming the kidney, a lack of guidance, self-motivation and accessibility were barriers to exercise. CONCLUSION: These results provide detailed insight into the development of interventions designed to increase physical activity in KTRs. They provide strong evidence that specific exercise guidelines are required for this population and that the healthcare system could have a key role in supporting KTRs to become more physically active. Interventions need to be multifaceted to appeal to the differing levels of support desired by KTRs. PATIENT OR PUBLIC CONTRIBUTION: KTRs were involved in the development of the interview topic guide to ensure all relevant topics were explored.

Intradialytic cycling does not exacerbate microparticles or circulating markers of systemic inflammation in haemodialysis patients.

PURPOSE: Patients receiving haemodialysis (HD) display elevated circulating microparticle (MP) concentration, tissue factor (TF) expression and markers of systemic inflammation, though regular intradialytic cycling (IDC) may have a therapeutic effect. This study investigated the impact of regular, moderate-intensity IDC on circulating MPs and inflammatory markers in unit-based HD patients. METHODS: Patients were cluster-randomised to intervention (n = 20, age: 51.4 ± 18.1 years, body mass: 77.6 ± 18.3 kg, mean ± SD) or no-exercise control (n = 20, 56.8 ± 14.0 years, 80.5 ± 26.5 kg). Intervention participants completed 30 min of moderate intensity (rating of perceived exertion [RPE] of 12-14) IDC, thrice weekly for 6 months. Pre-dialysis venous blood samples were obtained at 0, 3 and 6 months. Circulating MP phenotypes, cytokines, chemokine and MP TF expression were quantified using flow cytometry and cytometric bead array assays. RESULTS: Despite high exercise compliance (82%), no IDC-dependent effects were observed for any MP, cytokine or chemokine measure (p ≥ 0.051, ηρ2 ≤ 0.399) other than TNF-α (p = 0.001, ηρ2 = 0.186), though no significance was revealed upon post hoc analysis. CONCLUSION: Six months of regular, moderate-intensity IDC had no effect on MPs, cytokines or chemokines. This suggests that the exercise did not exacerbate thrombotic or inflammatory status, though further functional assays are required to confirm this. TRIAL REGISTRATION: ISRCTN1129707, prospectively registered on 05/03/2015.

The Codevelopment of "My Kidneys & Me": A Digital Self-management Program for People With Chronic Kidney Disease.

BACKGROUND: Health care self-management is important for people living with nondialysis chronic kidney disease (CKD). However, the few available resources are of variable quality. OBJECTIVE: This work describes the systematic codevelopment of "My Kidneys & Me" (MK&M), a theory-driven and evidence-based digital self-management resource for people with nondialysis CKD, guided by an established process used for the successful development of the diabetes education program MyDESMOND (Diabetes Education and Self-Management for Ongoing and Newly Diagnosed, DESMOND). METHODS: A multidisciplinary steering group comprising kidney health care professionals and researchers and specialists in the development of complex interventions and digital health provided expertise in the clinical and psychosocial aspects of CKD, self-management, digital health, and behavior change. A patient and public involvement group helped identify the needs and priorities of MK&M and co-design the resource. MK&M was developed in 2 sequential phases. Phase 1 involved the codevelopment process of the MK&M resource (content and materials), using Intervention Mapping (IM) as a framework. The first 4 IM steps guided the development process: needs assessment was conducted to describe the context of the intervention; intervention outcomes, performance objectives, and behavioral determinants were identified; theory- and evidence-based change methods and practical strategies to deliver change methods were selected; and program components were developed and refined. Phase 2 involved the adoption and adaptation of the existing MyDESMOND digital platform to suit the MK&M resource. RESULTS: The needs assessment identified that individuals with CKD have multiple differing needs and that delivering a self-management program digitally would enable accessible, tailored, and interactive information and support. The intended outcomes of MK&M were to improve and maintain effective self-management behaviors, including physical activity and lifestyle, improve knowledge, promote self-care skills, increase self-efficacy, and enhance well-being. This was achieved through the provision of content and materials designed to increase CKD knowledge and patient activation, reduce health risks, manage symptoms, and improve physical function. Theories and behavior change techniques selected include Self-Management Framework, Capability, Opportunity, Motivation Behavior model components of Behaviour Change Wheel and taxonomy of behavior change techniques, Health Action Process Approach Model, Common Sense Model, and Social Cognitive Theory. The program components developed comprised educational and behavior change sessions, health trackers (eg, monitoring blood pressure, symptoms, and exercise), goal-setting features, and forums for social support. The MyDESMOND digital platform represented an ideal existing platform to host MK&M; thus, the MyDESMOND interface and features were adopted and adapted for MK&M. CONCLUSIONS: Applying the IM framework enabled the systematic application of theory, empirical evidence, and practical perspectives in the codevelopment of MK&M content and materials. Adopting and adapting a preexisting platform provided a cost- and time-efficient approach for developing our digital intervention. In the next stage of work, the efficacy of MK&M in increasing patient activation will be tested in a randomized controlled trial.

A randomized controlled trial to investigate the effects of intra-dialytic cycling on left ventricular mass.

Cardiovascular disease is the leading cause of death for patients receiving hemodialysis. Since exercise mitigates many risk factors which drive cardiovascular disease for these patients, we assessed effects of a program of intra-dialytic cycling on left ventricular mass and other prognostically relevant measures of cardiovascular disease as evaluated by cardiac MRI (the CYCLE-HD trial). This was a prospective, open-label, single-blinded cluster-randomized controlled trial powered to detect a 15g difference in left ventricular mass measured between patients undergoing a six-month program of intra-dialytic cycling (exercise group) and patients continuing usual care (control group). Pre-specified secondary outcomes included measures of myocardial fibrosis, aortic stiffness, physical functioning, quality of life and ventricular arrhythmias. Outcomes were analyzed as intention-to-treat according to a pre-specified statistical analysis plan. Initially, 130 individuals were recruited and completed baseline assessments (65 each group). Ultimately, 101 patients completed the trial protocol (50 control group and 51 exercise group). The six-month program of intra-dialytic cycling resulted in a significant reduction in left ventricular mass between groups (-11.1g; 95% confidence interval -15.79, -6.43), which remained significant on sensitivity analysis (missing data imputed) (-9.92g; 14.68, -5.16). There were significant reductions in both native T1 mapping and aortic pulse wave velocity between groups favoring the intervention. There was no increase in either ventricular ectopic beats or complex ventricular arrhythmias as a result of exercise with no significant effect on physical function or quality of life. Thus, a six-month program of intradialytic cycling reduces left ventricular mass and is safe, deliverable and well tolerated.

Reductions in skeletal muscle mitochondrial mass are not restored following exercise training in patients with chronic kidney disease.

Patients with chronic kidney disease (CKD) exhibit reduced exercise capacity, poor physical function and symptoms of fatigue. The mechanisms that contribute to this are not clearly defined but may involve reductions in mitochondrial function, mass and biogenesis. Here we report on the effect of non-dialysis dependent CKD (NDD-CKD) on mitochondrial mass and basal expression of transcription factors involved in mitochondrial biogenesis compared to a healthy control cohort (HC). In addition, we sought to investigate the effect of a 12-week exercise-training programme on these aspects of mitochondrial dysfunction in a NDD-CKD cohort.For the comparison between NDD-CKD and HC populations, skeletal muscle biopsies were collected from the vastus lateralis (VL) of n=16 non-dialysis dependent CKD patient's stage 3b-5 (NDD-CKD) and n=16 healthy controls matched for age, gender and physical activity (HC). To investigate the effect of exercise training, VL biopsies were collected from n=17 NDD-CKD patients before and after a 12-week exercise intervention that was comprised of aerobic exercise (AE) or a combination of aerobic exercise and resistance training (CE). Mitochondrial mass was analysed by citrate synthase activity and mitochondrial protein content by Porin expression, whilst the expression of transcription factors involved in mitochondrial biogenesis were quantified by real-time qPCR. NDD-CKD patients exhibited a significant reduction in mitochondrial mass when compared to HC, coupled to a reduction in PGC-1α, NRF-1, Nrf2, TFam, mfn2 and SOD1/2 gene expression. 12-weeks of exercise training resulted in a significant increase in PGC-1α expression in both groups, with no further changes seen across indicators of mitochondrial biogenesis. No significant changes in mitochondrial mass were observed in response to either exercise programme. NDD-CKD patients exhibit reduced skeletal muscle mitochondrial mass and gene expression of transcription factors involved in mitochondrial biogenesis compared to HC. These reductions were not restored following 12-weeks of exercise training implying exercise resistance in this cohort. The reasons for this lack of improvement are currently unknown and require further investigation, as reversing the dysregulation of these processes in NDD-CKD may provide a therapeutic opportunity to improve muscle fatigue and dysfunction in this population.

Characteristics of effective home-based resistance training in patients with noncommunicable chronic diseases: a systematic scoping review of randomised controlled trials.

Skeletal muscle atrophy, dysfunction, and weakness are consequences of noncommunicable diseases which result in exercise and functional limitations which contribute to poor quality of life and increased mortality. Home-based resistance training may promote skeletal muscle health. Electronic-based systematic searches were performed identifying randomised controlled trials utilising home-based resistance training in patients with noncommunicable diseases defined as cancer, cardiovascular disease, diabetes mellitus (type 1 and 2), chronic kidney disease (including dialysis), and chronic respiratory disease (asthma, chronic obstructive pulmonary disease, pulmonary hypertension). A comparator group was defined as one containing "non-exercise" or "usual care". Of the 239 studies identified (published between 1996 and 2020), 22 met the inclusion criteria. Sixteen studies contained an adjunct aerobic training component. Study designs and outcome measures showed large variation. Reporting of the principles of training applied within interventions was poor. Heterogeneity in study characteristics, and poor reporting of training characteristics, prevents formal recommendations for optimising home-based resistance training. However, home-based interventions are less resource-intensive than supervised programmes and appear to have the ability to improve or preserve pertinent outcomes such as strength, functional ability, and quality of life; potentially reducing the risk of mortality in patients with chronic disease.

Skeletal muscle wasting in chronic kidney disease: the emerging role of microRNAs.

Skeletal muscle wasting is a common complication of chronic kidney disease (CKD), characterized by the loss of muscle mass, strength and function, which significantly increases the risk of morbidity and mortality in this population. Numerous complications associated with declining renal function and lifestyle activate catabolic pathways and impair muscle regeneration, resulting in substantial protein wasting. Evidence suggests that increasing skeletal muscle mass improves outcomes in CKD, making this a clinically important research focus. Despite extensive research, the pathogenesis of skeletal muscle wasting is not completely understood. It is widely recognized that microRNAs (miRNAs), a family of short non-coding RNAs, are pivotal in the regulation of skeletal muscle homoeostasis, with significant roles in regulating muscle growth, regeneration and metabolism. The abnormal expression of miRNAs in skeletal muscle during disease has been well described in cellular and animal models of muscle atrophy, and in recent years, the involvement of miRNAs in the regulation of muscle atrophy in CKD has been demonstrated. As this exciting field evolves, there is emerging evidence for the involvement of miRNAs in a beneficial crosstalk system between skeletal muscle and other organs that may potentially limit the progression of CKD. In this article, we describe the pathophysiological mechanisms of muscle wasting and explore the contribution of miRNAs to the development of muscle wasting in CKD. We also discuss advances in our understanding of miRNAs in muscle-organ crosstalk and summarize miRNA-based therapeutics currently in clinical trials.

The reliability and feasibility of non-contrast adenosine stress cardiovascular magnetic resonance T1 mapping in patients on haemodialysis.

BACKGROUND: Identifying coronary artery disease (CAD) in patients with end-stage renal disease (ESRD) is challenging. Adenosine stress native T1 mapping with cardiovascular magnetic resonance (CMR) may accurately detect obstructive CAD and microvascular dysfunction in the general population. This study assessed the feasibility and reliability of adenosine stress native T1 mapping in patients on haemodialysis. METHODS: The feasibility of undertaking rest and adenosine stress native T1 mapping using the single-shot Modified Look-Locker inversion recovery (MOLLI) sequence was assessed in 58 patients on maintenance haemodialysis using 3 T CMR. Ten patients underwent repeat stress CMR within 2 weeks for assessment of test-retest reliability of native T1, stress T1 and delta T1 (ΔT1). Interrater and intrarater agreement were assessed in 10 patients. Exploratory analyses were undertaken to assess associations between clinical variables and native T1 values in 51 patients on haemodialysis. RESULTS: Mean age of participants was 55 ± 15 years, 46 (79%) were male, and median dialysis vintage was 21 (8; 48) months. All patients completed the scan without complications. Mean native T1 rest, stress and ΔT1 were 1261 ± 57 ms, 1297 ± 50 ms and 2.9 ± 2.5%, respectively. Interrater and intrarater agreement of rest T1, stress T1 and ΔT1 were excellent, with intraclass correlation coefficients (ICC) > 0.9 for all. Test-retest reliability of rest and stress native T1 were excellent or good (CoV 1.2 and 1.5%; ICC, 0.79 and 0.69, respectively). Test-retest reliability of ΔT1 was moderate to poor (CoV 27.4%, ICC 0.55). On multivariate analysis, CAD, diabetes mellitus and resting native T1 time were independent determinants of ΔT1 (ß = - 0.275, p = 0.019; ß = - 0.297, p = 0.013; ß = - 0.455; p < 0.001, respectively). CONCLUSIONS: Rest and adenosine stress native T1 mapping is feasible and well-tolerated amongst patients with ESRD on haemodialysis. Although rater agreement of the technique is excellent, test-retest reliability of ΔT1 is moderate to poor. Prospective studies should evaluate the relationship between this technique and established methods of CAD assessment and association with outcomes.