Impaired Cardiac and Skeletal Muscle Energetics Following Anthracycline Therapy for Breast Cancer.

BACKGROUND: Anthracycline-related cardiac toxicity is a recognized consequence of cancer therapies. We assess resting cardiac and skeletal muscle energetics and myocyte, sarcomere, and mitochondrial integrity in patients with breast cancer receiving epirubicin. METHODS: In a prospective, mechanistic, observational, longitudinal study, we investigated chemotherapy-naive patients with breast cancer receiving epirubicin versus sex- and age-matched healthy controls. Resting energetic status of cardiac and skeletal muscle (phosphocreatine/gamma ATP and inorganic phosphate [Pi]/phosphocreatine, respectively) was assessed with 31P-magnetic resonance spectroscopy. Cardiac function and tissue characterization (magnetic resonance imaging and 2D-echocardiography), cardiac biomarkers (serum NT-pro-BNP and high-sensitivity troponin I), and structural assessments of skeletal muscle biopsies were obtained. All study assessments were performed before and after chemotherapy. RESULTS: Twenty-five female patients with breast cancer (median age, 53 years) received a mean epirubicin dose of 304 mg/m2, and 25 age/sex-matched controls were recruited. Despite comparable baseline cardiac and skeletal muscle energetics with the healthy controls, after chemotherapy, patients with breast cancer showed a reduction in cardiac phosphocreatine/gamma ATP ratio (2.0±0.7 versus 1.1±0.5; P=0.001) and an increase in skeletal muscle Pi/phosphocreatine ratio (0.1±0.1 versus 0.2±0.1; P=0.022). This occurred in the context of increases in left ventricular end-systolic and end-diastolic volumes (P=0.009 and P=0.008, respectively), T1 and T2 mapping (P=0.001 and P=0.028, respectively) but with preserved left ventricular ejection fraction, mass and global longitudinal strain, and no change in cardiac biomarkers. There was preservation of the mitochondrial copy number in skeletal muscle biopsies but a significant increase in areas of skeletal muscle degradation (P=0.001) in patients with breast cancer following chemotherapy. Patients with breast cancer demonstrated a reduction in skeletal muscle sarcomere number from the prechemotherapy stage compared with healthy controls (P=0.013). CONCLUSIONS: Contemporary doses of epirubicin for breast cancer treatment result in a significant reduction of cardiac and skeletal muscle high-energy 31P-metabolism alongside structural skeletal muscle changes. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT04467411.

Cardiovascular disease behavioural risk factors in rural interventions: cross-sectional study.

This study aims to (1) assess the distribution of variables within the population and the prevalence of cardiovascular disease (CVD) behavioural risk factors in patients, (2) identify target risk factor(s) for behaviour modification intervention, and (3) develop an analytical model to define cluster(s) of risk factors which could help make any generic intervention more targeted to the local patient population. Study patients with at least one CVD behavioural risk factor living in a rural region of the Scottish Highlands. The study used the STROBE methodology for cross-sectional studies. Demographic and clinical data of patients (n = 2025) in NHS Highlands hospital were collected at the point of admission for PCI between 04.01.2016 and 31.12.2019. Collected data distributions were analysed by CVD behavioural risk factors for prevalence, associations, and direction of associations. Cluster definition was measured by assignment of a unit score each for the overall level of prevalence and significance of associations, and general logistics modelling for direction and significance of the risk. The mean (SD) age was 69.47(± 10.93) years [95% CI (68.99-69.94)]. The key risk factors were hyperlipidaemia, hypertension, and elevated body mass index (BMI). Approximately 40% of the population have multiple risk factor counts of two. Analytical measures revealed a population risk factor cluster with elevated BMI [77.5% (1570/2025)] that is mostly either hyperlipidaemic [9.43%, co-eff. (17), P = 0.007] or hypertensive [22.72%, co-eff. (17), P = 0.99] as key risk factor clusters. Carefully modelled analyses revealed clustered risk associated with elevated BMI. This information would support a strategy for targeting risk factor clusters in novel interventions to improve implementation efficiency. Exposure to and outcome of an elevated BMI is linked more to the population's socio-economic outcomes rather than to regional rurality or urbanity.