Lifelong physiology of a former marathon world-record holder - the pros and cons of extreme cardiac remodeling.

In a 77-year-old former world-record holding male marathoner (2:08:33.6) this study sought to investigate the impact of lifelong intensive endurance exercise on cardiac structure, function and the trajectory of functional capacity (determined by maximal oxygen consumption, V̇O2max) throughout the adult lifespan. As a competitive runner, our athlete (DC) reported performing up to 150-300 miles/wk of moderate-to-vigorous exercise, and sustained 10-15 hours/wk of endurance exercise after retirement from competition. DC underwent maximal cardiopulmonary exercise testing in 1970 (aged 27yrs), 1991 (aged 49yrs) and 2020 (aged 77yrs) to determine V̇O2max. At his evaluation in 2020, DC also underwent comprehensive cardiac assessments including resting echocardiography, and resting and exercise cardiac magnetic resonance to quantify cardiac structure and function at rest and during peak supine exercise. DC's V̇O2max showed minimal change from 27yrs (69.7mL/kg/min) to 49yrs (68.1mL/kg/min), although it eventually declined by 36% by the age of 77yrs (43.6mL/kg/min). DC's V̇O2max at 77yrs, was equivalent to the 50th percentile for healthy 20-29 year-old males and 2.4 times the requirement for maintaining functional independence. This was partly due to marked ventricular dilatation (left-ventricular end-diastolic volume: 273mLs), which facilitates a large peak supine exercise stroke volume (200mLs) and cardiac output (22.2L/min). However, at the age of 78 years, DC developed palpitations and fatigue, and was found to be in atrial fibrillation requiring ablation procedures to revert his heart to sinus rhythm. Overall, this life study of a world champion marathon runner exemplifies the substantial benefits and potential side effects of many decades of intense endurance exercise.

Determinants of Impaired Peak Oxygen Uptake in Breast Cancer Survivors: JACC: CardioOncology Primer.

•Exercise intolerance is common among breast cancer survivors.•Exercise intolerance in breast cancer survivors is related to cardiac, vascular, and skeletal muscle impairments.•Holistic rehabilitation or pharmacological therapies are needed to address these impairments.

Physiological determinants of decreased peak leg oxygen uptake in chronic disease: a systematic review and meta-analysis.

This systematic review and meta-analysis examined the physiological mechanisms responsible for lower peak exercise leg oxygen uptake (V̇o2) in patients with chronic disease. Studies measuring peak leg V̇o2 (primary outcome) and its physiological determinants during large (cycle) or small muscle mass exercise (single-leg knee extension, SLKE) in patients with chronic disease were included in this meta-analysis. Pooled estimates for each outcome were reported as a weighted mean difference (WMD) between chronic disease and controls. We included 10 studies that measured peak leg V̇o2 in patients with chronic disease (n = 109, mean age: 45 yr; encompassing chronic obstructive pulmonary disease, COPD, heart failure with reduced ejection fraction, HFrEF, or chronic renal failure, RF) and age-matched controls (n = 88). In pooled analysis, peak leg V̇o2 (WMD; -0.23 L/min, 95% CI: -0.32 to -0.13), leg oxygen (O2) delivery (WMD: -0.27 L/min, 95% CI: -0.37 to -0.17), and muscle O2 diffusive conductance (WMD: -5.2 mL/min/mmHg, 95% CI: -7.1 to -3.2) were all significantly lower during cycle and SLKE exercise in chronic disease versus controls. These results highlight that during large and small muscle mass exercise in patients with COPD, HFrEF, or RF, there is no single factor causing peak V̇o2 limitations. Specifically, the lower peak V̇o2 in these pathologies is due to not only the expected impairments in convective O2 delivery but also impairments in muscle oxygen diffusive transport from capillary to mitochondria. Whether impaired muscle O2 transport is caused solely by inactivity or additional muscle pathology remains in question.NEW & NOTEWORTHY Peripheral (skeletal muscle and vasculature) factors contribute significantly to reduced exercise capacity during both large and small muscle mass exercise in chronic diseases such as COPD, HFrEF, or RF and should be important targets of therapy in addition to the primary organs (lungs, heart, and kidneys) affected by disease.

A Review on the Role of Exercise Training to Prevent a Decline in Cardiorespiratory Fitness and Cardiac Function in Breast Cancer Survivors.

PURPOSE: Improvements in diagnosis and treatment mean that the long-term health of breast cancer survivors (BCS) is increasingly dictated by cardiovascular comorbidities. This is partly a consequence of exposure to cardiotoxic therapies, which result in cardiac dysfunction and decreased cardiorespiratory fitness (CRF). Exercise training (ExT) is a key therapeutic strategy for secondary prevention and increasing CRF in adults with established cardiovascular disease. Exercise-based cardio-oncology rehabilitation (CORE) has been proposed as an emerging strategy to address CRF and cardiac impairment in BCS. This review aims to (1) provide an overview of the impact of breast cancer therapy on CRF; (2) provide an up-to-date summary of the effects of ExT on CRF and cardiac function in BCS undergoing cardiotoxic therapy; and (3) discuss how traditional ExT approaches can be adapted for BCS undergoing therapy. REVIEW METHODS: A literature review was performed based on an intensive literature search for systematic reviews and meta-analyses, randomized and non-randomized controlled trials and single-arm trials investigating the impact of exercise training or cardiac rehabilitation on CRF and/or cardiac function in BCS who are undergoing or have completed cardiotoxic cancer therapy. SUMMARY: Overall, current evidence suggests that ExT induces clinically meaningful benefits for CRF in BCS during and after therapy. There is also emerging evidence that ExT can improve peak exercise measures of cardiac function; however, there is a need for further research to understand how to adapt these effective ExT approaches into clinical CORE-based settings.

Cardio-oncology and Cancer Rehabilitation: Is an Integrated Approach Possible?

With significant improvements in the understanding of cancer biology, improved detection, and the use of novel adjuvant therapies, each year more Canadians are surviving a cancer diagnosis. Despite their effectiveness these therapies often result in short- and long-term deleterious effects to major organ systems, particularly cardiovascular. Cardio-oncology is an emerging field of study with the aim to improve cardiovascular health across the oncology disease spectrum. International guidelines distinguish "cardio-oncology" rehabilitation from "cancer" rehabilitation, but how this is navigated is currently unknown. How such care should be assessed and integrated acutely or in the longer term remains unknown. Accordingly, the aim of this article is to consider the cancer patient's needs beyond the scope of cardio-oncology rehabilitation to holistically integrate cancer rehabilitation across the disease trajectory.

Understanding Exercise Capacity: From Elite Athlete to HFpEF.

Exercise capacity is a spectrum that reflects an individual's functional capacity and the dynamic nature of cardiac remodelling along with respiratory and skeletal muscle systems. The relationship of increasing physical activity, increased cardiac mass and volumes, and improved cardiorespiratory fitness (CRF) is well established in the endurance athlete. However, less emphasis has been placed on the other end of the spectrum, which includes individuals with a more sedentary lifestyle and small hearts who are at increased risk of functional disability and poor clinical outcomes. Reduced CRF is an independent predictor of all-cause mortality and cardiovascular events determined by multiple inter-related exogenous and endogenous factors. In this review, we explore the relationship of physical activity, cardiac remodelling, and CRF across the exercise spectrum, emphasising the critical role of cardiac size in determining exercise capacity. In contrast to the large compliant left ventricle of the endurance athlete, an individual with a lifetime of physical inactivity is likely to have a small, stiff heart with reduced cardiac reserve. We propose that this might contribute to the development of heart failure with preserved ejection fraction in certain individuals, and is key to understanding the link between low CRF and increased risk of heart failure.

Effect of Exercise Training on Peak Aerobic Power After Heart Transplantation: A Brief Review.

Heart transplantation (HTP) is a life-saving therapy for selected individuals with end-stage refractory heart failure. Despite improvements in quality of life and survival, HTP recipients' peak aerobic power (peak VO2) remains up to 50% lower than age-matched healthy control subjects owing to abnormal cardiovascular and skeletal muscle function. Currently, little is known regarding the effect of exercise training (ET) to improve peak VO2 after HTP. This brief review aims to summarise existing evidence regarding the role of ET on peak VO2 and its determinants, highlights the upper limits of endurance performance in highly trained HTP athletes, and identifies areas for future HTP exercise rehabilitation research.

Cardiovascular responses to static handgrip exercise and postexercise ischemia in heart failure with preserved ejection fraction.

Heart failure with preserved ejection fraction (HFpEF) is characterized by reduced ability to sustain physical activity that may be due partly to disease-related changes in autonomic function that contribute to dysregulated cardiovascular control during muscular contraction. Thus, we used a combination of static handgrip exercise (HG) and postexercise ischemia (PEI) to examine the pressor response to exercise and isolate the skeletal muscle metaboreflex, respectively. Mean arterial pressure (MAP), heart rate (HR), cardiac output (CO), and total peripheral resistance (TPR) were assessed during 2-min of static HG at 30 and 40% of maximum voluntary contraction (MVC) and subsequent PEI in 16 patients with HFpEF and 17 healthy, similarly aged controls. Changes in MAP were lower in patients with HFpEF compared with controls during both 30%MVC (Δ11 ± 7 vs. Δ15 ± 8 mmHg) and 40%MVC (Δ19 ± 14 vs. Δ30 ± 8 mmHg), and a similar pattern of response was evident during PEI (30%MVC: Δ8 ± 5 vs. Δ12 ± 8 mmHg; 40%MVC: Δ13 ± 10 vs. Δ18 ± 9 mmHg) (group effect: P = 0.078 and P = 0.017 at 30% and 40% MVC, respectively). Changes in HR, CO, and TPR did not differ between groups during HG or PEI (P > 0.05). Taken together, these data suggest a reduced pressor response to static muscle contractions in patients with HFpEF compared with similarly aged controls that may be mediated partly by a blunted muscle metaboreflex. These findings support a disease-related dysregulation in neural cardiovascular control that may reduce an ability to sustain physical activity in HFpEF.NEW & NOTEWORTHY The current investigation has identified a diminution in the exercise-induced rise in arterial blood pressure (BP) that persisted during postexercise ischemia (PEI) in an intensity-dependent manner in patients with heart failure with preserved ejection fraction (HFpEF) compared with older, healthy controls. These findings suggest that the pressor response to exercise is reduced in patients with HFpEF, and this deficit may be mediated, in part, by a blunted muscle metaboreflex, highlighting the consequences of impaired neural cardiovascular control during exercise in this patient group.

Phase angle is associated with muscle health and cardiorespiratory fitness in older breast cancer survivors.

BACKGROUND & AIM: Phase angle (PhA) obtained from bioelectrical impedance analysis (BIA) is an indicator of cellular integrity and relates to several chronic conditions. The purpose of this secondary analysis was to evaluate the association of PhA with health-related physical fitness, namely, cardiorespiratory fitness, skeletal muscle volume, and myosteatosis (i.e. muscle health) in older breast cancer survivors. METHODS: Twenty-two women ≥60 years with a body mass index (BMI) ≥25 kg/m2 and who completed chemotherapy for early-stage breast cancer were included. BIA, cardiopulmonary exercise tests and magnetic resonance imaging scans were completed before and after eight weeks of time-restricted eating. RESULTS: At baseline, PhA was associated with cardiorespiratory fitness (R2 = 0.54, p < 0.01) and skeletal muscle volume (R2 = 0.83, p < 0.01) and myosteatosis (R2 = 0.25, p = 0.02). Results were similar at follow-up. CONCLUSION: Findings from this pilot study suggest that higher values of PhA are associated with better health-related physical fitness among older breast cancer survivors.

Time-Restricted Eating in Breast Cancer Survivors: Effects on Body Composition and Nutritional Status.

In this secondary analysis of an 8-wk single-arm feasibility study of weekday time-restricted eating (TRE), we explored the effects of TRE on body composition. Women (n = 22; ≥60 yr) who had completed chemotherapy for early-stage breast cancer and had a body mass index ≥25 kg/m2 were enrolled. Bioelectrical impedance analysis was performed before and after 8 wk of TRE, and nutritional status was evaluated by bioelectrical impedance vector analysis (BIVA). Body weight (p = 0.01) and total fat mass (p = 0.04) decreased with TRE. Phase angle was low (defined as ≤5.6°) in 86% of participants at baseline and did not change. Four participants who initially presented with obesity (>95% ellipse, BIVA) had favorable body composition modifications after TRE. Our study highlighted a less favorable body composition profile, poorer cell integrity and overhydration in these patients. BIVA was a useful method to assess body composition and hydration. A short TRE intervention was associated with decreased estimated fat mass and a favorable change in nutritional status in those with obesity.

Too Little of a Good Thing: Strong Associations Between Cardiac Size and Fitness Among Women.

BACKGROUND: Cardiorespiratory fitness (CRF) is associated with functional impairment and cardiac events, particularly heart failure (HF). However, the factors predisposing women to low CRF and HF remain unclear. OBJECTIVES: This study sought to evaluate the association between CRF and measures of ventricular size and function and to examine the potential mechanism linking these factors. METHODS: A total of 185 healthy women aged >30 years (51 ± 9 years) underwent assessment of CRF (peak volume of oxygen uptake [Vo2peak]) and biventricular volumes at rest and during exercise by using cardiac magnetic resonance (CMR). The relationships among Vo2peak, cardiac volumes, and echocardiographic measures of systolic and diastolic function were assessed using linear regression. The effect of cardiac size on cardiac reserve (change in cardiac function during exercise) was assessed by comparing quartiles of resting left ventricular end-diastolic volume (LVEDV). RESULTS: Vo2peak was strongly associated with resting measures of LVEDV and right ventricular end-diastolic volume (R2 = 0.58-0.63; P < 0.0001), but weakly associated with measures of resting left ventricular (LV) systolic and diastolic function (R2 = 0.01-0.06; P < 0.05). Increasing LVEDV quartiles were positively associated with cardiac reserve, with the smallest quartile showing the smallest reduction in LV end-systolic volume (quartile [Q]1: -4 mL vs Q4: -12 mL), smallest augmentation in LV stroke volume (Q1: +11 mL vs Q4: +20 mL) and cardiac output (Q1: +6.6 L/min vs Q4: +10.3 L/min) during exercise (interaction P < 0.001 for all). CONCLUSIONS: A small ventricle is strongly associated with low CRF because of the combined effect of a smaller resting stroke volume and an attenuated capacity to increase with exercise. The prognostic implications of low CRF in midlife highlight the need for further longitudinal studies to determine whether women with small ventricles are predisposed to functional impairment, exertional intolerance, and HF later in life.

Myocardial steatosis impairs left ventricular diastolic-systolic coupling in healthy humans.

Mounting evidence suggests that myocardial steatosis contributes to left ventricular diastolic dysfunction, but definitive evidence in humans is lacking due to confounding comorbidities. As such, we utilized a 48-h food restriction model to acutely increase myocardial triglyceride (mTG) content - measured by 1 H magnetic resonance spectroscopy - in 27 young healthy volunteers (13 men/14 women). Forty-eight hours of fasting caused a more than 3-fold increase in mTG content (P < 0.001). Diastolic function - defined as early diastolic circumferential strain rate (CSRd) - was unchanged following the 48-h fasting intervention, but systolic circumferential strain rate was elevated (P < 0.001), indicative of systolic-diastolic uncoupling. Indeed, in a separate control experiment in 10 individuals, administration of low-dose dobutamine (2 µg/kg/min) caused a similar change in systolic circumferential strain rate as was found during 48 h of food restriction, along with a proportionate increase in CSRd, such that the two metrics remained coupled. Taken together, these data indicate that myocardial steatosis contributes to diastolic dysfunction by impairing diastolic-systolic coupling in healthy adults, and suggest that steatosis may contribute to the progression of heart disease. KEY POINTS: Preclinical evidence strongly suggests that myocardial lipid accumulation (termed steatosis) is an important mechanism driving heart disease. Definitive evidence in humans is limited due to the confounding influence of multiple underlying comorbidities. Using a 48-h food restriction model to acutely increase myocardial triglyceride content in young healthy volunteers, we demonstrate an association between myocardial steatosis and left ventricular diastolic dysfunction. These data advance the hypothesis that myocardial steatosis may contribute to diastolic dysfunction and suggest myocardial steatosis as a putative therapeutic target.

Effect of Training on Vascular Function and Repair in Heart Failure With Preserved Ejection Fraction.

BACKGROUND: Exercise training improves peak oxygen uptake (V.O2peak) in heart failure with preserved ejection fraction (HFpEF). Multiple adaptations have been addressed, but the role of circulating endothelium-repairing cells and vascular function have not been well defined. OBJECTIVES: The authors investigated effects of moderate-intensity continuous training (MICT) and high-intensity interval training (HIIT) on vascular function and repair in HFpEF. METHODS: This study is a subanalysis of the OptimEx-Clin (Optimizing Exercise Training in Prevention and Treatment of Diastolic Heart Failure) study randomizing patients with HFpEF (n = 180) to HIIT, MICT, or guideline control. At baseline, 3, and 12 months, the authors measured peripheral arterial tonometry (valid baseline measurement in n = 109), flow-mediated dilation (n = 59), augmentation index (n = 94), and flow cytometry (n = 136) for endothelial progenitor cells and angiogenic T cells. Abnormal values were defined as outside 90% of published sex-specific reference values. RESULTS: At baseline, abnormal values (%) were observed for augmentation index in 66%, peripheral arterial tonometry in 17%, flow-mediated dilation in 25%, endothelial progenitor cells in 42%, and angiogenic T cells in 18%. These parameters did not change significantly after 3 or 12 months of HIIT or MICT. Results remained unchanged when confining analysis to patients with high adherence to training. CONCLUSIONS: In patients with HFpEF, high augmentation index was common, but endothelial function and levels of endothelium-repairing cells were normal in most patients. Aerobic exercise training did not change vascular function or cellular endothelial repair. Improved vascular function did not significantly contribute to the V.O2peak improvement after different training intensities in HFpEF, contrary to previous studies in heart failure with reduced ejection fraction and coronary artery disease. (Optimizing Exercise Training in Prevention and Treatment of Diastolic Heart Failure [OptimEx-Clin]; NCT02078947).

High-intensity interval training in cardiac rehabilitation: a multi-centre randomized controlled trial.

BACKGROUND: There is a lack of international consensus regarding the prescription of high-intensity interval training (HIIT) for people with coronary artery disease (CAD) attending cardiac rehabilitation (CR). AIMS: To assess the clinical effectiveness and safety of low-volume HIIT compared with moderate-intensity steady-state (MISS) exercise training for people with CAD. METHODS AND RESULTS: We conducted a multi-centre RCT, recruiting 382 patients from 6 outpatient CR centres. Participants were randomized to twice-weekly HIIT (n = 187) or MISS (n = 195) for 8 weeks. HIIT consisted of 10 × 1 min intervals of vigorous exercise (>85% maximum capacity) interspersed with 1 min periods of recovery. MISS was 20-40 min of moderate-intensity continuous exercise (60-80% maximum capacity). The primary outcome was the change in cardiorespiratory fitness [peak oxygen uptake (VO2 peak)] at 8 week follow-up. Secondary outcomes included cardiovascular disease risk markers, cardiac structure and function, adverse events, and health-related quality of life. At 8 weeks, VO2peak improved more with HIIT (2.37 mL.kg-1.min-1; SD, 3.11) compared with MISS (1.32 mL.kg-1.min-1; SD, 2.66). After adjusting for age, sex, and study site, the difference between arms was 1.04 mL.kg-1.min-1 (95% CI, 0.38 to 1.69; P = 0.002). Only one serious adverse event was possibly related to HIIT. CONCLUSIONS: In stable CAD, low-volume HIIT improved cardiorespiratory fitness more than MISS by a clinically meaningful margin. Low-volume HIIT is a safe, well-tolerated, and clinically effective intervention that produces short-term improvement in cardiorespiratory fitness. It should be considered by all CR programmes as an adjunct or alternative to MISS. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02784873. https://clinicaltrials.gov/ct2/show/NCT02784873.

Cardiac rehabilitation exercise training can improve cardiorespiratory fitness and quality of life for people with coronary artery disease, but sometimes, it is not effective. The intensity of the exercise training may be important. We conducted a randomized controlled trial to test if moderate-intensity exercise or high-intensity exercise was better.High-intensity interval training was more effective than moderate-intensity exercise training for improving cardiorespiratory fitness in people with coronary artery disease attending cardiac rehabilitation.High-intensity interval training was safe and well tolerated.

Implementation of weekday time-restricted eating to improve metabolic health in breast cancer survivors with overweight/obesity.

OBJECTIVE: This study aimed to evaluate the implementation of telephone-based delivery of weekday-only time-restricted eating (TRE), its preliminary efficacy for metabolic outcomes, and concurrent lifestyle changes. METHODS: Twenty-two breast cancer survivors aged 60+ years with overweight/obesity completed an 8-week feasibility study of 12 to 8 p.m. weekday-only ad libitum TRE. The intervention was delivered by one registered dietitian call, twice-daily automated text messages asking about eating start and stop times, and three support phone calls. Magnetic resonance imaging, venipuncture, and 3 days of diet records and accelerometry were performed at baseline and after intervention. RESULTS: Participants had a mean age of 66 (SD 5) years with BMI of 31.8 (4.8) kg/m2 . Intervention implementation was successful, including excellent adherence (98%), participant acceptability, and a low symptom profile and cost ($63/participant). There were no significant changes in individual components of metabolic syndrome, lipid profile, or hemoglobin A1c , despite clinically relevant changes occurring within individual participants. Magnetic resonance imaging-derived hepatic steatosis and thigh myosteatosis did not change. Dietary intake changes included reduced energy (-22%) and protein (-0.2 g/kg). Physical activity and sleep did not change. CONCLUSIONS: Eight weeks of telephone-delivered weekday TRE is a feasible, acceptable, low-symptom, and low-cost intervention. Future studies may consider a longer intervention length for more consistent metabolic improvements and counseling to enhance protein intake.

Rationale and design of IMPACT-women: a randomised controlled trial of the effect of time-restricted eating, healthy eating and reduced sedentary behaviour on metabolic health during chemotherapy for early-stage breast cancer.

Metabolic dysfunction and excess accumulation of adipose tissue are detrimental side effects from breast cancer treatment. Diet and physical activity are important treatments for metabolic abnormalities, yet patient compliance can be challenging during chemotherapy treatment. Time-restricted eating (TRE) is a feasible dietary pattern where eating is restricted to 8 h/d with water-only fasting for the remaining 16 h. The purpose of this study is to evaluate the effect of a multimodal intervention consisting of TRE, healthy eating, and reduced sedentary time during chemotherapy treatment for early-stage (I-III) breast cancer on accumulation of visceral fat (primary outcome), other fat deposition locations, metabolic syndrome and cardiovascular disease risk (secondary outcomes) compared with usual care. The study will be a two-site, two-arm, parallel-group superiority randomised control trial enrolling 130 women scheduled for chemotherapy for early-stage breast cancer. The intervention will be delivered by telephone, including 30-60-minute calls with a registered dietitian who will provide instructions on TRE, education and counselling on healthy eating, and goal setting for reducing sedentary time. The comparison group will receive usual cancer and supportive care including a single group-based nutrition class and healthy eating and physical activity guidelines. MRI, blood draws and assessment of blood pressure will be performed at baseline, after chemotherapy (primary end point), and 2-year follow-up. If our intervention is successful in attenuating the effect of chemotherapy on visceral fat accumulation and cardiometabolic dysfunction, it has the potential to reduce risk of cardiometabolic disease and related mortality among breast cancer survivors.

Exercise Leg Blood Flow Is Preserved in Long-term Breast Cancer Survivors Previously Treated With Anthracycline Chemotherapy.

PURPOSE: The objective of this investigation was to compare the acute hemodynamic responses during single-leg knee extension (SLKE) exercise between female breast cancer (BC) survivors previously treated with anthracycline chemotherapy and age- and sex-matched control (CON) subjects. METHODS: Fourteen BC survivors (age: 61 ± 7 yr; time post-anthracycline therapy: 12 ± 6 yr) and nine CON subjects (age: 59 ± 7 yr) performed SLKE exercise at 25%, 50%, and 75% of peak power output during which heart rate, blood pressure (BP), leg blood flow (Doppler ultrasonography), and vascular conductance (leg blood flow/mean BP) were measured. Quadriceps mass was estimated from thigh volume and skinfold measures. RESULTS: Breast cancer survivors had lower quadriceps mass compared with CON subjects (1803 ± 607 vs 2601 ± 1102 g, P = .04). No difference was found between groups for maximal SLKE power output (28 ± 11 vs 34 ± 17 W, P = .35), heart rate (109 ± 14 vs 103 ± 13 bpm, P = .36), or mean arterial BP (122 ± 18 vs 119 ± 26 mm Hg, P = .33). Rest and submaximal exercise mean arterial BP, leg blood flow (indexed to quadriceps muscle mass), and leg vascular conductance were not significantly different between BC survivors and CON subjects. CONCLUSION: Leg blood flow during submaximal SLKE exercise is preserved in long-term BC survivors previously treated with anthracycline chemotherapy.