Characterizing the influence of cardiorespiratory fitness on left atrial size and function in the general population.

Increased left atrial (LA) size and reduced LA function have been associated with heart failure and atrial fibrillation (AF) in at-risk populations. However, atrial remodeling has also been associated with exercise training and the relationship between fitness, LA size, and function has not been defined across the fitness spectrum. In a cross-sectional study of 559 ostensibly healthy participants, comprising 304 males (mean age, 46 ± 20 yr) and 255 females (mean age, 47 ± 15 yr), we sought to define the relationship between cardiorespiratory fitness (CRF), LA size, and function. We also aimed to interrogate sex differences in atrial factors influencing CRF. Echocardiographic measures included biplane measures of LA volumes indexed to body surface area (LAVi) and atrial deformation using two-dimensional speckle tracking. CRF was measured as peak oxygen consumption (V̇o2peak) during cardiopulmonary exercise testing (CPET). Using multivariable regression, age, sex, weight, and LAVi (P < 0.001 for all) predicted V̇o2peak (P < 0.001, R2 = 0.66 for combined model). After accounting for these variables, heart rate reserve added strength to the model (P < 0.001, R2 = 0.74) but LA strain parameters did not predict V̇o2peak. These findings add important nuance to the perception that LA size is a marker of cardiac pathology. LA size should be considered in the context of fitness, and it is likely that the adverse prognostic associations of increased LA size may be confined to those with LA enlargement and low fitness.NEW & NOTEWORTHY Left atrial (LA) structure better predicts cardiorespiratory fitness (CRF) than LA function. LA function adds little statistical value to predictive models of peak oxygen uptake (V̇o2peak) in healthy individuals, suggesting limited discriminatory for CRF once LA size is factored. In the wider population of ostensibly healthy individuals, the association between increased LA volume and higher CRF provides an important counter to the association between atrial enlargement and heart failure symptoms in those with cardiac pathology.

Prescribing Exercise in Early-Stage Breast Cancer During Chemotherapy: A Simple Periodized Approach to Align With the Cyclic Phases of Chemotherapy.

ABSTRACT: Bigaran, A, Howden, EJ, Foulkes, S, Janssens, K, Beaudry, R, Haykowsky, MJ, La Gerche, A, Fraser, SF, and Selig, SE. Prescribing exercise in early-stage breast cancer during chemotherapy: a simple periodized approach to align with the cyclic phases of chemotherapy. J Strength Cond Res 36(10): 2934-2941, 2022-To evaluate whether a periodized aerobic and resistance training plan aligned to the anthracycline chemotherapy (AC) cycles would be well tolerated, feasible, and attenuate the decline in peak oxygen uptake (V̇o2peak) in breast cancer (BC) patients. Twenty-eight women with early-stage BC treated with AC self-selected to undertake exercise training (EX 47 ± 9 years, n = 14) or usual care (53 ± 9 years, n = 14) for 12 weeks as part of a nonrandomized controlled trial. The periodized EX was aligned to the cyclic phases of AC, including AC taper and nontaper weeks. Outcome measures included cardiopulmonary exercise testing. Attendance and adherence variables (relative dose intensity [RDI] and volume load) were calculated to quantify the dose of EX completed relative to the amount of EX prescribed. The mean session attendance was 76% (range 46-88%). The mean ± SD prescribed and completed dose of aerobic training was 332.3 ± 48.7 MET h·wk-1 and 380.6 ± 53.2 MET h·wk-1 (p = 0.02), equating to a mean RDI of 89 ± 17%. For resistance training, the prescribed and completed cumulative dose was 128,264 ± 54,578 and 77,487 ± 26,108 kg (p < 0.001), equating to an RDI of 60 ± 11%. Adherence to the AC taper week RDI (52 ± 14%) for resistance training was significantly lower than the non-AC taper week (72 ± 8%, p = 0.02). The most frequent cause for EX interruption was hospitalization (35%), whereas AC-related illness was the most common cause for missed (57%) or modified EX sessions (64%). This periodized approach was mostly well tolerated for patients with BC. We speculate that a periodized approach may be both more palatable and useful, although this requires further investigation in a randomized controlled trial.

Increased vascular stiffness in children exposed in utero but not children exposed postnatally to emissions from a coal mine fire.

Background: Chronic, low-intensity air pollution exposure has been consistently associated with increased atherosclerosis in adults. However, there was limited research regarding the implications of acute, high-intensity air pollution exposure during childhood. We aimed to determine whether there were any associations between early-life exposure to such an episode and early-life vascular function changes. Methods: We conducted a prospective cohort study of children (<9 years old) who lived in the vicinity of the Hazelwood coal mine fire (n = 206). Vascular function was measured using noninvasive diagnostic methods including carotid intima-media thickness and pulse wave velocity (PWV). Exposure estimates were calculated from prognostic models and location diaries during the exposure period completed by each participant's parent. Linear mixed-effects models were used to determine whether there were any associations between exposure and changes in vascular outcomes at the 3- and 7-year follow-ups and over time. Results: At the 7-year follow-up, each 10 µg/m3 increase in daily PM2.5 in utero was associated with increased PWV (ß = 0.13 m/s; 95% confidence interval [CI] = 0.02, 0.24; P = 0.02). The association between in utero exposure to daily PM2.5 was not altered by adjustment for covariates, body mass index, and maternal fire stress. Each 1 µg/m3 increase in background PM2.5 was associated with increased PWV (ß = 0.68 m/s; 95% CI = 0.10, 1.26; P = 0.025), in children from the in utero exposure group. There was a trend toward smaller PWV (ß = -0.17 m/s; 95% CI = -0.366, 0.02) from the 3- to 7-year follow-up clinic suggesting that the deficits observed previously in children exposed postnatally did not persist. Conclusion: There was a moderate improvement in vascular stiffness of children exposed to PM2.5 from a local coal mine fire in infancy. There was a mild increase in vascular stiffness in children exposed to PM2.5 from a local coal mine fire while their mothers were pregnant.

Traditional markers of cardiac toxicity fail to detect marked reductions in cardiorespiratory fitness among cancer patients undergoing anti-cancer treatment.

AIMS: Left ventricular ejection fraction (LVEF) is standard of care for evaluating chemotherapy-associated cardiotoxicity, although global longitudinal strain (GLS) offers advantages. However, neither change in LVEF or GLS has been associated with short-term symptoms, functional capacity, or long-term heart failure (HF) risk. We sought to determine whether an integrative measure of cardiovascular function (VO2peak) that is strongly associated with HF risk would be more sensitive to cardiac damage induced by cancer treatment than LVEF, GLS, or cardiac biomarkers. METHODS AND RESULTS: Patients (n = 206, 53 ± 13 years, 35% male) scheduled to commence anti-cancer treatment completed assessment prior to, and within 6 months after therapy. Changes in echocardiographic measures of LV function (LVEF, GLS), cardiac biomarkers (troponin and BNP), and cardiorespiratory fitness (VO2peak) were measured. LV function was normal prior to treatment (LVEF 61 ± 5%; GLS -19.4 ± 2.1), but VO2peak was only 88 ± 26% of age-predicted. After treatment, VO2peak was reduced by 7 ± 15% (equivalent of 7 years normal ageing, P < 0.0001) and the rates of functional disability (defined as VO2peak ≤ 18 mL/min/kg) almost doubled (15% vs. 26%, P = 0.016). In contrast, small, reductions in LVEF (59 ± 5% vs. 58 ± 5%, P = 0.03) and GLS (-19.4 ± 2.1 vs. -18.9 ± 2.2, P = 0.002) and an increase in troponin levels (4.0 ± 6.9 vs. 26.4 ± 26.2 ng/mL, P < 0.0001) were observed. CONCLUSION: Anti-cancer treatment is associated with marked reductions in functional capacity that occur independent of reductions in LVEF and GLS. The assessment of VO2peak prior to, and following treatment may be a more sensitive means of identifying patients at increased risk of HF.

The effect of exercise training on cardiometabolic health in men with prostate cancer receiving androgen deprivation therapy: a systematic review and meta-analysis.

BACKGROUND: Growing evidence suggests that men exposed to androgen deprivation therapy (ADT) have an increased risk of cardiovascular disease. While exercise has shown to attenuate some adverse effects of ADT, the effects on cardiometabolic health have not been systematically evaluated. OBJECTIVE: To evaluate the effect of exercise on cardiometabolic health in men with prostate cancer (PCa) receiving ADT. METHODS: A systematic literature search of MEDLINE, EMBASE, CINHAL, SCOPUS, WEB OF SCIENCE and SPORTSDICUS from database inception to April 2020 was performed. A quantitative synthesis using Cohens d effect size and a meta-analysis using random-effects models were conducted. RESULTS: Overall, fourteen randomised controlled trials (RCTs) and four non-randomised studies were included. Eleven RCTs (n = 939 patients) were included in the meta-analysis. Exercise training improved the 400-m-walk test (MD -10.11 s, 95% CI [-14.34, -5.88]; p < 0·00001), diastolic blood pressure (-2.22 mmHg, [-3.82, -0.61]; p = 0.007), fasting blood glucose (-0.38 mmol/L, [-0.65, -0.11]; p = 0.006), C-reactive protein (-1.16 mg/L, [-2.11, -0.20]; p = 0.02), whole-body lean mass (0.70 kg, [0.39, 1.01]; p < 0.0001), appendicular lean mass (0.59 kg, [0.43, 0.76]; p < 0.00001), whole-body fat mass (-0.67 kg, [-1.08, -0.27]; p = 0.001), whole-body fat percentage (-0.79%, [-1.16, -0.42]; p < 0.0001), and trunk fat mass (-0.49 kg, [-0.87, -0.12]; p = 0.01), compared to usual care. No significant effects on systolic blood pressure or blood lipid metabolism were detected. CONCLUSIONS: In a small subset of evaluated studies, exercise may favourably improve some but not all markers of cardiometabolic health. Future exercise intervention trials with cardiometabolic outcomes as primary endpoints are needed to confirm these initial findings.

Determinants of exercise intolerance in breast cancer patients prior to anthracycline chemotherapy.

Women with early-stage breast cancer have reduced peak exercise oxygen uptake (peak VO2 ). The purpose of this study was to evaluate peak VO2 and right (RV) and left (LV) ventricular function prior to adjuvant chemotherapy. Twenty-nine early-stage breast cancer patients (mean age: 48 years) and 10 age-matched healthy women were studied. Participants performed an upright cycle exercise test with expired gas analysis to measure peak VO2 . RV and LV volumes and function were measured at rest, submaximal and peak supine cycle exercise using cardiac magnetic resonance imaging. Peak VO2 was significantly lower in breast cancer patients versus controls (1.7 ± 0.4 vs. 2.3 ± 0.5 L/min, P = 0.0013; 25 ± 6 vs. 35 ± 6 mL/kg/min, P = 0.00009). No significant difference was found between groups for peak upright exercise heart rate (174 ± 13 vs. 169 ± 16 bpm, P = 0.39). Rest, submaximal and peak exercise RV and LV end-diastolic and end-systolic volume index, stroke index, and cardiac index were significantly lower in breast cancer patients versus controls (P < 0.05 for all). No significant difference was found between groups for rest and exercise RV and LV ejection fraction. Despite preserved RV and LV ejection fraction, the decreased peak VO2 in early-stage breast cancer patients prior to adjuvant chemotherapy is due in part to decreased peak cardiac index secondary to reductions in RV and LV end-diastolic volumes.

Persistent Impairment in Cardiopulmonary Fitness after Breast Cancer Chemotherapy.

PURPOSE: Anthracycline chemotherapy (AC) is associated with acute reductions in cardiopulmonary fitness (V˙O2peak). We sought to determine whether changes in V˙O2peak and cardiac function persisted at 12 months post-AC completion, and whether changes in cardiac function explain the heightened long-term heart failure risk. METHODS: Women with breast cancer scheduled for AC (n = 28) who participated in a nonrandomized trial of exercise training (ET; n = 14) or usual care (UC; n = 14) during AC completed a follow-up evaluation 12 months post-AC completion (16 months from baseline). At baseline, 4 months, and 16 months, participants underwent a resting echocardiogram (left ventricular ejection fraction; global longitudinal strain), a blood sample (troponin; B-type natriuretic peptide), a cardiopulmonary exercise test, and cardiac MRI measures of stroke volume (SV), heart rate, and cardiac output (Qc) at rest and during intense exercise. RESULTS: Seventeen women (UC, n = 8; ET, n = 9) completed evaluation at baseline, 4 months, and 16 months. At 4 months, AC was associated with 18% and 6% reductions in V˙O2peak in the UC and ET groups, respectively, which persisted at 16 months (UC, -16%; ET, -7%) and was not attenuated by ET (interaction, P = 0.10). Exercise Qc was lower at 16 months compared with baseline and 4 months (P < 0.001), which was due to a blunted augmentation of SV during exercise (P = 0.032; a 14% reduction in peak SV), with no changes in heart rate response. There was a small reduction in resting left ventricular ejection fraction (baseline to 4 months) and global longitudinal strain (between 4 and 16 months) and an increase in troponin (baseline to 4 months), but only exercise Qc was associated with V˙O2peak (R = 0.47, P < 0.01). CONCLUSION: Marked reductions in V˙O2peak persisted 12 months after anthracycline-based chemotherapy, which was associated with impaired exercise cardiac function. CLINICAL TRIAL REGISTRATION: ACTRN12616001602415.

Exercise as a diagnostic and therapeutic tool for the prevention of cardiovascular dysfunction in breast cancer patients.

BACKGROUND: Anthracycline chemotherapy may be associated with decreased cardiac function and functional capacity measured as the peak oxygen uptake during exercise ( V·O2 peak). We sought to determine (a) whether a structured exercise training program would attenuate reductions in V·O2 peak and (b) whether exercise cardiac imaging is a more sensitive marker of cardiac injury than the current standard of care resting left ventricular ejection fraction (LVEF). METHODS: Twenty-eight patients with early stage breast cancer undergoing anthracycline chemotherapy were able to choose between exercise training (mean ± SD age 47 ± 9 years, n = 14) or usual care (mean ± SD age 53 ± 9 years, n = 14). Measurements performed before and after anthracycline chemotherapy included cardiopulmonary exercise testing to determine V·O2 peak and functional disability ( V·O2 peak < 18 ml/min/kg), resting echocardiography (LVEF and global longitudinal strain), cardiac biomarkers (troponin and B-type natriuretic peptide) and exercise cardiac magnetic resonance imaging to determine stroke volume and peak cardiac output. The exercise training group completed 2 × 60 minute supervised exercise sessions per week. RESULTS: Decreases in V·O2 peak during chemotherapy were attenuated with exercise training (15 vs. 4% reduction, P = 0.010) and fewer participants in the exercise training group met the functional disability criteria after anthracycline chemotherapy compared with those in the usual care group (7 vs. 50%, P = 0.01). Compared with the baseline, the peak exercise heart rate was higher and the stroke volume was lower after chemotherapy ( P = 0.003 and P = 0.06, respectively). There was a reduction in resting LVEF (from 63 ± 5 to 60 ± 5%, P = 0.002) and an increase in troponin (from 2.9 ± 1.3 to 28.5 ± 22.4 ng/mL, P < 0.0001), but no difference was observed between the usual care and exercise training group. The baseline peak cardiac output was the strongest predictor of functional capacity after anthracycline chemotherapy in a model containing age and resting cardiac function (LVEF and global longitudinal strain). CONCLUSIONS: The peak exercise cardiac output can identify patients at risk of chemotherapy-induced functional disability, whereas current clinical standards are unhelpful. Functional disability can be prevented with exercise training.