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.

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.

Effects of aging and endurance exercise training on cardiorespiratory fitness and cardiac structure and function in healthy midlife and older women.

Cardiovascular disease (CVD) remains the leading cause of morbidity and mortality in women in developed societies. Unfavorable structural and functional adaptations within the heart and central blood vessels with sedentary aging in women can act as the substrate for the development of debilitating CVD conditions such as heart failure with preserved ejection fraction (HFpEF). The large decline in cardiorespiratory fitness, as indicated by maximal or peak oxygen uptake (V̇o2max and V̇o2peak, respectively), that occurs in women as they age significantly affects their health and chronic disease status, as well as the risk of cardiovascular and all-cause mortality. Midlife and older women who have performed structured endurance exercise training for several years or decades of their adult lives exhibit a V̇o2max and cardiac and vascular structure and function that are on par or even superior to much younger sedentary women. Therefore, regular endurance exercise training appears to be an effective preventative strategy for mitigating the adverse physiological cardiovascular adaptations associated with sedentary aging in women. Herein, we narratively describe the aging and short- and long-term endurance exercise training adaptations in V̇o2max, cardiac structure, and left ventricular systolic and diastolic function at rest and exercise in midlife and older women. The role of circulating estrogens on cardiac structure and function is described for consideration in the timing of exercise interventions to maximize beneficial adaptations. Current research gaps and potential areas for future investigation to advance our understanding in this critical knowledge area are highlighted.

Associations between symptoms and functional capacity in patients after COVID-19 infection and community controls.

BACKGROUND: Post-acute sequelae of COVID-19 (PASC or 'long COVID') reflect ongoing symptoms, but these are non-specific and common in the wider community. Few reports of PASC have been compared with a control group. AIMS: To compare symptoms and objective impairment of functional capacity in patients with previous COVID-19 infection with uninfected community controls. METHODS: In this community-based, cross-sectional study of functional capacity, 562 patients from Western Melbourne who had recovered from COVID-19 infections in 2021 and 2022 were compared with controls from the same community and tested for functional capacity pre-COVID-19. Functional impairment (<85% of the predicted response) was assessed using the Duke Activity Status Index (DASI) and 6-min walk distance (6MWD) test. A subgroup underwent cardiopulmonary exercise testing before and after exercise training. RESULTS: Of 562 respondents (age 54 ± 12 years, 69% women), 389 were symptomatic. Functional impairment (<85% predicted metabolic equivalent of tasks) was documented by DASI in 149 participants (27%), and abnormal 6MWD (<85% predicted) was observed in 14% of the symptomatic participants. Despite fewer risk factors and younger age, patients with COVID-19 had lower functional capacity by 6MWD (P < 0.001) and more depression (P < 0.001) than controls. In a pilot group of seven participants (age 58 ± 12 years, two women, VO2 18.9 ± 5.7 mL/kg/min), repeat testing after exercise training showed a 20% increase in peak workload. CONCLUSIONS: Although most participants (69%) had symptoms consistent with long COVID, significant subjective functional impairment was documented in 27% and objective functional impairment in 14%. An exercise training programme might be beneficial for appropriately selected patients.

Influence of exercise training on the left atrium: implications for atrial fibrillation, heart failure, and stroke.

The left atrium (LA) plays a critical role in receiving pulmonary venous return and modulating left ventricular (LV) filling. With the onset of exercise, LA function contributes to the augmentation in stroke volume. Due to the growing focus on atrial imaging, there is now evidence that structural remodeling and dysfunction of the LA is associated with adverse outcomes including incident cardiovascular disease. In patients with established disease, pathological changes in atrial structure and function are associated with exercise intolerance, increased hospital admissions and mortality, independent of left ventricular function. Exercise training is widely recommended in patients with cardiovascular disease to improve patient outcomes and maintain functional capacity. There are widely documented changes in LV function with exercise, yet less attention has been given to the LA. In this review, we first describe LA physiology at rest and during exercise, before exploring its association with cardiac disease outcomes including atrial fibrillation, heart failure, and stroke. The adaptation of the LA to short- and longer-term exercise training is evaluated through review of longitudinal studies of exercise training in healthy participants free of cardiovascular disease and athletes. We then consider the changes in LA structure and function among patients with established disease, where adverse atrial remodeling may be implicated in the disease process. Finally, we consider important future directions for assessment of atrial structure and function using novel imaging modalities, in response to acute and chronic exercise.

A Clinical Guide for Assessment and Prescription of Exercise and Physical Activity in Cardiac Rehabilitation. A CSANZ Position Statement.

Patients with cardiovascular disease benefit from cardiac rehabilitation, which includes structured exercise and physical activity as core components. This position statement provides pragmatic, evidence-based guidance for the assessment and prescription of exercise and physical activity for cardiac rehabilitation clinicians, recognising the latest international guidelines, scientific evidence and the increasing use of technology and virtual delivery methods. The patient-centred assessment and prescription of aerobic exercise, resistance exercise and physical activity have been addressed, including progression and safety considerations.

Vascular Aging Is Accelerated in Hematological Cancer Survivors Who Undergo Allogeneic Stem Cell Transplant.

BACKGROUND: Survivors of allogeneic stem cell transplant (SCT) receive intensive cancer treatments that are associated with cardiovascular dysfunction. Markers of vascular age can indicate early signs of adverse (cardio)vascular changes; however, the impact of SCT on these makers is unknown. We aimed to determine the short (3 months) and longer-term (≥2 years) effect of SCT on markers of vascular age in hematologic cancer survivors compared with an age-matched noncancer control group. METHODS: The short-term effects of SCT, markers of vascular age (aortic compliance, arterial elastance, and ventricular-vascular coupling) were assessed via cardiac magnetic resonance imaging (cardiac and aortic volumes) before and ≈3 months post-SCT in 13 short-term survivors and compared with 11 controls. The longer-term impact was assessed by comparing 14 long-term survivors (6.5 [2-20] years post-SCT) to the short-term survivors (post-SCT) and controls (n=16). RESULTS: The groups were similar for age and body mass index. In the short-term survivors, no significant group-by-time interactions were observed for any markers of vascular aging from pretransplant to posttransplant (net difference for change in compliance between groups -0.07 [95% CI, -1.49 to 1.35]). For the time-course analysis, aortic compliance was significantly lower in both SCT groups (overall P=0.007) compared with controls, whereas ventricular-vascular coupling was higher in both survivor groups as was arterial elastance in long-term SCT survivors (ie, worse; P<0.01 for all). CONCLUSION: This study provides evidence of an accelerated vascular aging phenotype in allogeneic SCT survivors and provides insight into the increased burden of cardiovascular disease among hematologic cancer survivors.

Measurement of Stroke Volume With Echocardiography Compared to Gold Standard Cardiac Magnetic Resonance Imaging: An Observational Study.

OBJECTIVES: The authors aimed to compare the assessment of left ventricular (LV) stroke volume with transthoracic echocardiography (TTE) using 2- and 3-dimensional (2D and 3D) Doppler and volumetric techniques with gold standard cardiac magnetic resonance imaging (CMR). DESIGN: An observational study. SETTING: A medical research institute. PARTICIPANTS: A total of 187 volunteer participants free of known structural heart disease. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: LV stroke volume was measured with TTE using the following 4 techniques: LV outflow tract (LVOT) pulsed wave Doppler with 2D LVOT area, LVOT pulsed wave Doppler with 3D LVOT area, 2D volumetric (Simpson's biplane), and 3D volumetric techniques. This was compared with gold standard CMR. Stroke volume measured with echocardiography underestimated stroke volume compared to CMR by all techniques (p < 0.001 for all values compared to CMR). The LVOT Doppler stroke volume with a 3D area most closely agreed with CMR, with a bias of 6.35%. This bias progressively increased with 3D volumetric (13.4%), LVOT Doppler with a 2D area (15.1%), and 2D volumetric (18.3%) stroke volume techniques, with wider limits of agreement. CONCLUSION: Of the 4 echocardiographic LV stroke volume measurement methods the authors assessed, stroke volume with LVOT Doppler using 3D measurement of LVOT area most closely approximates gold standard CMR.

Cellular Mechanisms Mediating Exercise-Induced Protection against Cardiotoxic Anthracycline Cancer Therapy.

Anthracyclines such as doxorubicin are widely used chemotherapy drugs. A common side effect of anthracycline therapy is cardiotoxicity, which can compromise heart function and lead to dilated cardiomyopathy and heart failure. Dexrazoxane and heart failure medications (i.e., beta blockers and drugs targeting the renin-angiotensin system) are prescribed for the primary prevention of cancer therapy-related cardiotoxicity and for the management of cardiac dysfunction and symptoms if they arise during chemotherapy. However, there is a clear need for new therapies to combat the cardiotoxic effects of cancer drugs. Exercise is a cardioprotective stimulus that has recently been shown to improve heart function and prevent functional disability in breast cancer patients undergoing anthracycline chemotherapy. Evidence from preclinical studies supports the use of exercise training to prevent or attenuate the damaging effects of anthracyclines on the cardiovascular system. In this review, we summarise findings from experimental models which provide insight into cellular mechanisms by which exercise may protect the heart from anthracycline-mediated damage, and identify knowledge gaps that require further investigation. Improved understanding of the mechanisms by which exercise protects the heart from anthracyclines may lead to the development of novel therapies to treat cancer therapy-related cardiotoxicity.

SERCA2a Agonist Effects on Cardiac Performance During Exercise in Heart Failure With Preserved Ejection Fraction.

BACKGROUND: Impaired ventricular relaxation influences left ventricular pressures during exercise in heart failure with preserved ejection fraction (HFpEF). Sarco/endoplasmic reticulum calcium-adenosine triphosphatase (SERCA2a) facilitates myocardial relaxation by increasing calcium reuptake and is impaired in HFpEF. OBJECTIVES: This study sought to investigate the effects of istaroxime, a SERCA2 agonist, on lusitropic and hemodynamic function during exercise in patients with HFpEF and control subjects. METHODS: Eleven control subjects (7 male, 4 female) and 15 patients with HFpEF (8 male, 7 female) performed upright cycle exercise with right-sided heart catheterization. Participants received istaroxime (0.5 µg/kg/min) or saline placebo (single-blind, crossover design). Cardiac output, pulmonary capillary wedge pressure (PCWP), and diastolic function were measured at rest and during submaximal exercise. In an exploratory analysis (Hedge's g), 7 patients with HFpEF received higher-dose istaroxime (1.0 µg/kg/min). End-systolic elastance (Ees) was calculated by dividing systolic blood pressure (SBP) × 0.9 by end-systolic volume (ESV) (on 3-dimensional echocardiography). RESULTS: Patients with HFpEF had higher PCWP (25 ± 10 mm Hg vs 12 ± 5 mm Hg; P < 0.001) and lower tissue Doppler velocities during exercise. Istaroxime (0.5 µg/kg/min) had no effect on resting or exercise measures in patients with HFpEF or control subjects. Control subjects had a larger increase in Ees (Δ 1.55 ± 0.99 mm Hg/mL vs Δ 0.86 ± 1.31 mm Hg/mL; P = 0.03), driven by lower ESV. Comparing placebo and istaroxime 1.0 µg/kg/min during exercise, PCWP during the 1.0 µg/kg/min istaroxime dose was slightly lower (Δ 2.2 mm Hg; Hedge's g = 0.30). There were no effects on diastolic function, but there were increases in SBP and s', suggesting a mild inotropic effect. CONCLUSIONS: Low-dose istaroxime had no effect on cardiac filling pressure or parameters of relaxation in patients with HFpEF during exercise. Higher doses of istaroxime may have been more effective in reducing exercise PCWP in patients with HFpEF. (Hemodynamic Response to Exercise in HFpEF Patients After Upregulation of SERCA2a; NCT02772068).

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.

Atrial Fibrillation Ablation for Heart Failure With Preserved Ejection Fraction: A Randomized Controlled Trial.

BACKGROUND: Patients with heart failure with preserved ejection fraction (HFpEF) frequently develop atrial fibrillation (AF). There are no randomized trials examining the effects of AF ablation on HFpEF outcomes. OBJECTIVES: The aim of this study is to compare the effects of AF ablation vs usual medical therapy on markers of HFpEF severity, including exercise hemodynamics, natriuretic peptide levels, and patient symptoms. METHODS: Patients with concomitant AF and HFpEF underwent exercise right heart catheterization and cardiopulmonary exercise testing. HFpEF was confirmed with pulmonary capillary wedge pressure (PCWP) of 15 mm Hg at rest or ≥25 mm Hg on exercise. Patients were randomized to AF ablation vs medical therapy, with investigations repeated at 6 months. The primary outcome was change in peak exercise PCWP on follow-up. RESULTS: A total of 31 patients (mean age: 66.1 years; 51.6% females, 80.6% persistent AF) were randomized to AF ablation (n = 16) vs medical therapy (n = 15). Baseline characteristics were comparable across both groups. At 6 months, ablation reduced the primary outcome of peak PCWP from baseline (30.4 ± 4.2 to 25.4 ± 4.5 mm Hg; P < 0.01). Improvements were also seen in peak relative VO2 (20.2 ± 5.9 to 23.1 ± 7.2 mL/kg/min; P < 0.01), N-terminal pro-B-type natriuretic peptide levels (794 ± 698 to 141 ± 60 ng/L; P = 0.04), and MLHF (Minnesota Living with Heart Failure) score (51 ± -21.9 to 16.6 ± 17.5; P < 0.01). No differences were detected in the medical arm. Following ablation, 50% no longer met exercise right heart catheterization-based criteria for HFpEF vs 7% in the medical arm (P = 0.02). CONCLUSIONS: AF ablation improves invasive exercise hemodynamic parameters, exercise capacity, and quality of life in patients with concomitant AF and HFpEF.

Reduced cardiovascular reserve capacity in long-term allogeneic stem cell transplant survivors.

Premature cardiovascular mortality is increased in long-term allogeneic stem cell transplant (allo-SCT) survivors, but little information exists regarding subclinical cardiovascular dysfunction in this population. We compared peak oxygen uptake ([Formula: see text]O2peak), a prognostic cardiovascular marker, and its determinants between long-term allo-SCT survivors and non-cancer controls. Fourteen allo-SCT survivors (mean ± SD, 44 ± 15 years, 50% male, median time since allo-SCT: 6.5 years [range 2-20]) and 14 age- and sex-matched controls (46 ± 13 years, 50% male) underwent cardiopulmonary exercise testing to quantify [Formula: see text]O2peak. Resting echocardiography (left-ventricular ejection fraction and strain), exercise cardiac MRI (peak cardiac and stroke volume index [CIpeak, SVIpeak]), biochemistry (hemoglobin, troponin-I, B-natriuretic peptide), dual-energy x-ray absorptiometry (lean [LM] and fat [FM] mass, percent body fat [%BF]) and Fick-principal calculation (arteriovenous oxygen difference) were also performed. Survivors exhibited impaired [Formula: see text]O2peak as compared with controls (25.9 ± 5.1 vs. 33.7 ± 6.5 ml kg-1 min-1, p = 0.002), which coincided with reduced CIpeak (6.6 ± 0.8 vs. 8.6 ± 1.9 L min-1 m-2; p = 0.001) secondary to reduced SVIpeak (48 ± 4 vs. 61 ± 8 ml m-2; p < 0.001) rather than chronotropic impairment, and higher %BF (difference, 7.9%, p = 0.007) due to greater FM (5.8 kg; p = 0.069) and lower LM (4.3 kg, p = 0.25). All other measures were similar between groups. Despite comparable resting cardiac function and biomarker profiles, survivors exhibited reduced [Formula: see text]O2peak and exercise cardiac function and increased %BF relative to controls. These results highlight potential therapeutic avenues and the utility of exercise-based cardiovascular assessment in unmasking cardiovascular dysfunction in allo-SCT survivors.

Exercise for the Prevention of Anthracycline-Induced Functional Disability and Cardiac Dysfunction: The BREXIT Study.

BACKGROUND: Breast cancer survivors treated with anthracycline-based chemotherapy (AC) have increased risk of functional limitation and cardiac dysfunction. We conducted a 12-month randomized controlled trial in 104 patients with early-stage breast cancer scheduled for AC to determine whether 12 months of exercise training (ExT) could attenuate functional disability (primary end point), improve cardiorespiratory fitness (VO2peak), and prevent cardiac dysfunction. METHODS: Women 40 to 75 years of age with stage I to III breast cancer scheduled for AC were randomized to 3 to 4 days per week aerobic and resistance ExT for 12 months (n=52) or usual care (UC; n=52). Functional measures were performed at baseline, at 4 weeks after AC (4 months), and at 12 months, comprising: (1) cardiopulmonary exercise testing to quantify VO2peak and functional disability (VO2peak ≤18.0 mL·kg-1·min-1); (2) cardiac reserve (response from rest to peak exercise), quantified with exercise cardiac magnetic resonance measures to determine changes in left and right ventricular ejection fraction, cardiac output, and stroke volume; (3) standard-of-care echocardiography-derived resting left ventricular ejection fraction and global longitudinal strain; and (4) biochemistry (troponin and BNP [B-type natriuretic peptide]). RESULTS: Among 104 participants randomized, greater study attrition was observed among UC participants (P=0.031), with 93 women assessed at 4 months (ExT, n=49; UC, n=44) and 87 women assessed at 12 months (ExT, n=49; UC, n=38). ExT attenuated functional disability at 4 months (odds ratio, 0.32 [95% CI, 0.11-0.94]; P=0.03) but not at 12 months (odds ratio, 0.27 [95% CI, 0.06-1.12]; P=0.07). In a per-protocol analysis, functional disability was prevented entirely at 12 months among participants adherent to ExT (ExT, 0% versus UC, 20%; P=0.005). Compared with UC at 12 months, ExT was associated with a net 3.5-mL·kg-1·min-1 improvement in VO2peak that coincided with greater cardiac output, stroke volume, and left and right ventricular ejection fraction reserve (P<0.001 for all). There was no effect of ExT on resting measures of left ventricular function. Postchemotherapy troponin increased less in ExT than in UC (8-fold versus 16-fold increase; P=0.002). There were no changes in BNP in either group. CONCLUSIONS: In women with early-stage breast cancer undergoing AC, 12 months of ExT did not attenuate functional disability, but provided large, clinically meaningful benefits on VO2peak and cardiac reserve. REGISTRATION: URL: https://www.anzctr.org.au/; Unique identifier: ACTRN12617001408370.

Determinants of oxygen utilization in breast cancer: Similarities between heart failure with preserved ejection fraction.

Reduced exercise tolerance and fatigue are hallmark features in both breast cancer (BC) and heart failure with preserved ejection fraction (HFpEF) and are associated with decreased physical function and quality of life. This brief review focuses on the mechanisms of exercise intolerance in women with BC across the survivorship continuum and highlights how these disturbances within the oxygen transport cascade are similar to that of HFpEF patients. Specifically, the role that impaired cardiac, peripheral vascular and skeletal muscle function play in limiting peak oxygen uptake are discussed. We propose that women with BC are at increased risk of developing HFpEF potentially due to the adverse effects of chemotherapy and concurrent adverse lifestyle behaviors on cardiovascular and skeletal muscle function.

Heart Failure With Preserved Ejection Fraction as an Exercise Deficiency Syndrome: JACC Focus Seminar 2/4.

Across differing spectrums of cardiac function and cardiac pathologies, there are strong associations between measures of cardiorespiratory fitness and burden of symptoms, quality of life, and prognosis. In this part 2 of a 4-part series, we contend that there is a strong association among physical activity, cardiorespiratory fitness, and cardiac function. We argue that a chronic lack of exercise is a major risk factor for heart failure with preserved ejection fraction in some patients. In support of this hypothesis, increasing physical activity is associated with greater cardiac mass, greater stroke volumes, greater cardiac output and peak oxygen consumption, and fewer clinical events. Conversely, physical inactivity results in cardiac atrophy, reduced output, reduced chamber size, and decreased ability to augment cardiac performance with exercise. Moreover, physical inactivity is a strong predictor of heart failure risk and death. In sum, exercise deficiency should be considered part of the broad heart failure with preserved ejection fraction phenotype.

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.

Preventing the adverse cardiovascular consequences of allogeneic stem cell transplantation with a multi-faceted exercise intervention: the ALLO-Active trial protocol.

BACKGROUND: Allogeneic stem cell transplantation (allo-SCT) is a potentially lifesaving treatment for high-risk hematological malignancy, but survivors experience markedly elevated rates of cardiovascular disease and associated functional impairment. Mounting evidence suggests regular exercise, combined with a reduction in sedentary time through replacement with light exercise may be a useful therapeutic strategy for the prevention of cardiovascular comorbidities. However, this type of intervention has yet to be evaluated in patients undergoing allo-SCT. The ALLO-Active study will evaluate the efficacy of a ~ 4 month multi-faceted exercise intervention, commenced upon admission for allo-SCT, to preserve peak oxygen uptake (VO2peak) and peak cardiac output, compared with usual care. The study will also evaluate the effect of the intervention on functional independence, quality of life, and symptoms of fatigue. METHODS: Sixty adults with hematological malignancy scheduled for allo-SCT will be randomly assigned to usual care (n = 30) or the exercise and sedentary behaviour intervention (n = 30). Participants assigned to the intervention will complete a thrice weekly aerobic and progressive resistance training program and concomitantly aim to reduce daily sedentary time by 30 min with short, frequent, light-intensity exercise bouts. Participants will undergo testing prior to, immediately after inpatient discharge, and 12 weeks after discharge. To address aim 1, VO2peak and peak cardiac output (multiple primary outcomes, p < 0.025) will be assessed via cardiopulmonary exercise testing and exercise cardiac magnetic resonance imaging, respectively. Secondary outcomes include functional independence (defined as VO2peak ≥ 18.mL.kg-1.min-1), quality of life, and fatigue (assessed via validated questionnaire). Exploratory outcomes will include indices of resting cardiac, vascular, and skeletal muscle structure and function, cardiovascular biomarkers, anxiety and depression, transplant outcomes (e.g., engraftment, graft-versus-host disease), and habitual physical activity, sedentary time, and sleep. DISCUSSION: Multi-faceted exercise programs are a promising approach for ameliorating the cardiovascular consequences of allo-SCT. If this intervention proves to be effective, it will contribute to the development of evidence-based exercise guidelines for patients undergoing allo-SCT and assist with optimising the balance between acute cancer management and long-term health. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR), ID: 12619000741189 . Registered 17 May 2019.