Effect of Arm-Ergometry Versus Treadmill Supervised Exercise on Cardiorespiratory Fitness and Walking Distances in Patients With Peripheral Artery Disease: The ARMEX Randomized Clinical Trial.

PURPOSE: To compare arm-ergometry and treadmill supervised exercise training on cardiorespiratory fitness and walking distances in patients with peripheral artery disease (PAD). METHODS: ARMEX was a single-center, single-blinded, parallel group, non-inferiority trial enrolling symptomatic patients with PAD. Patients were randomized (1:1 ratio) to a 12-wk arm-ergometry (AEx) or standard treadmill (TEx) supervised exercise training protocol. The powered primary end point was the change in peak oxygen uptake (VO2) at 12 wk, measured on a treadmill cardiopulmonary exercise test (CPX). Secondary outcomes included changes in VO2 at the first ventilatory threshold (VT-1), ventilatory efficiency (ratio of minute ventilation [VE] to carbon dioxide production [VCO2], VE/VCO2), walking distances by CPX and 6-min walking test (6MWT), and self-reported walking limitations. RESULTS: Fifty-six patients (66 ± 8 yr; 88% male) were randomized (AEx, n = 28; TEx, n = 28). At 12 wk, VO2peak change was not significantly different between groups (0.75 mL/kg/min; 95% CI, -0.94 to 2.44; P= .378), despite a significant increase only in AEx. VO2 at VT-1 improved in both groups without between-group differences, and VE/VCO2 slope improved more in AEx. The TEx attained greater improvements in walking distance by CPX (121.08 m; 95% CI, 24.49-217.66; P= .015) and 6MWT (25.08 m; 95% CI, 5.87-44.29; P= .012) and self-perceived walking distance. CONCLUSIONS: Arm-ergometry was noninferior to standard treadmill training for VO2peak, and treadmill training was associated with greater improvements in walking distance. Our data support the use of treadmill as a first-line choice in patients with PAD to enhance walking capacity, but arm-ergometry could be an option in selected patients.

Cost-effectiveness analysis of a cardio-oncology rehabilitation framework compared to an exercise intervention for cancer survivors with high cardiovascular risk.

BACKGROUND: A cardio-oncology rehabilitation model among cancer survivors showed superior results comparing to a community-based exercise intervention. However, questions remain about its cost-effectiveness. AIMS: To assess the cost-effectiveness of a center-based cardiac rehabilitation (CBCR) program when compared to usual care encompassing a community-based exercise training (CBET), among cancer survivors with high cardiovascular risk. METHODS: The CORE study was a single-center, prospective, randomized controlled trial; 80 adult cancer survivors with previous exposure to cardiotoxic cancer treatment and/or with previous cardiovascular disease were assigned (1:1 ratio) to an 8-week CBCR or CBET, twice/week. Cost-effectiveness was a pre-specified secondary endpoint. Outcomes included healthcare resource use and costs, quality-adjusted life-years (QALYs) and cost-effectiveness; incremental cost-effectiveness ratio (ICER) was computed from a societal perspective. RESULTS: 75 patients completed the study (CBCR N=38; CBET N=37). The CBCR had significantly higher cost per patient (477.76 ± 39.08€) compared to CBET group (339.32 ± 53.88€), with a significant between-group difference 138.44€ (95% CI, 116.82 to 160.05€, p<0.01). A between-group difference by 0.100 points in QALYs was observed, favouring the CBCR (95% CI, -0.163 to -0.037, p=0.002). When CBCR was compared with CBET, the ICER was €1,383.24 per QALY gained; at a willingness-to-pay threshold of €5,000 per QALY, the probability of CBCR being cost-effective was 99.9% (95% CI, 99.4 to 100.0). CONCLUSION: The CORE trial shows that a CBCR is a cost-effective intervention in the management of cancer survivors with high cardiovascular risk, reinforcing the potential benefits of this multidisciplinary approach in supportive care of this specific subset of cancer patients.

The CORE study was a randomized clinical trial including 80 cancer survivors with high cardiovascular risk; an 8-week cardio-oncology rehabilitation framework promoted superior results on cardiorespiratory fitness (peak oxygen consumption) and quality of life, but questions remained about the cost-effectiveness of this option. This study findings suggest that: a center-based cardiac rehabilitation proved to be cost-effective, when compared to usual care encompassing community-based exercise training the value-added of a comprehensive approach delivered in an oncological setting reinforce the potential benefits of including this intervention in supportive care of a specific subset of cancer patients, within existing contemporary cardiac rehabilitation resources and infrastructures.

Effect of physical exercise on immune, inflammatory, cardiometabolic biomarkers, and fatty acids of breast cancer survivors: results from the MAMA_MOVE Gaia After Treatment trial.

PURPOSE: Physical exercise has positive effects on clinical outcomes of breast cancer survivors such as quality of life, fatigue, anxiety, depression, body mass index, and physical fitness. We aimed to study its impact on immune, inflammatory, cardiometabolic, and fatty acids (FA) biomarkers. METHODS: An exploratory sub-analysis of the MAMA_MOVE Gaia After Treatment trial (NCT04024280, registered July 18, 2019) was performed. Blood sample collections occurred during the control phase and at eight weeks of the intervention phase. Samples were subjected to complete leukocyte counts, cytokine, and cardiometabolic marker evaluation using flow cytometry, enzyme-linked immunoassays, and gas chromatography. RESULTS: Ninety-three percent of the 15 participants had body mass index ≥ 25 kg/m2. We observed a decrease of the plasmatic saturated FA C20:0 [median difference - 0.08% (p = 0.048); mean difference - 0.1 (95%CI - 0.1, - 0.0)], positively associated with younger ages. A tendency to increase the saturated FA C18:0 and the ratio of unsaturated/saturated FA and a tendency to decrease neutrophils (within the normal range) and interferon-gamma were observed. CONCLUSIONS: Positive trends of physical exercise on circulating immune cells, inflammatory cytokines, and plasmatic FA were observed. Larger studies will further elucidate the implications of physical exercise on metabolism. These exploratory findings may contribute to future hypothesis-driven research and contribute to meta-analyses.

Exercise Training Benefits Health-Related Quality of Life and Functional Capacity during Breast Cancer Chemotherapy: A Randomized Controlled Trial.

PURPOSE: To examine the effectiveness of a supervised exercise training program (SETP) on health-related quality of life (HRQoL) and functional capacity in women with breast cancer (BC) undergoing chemotherapy. METHODS: Ninety-three women with early-stage BC were randomly allocated to a SETP plus usual care (exercise, n = 47) or usual care alone (UC, n = 46). The SETP included three sessions per week, combining aerobic and resistance training, conducted concurrently over the chemotherapy. The EORTC Cancer Quality-of-Life-Questionnaire-Core-30 (QLQ-C30) and the BC-specific module (QLQ-BR23) were used to assess HRQoL. Functional capacity was analyzed by maximum voluntary handgrip strength (MVHS) and by the 30-s chair sit-to-stand test (30-s CST). These endpoints were assessed at baseline (t0); middle (t1; after 8 or 12 wk of t0); and at the end of chemotherapy (t2; after 20 wk of t0). Mean changes from baseline were assessed by an intention-to-treat approach. RESULTS: Mixed linear model analyses showed that Exercise group experienced less deterioration in several domains of QLQ-C30 at t2, including in global health status/QoL (Δ = 9.39 units; P = 0.034), QLQ-C30 summary score (Δ = 8.08 units; P < 0.001), physical (Δ = 15.14 units; P < 0.001), role ( Δ = 21.81 units; P < 0.001), cognitive (Δ = 9.16 units; P = 0.032) and social functioning (Δ = 11.67 units; P = 0.038), compared with the UC group. Similarly, Exercise group exhibited significant lower levels of fatigue (Δ = -20.19 units; P < 0.001) and appetite loss (Δ = -13.69 units; P = 0.034), compared with the UC group. Significant between-group differences were observed on MVHS of the tumor/surgery upper limb side (Δ = 2.64 kg; P < 0.001) and contralateral limb (Δ = 2.22 kg; P < 0.001), and on the 30-s CST score (Δ = 3.56repetitions; P < 0.001), favoring the Exercise group. No differences were observed on QLQ-BR23 domains. CONCLUSIONS: Exercise training was an effective complementary therapy to prevent the deterioration of HRQoL and functional capacity during chemotherapy in women with early-stage BC.

Cardio-Oncology Rehabilitation for Cancer Survivors With High Cardiovascular Risk: A Randomized Clinical Trial.

Importance: Cardiovascular disease is a leading cause of morbidity in cancer survivors, which makes strategies aimed at mitigating cardiovascular risk a subject of major contemporary importance. Objective: To assess whether a center-based cardiac rehabilitation (CBCR) framework compared with usual care encompassing community-based exercise training (CBET) is superior for cardiorespiratory fitness improvement and cardiovascular risk factor control among cancer survivors with high cardiovascular risk. Design, Setting, and Participants: This prospective, single-center, randomized clinical trial (CORE trial) included adult cancer survivors who had exposure to cardiotoxic cancer treatment and/or previous cardiovascular disease. Enrollment took place from March 1, 2021, to March 31, 2022. End points were assessed at baseline and after the 8-week intervention. Interventions: Participants were randomly assigned in a 1:1 ratio to 8 weeks of CBCR or CBET. The combined aerobic and resistance exercise sessions were performed twice a week. Main Outcomes and Measures: The powered primary efficacy measure was change in peak oxygen consumption (V̇o2) at 2 months. Secondary outcomes included handgrip maximal strength, functional performance, blood pressure (BP), body composition, body mass index (BMI; calculated as weight in kilograms divided by height in meters squared), lipid profile, plasma biomarker levels, physical activity (PA) levels, psychological distress, quality of life (QOL), and health literacy. Results: A total of 75 participants completed the study (mean [SD] age, 53.6 [12.3] years; 58 [77.3%] female), with 38 in the CBCR group and 37 in the CBET group. Participants in CBCR achieved a greater mean (SD) increase in peak V̇o2 than those in CBET (2.1 [2.8] mL/kg/min vs 0.8 [2.5] mL/kg/min), with a between-group mean difference of 1.3 mL/kg/min (95% CI, 0.1-2.6 mL/kg/min; P = .03). Compared with the CBET group, the CBCR group also attained a greater mean (SD) reduction in systolic BP (-12.3 [11.8] mm Hg vs -1.9 [12.9] mm Hg; P < .001), diastolic BP (-5.0 [5.7] mm Hg vs -0.5 [7.0] mm Hg; P = .003), and BMI (-1.2 [0.9] vs 0.2 [0.7]; P < .001) and greater mean (SD) improvements in PA levels (1035.2 [735.7] metabolic equivalents [METs]/min/wk vs 34.1 [424.4] METs/min/wk; P < .001), QOL (14.0 [10.0] points vs 0.4 [12.9] points; P < .001), and health literacy scores (2.7 [1.6] points vs 0.1 [1.4] points; P < .001). Exercise adherence was significantly higher in the CBCR group than in the CBET group (mean [SD] sessions completed, 90.3% [11.8%] vs 68.4% [22.1%]; P < .001). Conclusion and Relevance: The CORE trial showed that a cardio-oncology rehabilitation model among cancer survivors with high cardiovascular risk was associated with greater improvements in peak V̇o2 compared with usual care encompassing an exercise intervention in a community setting. The CBCR also showed superior results in exercise adherence, cardiovascular risk factor control, QOL, and health literacy. Trial Registration: ClinicalTrials.gov Identifier: NCT05132998.

Sixty years of the Bruce protocol: reappraising the contemporary role of exercise stress testing with electrocardiographic monitoring.

The cardiovascular response to exercise has long been a focus of interest. Over a century ago, the first descriptions of electrocardiographic changes occurring during exercise highlighted the possible relevance of this dynamic assessment. In this background, the inception of the Bruce protocol circa 60 years ago allowed for a major leap in this field by providing a standardized framework with which to address this issue, by means of an integrated and structured methodology. Since then, exercise stress testing with electrocardiographic monitoring (ExECG) has become one of the most widely appraised tests in cardiovascular medicine. Notably, past few decades have been profoundly marked by substantial advances in the approach to cardiovascular disease, challenging prior notions concerning both its physiopathology and overall management. Among these, the ever-evolving presentations of cardiovascular disease coupled with the development and implementation of several novel diagnostic modalities (both invasive and noninvasive) has led to a shifting paradigm in the application of ExECG. This technique, however, has continuously shown to be of added value across various momentums of the cardiovascular continuum, as depicted in several contemporary guidelines. This review provides a pragmatical reflexion on the development of ExECG, presenting a comprehensive overview concerning the current role of this modality, its challenges, and its future perspectives.

Effects of a Physical Exercise Program on Quality of Life and Physical Fitness of Breast Cancer Survivors: the MAMA_MOVE Gaia After Treatment Trial.

To assess the effects of a group class physical exercise program on health-related quality of life (HRQOL), physical fitness and activity, and safety in early breast cancer women after treatment, a double-phase trial [16-week control phase (CP) followed by a 16-week intervention phase (IP)] was designed. Outcomes were evaluated at baseline (T1), 8 (T2) and 16 (T3) weeks (CP), and 24 (T4) and 32 (T5) weeks (IP). The primary endpoint was global health status. Out of 82 enrolled patients, 37 completed the IP. Global health status decreased (-10,1; 95% CI -19.8 to -0.4; p = 0.040) during the CP and stabilized during the IP. Physical and sexual functioning increased during the IP (p = 0.008; p = 0.017), while cardiorespiratory fitness increased in the CP (p = 0.004). Upper limb strength and lower limb functionality increased during both phases [CP: p < 0.0001, p = 0.001 (surgical and nonsurgical arm), p = 0.028; IP: p < 0.0001, p = 0.002, p = 0.009]. Body mass index decreased in the IP (p = 0.026). Waist circumference increased in the CP (p = 0.001) and decreased in the IP (p = 0.010); sedentary behaviours and moderate and vigorous physical activity did not change. Adherence to 70% of the sessions was reported in 54% of patients. No serious adverse events related to the intervention were reported. In conclusion, the physical exercise program was able to prevent the decline in global health status and to improve other domains of HRQOL and physical fitness. As physical exercise is not the standard of care in many countries, the implementation of group class programs might be an option.

Effects of walking football on adherence, safety, quality of life and physical fitness in patients with prostate cancer: Findings from the PROSTATA_MOVE randomized controlled trial.

Aims: To analyze the feasibility and impact of a walking football (WF) program on quality of life (QoL), cardiorespiratory fitness (CRF), muscle strength, and balance program in men with prostate cancer under androgen deprivation therapy (ADT). Methods: Fifty patients with prostate cancer (stages IIb-IVb) under ADT were randomized to a 16-week WF program plus usual care (n=25) or usual care control group (n=25). The WF program consisted of three 90-minute sessions per week. Recruitment, withdrawal, adherence, enjoyment rate, and safety of the intervention were recorded throughout the study. Cardiorespiratory fitness was assessed before and after the interventions, while handgrip strength, lower limb muscle strength, static balance, and QoL were assessed before, during (week 8), and after (week 16) the interventions. Adverse events during sessions were also recorded. Results: The WF group showed high levels of adherence (81.6 ± 15.9%) and enjoyment rate (4.5 ± 0.5 out of 5 points). In the intention-to-treat analysis, the WF group showed an improvement in chair sit-to-stand (p=0.035) compared to the control group. Within-group comparisons showed that handgrip strength in the dominant upper limb (p=0.024), maximal isometric muscle strength in the non-dominant lower limb (p=0.006), and balance in the dominant limb (p=0.009) improved over time in the WF group but not in the usual care group. The results obtained from the per-protocol analysis indicate that CRF improved significantly in the WF group as compared to the control group (p=0.035). Within-group analysis revealed that CRF (p=0.036), muscle strength in dominant (p=0.006) and non-dominant (p=0.001) lower limbs, and balance in the non-dominant lower limb (p=0.023) improved after 16 weeks of WF, but not in the control group. One major traumatic injury (muscle tear) was reported with a complete recovery before the end of the intervention. Conclusion: This study suggests that WF is feasible, safe, and enjoyable in patients with prostate cancer under hormonal therapy. Furthermore, patients who adhere to the WF program can expect cardiorespiratory fitness, muscle strength, and balance improvements. Clinical trials registration: clinicaltrials.gov, identifier NCT04062162.

Effects of exercise training on cardiac toxicity markers in women with breast cancer undergoing chemotherapy with anthracyclines: a randomized controlled trial.

AIMS: Exercise training has been suggested to prevent anthracycline-related cardiac dysfunction, but clinicalbased evidence is scarce. We investigated the effects of a supervised exercise training programme (SETP) on cardiac toxicity markers in women with breast cancer (BC) receiving anthracycline-containing chemotherapy. METHODS AND RESULTS: Ninety-three women with early-stage breast cancer were randomly allocated to a supervised exercise training programme (SETP) plus usual care group (Exercise, n = 47) or usual care alone group (UC, n = 46). The SETP consisted of three sessions per week, combining aerobic and resistance training, conducted concurrently across the anthracycline-containing chemotherapy length. The primary endpoint was the change in left ventricular ejection fraction (LVEF) from baseline to the end of anthracycline cycles. Secondary endpoints included global longitudinal strain (GLS) and other conventional echocardiographic parameters, cardiorespiratory fitness (estimated peak VO2), circulating biomarkers (NT-proBNP, hs-TnT), and safety of the SETP. The study endpoints were also assessed 3 months after the end of anthracycline cycles. All patients were prescribed four cycles of doxorubicin plus cyclophosphamide (AC). No significant between-group differences in LVEF change were seen at the end of AC [mean difference: 0.7%; 95% confidence interval (CI): -0.8, 2.3; P = 0.349] and 3 months after AC (1.1%; 95% CI: -0.5, 2.6; P = 0.196). Compared to the usual care (UC) group, the estimated peak VO2 increased in the Exercise group at the end of AC (1.6 mL O2·kg-1·min-1; 95% CI: 0.06, 3.1; P = 0.041) and 3 months after AC (3.1 mL O2·kg-1·min-1; 95% CI: 1.4, 4.7; P < 0.001). No between-group differences were found in the remaining secondary endpoints. No serious adverse events were observed during SETP. CONCLUSION: Exercise training was safe during chemotherapy and significantly improved cardiorespiratory fitness. No significant effects were seen on cardiac toxicity markers (LVEF or GLS) as compared to the usual care. TRIAL REGISTRATION: Mama Move Gaia on treatment trial ISRCTN32617901.

Breast cancer patients are often treated with chemotherapy. Despite the clinical benefit, some of these drugs increase the risk of cardiac toxicity and impair patients' cardiorespiratory fitness. Exercise training has been proposed as a preventive approach, but clinical-based evidence is scarce. The results of this trial showed that an exercise training programme, combining aerobic training and resistance training, conducted during chemotherapy, did not significantly attenuate the decline in conventional cardiac function parameters when compared to usual care. However, the results of this trial showed that the training programme was safe and significantly improved cardiorespiratory fitness.

Maximal Exercise Improves the Levels of Endothelial Progenitor Cells in Heart Failure Patients.

The impact of exercise on the levels of endothelial progenitor cells (EPCs), a marker of endothelial repair and angiogenesis, and circulating endothelial cells (CECs), an indicator of endothelial damage, in heart failure patients is largely unknown. This study aims to evaluate the effects of a single exercise bout on the circulating levels of EPCs and CECs in heart failure patients. Thirteen patients with heart failure underwent a symptom-limited maximal cardiopulmonary exercise test to assess exercise capacity. Before and after exercise testing, blood samples were collected to quantify EPCs and CECs by flow cytometry. The circulating levels of both cells were also compared to the resting levels of 13 volunteers (age-matched group). The maximal exercise bout increased the levels of EPCs by 0.5% [95% Confidence Interval, 0.07 to 0.93%], from 4.2 × 10-3 ± 1.5 × 10-3% to 4.7 × 10-3 ± 1.8 × 10-3% (p = 0.02). No changes were observed in the levels of CECs. At baseline, HF patients presented reduced levels of EPCs compared to the age-matched group (p = 0.03), but the exercise bout enhanced circulating EPCs to a level comparable to the age-matched group (4.7 × 10-3 ± 1.8 × 10-3% vs. 5.4 × 10-3 ± 1.7 × 10-3%, respectively, p = 0.14). An acute bout of exercise improves the potential of endothelial repair and angiogenesis capacity by increasing the circulating levels of EPCs in patients with heart failure.

Adherence, safety, and satisfaction of a cardio-oncology rehabilitation program framework versus community exercise training for cancer survivors: findings from the CORE trial.

PURPOSE: To assess safety, satisfaction, and overall adherence of a center-based cardiac rehabilitation (CBCR) program for cancer survivors at increased cardiovascular (CV) risk, compared to community-based exercise training (CBET). METHODS: The CORE study was a single-center, prospective, randomized controlled trial enrolling cancer survivors exposed to cardiotoxic cancer treatment and/or with previous CV disease. Participants were randomized to an 8-week CBCR program or CBET, twice a week. Overall feasibility (consent, retention, and completion rates), intervention adherence (percentage of exercise sessions attended), and safety were assessed. Adverse events (AEs) were registered, and participants' satisfaction was measured at the end of the study. RESULTS: Eighty out of 116 potentially eligible individuals were included; consent rate was 72.4%, and 77 (96.2%) started the study (retention rate 100% in CBCR vs 92.5% in CBET); completion rate was 92.5%. Intervention adherence was higher in CBCR (90.3 ± 11.8% vs 68.4 ± 22.1%, p < 0.001). Exercise-related AEs were mainly related to musculoskeletal conditions in both groups (7 in CBCR vs 20 in CBET, p < 0.001), accounting for exercise prescription modification in 47 sessions (18 (3.3%) in CBCR vs 29 (7.2%) in CBET, p = 0.006), none motivating exercise discontinuation. No participants reported major CV events. Overall, the satisfaction with the different aspects of the programs (e.g., expectations, monitoring) was higher in the CBCR. CONCLUSION: This exploratory analysis of the CORE trial suggests that both exercise-based interventions are feasible and safe in this setting. The higher intervention adherence and patient satisfaction in CBCR suggest that this comprehensive approach could be of interest in this population.

Impact of a COmprehensive cardiac REhabilitation framework among high cardiovascular risk cancer survivors: Protocol for the CORE trial.

BACKGROUND: Cancer survivors are challenging patients, as they often present increased cardiovascular risk. In this background, cardio-oncology rehabilitation frameworks for specific cancer patients have been proposed. However, optimal program designs, as well as their overall safety and efficacy in different subsets of patients, are not fully ascertained. DESIGN: Single-center, pragmatic, prospective, randomized controlled trial performed in Portugal aiming to evaluate the impact of a center-based cardiac rehabilitation program, consisting of exercise training, nutritional counselling, psychosocial management and lifestyle behavior change, compared to community-based exercise training, in cancer survivors. METHODS: Adult cancer survivors (N = 80) exposed to cardiotoxic cancer treatment and/or with previous cardiovascular disease will be randomized (1:1) to receive either an eight-week cardiac rehabilitation program or community-based exercise training. Primary endpoint is cardiorespiratory fitness; secondary endpoints are physical activity, psychosocial parameters, blood pressure, body composition, lipids and inflammatory parameters. Physical function, quality of life, fatigue, health literacy, and feasibility will be assessed; a cost-effectiveness evaluation will also be performed. Between-group differences at baseline and in the change from baseline to the end of the study will be tested with unpaired t-tests or Mann-Whitney U test. Paired t-tests or Wilcoxon signed-rank test will be performed for within-group comparisons. CONCLUSION: This trial will address the overall impact of a contemporary cardiac rehabilitation program framework in cancer survivors, as compared to a community-based exercise training. Given the higher cardiovascular risk in several groups of cancer patients, our results could provide novel insights into optimized preventive strategies in this complex patient population.

Impact of physical exercise programs in breast cancer survivors on health-related quality of life, physical fitness, and body composition: Evidence from systematic reviews and meta-analyses.

Background: Breast cancer is the most common cancer worldwide, and despite remarkable progress in its treatment, the survivors' quality of life is hampered by treatment-related side effects that impair psychosocial and physiological outcomes. Several studies have established the benefits of physical exercise in breast cancer survivors in recent years. Physical exercise reduces the impact of treatment-related adverse events to promote a better quality of life and functional outcomes. Aim: This study aims to provide an overview of systematic reviews and meta-analyses on the effect of physical exercise on the health-related quality of life, cardiorespiratory fitness, muscle strength, and body composition of breast cancer survivors. Methods: PubMed and Cochrane databases were searched for systematic reviews and meta-analyses from January 2010 to October 2022. The main focus was ascertaining the effectiveness of physical exercise in breast cancer survivors undergoing curative treatment (surgery and/or radiotherapy and/or chemotherapy). Two reviewers independently screened the literature, extracted the data, and assessed the risk of bias in the included studies. Results: A total of 101 studies were identified, and 12 were yielded for final analysis. The eligible studies included nine systematic reviews/meta-analyses, one meta-analysis/meta-regression, and two systematic reviews. The number of randomised clinical trials included in each review varied from 11 to 63, and the number of participants was from 214 to 5761. A positive and significant effect of different physical exercise interventions on health-related quality of life was reported in 83.3% (10 studies) of the eligible studies. Physical exercise also improved cardiorespiratory fitness (3 studies; 25%) and showed to be effective in reducing body weight (3 studies; 25%) and waist circumference (4 studies; 33.3%). Conclusions: Our results suggest that physical exercise is an effective strategy that positively affects breast cancer survivors' quality of life, cardiorespiratory fitness, and body composition. Healthcare professionals should foster the adoption of physical exercise interventions to achieve better health outcomes following breast cancer treatments. Systematic review registration: https://inplasy.com/inplasy-2022-11-0053/, identifier INPLASY2022110053.

Acute Impact of Cancer Treatment on Head and Neck Cancer Patients: FIT4TREATMENT.

Head and neck cancer (HNC) treatment's toxicities impact several health domains. Exercise training (ET) may be beneficial. This prospective observational study (NCT04996147) aimed to analyse the acute impact of HNC curative multimodal treatment on health-related quality of life (HRQoL), nutritional status, physical and cognitive functions, and ET preferences. Eighteen patients with stage III/IV HNC were evaluated at baseline (T0), and 10 patients were evaluated at the end of treatment (T1), 7 of them after radical chemoradiotherapy (rCRT). At T0, the majority referred a good HRQoL on the EORTC QLQ-C30 questionnaire (median score: 70.8), were moderately malnourished or at risk of malnutrition (78%), recognized the benefits of an ET program, and were willing to participate (78%). After rCRT, there was worsening in HRQoL (75 vs. 50 score, p = 0.014), dysphagia severity (Eating Assessment Tool: 7 vs. 31, p = 0.027; Functional Oral Intake Scale: 6 vs. 4, p = 0.041), handgrip strength (dominant: 40.9 vs. 35.8 kgf, p = 0.027; nondominant: 37.2 vs. 33.9 kgf, p = 0.043), and nutritional status (Patient-Generated Subjective Global Assessment: 7 vs. 18, p = 0.028). HNC patients subjected to radical treatment represent a vulnerable population that might benefit from multimodal supportive care strategies including an ET program.

Reduced Levels of Circulating Endothelial Cells and Endothelial Progenitor Cells in Patients with Heart Failure with Reduced Ejection Fraction.

BACKGROUND: Endothelial dysfunction has been suggested as a potential mechanism contributing to the development and progression of heart failure (HF). Levels of circulating endothelial cells (CECs), endothelial progenitor cells (EPCs), and hematopoietic stem and progenitor cells (HSPCs) have been recognized as useful markers of vascular damage and endothelial repair in response to tissue injury. AIMS: To evaluate the circulating levels of EPCs, CECs, and HSPCs among patients with HF with reduced ejection fraction (HFrEF). METHODS: In 82 individuals (42 patients with HFrEF and 42 age-matched subjects without established cardiovascular disease), peripheral blood was drawn and levels of EPCs, CECs, and HSPCs were quantified by flow cytometry. RESULTS: Patients with HFrEF showed lower levels of circulating EPCs (5.28 × 10-3 ± 6.83 × 10-4% vs. 7.76 × 10-3 ± 4.91 × 10-4%, p ≤0.001) and CECs (5.11 × 10-3 ± 7.87 × 10-4% vs. 6.51 × 10-3 ± 5.21 × 10-4%, p = 0.005) when compared to the age-matched group. Circulating levels of HSPCs were not significantly different between groups (p = 0.590). Additionally, the number of EPCs and CECs was significantly higher in HFrEF patients with overweight/obesity (n = 24) compared to patients with normal weight (n = 17). CONCLUSION: Circulating levels of EPCs and CECs were significantly decreased in patients with HFrEF in comparison to age-matched subjects without established cardiovascular disease, suggesting that the levels of CECs and EPCs may be potential biomarkers of the cellular response to vascular injury in patients with HFrEF.

Current role and future perspectives of cardiac rehabilitation in coronary heart disease.

Ischaemic heart disease (IHD) is a major cause of morbidity and mortality worldwide. While there have been major advances in this field, these patients are still a higher risk subgroup. As such, strategies to mitigate risk and tailor secondary prevention measures are of the utmost relevance. Cardiac rehabilitation (CR), encompassing several domains including exercise training, cardiovascular risk factor optimization, nutritional and psychological assessments, as well as other ancillary interventions has shown to be one of the pillars in the contemporary management of patients with IHD. Indeed, CR is associated with several benefits in this population, ranging from functional capacity to improvements in outcomes. Whilst this, there are still several issues concerning the optimal application of CR which are still not fully ascertained, such as lack of referral and completion, as well as questions related to programme design (particularly among patients with multiple comorbidities). In this review, we aim at presenting a pragmatic overview on the current role of CR in the management of individuals with IHD, while also discussing some of the caveats in the current data, as well as future concepts which could help improve the uptake and personalization of this pivotal time-tested intervention.

Standardized exercise training is feasible, safe, and effective in pulmonary arterial and chronic thromboembolic pulmonary hypertension: results from a large European multicentre randomized controlled trial.

AIMS: This prospective, randomized, controlled, multicentre study aimed to evaluate efficacy and safety of exercise training in patients with pulmonary arterial (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH). METHODS AND RESULTS: For the first time a specialized PAH/CTEPH rehabilitation programme was implemented in 11 centres across 10 European countries. Out of 129 enrolled patients, 116 patients (58 vs. 58 randomized into a training or usual care control group) on disease-targeted medication completed the study [85 female; mean age 53.6 ± 12.5 years; mean pulmonary arterial pressure 46.6 ± 15.1 mmHg; World Health Organization (WHO) functional class II 53%, III 46%; PAH n = 98; CTEPH n = 18]. Patients of the training group performed a standardized in-hospital rehabilitation with mean duration of 25 days [95% confidence interval (CI) 17-33 days], which was continued at home. The primary endpoint, change of 6-min walking distance, significantly improved by 34.1 ± 8.3 m in the training compared with the control group (95% CI, 18-51 m; P < 0.0001). Exercise training was feasible, safe, and well-tolerated. Secondary endpoints showed improvements in quality of life (short-form health survey 36 mental health 7.3 ± 2.5, P = 0.004), WHO-functional class (training vs. control: improvement 9:1, worsening 4:3; χ2P = 0.027) and peak oxygen consumption (0.9 ± 0.5 mL/min/kg, P = 0.048) compared with the control group. CONCLUSION: This is the first multicentre and so far the largest randomized, controlled study on feasibility, safety, and efficacy of exercise training as add-on to medical therapy in PAH and CTEPH. Within this study, a standardized specialized training programme with in-hospital start was successfully established in 10 European countries.

Effects of exercise on endothelial progenitor cells in patients with cardiovascular disease: A systematic review and meta-analysis of randomized controlled trials.

The therapeutic potential of exercise training in the mobilization of endothelial progenitor cells (EPCs) into the peripheral blood in patients with cardiovascular disease is not yet clear. A systematic review and meta-analysis was performed in order to assess the effectiveness of exercise training in increasing the number of circulating EPCs in patients with cardiovascular disease. A literature search was conducted across the PubMed, Scopus, Web of Science and EBSCO databases, including the reference lists of relevant papers. The quality of randomized clinical trials was evaluated using the PEDro scale. The primary outcome data were circulating EPC levels. Six studies (236 participants) - three on heart failure (n=111), one on peripheral arterial disease (n=40) and two on coronary artery disease (n=85) - were included. There was an increase in EPC levels in the exercise training groups (effect size [ES]=0.57; 95% CI: 0.01-1.12), with considerable heterogeneity (I2=75.6%; p<0.001). In subgroup analyses, patients with heart failure showed a significant increase in EPCs in the exercise training groups (ES=0.52; 95% CI: 0.15-0.90), with low heterogeneity (I2=0.0%; p=0.648), while no significant increase (ES=0.67; 95% CI: -0.70-2.04; I2=91.2%; p<0.001) was observed in patients with arterial disease. The only study in patients with peripheral arterial disease showed a significant increase in EPC levels. This meta-analysis indicates that exercise training may be a therapeutic option to improve EPC levels and potentially to enhance endothelial function and repair in patients with heart failure.

[Predictors of changes in functional capacity on a cardiac rehabilitation program]. / Fatores preditores da evolução da capacidade funcional num programa de reabilitação cardíaca.

INTRODUCTION: The effectiveness of cardiac rehabilitation programs (CRP) strongly influences the recovery of functional capacity (FC), resulting in improved prognosis and survival. OBJECTIVE: To determine the cardiovascular risk factors that predict changes in FC in patients on CRP. METHODS: We performed a cross-sectional descriptive retrospective study of patients who began a CRP between January 2008 and December 2013. The dependent variable was changes in FC estimated in metabolic equivalents (METs) achieved in stress testing at the beginning and end of the phase II program. The independent variables were age, gender, dyslipidemia, diabetes, smoking, body mass index, physical activity level and reason for referral to the CRP. RESULTS: The sample included 1399 patients, of whom 1125 (80.4%) completed the program. FC improved in most patients (93%), with a mean gain of 1.45 ± 1.19 METs. Patients aged 45 -65 and over 65 years achieved a greater increase in FC compared with other age groups. Patients admitted to the CRP after coronary artery bypass graft surgery obtained a greater improvement in FC compared to patients with acute coronary syndrome. Non-diabetic patients benefited more than diabetic patients. No significant differences were seen between the groups in the other variables. CONCLUSION: This study highlights the need for new and individualized approaches in certain subgroups of patients on CRP.