A Cardiac Rehabilitation Program Increases the Acute Response of Endothelial Progenitor Cells to Maximal Exercise in Heart Failure Patients.

Purpose: The purpose of this study was to investigate the effect of a cardiac rehabilitation program on the acute response on endothelial progenitor cells and circulating endothelial cells after maximal exercise in patients with chronic heart failure of different severity. Methods: Forty-four chronic heart failure patients were enrolled in a 36-session cardiac rehabilitation program. All patients underwent an initial maximal cardiopulmonary exercise test before and a final maximal cardiopulmonary exercise test after the cardiac rehabilitation program. The patients were divided in two groups of severity according to the median value of peak VO2. Blood was collected at 4 time points; 2 time points at rest, and 2 time points after each cardiopulmonary exercise test. Five endothelial cellular populations were quantified by flow cytometry. Results: Although there was a higher increase in the mobilization of subgroups of endothelial progenitor cells and circulating endothelial cells after the final cardiopulmonary exercise test compared to the initial test within each severity group (p < 0.05), no significant differences between severity groups were observed (p > 0.05). Conclusions: A 36-session cardiac rehabilitation program had similar beneficial effects on the acute response of endothelial progenitor cells and circulating endothelial cells after maximal exercise in patients with chronic heart failure of different severity.

Effects of High-Intensity Interval Exercise Training on Skeletal Myopathy of Chronic Heart Failure.

BACKGROUND: It remains controversial which type of exercise elicits optimum adaptations on skeletal myopathy of heart failure (HF). Our aim was to evaluate the effect of high-intensity interval training (HIIT), with or without the addition of strength training, on skeletal muscle of HF patients. METHODS AND RESULTS: Thirteen male HF patients (age 51 ± 13 years, body mass index 27 ± 4 kg/m2) participated in either an HIIT (AER) or an HIIT combined with strength training (COM) 3-month program. Biopsy samples were obtained from the vastus lateralis. Analyses were performed on muscle fiber type, cross-section area (CSA), capillary density, and mRNA expression of insulin-like growth factor (IGF) 1 isoforms (ie, IGF-1Ea, IGF-1Eb, IGF-1Ec), type-1 receptor (IGF-1R), and binding protein 3 (IGFBP-3). Increased expression of IGF-1Ea, IGF-1Eb, IGF-1Ec, and IGFBP-3 transcripts was found (1.7 ± 0.8, 1.5 ± 0.8, 2.0 ± 1.32.4 ± 1.4 fold changes, respectively; P < .05). Type I fibers increased by 21% (42 ± 10% to 51 ± 7%; P < .001) and capillary/fiber ratio increased by 24% (1.27 ± 0.22 to 1.57 ± 0.41; P = .005) in both groups as a whole. Fibers' mean CSA increased by 10% in total, but the increase in type I fibers' CSA was greater after AER than COM (15% vs 6%; P < .05). The increased CSA correlated with the increased expression of IGF-1Ea and IGF-1Εb. CONCLUSIONS: HIIT reverses skeletal myopathy of HF patients, with the adaptive responses of the IGF-1 bioregulation system possibly contributing to these effects. AER program seemed to be superior to COM to induce muscle hypertrophy.

Effects of combined aerobic, resistance and inspiratory training in patients with pulmonary hypertension: A systematic review.

BACKGROUND: Pulmonary hypertension (PH) is a serious progressive disorder of the modern world, characterized by endothelial dysfunction and impaired vasoreactivity. Patients with PH usually present exercise intolerance from the very early stages and reduced exercise capacity. Exercise training has been shown to have beneficial effects in patients with cardiovascular comorbidities. However, data regarding the effects of combined exercise training programs in patients with PH still remains limited. AIM: To investigate the effects of combined exercise training programs on exercise capacity and quality of life in patients with PH. METHODS: Our search included all available randomized controlled trials (RCTs) regarding combined aerobic, resistance and inspiratory training programs in patients with PH in 4 databases (Pubmed, PEDro, Embase, CINAHL) from 2012 to 2022. Five RCTs were included in the final analysis. Functional capacity, assessed by peak VO2 or 6-min walking test (6MWT), as well as quality of life, assessed by the SF-36 questionnaire, were set as the primary outcomes in our study. RESULTS: Peak VO2 was measured in 4 out of the 5 RCTs while 6MWT was measured in all RCTs. Both indices of functional capacity were significantly increased in patients with PH who underwent combined exercise training compared to the controls in all of the included RCTs (P < 0.05). Quality of life was measured in 4 out of 5 RCTs. Although patients improved their quality of life in each group, however, only 2 RCTs demonstrated further improvement in patients performing combined training compared to controls. CONCLUSION: By this systematic review, we have demonstrated that combined aerobic, resistance and inspiratory exercise training is safe and has beneficial effects on aerobic capacity and quality of life in patients with PH. Such exercise training regimen may be part of the therapeutic strategy of the syndrome.

Safety and effectiveness of neuromuscular electrical stimulation in cardiac surgery: A systematic review.

BACKGROUND: Lack of mobilization and prolonged stay in the intensive care unit (ICU) are major factors resulting in the development of ICU-acquired muscle weakness (ICUAW). ICUAW is a type of skeletal muscle dysfunction and a common complication of patients after cardiac surgery, and may be a risk factor for prolonged duration of mechanical ventilation, associated with a higher risk of readmission and higher mortality. Early mobilization in the ICU after cardiac surgery has been found to be low with a significant trend to increase over ICU stay and is also associated with a reduced duration of mechanical ventilation and ICU length of stay. Neuromuscular electrical stimulation (NMES) is an alternative modality of exercise in patients with muscle weakness. A major advantage of NMES is that it can be applied even in sedated patients in the ICU, a fact that might enhance early mobilization in these patients. AIM: To evaluate safety, feasibility and effectiveness of NMES on functional capacity and muscle strength in patients before and after cardiac surgery. METHODS: We performed a search on Pubmed, Physiotherapy Evidence Database (PEDro), Embase and CINAHL databases, selecting papers published between December 2012 and April 2023 and identified published randomized controlled trials (RCTs) that included implementation of NMES in patients before after cardiac surgery. RCTs were assessed for methodological rigor and risk of bias via the PEDro. The primary outcomes were safety and functional capacity and the secondary outcomes were muscle strength and function. RESULTS: Ten studies were included in our systematic review, resulting in 703 participants. Almost half of them performed NMES and the other half were included in the control group, treated with usual care. Nine studies investigated patients after cardiac surgery and 1 study before cardiac surgery. Functional capacity was assessed in 8 studies via 6MWT or other indices, and improved only in 1 study before and in 1 after cardiac surgery. Nine studies explored the effects of NMES on muscle strength and function and, most of them, found increase of muscle strength and improvement in muscle function after NMES. NMES was safe in all studies without any significant complication. CONCLUSION: NMES is safe, feasible and has beneficial effects on muscle strength and function in patients after cardiac surgery, but has no significant effect on functional capacity.

Safety and Feasibility of Neuromuscular Electrical Stimulation in Patients with Extracorporeal Membrane Oxygenation.

Background/Objectives: The aim of this study was to investigate the feasibility and safety of neuromuscular electrical stimulation (NMES) in patients on extracorporeal membrane oxygenation (ECMO) and thoroughly assess any potential adverse events. Methods: We conducted a prospective observational study assessing safety and feasibility, including 16 ICU patients on ECMO support who were admitted to the cardiac surgery ICU from January 2022 to December 2023. The majority of patients were females (63%) on veno-arterial (VA)-ECMO (81%), while the main cause was cardiogenic shock (81%) compared to respiratory failure. Patients underwent a 45 min NMES session while on ECMO support that included a warm-up phase of 5 min, a main phase of 35 min, and a recovery phase of 5 min. NMES was implemented on vastus lateralis, vastus medialis, gastrocnemius, and peroneus longus muscles of both lower extremities. Two stimulators delivered biphasic, symmetric impulses of 75 Hz, with a 400 µsec pulse duration, 5 sec on (1.6 sec ramp up and 0.8 sec ramp down) and 21 sec off. The intensity levels aimed to cause visible contractions and be well tolerated. Primary outcomes of this study were feasibility and safety, evaluated by whether NMES sessions were successfully achieved, and by any adverse events and complications. Secondary outcomes included indices of rhabdomyolysis from biochemical blood tests 24 h after the application of NMES. Results: All patients successfully completed their NMES session, with no adverse events or complications. The majority of patients achieved type 4 and 5 qualities of muscle contraction. Conclusions: NMES is a safe and feasible exercise methodology for patients supported with ECMO.

Neuromuscular electrical stimulation for preventing skeletal-muscle weakness and wasting in critically ill patients: a systematic review.

BACKGROUND: Neuromuscular electrical stimulation (NMES) therapy may be useful in early musculoskeletal rehabilitation during acute critical illness. The objective of this systematic review was to evaluate the effectiveness of NMES for preventing skeletal-muscle weakness and wasting in critically ill patients, in comparison with usual care. METHODS: We searched PubMed, CENTRAL, CINAHL, Web of Science, and PEDro to identify randomized controlled trials exploring the effect of NMES in critically ill patients, which had a well-defined NMES protocol, provided outcomes related to skeletal-muscle strength and/or mass, and for which full text was available. Two independent reviewers extracted data on muscle-related outcomes (strength and mass), and participant and intervention characteristics, and assessed the methodological quality of the studies. Owing to the lack of means and standard deviations (SDs) in some studies, as well as the lack of baseline measurements in two studies, it was impossible to conduct a full meta-analysis. When means and SDs were provided, the effect sizes of individual outcomes were calculated, and otherwise, a qualitative analysis was performed. RESULTS: The search yielded 8 eligible studies involving 172 patients. The methodological quality of the studies was moderate to high. Five studies reported an increase in strength or better preservation of strength with NMES, with one study having a large effect size. Two studies found better preservation of muscle mass with NMES, with small to moderate effect sizes, while no significant benefits were found in two other studies. CONCLUSIONS: NMES added to usual care proved to be more effective than usual care alone for preventing skeletal-muscle weakness in critically ill patients. However, there is inconclusive evidence for its benefit in prevention of muscle wasting.

Post Hospital Discharge Functional Recovery of Critical Illness Survivors. Systematic Review.

Background: Millions of people face critical illnesses and need to be hospitalized in an Intensive Care Unit (ICU) annually worldwide. Despite the fact that survival rates of these patients have increased, they develop various cognitive, psychological and functional impairments. This study aims to investigate the significance of the recovery interventions following intensive care unit discharge, the effectiveness of the rehabilitative protocols and their possible deficits. Methods: MEDLINE (PubMed) and Physiotherapy Evidence Database (PEDro) were searched for studies analyzing the recovery potentials post-ICU among adults, who spent at least 48 hours at the ICU. Methodological quality of the studies was assessed via PEDro Scale. Results: Nine randomized controlled trials were included. These took place mainly at specialized rehabilitation gyms as well as patients home environments. Studies analyses showed that treatment group showed improvement in functional ability in relation to control group. Nevertheless, differences between two groups were not statistically significant (P<0.05). The majority of studies assessed cardiorespiratory endurance and muscular strength. Conclusions: The included rehabilitation programs were determined to be effective. Although they didn't prove any statistically significant difference between groups, quality of life enhancements and stress reduction were reported. Hence, new randomized controlled trials are required in order to provide more accurate data on the potential benefits of rehabilitation strategies among post-ICU patients.

Effectiveness of high intensity interval training on cardiorespiratory fitness and endothelial function in type 2 diabetes: A systematic review.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a chronic metabolic syndrome characterized by insulin resistance and hyperglycemia that may lead to endothelial dysfunction, reduced functional capacity and exercise intolerance. Regular aerobic exercise has been promoted as the most beneficial non-pharmacological treatment of cardiovascular diseases. High intensity interval training (HIIT) seems to be superior than moderate-intensity continuous training (MICT) in cardiovascular diseases by improving brachial artery flow-mediated dilation (FMD) and cardiorespiratory fitness to a greater extent. However, the beneficial effects of HIIT in patients with T2DM still remain under investigation and number of studies is limited. AIM: To evaluate the effectiveness of high intensity interval training on cardiorespiratory fitness and endothelial function in patients with T2DM. METHODS: We performed a search on PubMed, PEDro and CINAHL databases, selecting papers published between December 2012 and December 2022 and identified published randomized controlled trials (RCTs) in the English language that included community or outpatient exercise training programs in patients with T2DM. RCTs were assessed for methodological rigor and risk of bias via the Physiotherapy Evidence Database (PEDro). The primary outcome was peak VO2 and the secondary outcome was endothelial function assessed either by FMD or other indices of microcirculation. RESULTS: Twelve studies were included in our systematic review. The 12 RCTs resulted in 661 participants in total. HIIT was performed in 310 patients (46.8%), MICT to 271 and the rest 80 belonged to the control group. Peak VO2 increased in 10 out of 12 studies after HIIT. Ten studies compared HIIT with other exercise regimens (MICT or strength endurance) and 4 of them demonstrated additional beneficial effects of HIIT over MICT or other exercise regimens. Moreover, 4 studies explored the effects of HIIT on endothelial function and FMD in T2DM patients. In 2 of them, HIIT further improved endothelial function compared to MICT and/or the control group while in the rest 2 studies no differences between HIIT and MICT were observed. CONCLUSION: Regular aerobic exercise training has beneficial effects on cardiorespiratory fitness and endothelial function in T2DM patients. HIIT may be superior by improving these parameters to a greater extent than MICT.

The Effects of a Cardiac Rehabilitation Program on Endothelial Progenitor Cells and Inflammatory Profile in Patients with Chronic Heart Failure of Different Severity.

Endothelial dysfunction and inflammation are common pathophysiological characteristics of chronic heart failure (CHF). Endothelial progenitor cells (EPCs) are recognized as useful markers of vascular damage and endothelial repair. The aim of this study was to investigate the effects of a cardiac rehabilitation program on EPCs and inflammatory profile in CHF patients of different severity. Forty-four patients with stable CHF underwent a 36-session cardiac rehabilitation program. They were separated into two different subgroups each time, according to the median peak VO2, predicted peak VO2, VE/VCO2 slope, and ejection fraction. EPCs, C-reactive protein (CRP), interleukin 6 (IL-6), interleukin 10 (IL-10), and vascular endothelial growth factor (VEGF) were measured. Flow cytometry was used for the quantification of EPCs. Mobilization of EPCs increased and the inflammatory profile improved within each severity group (p < 0.05) after the cardiac rehabilitation program, but there were no statistically significant differences between groups (p > 0.05). A 36-session cardiac rehabilitation program has similar beneficial effects on the mobilization of EPCs and on the inflammatory profile in patients with CHF of different severity.

Exercise Training Effects on Circulating Endothelial and Progenitor Cells in Heart Failure.

Heart failure (HF) is a major public health issue worldwide with increased prevalence and a high number of hospitalizations. Patients with chronic HF and either reduced ejection fraction (HFrEF) or mildly reduced ejection fraction (HFmrEF) present vascular endothelial dysfunction and significantly decreased circulating levels of endothelial progenitor cells (EPCs). EPCs are bone marrow-derived cells involved in endothelium regeneration, homeostasis, and neovascularization. One of the unsolved issues in the field of EPCs is the lack of an established method of identification. The most widely approved method is the use of monoclonal antibodies and fluorescence-activated cell sorting (FACS) analysis via flow cytometry. The most frequently used markers are CD34, VEGFR-2, CD45, CD31, CD144, and CD146. Exercise training has demonstrated beneficial effects on EPCs by increasing their number in peripheral circulation and improving their functional capacities in patients with HFrEF or HFmrEF. There are two potential mechanisms of EPCs mobilization: shear stress and the hypoxic/ischemic stimulus. The combination of both leads to the release of EPCs in circulation promoting their repairment properties on the vascular endothelium barrier. EPCs are important therapeutic targets and one of the most promising fields in heart failure and, therefore, individualized exercise training programs should be developed in rehabilitation centers.

Impact of supervised aerobic exercise on clinical physiological and mental parameters of people living with HIV: a systematic review and meta-analyses of randomized controlled trials.

Background: The benefits derived from supervised aerobic exercise in people living with human immunofeficiency virus- HIV (PLWH) have not yet been clearly identified.Objective: To evaluate the impact of supervised aerobic exercise on immunological, cardiorespiratory, pulmonary, hemodynamic and mental parameters of PLWH.Methods: A systematic review was carried out in accordance to PRISMA guidelines. PubMed, Physiotherapy Evidence Database (PEDro) and Cochrane Central Register of Controlled Trials (CENTRAL) were screened up to August 2021, for the identification of English written randomized trials, with participants aged 18 years and older, at any stage of the disease, with or without co-morbidities. The risk of bias assessment was conducted according to the Cochrane Collaboration's tool for assessing risk of bias. Meta- analyses were conducted using continuous, inverse variance, random-effects model.Results: Ten studies were suitable for meta-analysis based on inclusion criteria. Supervised aerobic exercise appeared to have beneficial effects on depressive symptoms [mean difference (MD)= -4.18 (confidence interval (CI)= (-6.55)-(-1.81), Z = 3.46, p = 0.0005, I2=0%, n = 2], forced expiratory volume in 1 sec [MD = 0.70, CI = 0.39-1.00, Z = 4.41, p < 0.0001, I2=0%, n = 2], and on the maximum oxygen uptake [MD = 1.38, CI = -0.02-2.78, Z = 1.94, p = 0.05, I2=94%, n = 4] of PLWH. No exercise effect was found for CD4 T-cell count (p = 0.16, n = 5), systolic blood pressure (p = 0.91, n = 2) and diastolic blood pressure (p = 0.72, n = 2).Conclusions: Supervised continuous aerobic exercise may improve lung function, depressive symptomatology and aerobic capacity of PLWH, however, the small number of available studies and the high heterogeneity concerning VO2max demonstrate the need for more research in this area.

The effectiveness of immersive virtual reality in physical recovery of stroke patients: A systematic review.

Background: Over the past few years, technological innovations have been increasingly employed to augment the rehabilitation of stroke patients. Virtual reality (VR) has gained attention through its ability to deliver a customized training session and to increase patients' engagement. Virtual reality rehabilitation programs allow the patient to perform a therapeutic program tailored to his/her needs while interacting with a computer-simulated environment. Purpose: This study aims to investigate the effectiveness of a fully immersive rehabilitation program using a commercially available head-mounted display in stroke patients. Methods: A systematic search was conducted in three databases, namely, PubMed, Google Scholar, and PEDro. Four hundred thirty-two references were identified. The keywords used for the literature search were in English, which are given as follows: immersive, virtual reality, neurorehabilitation, stroke, and head-mounted display. Additionally, applicable articles were identified through screening reference lists of relevant articles. Results: Only 12 studies used head-mounted display for immersing the patient into the virtual world. Apart from the feasibility of this new technology, a range of benefits were identified, especially in terms of functional ability as measured by FIM or Barthel, the Action Research arm Test, Box and Block Test, Fugl-Meyer assessment of physical performance, strength, and balance outcomes. Conclusion: The results from this review support the potential beneficial effect of fully immersive virtual reality in the rehabilitation of stroke patients, maximizing recovery through increased motivation and adherence.

Effects of interval cycle training with or without strength training on vascular reactivity in heart failure patients.

BACKGROUND: Exercise training confers beneficial effects on vascular reactivity in patients with chronic heart failure (CHF). This randomized study compares the effects of interval cycle training combined with strength training versus interval training alone on vascular reactivity in CHF patients. METHODS: Twenty-eight consecutive stable CHF patients (23 males, 53 ± 10 years, 28.4 ± 4.1 kg/m(2), left ventricular ejection fraction of 37 ± 12%) were randomly assigned to 3 times' weekly training sessions for 3 months, consisting of a) 40 minutes of interval cycle training (n = 14), versus b) 20 minutes of similar interval training plus 20 minutes of strength training of the quadriceps, hamstrings, muscles of the shoulder and biceps brachialis (n = 14). The work/recovery ratio of each session was 30/60 seconds. The intensity of interval training was set at 50% of the peak workload achieved at the steep ramp test (consisted of a 25-Watt increase on a cycle ergometer every 10 seconds until exhaustion). All patients underwent maximal, symptom-limited cardiopulmonary exercise testing and ultrasound evaluation of vascular reactivity by flow-mediated vasodilation (FMD) before and after the program. RESULTS: A significant improvement in FMD was observed in the combined training group (P = 0.002), in contrast to the interval training alone group (P = NS); the improvement was significantly greater in the combined training than in the interval training alone group (P < .05). Peak oxygen uptake increased significantly and similarly in both groups, in the interval training group (P = .03), and in the combined training group (P = .006). No significant correlation was found between FMD improvement and cardiopulmonary exercise parameters. CONCLUSIONS: A combined high-intensity, interval cycle exercise with strength training induces a greater beneficial effect on vascular reactivity rather than interval exercise training alone in CHF patients.

Maximum inspiratory pressure, a surrogate parameter for the assessment of ICU-acquired weakness.

BACKGROUND: Physical examination has been advocated as a primary determinant of ICU-acquired weakness (ICU-AW). The purpose of the study is to investigate ICU-AW development by using Maximum Inspiratory Pressure (MIP) as a surrogate parameter of the standardized method to evaluate patients' peripheral muscle strength. METHODS: Seventy-four patients were recruited in the study and prospectively evaluated in a multidisciplinary university ICU towards the appearance of ICU-AW. APACHE II admission score was 16 ± 6 and ICU stay 26 ± 18 days. ICU-AW was diagnosed with the Medical Research Council (MRC) scale for the clinical evaluation of muscle strength. MIP was measured using the unidirectional valve method, independently of the patients' ability to cooperate. RESULTS: A significant correlation was found between MIP and MRC (r = 0.68, p < 0.001). Patients that developed ICU-AW (MRC<48) had a longer weaning period compared to non ICU-AW patients (12 ± 14 versus 2 ± 3 days, p < 0.01). A cut-off point of 36 cmH2O for MIP was defined by ROC curve analysis for ICU-AW diagnosis (88% sensitivity,76% specificity). Patients with MIP below the cut-off point of 36 cmH2O had a significant greater weaning period (10 ± 14 versus 3 ± 3 days, p = 0.004) also shown by Kaplan-Meier analysis (log-rank:8.2;p = 0.004). CONCLUSIONS: MIP estimated using the unidirectional valve method may be a potential surrogate parameter for the assessment of muscle strength compromise, useful for the early detection of ICU-AW.

Exercise training in heart transplantation.

Heart transplantation remains the gold standard in the treatment of end-stage heart failure (HF). Heart transplantation patients present lower exercise capacity due to cardiovascular and musculoskeletal alterations leading thus to poor quality of life and reduction in the ability of daily self-service. Impaired vascular function and diastolic dysfunction cause lower cardiac output while decreased skeletal muscle oxidative fibers, enzymes and capillarity cause arteriovenous oxygen difference, leading thus to decreased peak oxygen uptake in heart transplant recipients. Exercise training improves exercise capacity, cardiac and vascular endothelial function in heart transplant recipients. Pre-rehabilitation regular aerobic or combined exercise is beneficial for patients with end-stage HF awaiting heart transplantation in order to maintain a higher fitness level and reduce complications afterwards like intensive care unit acquired weakness or cardiac cachexia. All hospitalized patients after heart transplantation should be referred to early mobilization of skeletal muscles through kinesiotherapy of the upper and lower limbs and respiratory physiotherapy in order to prevent infections of the respiratory system prior to hospital discharge. Moreover, all heart transplant recipients after hospital discharge who have not already participated in an early cardiac rehabilitation program should be referred to a rehabilitation center by their health care provider. Although high intensity interval training seems to have more benefits than moderate intensity continuous training, especially in stable transplant patients, individualized training based on the abilities and needs of each patient still remains the most appropriate approach. Cardiac rehabilitation appears to be safe in heart transplant patients. However, long-term follow-up data is incomplete and, therefore, further high quality and adequately-powered studies are needed to demonstrate the long-term benefits of exercise training in this population.

Acute Cardiorespiratory Responses to Different Exercise Modalities in Chronic Heart Failure Patients-A Pilot Study.

The purpose of this study was to compare the acute cardiorespiratory responses and time spent above different %VO2peak intensities between three "iso-work" protocols: (a) a high intensity interval training protocol (HIIT), (b) a higher intensity continuous protocol (CON70) and (c) a lower intensity continuous protocol (CON50) in patients with chronic heart failure (CHF). Ten male CHF patients (aged 55.1 ± 16.2 years) performed in separate days a single session of a HIIT protocol consisted of 4 sets × 4 min cycling at 80% VO2peak with 3 min of recovery at 50% VO2peak, a CON70 protocol corresponding to 70% VO2peak and a CON50 protocol corresponding to 50% VO2peak. Cardiopulmonary data were collected by an online gas analysis system. The HIIT and CON70 elicited higher cardiorespiratory responses compared to CON50 with no differences between them (p > 0.05). In HIIT and CON70, patients exercised longer at >80% and >90% VO2peak. The completion rate was 100% for the three protocols. Not any adverse events were observed in either protocol. Both HIIT and CON70 elicited a stronger physiological stimulus and required shorter time than CON50. Both HIIT and CON70 also induced comparable hemodynamic responses and ventilatory demand.

Epigenetic effects following acute and chronic exercise in cardiovascular disease: A systematic review.

INTRODUCTION: Acute exercise and exercise training may confer epigenetic modifications in healthy subjects. Epigenetic effects after exercise have been showed in patients with cardiovascular disease. The aim of this systematic review was to summarize the evidence from available clinical trials that study epigenetic adaptations after exercise in patients with cardiovascular disease. METHODS: The search strategy was performed in PubMed and CENTRAL databases on articles published until September 2020. Studies with titles and abstracts relevant to exercise epigenetic modification applied to cardiovascular patients were fully examined. Inclusion and exclusion criteria were utilized for studies screening. Quality assessment with PEDro scale and evaluation by two independent reviewers was performed. RESULTS: Of the 1714 articles retrieved, 88 articles were assessed for eligibility criteria and 8 articles matched our search criteria and finally included in the systematic analysis. The acute exercise epigenetic (miRNAs) effects were assessed in three studies and the chronic exercise training effects (miRNAs and DNA methylation) in six studies. The results have shown that there is possibly an acute significant exercise effect on epigenetic targets which is more evident after chronic exercise training. CONCLUSIONS: By the present systematic review, we provide preliminary evidence of beneficial epigenetic adaptations following acute and chronic exercise in patients with cardiovascular disease. More controlled studies are needed to confirm such evidence.

Exercise Training Enhances Angiogenesis-Related Gene Responses in Skeletal Muscle of Patients with Chronic Heart Failure.

Peripheral myopathy consists of a hallmark of heart failure (HF). Exercise enhanced skeletal muscle angiogenesis, and thus, it can be further beneficial towards the HF-induced myopathy. However, there is limited evidence regarding the exercise type that elicits optimum angiogenic responses of skeletal muscle in HF patients. This study aimed to (a) compare the effects of a high-intensity-interval-training (HIIT) or combined HIIT with strength training (COM) exercise protocol on the expression of angiogenesis-related factors in skeletal muscle of HF patients, and (b) examine the potential associations between the expression of those genes and capillarization in the trained muscles. Thirteen male patients with chronic HF (age: 51 ± 13 y; BMI: 27 ± 4 kg/m2) were randomly assigned to a 3-month exercise program that consisted of either HIIT (N = 6) or COM training (N = 7). Vastus lateralis muscle biopsies were performed pre- and post-training. RT-PCR was used to quantify the fold changes in mRNA expression of vascular endothelial growth factor (VEGF), vascular endothelial growth factor receptor 2 (VEGFR-2), hypoxia-inducible factor 1 alpha (HIF-1α), angiopoietin 1 (Ang-1), angiopoietin 2 (Ang-2), angiopoietin receptor (Tie2), and matrix metallopeptidase 9 (MMP-9), and immunohistochemistry to assess capillarization in skeletal muscle post-training. There was an overall increase in the expression levels of VEGF, VEGFR-2, HIF-1α, Ang2, and MMP9 post-training, while these changes were not different among groups. Changes in capillary-to-fibre ratio were found to be strongly associated with Tie2 and HIF-1α expression. This was the first study demonstrating that both HIIT and combined HIIT with strength training enhanced similarly the expression profile of angiogenic factors in skeletal muscle of HF patients, possibly driving the angiogenic program in the trained muscles, although those gene expression increases were found to be only partially related with muscle capillarization.

Effects of exercise training on diastolic and systolic dysfunction in patients with chronic heart failure.

BACKGROUND: Chronic heart failure (CHF) is a complex syndrome characterized by a progressive reduction of the left ventricular (LV) contractility, low exercise tolerance, and increased mortality and morbidity. Diastolic dysfunction (DD) of the LV, is a keystone in the pathophysiology of CHF and plays a major role in the progression of most cardiac diseases. Also, it is well estimated that exercise training induces several beneficial effects on patients with CHF. AIM: To evaluate the impact of a cardiac rehabilitation program on the DD and LV ejection fraction (EF) in patients with CHF. METHODS: Thirty-two stable patients with CHF (age: 56 ± 10 years, EF: 32% ± 8%, 88% men) participated in an exercise rehabilitation program. They were randomly assigned to aerobic exercise (AER) or combined aerobic and strength training (COM), based on age and peak oxygen uptake, as stratified randomization criteria. Before and after the program, they underwent a symptom-limited maximal cardiopulmonary exercise testing (CPET) and serial echocardiography evaluation to evaluate peak oxygen uptake (VO2peak), peak workload (Wpeak), DD grade, right ventricular systolic pressure (RVSP), and EF. RESULTS: The whole cohort improved VO2peak, and Wpeak, as well as DD grade (P < 0.05). Overall, 9 patients (28.1%) improved DD grade, while 23 (71.9%) remained at the same DD grade; this was a significant difference, considering DD grade at baseline (P < 0.05). In addition, the whole cohort improved RVSP and EF (P < 0.05). Not any between-group differences were observed in the variables assessed (P > 0.05). CONCLUSION: Exercise rehabilitation improves indices of diastolic and systolic dysfunction. Exercise protocol was not observed to affect outcomes. These results need to be further investigated in larger samples.

The acute and long-term effects of a cardiac rehabilitation program on endothelial progenitor cells in chronic heart failure patients: Comparing two different exercise training protocols.

BACKGROUND: Vascular endothelial dysfunction is an underlying pathophysiological feature of chronic heart failure (CHF). Endothelial progenitor cells (EPCs) are also impaired. The purpose of the study was to assess the effect of a cardiac rehabilitation (CR) program on the increase of EPCs at rest and on the acute response after maximal exercise in patients with CHF and investigate whether there were differences between two exercise training protocols and patients of NYHA II and III classes. METHODS: Forty-four patients with stable CHF enrolled in a 36-session CR program and were randomized in one training protocol; either high-intensity interval training (HIIT) or HIIT combined with muscle strength (COM). All patients underwent maximum cardiopulmonary exercise testing (CPET) before and after the CR program and venous blood was drawn before and after each CPET. Five endothelial cellular populations, expressed as cells/106 enucleated cells, were quantified by flow cytometry. RESULTS: An increase in all endothelial cellular populations at rest was observed after the CR program (p < 0.01). The acute response after maximum exercise increased in 4 out of 5 endothelial cellular populations after rehabilitation. Although there was increase in EPCs at rest and the acute response after rehabilitation in each exercise training group and each NYHA class, there were no differences between HIIT and COM groups or NYHA II and NYHA III classes (p > 0.05). CONCLUSIONS: A 36-session CR program increases the acute response after maximum CPET and stimulates the long-term mobilization of EPCs at rest in patients with CHF. These benefits seem to be similar between HIIT and COM exercise training protocols and between patients of different functional classes.