Exercise Training Research Articles

Effects of variation in exercise training load on cognitive performances and neurotrophic biomarkers in patients with coronary artery disease.

This study compared the effects of linear (LP) and nonlinear (NLP) training periodization on cognitive functions, neurotrophic biomarkers [plasma brain-derived neurotrophic factor (BDNF), insulin-like growth factor-1 (IGF-1)], and cathepsin-B in patients with coronary artery disease (CAD). Forty-four patients with CAD reported to our laboratory on two occasions to undergo testing procedures before and after training sessions, and were then blindly randomized to NLP or LP for 36 training sessions. Visit 1 included blood samples and a maximal cardiopulmonary exercise testing to get maximal oxygen uptake (V̇o2peak). Visit 2 included cognitive functions assessment. Thirty-nine patients completed the study (LP: n = 20, NLP: n = 19), with no observed changes in cognitive performances after the training intervention in either group. IGF-1 concentration decreased in both groups (time-effect: P < 0.001), whereas BDNF concentration increased (time-effect: P < 0.05) without group interaction, and cathepsin-B did not change after the intervention. Associations were found between ΔV̇o2peak and ΔBDNF (R2 = 0.18, P = 0.04), and ΔIGF-1 and Δshort-term/working memory (R2 = 0.17, P = 0.01) in the pooled sample, with ΔIGF-1 and ΔBDNF accounting for 10% of the variance in Δshort-term/working memory. In the LP group, associations were found between ΔV̇o2peak and ΔBDNF (R2 = 0.45, P = 0.02), ΔBDNF and Δshort-term/working memory (R2 = 0.62, P = 0.004), ΔIGF-1 and Δshort-term/working memory (R2 = 0.31, P = 0.01), and ΔIGF-1 and Δexecutive function (R2 = 0.22, P = 0.04). This study indicates that linear and nonlinear training periodization led to an increase in BDNF, and a decrease in IGF-1, without change in cognitive function in individuals with stable CAD.NEW & NOTEWORTHY We used a novel and supervised iso-energetic training, integrating both moderate- and high-intensity aerobic exercises. Our findings indicate that greater variation in training load did not yield cognitive enhancements, although both protocols exhibited positive effects on brain-derived neurotrophic factor (BDNF) levels. Moreover, this study establishes a clear positive association between short-term and working memory and neurotrophic biomarkers. In addition, the independent predictive value of change in insulin-like growth factor-1 (IGF-1) on improvement in short-term and working memory highlight the close relationship between neurotrophic markers and cognition. Consequently, our results advocate for exercise training interventions targeting neurotrophic biomarkers to enhance cognitive function among individuals with coronary artery disease.

The Effect of Multi-Ingredient Protein versus Collagen Supplementation on Satellite Cell Properties in Males and Females

ABSTRACT Introduction Skeletal muscle satellite cells (SC) contribute to the adaptive process of resistance exercise training (RET) and may be influenced by nutritional supplementation. However, little research exists on the impact of multi-ingredient supplementation on the SC response to RET. Purpose We tested the effect of a multi-ingredient supplement (MIS) including whey protein, creatine, leucine, calcium citrate, and vitamin D on SC content and activity as well as myonuclear accretion, SC and myonuclear domain compared with a collagen control (COL) throughout a 10-wk RET program. Methods Twenty-six participants underwent a 10-wk linear RET program while consuming either the MIS or COL supplement twice daily. Muscle biopsies were taken from the vastus lateralis at baseline and 48 h after a bout of damaging exercise, before and after RET. Muscle tissue was analyzed for SC and myonuclear content, domain, acute SC activation, and fiber cross-sectional area (fCSA). Results MIS resulted in a greater increase in type II fCSA following 10 wk of RET (effect size (ES) = 0.89) but not myonuclear accretion or SC content. Change in myonuclei per fiber was positively correlated with type I and II and total fiber hypertrophy in the COL group only, indicating a robust independent effect of MIS on fCSA. Myonuclear domain increased similarly in both groups, whereas SC domain remained unchanged following RET. SC activation was similar between groups for all fiber types in the untrained state but showed a trend toward greater increases with MIS after RET (ES = 0.70). Conclusions SC responses to acute damaging exercise and long-term RET are predominantly similar in MIS and COL groups. However, MIS can induce greater increases in type II fCSA with RET and potentially SC activation following damage in the trained state.

Exercise improves muscle mitochondrial dysfunction-associated lipid profile under circadian rhythm disturbance.

We investigated whether endurance exercise training (EXT) ameliorates circadian rhythm (CR)-induced risk factors by improving skeletal muscle (SKM) mitochondrial biogenesis, reducing oxidative stress, and modulating apoptotic protein expression. We distinguished between regular and shift workers using the National Health and Nutrition Examination Survey (NHANES) and investigated the health problems caused by shift work (CR disturbance) and the potential therapeutic effects of exercise. In our animal study, 36 rats underwent 12 weeks of CR disturbance, divided into regular and irregular CR groups. These groups were further split into EXT (n = 12) and sedentary (n = 12) for an additional 8 weeks. We analyzed SKM tissue to understand the molecular changes induced by CR and EXT. NHANES data were analyzed using SAS 9.4 and Prism 8 software, while experimental animal data were analyzed using Prism 8 software. The statistical procedures used in each experiment are indicated in the figure legends. Our studies showed that CR disturbance increases dyslipidemia, alters circadian clock proteins (BMAL1, PER2), raises apoptotic protein levels, and reduces mitochondrial biogenesis in SKM. EXT improved LDL-C and HDLC levels without affecting muscle BMAL1 expression. It also enhanced mitochondrial biogenesis (AMPK, PGC-1α, Tfam, NADH-UO, COX-I), antioxidant levels (Catalase, SOD1, SOD2), and apoptotic protein (p53, Bax/Bcl2) expression or activity in SKM. We demonstrated that shift work-induced CR disturbance leads to dyslipidemia, diminished mitochondrial biogenesis, and reduced antioxidant capacity in SKM. However, EXT can counteract dyslipidemia under CR disturbance, potentially lowering the risk of cardiovascular disorders.

EFFECTS OF EXERCISE TRAINING ON THE AUTONOMIC NERVOUS SYSTEM IN HYPERTENSION: A COMPREHENSIVE REVIEW

Background: Cardiovascular diseases, significant health burdens globally, and conditions, including prevalent heart failure and hypertension, lead to increased hospitalizations, especially in the elderly, and account for substantial medical expenditures in developed nations. The emergence of hypertension as major global health challenges has intensified the focus on understanding and managing these conditions. Central to this endeavour is the exploration of the autonomic nervous systems role, particularly sympathetic nerve activity (SNA), in the pathophysiology of these diseases.Exercise training, a key non-pharmacological approach, has shown promise in mitigating these effects and reducing CVD risks, though the exact mechanisms remain under investigation. Objectives: To evaluate the effects of exercise training on sympathetic nervous activity on hypertensive individuals Method:A comprehensive review of observational, experimental, randomized control trial, cross-sectional studies were performed. SCOPUS, Google scholar, EBSCO and PubMed were searched using the terms exercise training, autonomic nervous activity, hypertension. Result: A total of 426 studies were identified of which 13 studies were published between 2010-2023 and were included in the study. Out of 426 studies, 12 studies which were included in our study showed positive effects of exercise training on the autonomic nervous system on hypertensive individuals Conclusion: This study concluded that there is significant relation between the exercise training and autonomic nervous system in hypertension.

ВЗАИМОСВЯЗЬ УТОЛЩЕНИЯ СВОДА СТОПЫ И РАЗВИТИЯ ЦНС У ДЕТЕЙ. (ОБЗОР ЛИТЕРАТУРЫ)

Today, the World Health Organization believes that musculoskeletal disorders in children occupy a leading position. According to statistics provided by Russian orthopedists over the past year, 24.2 - 67.3% of schoolchildren, depending on the region, have longitudinal or transverse flat feet. The second most common disorder in children is developmental disorders in the field of intellectual activity. Motor activity is a natural need for people to move. Intellectual development is understood as a set of various cognitive functions of an individual in society: from thinking, as well as perception, to the imagination and thinking of a person. Therefore, studying the relationship between the musculoskeletal and nervous systems in children is an important task of our time. The purpose of our study was to assess the relationship between thickening of the arch of the foot and the development of the central nervous system in children, through the prism of scientific works of orthopedists, pediatricians, neurologists and psychologists. Our review of the literature proves the importance of studying this problem and the need for a clinical study. To improve diagnostics, it is necessary to create a combined universal assessment system that will allow comparing results and conducting a mathematical analysis of the initial state of the musculoskeletal system and intellectual level in children, as well as to analyze changes in the course of therapy. Also, in our opinion, it is necessary to develop a set of exercises for therapeutic physical training that will not only strengthen muscles, form the arches of the feet, but also simultaneously train the frontal lobes of the brain, which will enhance concentration and develop memory. Therefore, we consider it necessary to expand the range and conduct extensive studies with a large sample size.

Exercise training ameliorates carbon tetrachloride-induced liver fibrosis and anxiety-like behaviors.

Chronic liver diseases and cirrhosis are associated with mood disorders. Regular exercise has various beneficial effects on multiple organs, including the liver and brain. However, the therapeutic effect of exercise on liver fibrosis concomitant with mood disorders, such as anxiety, has not been evaluated. In this study, the effects of exercise training on liver fibrosis-related anxiety-like behaviors were evaluated. Male C57/BL6 mice were divided into four groups: vehicle-sedentary, vehicle-exercise, carbon tetrachloride (CCl4)-sedentary, and CCl4-exercise. Liver fibrosis was induced by CCl4 administration for 8 weeks, exercise was applied in the form of voluntary wheel running. After intervention, anxiety-like behavior was assessed using the elevated plus maze. CCl4 increased liver and serum fibrotic markers, as measured by blood analysis, histochemistry, and qRT-PCR, and these changes were attenuated by exercise training. CCl4 induced anxiety-like behavior, which was ameliorated by exercise training. In the hippocampus, CCl4-induced changes in mRNA and protein levels of factors related to anxiety, including BDNF and nNOS, were reversed by exercise. These results suggested that hepatic fibrosis-related anxiety-like behaviors are induced by excess hippocampal nNOS, and the beneficial effects of exercise were mediated by increases in BDNF and reductions in nNOS. The percentage of fibrotic area was negatively correlated with anti-anxiety behavior and positively associated with hippocampal nNOS protein levels. Liver fibrosis-related anxiety-like behaviors could be alleviated through the regulation of hippocampal BDNF and nNOS via exercise training. These results support the therapeutic value of exercise by targeting the mechanisms underlying liver fibrosis and associated anxiety.

The impact of exercise training in Fontan procedure patients: a systematic review and meta-analysis

Abstract Background Patients undergoing the Fontan procedure experience long-term complications related to decreased exercise capacity. Exercise training(ET) has emerged as a non-pharmacological solution for increasing cardiorespiratory fitness. However, the effect and safety of exercise training in patients following the Fontan procedure are still unclear. Objectives We aimed to perform a meta-analysis comparing ET versus no exercise intervention for patients following Fontan operation in efficacy and safety outcomes. Methods We systematically searched PubMed, Embase, and Cochrane databases on November 23, 2023, for randomized controlled trials (RCTs) comparing ET, including aerobic, endurance, or inspiratory muscle training, versus no exercise intervention in patients following Fontan operation. We computed mean differences (MD) with a 95% confidence interval (CI) for continuous endpoints. The primary endpoint was (1) peak O2 consumption. Our study also included the secondary endpoints of: (2) maximum workload; (3) peak heart rate(HR); and (4) peak saturation of O2. We performed a subgroup analysis between different exercise therapies. Results This meta-analysis included five RCTs and 154 patients. Follow-up ranged from 3 to 6 months. Regarding ET, two studies used aerobics, one used endurance, and three used inspiratory muscle therapy as exercise therapy for patients with Fontan operations. Our findings on the maximum workload endpoint were more significant for exercise therapy (MD 20.98W; 95% CI 5.32 to 36.65; p&amp;lt;0.01; Fig. 1A) compared to no intervention group. However, there was no significant difference in peak oxygen (MD 2.03 ml/kg/min; 95% CI -0.29 to 4.35; p=0.095; Fig. 1B), peak HR (MD 1.10 bpm; 95% CI -4.07 to 6.27; p=0.68); and peak saturation of O2 (MD 0.39%; 95% CI -1.93 to 2.72; p=0.74). A subgroup analysis between different ET types (aerobic vs. endurance vs. inspiratory muscle training) showed no significant subgroup interaction(p=0.91; Fig. 1B). Conclusion In this meta-analysis, ET is associated with a slight increase in maximum workload in patients following the Fontan procedure. Further multicenter RCTs are warranted to assess the efficacy of comparing different types of ET and their impact on peak oxygen consumption.

Physical activity habits among members of the Athens Medical Society in Greece

Abstract Introduction Benefits of regular physical activity and exercise are well documented. Healthcare workers play a crucial role in counseling and appropriately referring their patients to adopt physical activity. However, doctors’ exercise habits range between different medical specialties and health service infrastructure. Purpose In this study, we assess physicians’ exercise performance according to the recommendations of 2020 ESC Guidelines. Methods The population of this cross-sectional study comprised 742 physicians of the Athens Medical Society (AMS), Greece. The study instrument was a self-administered questionnaire mailed in October 2023 to investigate physicians’ exercise habits, baseline characteristics of population, specialty, and health service infrastructure [Greek National Healthcare System (GNHS) or Private Practice (PP)]. European Society of Cardiology (ESC) Guidelines recommend at least 150 min/week of moderate-intensity exercise in all healthy adults. Subjects were divided in two groups according to their compliance to ESC Guidelines: 1. Moderate-intensity endurance exercise training per week ≥ 150 min (Group A); 2. Moderate-intensity endurance exercise training per week &amp;lt;150 min (Group B). Results The recommended exercise training per week goal is achieved by the majority of AMS members (53.4%) with an estimated mean exercise endurance training time of 240 ± 285 minutes. Between Group A and Group B there was no difference in age (50±12years vs. 50±13years, p=0.73), whereas there was significant difference in male sex prevalence (58% vs. 43%, p &amp;lt;0.001), in Body Mass Index (24.7 ± 3.8 kg/m2 vs. 26.2 ± 4.7 kg/m2, p &amp;lt;0.001), in Smoking habits (17.4% vs. 23.5%, p=0.04), in diabetes mellitus incidence (6.6% vs. 11.8%, p= 0.01) and in the use of activity monitoring wearables (45.2% vs. 29.8%, p&amp;lt;0.001). Interestingly, there was significant difference between GNHS and PP doctors representation in Group A and B with more doctors in the PP categorized in the Group A (p=0.008) (Figure 1). Importantly, logistic regression analysis revealed that even after adjustment for the aforementioned confounders there was significant under-representation of the GNHS in the Group A or otherwise doctors in the GNHS have 33% decrease odds of achieving the recommended exercise training per week (Odds Ratio: 0.676, 95%CI 0.484, 0.943, p=0.02) (Table 1). Conclusion A significant proportion of the AMS members follows the recommended ESC guidelines for minimum exercise training per week. Several factors affect their adherence to exercise time recommendation. Interestingly, AMS doctors working on the GNHS independently of other factors are less adherent to exercise recommendations. These findings emphasize the need to strengthen prevention strategies to AMS.

A prehabilitation programme is feasible and acceptable for mild-to-moderately frail patients undergoing cardiac surgeries

Abstract Background Preoperative frailty is a strong prognostication in cardiac surgical patients to predict poorer health outcomes. Intervening at the preoperative stage through prehabilitation is gaining increasing research attention. Previous studies tested a single frailty-reversing strategy, either nutritional or exercise, the exercise protocols were mainly aerobic-focused, which deviates from the exercise prescription principles suggested for frailty management, rendering an effective prehabilitation intervention is yet to be developed in cardiac surgical patients. Purpose This study aimed to examine the preliminary effects and explore the feasibility of a multi-component frailty-specific prehabilitation programme for mild-to-moderately frail patients undergoing cardiac surgeries/procedures. We hypothesised that compared with patients who receive usual care, patients awaiting cardiac surgeries who participate in the prehabilitation programme would have improved functional capacity, frailty status, quality of life and psychological outcomes, increased serum albumin and reduced C-reactive protein. Methods This study adopted a mixed-method design comprising a pilot randomised controlled trial and a qualitative study. Adult patients with a Clinical Frailty Scale score between 4 and 6, waiting for coronary artery bypass grafting surgery and/or valve repair/replacement, with at least 5 weeks of procedural waiting time and without contraindications for exercise were recruited. They were randomized in a 1:1 ratio to receive the prehabilitation programme or usual care. The programme comprised a structured preoperative education, nutritional optimization, stress management; and a multi-component exercise training with 3 sessions/week and 60 minutes/session. The exercise training lasted at least 4 weeks and maintained throughout the preoperative period. Results Twenty participants were randomized into the intervention (n = 11) or control (n = 9) group. The programme was feasible, acceptable and no severe adverse events were recorded. The lost to follow-up rate was 7.9%, and the overall attendance was 96%. The intervention group showed significantly greater improvement in functional capacity, frailty status and psychological outcomes than the control group at post-intervention. Participants gave positive comments about the programme and its delivery mode. They expressed that the one-on-one home-based practice enabled them greater confidence to overcome kinesiophobia. Two participants voiced out the preference for exclusive home-based training, rather than having hospital-based training in the first two weeks. Conclusion(s) The prehabilitation programme is feasible and acceptable for patients waiting for cardiac surgeries. It improves the functional performance, frailty status and psychological outcomes in these patients. A full-scale randomised controlled trial is warranted to investigate its longer-term and clinical effects.

Application of resistance exercise training combined with CT image evaluation in postoperative functional rehabilitation and fracture risk prediction of elderly femurs

ObjectiveTo evaluate the overall functional recovery of femoral patients, improve recovery ability, and prevent fractures in the elderly. MethodsA group of elderly femoral postoperative participants were selected and randomly divided into resistance exercise training and routine rehabilitation training. Simultaneously, a control group (without a history of fractures) and a fracture group (with a history of fractures) were designed to predict fracture risk. Finally, computerized tomography was used to evaluate the functional rehabilitation status. ResultsThe resistance exercise training group showed significantly better performance in functional rehabilitation and fracture risk prediction than the control group, and the decrease in Barthel index at 12 weeks after surgery in this group was 6.25 (P > 0.001). The age, gender, and volumetric bone density between the control group and the fracture group showed P > 0.001, and the differences were statistically significant. The average age of the control group was significantly higher than that of the fracture group, and the proportion of males in the fracture group was significantly higher than that of the control group. The intramuscular fat content of the iliopsoas muscle in the fracture group was significantly lower than that in the control group, P = 0.004. This indicated that lower intramuscular fat content of the iliopsoas muscle was associated with higher fracture risk, as participants with lower intramuscular fat content of the iliopsoas muscle had less bone protection, resulting in an increased risk of fracture. The difference in body mass index between the two groups was not statistically significant, P = 0.737, indicating that the impact of this parameter on fracture risk was not significant in this study. ConclusionResistance exercise training combined with CT image evaluation is an effective rehabilitation strategy with high clinical application value. This study provides reliable empirical evidence for the application of resistance exercise training and the combination of CT image evaluation, and provides guidance for the optimization of clinical rehabilitation strategies.

Effect of incremental exercise training interventions in a Cardiac Rehabilitation Program following myocardial infarction

Abstract Background Exercise-based cardiac rehabilitation is recommended after myocardial infarction (MI) to improve prognosis, quality of life and control of cardiovascular risk factors. However, the specific impact of different exercise training interventions remains incompletely understood. Purpose To study the health outcomes of three incremental exercise training interventions during a Cardiac Rehabilitation Program (CRP) following MI. Methods We implemented a post-MI Phase 2 CRP in 2022. After initial exercise testing, a 3-month, individualized aerobic and strength ambulatory training program was provided by Cardiologists and Physical Medicine and Rehabilitation physicians (Group 1, n=58). Additionally, a subset of patients received one session of supervised teaching of aerobic and strength training by physiotherapists (Group 2, n=19), and another subset received 8-20 sessions of in-hospital supervised training (Group 3, n=13). Exercise testing was repeated at the end of Phase 2 and peak oxygen consumption (peak VO2) was measured. We analysed quality of life (SF-36), depression (PHQ2), anxiety (GAD2), adherence to Mediterranean diet (PREDIMED) and pharmacological treatment (Morisky-Green), and weekly physical activity (IPAQ). Health outcomes were compared at the beginning and after Phase 2 CRP. Results The cohort comprised 90 patients who completed Phase 2 CRP (mean age 61.2±10.8 years, 84.4% male and 47.8% smokers). Reductions in systolic blood pressure (-10.3±13.8mmHg), LDL cholesterol (-60.7±35.4mg/dL), weight (-2.8±6.6kg, -3±7.8%) and body mass index (-1±2.2) were attained (p&amp;lt;0.05). Smoking abstinence was accomplished in 88.4% of smokers and most patients achieved an LDL&amp;lt;55mg/dL (81.1%). Improvements in quality of life (SF-36 +10.4±19.4 points, p&amp;lt;0.001) and anxiety and depression symptoms (PHQ2 -0.5±1.6 points and GAD2 -0.6±1.6 points, p&amp;lt;0.01) were noted. An increase in peak VO2 (+5.12±5.44ml/kg/min, +23.5±27.4% from baseline, p&amp;lt;0.001) and predicted functional capacity (+13.4±23.8%, p&amp;lt;0.001) was achieved. Patients increased their reported weekly physical activity by 2520.3±2935.4 METS/week (+132% from baseline, p&amp;lt;0.001) and most of them were adherent to Mediterranean diet (91.1%) and pharmacological treatment (95.6%). Patients achieved similar health outcomes regardless of their exercise training group, except for patients in Group 3, who experienced a more pronounced improvement in peak VO2 (+8.1±6.4ml/kg/min, +37.8±34.7% from baseline; p&amp;lt;0.05) and a trend towards higher increase in predicted functional capacity (+21.7±19.2%, p&amp;lt;0.25) and greater weight loss (-5.5±9.4kg, -5.9±9.6%; p&amp;lt;0.2). Conclusions Supervised in-hospital training during a Phase 2 CRP provides superior physical fitness improvements and more pronounced weight loss in MI patients. However, a Phase 2 CRP based on ambulatory training provides similar benefits regarding other health outcomes, such as control of cardiovascular risk factors and quality of life amelioration.Exercise training interventions in a CRP

Moderate intensity exercise training ameliorates the heart failure with preserved ejection fraction phenotype in a preclinical model by improving cardiometabolic fitness

Abstract Introduction and Aim Exercise intolerance is a hallmark feature of patients with heart failure with preserved ejection fraction (HFpEF).While clinical evidence suggests potential benefits of exercise training in HFpEF, its mechanisms remain largely unknown.In this study, we used a translationally relevant murine model of cardiometabolic HFpEF(1) to assess whether moderate intensity continuous training(MICT) can ameliorate the HFpEF phenotype in mice and promote cardiometabolic health. Methods Twenty-five adult, male C57BL/6N were fed with the combination of high fat diet(HFD;D12492,Research diet)and L-NAME(0.5 g/L,in drinking water) for 15 weeks to elicit HFpEF as previously described(1).After the establishment of the HFpEF phenotype, mice were randomized in two groups:sedentary(SED,n= 10) and exercised(MICT,n=15)mice.MICT was carried out according to the protocol:running on 10-degree positive inclination treadmill for 8 consecutive weeks,5 times/week,60 minutes/day,at a speed gradually increasing from 0.1 to 0.2 m/sec on a weekly basis.Morphometry, echocardiography(TTE),isoproterenol-induced stress echocardiography(SE),time domain nuclear magnetic resonance, and treadmill exhaustion tests were performed at the beginning and end of MICT.Additionally, at the end of MICT blood and tissues were collected for proteomics analysis(Fig1).Non-trained male C57BL/6N mice(37w) were used as controls for the HFpEF mice. Results Before randomization, all HFpEF mice were similar in terms of phenotypic characteristics. Compared to SED mice, MICT induced a significantly decrease in body weight driven by a reduction of total fat mass with an increased in lean mass(Fig2A+B).Interestingly, MICT had no impact on skeletal muscle mass for all different muscle groups evaluated (extensor digitorum longus, soleus and tibialis anterior).Importantly, MICT led to a significant improvement in exercise capacity in HFpEF mice, as shown by increased running distance and time, surpassing even the running distance seen in non-HFpEF mice (SED:62.8±18.7,MICT:305.7±13.9,non-HFpEF mice: 129.72±15.2meters,p&amp;lt;0.001).Preclinical surrogate of HFpEF such as pulmonary congestion, evaluated by index lung weights, improved after aerobic training.Following MICT there was a marked improvement in diastolic dysfunction(measured by E/E’ratio) both at rest(SED:36.5±3.3,MICT:23.3±5.09,p&amp;lt;0.001) and after isoproterenol challenge(SED:42.6±15.1,MICT:26.09±3.75,p&amp;lt;0.001)(Fig2C).Moreover, the wet cardiac mass was lower in the MICT group(Fig2A), suggesting potential amelioration in cardiac hypertrophy following aerobic training. Conclusion Eight weeks of supervised MICT on treadmill improves functional status, exercise capacity, and diastolic function in a cardiometabolic HFpEF murine model.The most significant effects were seen on weight loss and fat mass reduction.Our findings suggest a beneficial impact of aerobic exercise in mitigating HFpEF by improving metabolic fitness in the preclinical HFpEF model.Fig1-Study DesignFig2-Characteristics SED vs MICT groups

A systematic review and meta-analysis of health-related quality of life (HRQoL) outcomes in randomised controlled trials for pulmonary arterial hypertension (PAH)

Abstract Introduction ESC guidelines recognise the under use of disease-specific health-related quality of life (HRQoL) instruments. These include CAMPHOR, PAH-SYMPACT, Emphasis-10 and Living with Pulmonary Hypertension (LPH). Patients highly value HRQoL as a treatment outcome in PAH. This is the first meta-analysis to evaluate HRQoL instruments and outcomes in RCTs in pulmonary arterial hypertension (PAH). Purpose To evaluate which PAH-RCT interventions improve HRQoL outcomes and compare the suitability of HRQoL instruments used. Method We searched MEDLINE (Jan 1970 to Dec 2023) and Cochrane Library from Jan 1990 to Dec 2023 (EMBASE, CT.gov, ICTRP, CINAHL) for RCTs in PAH. Abstracts and unpublished studies were excluded and PRISMA reporting structure followed. Trials meeting final selection criteria included HRQoL instruments sufficiently powered to detect a minimal clinically important difference (MCID). Effective sample sizes were calculated in GPower3.1 from a two independent means model for 80% power, 5% significance, one-tailed test. Meta-analysis was performed in SPSSv28.1. Full search criteria are registered on PROSPERO (ID: CRD42024484021). Results After removal of duplicates, 896 records were screened, 43 studies included a HRQoL endpoint. 8 studies were included in the meta-analysis after exclusion for insufficient data (n=10) or power (n=25). 3 of these did not meet the MCID (&amp;gt;33m) for six-minute walk distance (6MWD) and evaluated separately to discriminate accuracy of HRQoL instrument. Instruments available for comparison were Short Form-36(SF-36), EuroQol (EQ-5D-5L) and Living with Pulmonary Hypertension (LPH). Studies not reaching MCID for 6MWD also showed no change in HRQoL (figure 1). Ambrisentan and exercise training demonstrate a significant improvement (p&amp;lt;0.05) in SF-36 physical(P) component (figure 2). This component was anchored to determine 6MWD MCID; other HRQoL values responded variably. Utility weighting to account for geographical variation was not reported with EQ-5D-5L and SF-36 in multicentre studies however AIR 2002 (Iloprost) was significant for both EQ-5D-5L instruments. The total component score of the disease-specific LPH was more sensitive to functional improvements and overall change in HRQoL compared to EQ-5D-5L (p&amp;lt;0.05). Conclusion Fewer than 10% of all RCTs in PAH have adequately considered a HRQoL outcome measure. 8 RCTs were powered to assess HRQoL. Iloprost, ambrisentan, riociguat and exercise training interventions demonstrate significant improvement in HRQoL. LPH was the only PAH-instrument powered to detect change. LPH was more sensitive to HRQoL than generic instruments and is multidimensional. Geographical indexing should be considered for generic instruments such as EQ-5D-5L and SF-36 in multicentre trials. As a highly valued outcome for patients, future studies should prioritise HRQoL as an endpoint.Figure 1Figure 2

Efficacy of online japanese intensive cardiac rehabilitation for secondary prevention for coronary artery disease: a comprehensive program including exercise, nutrition, mindfulness, and group support

Abstract Background/Introduction While comprehensive programs for cardiac rehabilitation are recommended for patients with coronary artery disease (CAD), systematic programs including nutrition, stress-management, and behavior change have not been clearly established. Purpose To comprehensively change the lifestyle of patients with CAD as secondary prevention, we developed an online based educational program "intensive cardiac rehabilitation for Japanese patients with CAD (J-ICR)" modifying ICR, a regimen covered by health insurance in the United States, to the program that has affinity with Japanese. Methods Online J-ICR program is set up as sessions for maintenance-phase CAD patients using an online application. J-ICR has 12 sessions held weekly for 3 hours per session, total 36 hours, aimed to integrate 4 components: 1) exercise guidance based on exercise prescription which contain aerobic exercise, resistance training, and multi-component exercise through online platforms, 2) dietary education focusing on "the Japan Diet", 3) stress management utilizing mindfulness, and 4) group support to enhance patient and medical-staff interaction. Twenty-two participants were randomly separated to Early Phase group and Late phase group. For verification of the efficacy of this program, we survey the adherence to the program and compared the changes in risk factor of CAD at 3 months defining Early phase group as intervention group and Late phase group as control. (Fig.1). Results After excluding 3 participants who withdrawn to participate, the remaining 19 participants were conducted the evaluation and 10 participants were in intervention group and 9 participants in control group, respectively. As for patient characteristics, the mean age was 66 years old, and all participants were male. History of CVD was comprising 8 cases of myocardial infarction and 15 cases of angina pectoris. As for the risk factors of CVD, there were not significant differences in mean low density lipoprotein (LDL) cholesterol (Intervention group 71.5mg/dl vs Control group 83.4mg/dl; p=0.12) or systolic blood pressure (SBP) (126mmHg vs 130mmHg; p=0.40) at base line between two groups. The average participating rate in program was 93.8% and there was no dropped out participant during the program in investigation group. After 3months, LDL cholesterol was not significantly decreased in both groups (mean reduction of Intervention group -0.3mg/dl, p=0.93 and control group -3.8mg/dl, p=0.43, respectively). However, there was significant reduction of SBP in intervention group (mean reduction 5.6mmHg, p=0.02) but in control group (mean reduction 2.4mmHg, p=0.42). (Fig.2). Conclusions This randomized controlled study showed the good adherence of J-ICR program and it suggested that J-ICR program has the effect on lowering systolic blood pressure at 3 months. Longer follow up data and the results of more participants are warranted to clarify the efficacy in real world prevention of CVD.

Associations of Cardiac myosin binding protein C to Troponin I in patients with chronic heart failure during exercise. A substudy of the SMARTEX-HF trial

Abstract Aim Cardiac myosin binding protein C (cMyC) has shown promise being more sensitive than cardiac troponins, rising faster after myocardial infarction[i]. Its association to hs-cTnI in heart failure patients during physical activity is not known. The aim of this study was to assess the association between a novel biomarker: cMyC and the clinically used high sensitivity cardiac Troponin I (hs-cTnI) during a 12-week exercise training program in patients with chronic symptomatic heart failure with reduced ejection fraction (HFrEF). The changes of biomarkers in plasma levels in an intervention group, performing structured exercise programs, were compared to those in a control group, instructed to perform regular recommended exercise (RRE) according to current guidelines. Methods and results This was a post hoc analysis of the SMARTEX-HF trial in 215 patients with symptomatic heart failure (HF) with Left Ventricular Ejection Fraction (LVEF) &amp;lt;35% and NYHA II-III. The patients were randomly assigned to High Intensity Interval Training (HIIT, n=77), Moderate Continuous Training (MCT, n=65) or RRE, (n=73) for 12 weeks. Measurements and clinical data were acquired before and after the 12-week intervention. In 191 patients, plasma was available for hs-cTnI testing and in 189 patients plasma was available for cMyC testing. Due to the lack of a normal distribution, the values were log transformed. There was a significant association of change in log hs-cTnI and change in log cMyC (Pearson correlation R=0.52 (95% CI 0.37- 0.66) p&amp;lt;0.001) (Figure 1). For any 10% increase in cMyC level, the ratio of the hs-cTnI level increased with approximately 5% (Figure 2). There was no association between the levels of cMyC at baseline and change in hs-cTnI at 12 weeks. Conclusion Changes in levels of the novel biomarker cMyC was significantly associated with hs-cTnI plasma levels in patients with symptomatic chronic HFrEF during a structured 12 week exercise training program. Being more sensitive, it may indicate a role as a future marker of subclinical myocardial damage.Models with adjustmentsMarginal effect at the mean

Activation patterns of intracellular signaling pathways in cardiac hypertrophy induced by different exercise modes in rats

Abstract Introduction Cardiac remodeling and hypertrophy cause as adaptive responses to physiological and pathological stimuli. Physiological cardiac hypertrophy is characterized by normal or enhanced cardiac function and myocardial metabolism, and induces concentric and eccentric hypertrophy by different exercise modes, without cardiac dysfunction and fibrosis. Each formative mechanism of cardiac hypertrophy is regulated by distinct and/or similar cellular signaling pathways. Activation of cardiac intracellular signaling pathway of phosphoinositide 3- kinase (PI3K) is involved in an underlying mechanism of developed eccentric cardiac hypertrophy by aerobic exercise training (AT). However, the activation patterns of intracellular signaling pathways of physiological cardiac hypertrophy by different exercise modes remain unclear. Purpose The purpose of this study was to investigate the activation patterns of intracellular signaling pathways in cardiac hypertrophy induced by different exercise modes, including AT, resistance training (RT), and high intensity interval training (HIIT). Methods Forty male 10-week-old Sprague-Dawley (SD) rats were divided into four groups; sedentary control (Con, n=10), AT (treadmill running, 60 min at 30 m/min, 5 days/wk for 8 wk, n=10), RT (ladder climbing, 8-10 sets/day, 3 d/wk for 8 wk, n=10), HIIT (14 repeats of 20-s swimming session with 10-s pause between sessions, 4 d/wk for 6 wk from 12-wk-old, n=10) groups. As a cardiac hypertrophic intracellular signaling pathways, PI3K protein expression level and mTOR and MAPK (ERK1/2, JNK1/2 and p38) phosphorylation levels in rat hearts were measured by Western blotting analysis. Results The hearts of rats in each training group developed cardiac hypertrophy. Moreover, the enzyme activity of oxidative phosphorylation in the skeletal muscle was promoted in the AT group, the oxidative phosphorylation and glycolytic enzyme activities were promoted in the HIIT group, and muscle hypertrophy occurred in the RT group. Levels of PI3K protein expression and mTOR phosphorylation in the heart were significantly higher in the AT, RT, and HIIT groups as compared to the Con group (each p&amp;lt;0.05). Additionally, p38 phosphorylation level in the heart was significantly higher in the RT group as compared to the Con, AT, and HIIT groups (each p&amp;lt;0.05). Furthermore, p44 ERK phosphorylation level in the heart of the RT group was significantly higher than that in the AT and HIIT groups (each p&amp;lt;0.05), but p42 ERK phosphorylation level did not differ among four groups. JNK1/2 (p46/p54) phosphorylation level in the heart was significantly higher in the RT group as compared to the Con group (p&amp;lt;0.05). Conclusion These findings suggest that the activation of PI3K-mTOR signaling pathway in the heart may be involved in the development of AT, RT and HIIT-induced cardiac hypertrophy, and the MAPK signaling activation may affect the development of cardiac hypertrophy by RT.

Chronotropic incompetence predictors in a Cardiac Rehabilitation Program following myocardial infarction

Abstract Background Chronotropic incompetence (CI) has been described in many patients after myocardial infarction (MI) and can negatively affect physical capacity, especially if negative chronotropic therapy (NCT) is prescribed. Prediction of CI after MI could be useful for tailored medical therapy and exercise training prescription. Purpose We aim to predict CI on initial exercise ECG testing (ExECG) in MI patients submitted to a Cardiac Rehabilitation Program (CRP). Methods Patients with ST-segment elevation MI (STEMI) or occlusion MI (OMI) submitted to our CRP were prospectively included. After an initial follow-up phase of clinical stabilization and medical therapy optimization, ExECG (conventional or cardiopulmonary) was performed. Peak VO2 and chronotropic reserve index [(maximum heart rate – resting heart rate) / ([220-age] – resting heart rate)] were measured. Chronotropic incompetence was defined as &amp;lt;80% chronotropic reserve index (≤62% in patients treated with NCT). Pharmacological therapy with NCT was registered in absolute and equivalent doses per bisoprolol 2.5mg units (B2.5EU). The effect of NCT on CI was studied by ANOVA test, and predictors of CI by binary logistic regression analysis. The model was tested by area under the curve (AUC) analysis in receiver operating characteristic curves. A p&amp;lt;0.05 was considered statistically significant. Results The cohort comprised 143 patients, mostly middle-aged (mean 60.3±15.8 years) males (85.3%) with anterior or inferior MI (44.8% and 44.8%, respectively). Mean left ventricular ejection fraction (LVEF) was 52.4±10.6% and 36.4% depicted LVEF&amp;lt;50%. NCT was prescribed in most patients (n=125, 87.4%), and median equivalent dose was 1 [0.5-1] B2.5EU. CI was noted on more than half of the population on initial ExECG (n=75, 52.4%). Higher NCT doses per B2.5EU associated with worse mean chronotropic reserve indexes: 72.8±24.4% in patients without NCT; 71.7±18.7% in patients with 0.5 B2.5EU; 62.8±18.2% in patients with 1 B2.5EU; and 58.7±16.9% in patients with ≥2 B2.5EU (ANOVA p=0.04). On binary logistic regression analysis, only two variables were independent predictors of CI: diabetes mellitus (HR 3.02 [1.26-7.23], p=0.01) and LVEF (0.97 [0.94-0.99] per increased %, p=0.04). However, the predictive power of the model was poor (AUC 0.62 [0.53-0.71], p=0.01). Conclusions Chronotropic incompetence after a MI is associated with lower LVEF, diabetes mellitus, and higher doses of NCT. Although significant interindividual variability exists in chronotropic response in the post-infarction period, these factors could be taken into consideration for tailored prescription (or deprescription), especially in patients who may not derive any prognostic benefit from NCT.Chronotropic incompetence in CRP

Signal-morphology impedance cardiography is a non-invasive tool to predict responses to exercise based cardiac rehabilitation in chronic heart failure patients

Abstract Background All the studies and meta-analyses showed beneficial effects of the exercise based cardiac rehabilitation (ExBCR) on peak value of oxygen uptake (VO2peak) in patient with chronic heart failure (CHF). It is widely recognized that changes in VO2peak induced by training (ΔVO2peak) have a prognostic value. A 5.0% increase in ΔVO2peak has been associated with a significant clinical improvement1. However, 20 to 30 % of CHF are non-responders to ExBCR. The Signal-Morphology Impedance Cardiography (SM-ICGTM) technology has allowed previous researchers to show the role of cardiac output (CO) on DVO2peak2. CO responses may be partly attributed to the peak ejection flow velocity that can explain the impaired response to ExBCR. Purpose The study aimed to establish whether SM-ICGTM is an appropriate technology to predict responses to ExBCR in CHF patients. Methods A retrospective study was conducted on 65 CHF patients (LVEF: 29.0±8.3%). All patients performed a cardiopulmonary exercise test (CPET) on bicycle to determine ventilation (VE) and VO2peak before and after 20 ExBCR sessions. In addition, stroke volume (SV), heart rate (HR), and CO were continuously monitored by SM-ICGTM (PhysioFlow® Lab1). The value of peak ejection flow velocity, so called CTi by the manufacturer, was calculated as the peak of the first mathematical derivative over the time of the impedance waveform during the systole and measured by PhysioFlow® throughout the test. For the analysis of training response patients were divided in two groups: the normal CTi profile which was characterized by an initial increase followed by a plateau until CPET exhaustion, and the abnormal CTi response if CTi decreased at the onset of CPET or increased then decreased before exhaustion. Statistical analyses were performed with JASP. The significant level was set at p value &amp;lt; 0.05 for 95% confidence interval. Results Our study population consisted in 32 patients who presented a normal CTi profile and 33 with an abnormal CTi profile. As shown in Table 1, no significant difference was found at baseline between both groups. ExBCR induced significant changes in VO2peak even if 29 % patients were non-responders. Patients with normal CTi profile presented a greater DVO2peak compared to patients with abnormal CTi profile (28 ± 30 vs. 14 ± 19 %, p&amp;lt;0.01). 78% of patients with normal CTi profile versus only 64% of patients with abnormal CTi profile were ExBCR responders. The logistic regression showed that patient with normal CTi profile were 3.3 time more likely to present a ΔVO2peak ≥ 5%. Conclusion Exercise CTi profiles determined by SM-ICGTM prove to be an interesting tool to help predicting ExBCR responses in CHF patients and maybe highlighting the hemodynamic determinants of VO2 responses to exercise training.

Do patients maintain improvement in physical capacity achieved after hybrid telerehabilitation implemented as part of managed care after acute myocardial infarction program at one-year follow-up?

Abstract Background Managed Care after Acute Myocardial Infarction (MC-AMI) is a one-year comprehensive care program dedicated to patients with acute coronary syndrome introduced in Poland. It includes acute intervention, complex revascularization, implantation of cardiovascular electronic devices (in case of indications), rehabilitation or hybrid rehabilitation (HTR) and scheduled outpatient follow-up. HTR is a unique component of MC-AMI program. Purpose The purpose of this study was to evaluate whether the effect of improving physical capacity achieved after 5-week HTR was maintained during one-year follow-up. Methods The study enrolled 84 patients (90% males, aged 57.5 ± 10.2 years, LVEF 54,6 ± 6.8%) who underwent a 5-week HTR based on Nordic walking training and completed the entire one-year MC-AMI program. Unless there were contraindications, HTR began no later than 14 days after discharge from the hospital and consisted of an initial phase (1 week) conducted in an outpatient center and 4 weeks of telemonitored exercise training at home, five times weekly. Exercise capacity was assessed by comparing the exercise test results at baseline (before HTR), immediately after HTR and at the end of one-year MC-AMI program. Results HTR resulted in significant improvement in workload [METS] and workload duration in exercise test. This valuable effects were maintained after one-year follow-up. All results are presented in Table 1 and Figure 1. Conclusion The improvement in physical capacity achieved after 5-week of the hybrid telerehabilitation was maintained in patients who completed MC-AMI program in one-year follow-up.

Regular supervised exercise training improves endothelial function, early atherosclerosis, arterial stiffness and endothelial progenitor cells in PCI patients

Abstract Backgrounds A disrupted balance between endothelial injury and repair induces endothelial dysfunction and endothelial progenitor cells (EPC) augment vascular repair. So, exercise improves endothelial function through increased numbers of EPC. We investigated the effect of training on vascular health by measuring the number of circulating EPC, and assessing flow-mediated dilation (FMD), brachial-ankle pulse wave velocity (baPWV) and carotid intima-media thickness (IMT) in patients with percutaneous coronary intervention (PCI). Methods Fifty-nine patients who were done PCI recently were randomized to full medical treatments or additional 3 months regular supervised exercise program (4 times a week, 1 hr a day). FMD, baPWV, carotid IMT, HOMA, hs-CRP and lipid profiles were measured and circulating CD34/KDR, CD34/CD117 and CD34/CD133 EPC were quantified by flow cytometry at baselines and after 3 months. Results Finally 23 patients joined exercise program(control, N=28). There was no significant difference of baseline characteristics and medication between 2 groups. After 3 months, FMD improved significantly in exercise group (6.62% to 11.48%) compared with control group (7.61% to 8.45%) (P&amp;lt;0.001) (fig 1). Carotid IMT reduced significantly in exercise group (0.759mm to 0.707mm) compared with control group (P=0.015) (fig 2). ba-PWV reduced significantly in exercise group (1529cmm/s to 1455 cmm/s) compared with control group (P=0.016) (fig 3). Numbers of CD34/KDR, CD34/CD117 and CD34/CD133 EPCs increased significantly after exercise compared with control group (P= 0.041, 0.011, 0.022, respectively) (fig 4). We also could see to reduce waist to hip ratio in exercise group compared with control group (P&amp;lt;0.001). Conclusions Three months regular supervised exercise improved FMD, ba-PWV, carotid IMT and waist to hip ratio in PCI patients. and it augmented numbers of circulating EPCs. Our results showed that exercise contributes to additional improvement of vascular health in PCI patients with optimal medical treatments.