Recommendation Of Regular Exercise Research Articles

Impact of high-intensity exercise training (HIIT) versus moderate continuous training (MCT) on skeletal muscle alterations in HFrEF: a substudy of the SMART-EX trial

Abstract Background Skeletal muscle dysfunction contributes to exercise intolerance in chronic heart failure. The randomized multicenter Study of Myocardial Recovery After Exercise Training in Heart Failure (SMART-EX) has shown that high-intensity exercise training (HIIT) but not moderate continuous training (MCT) reduced the left ventricular end diastolic diameter. Both training modalities significantly increased exercise tolerance as determined by cardiopulmonary exercise testing (CPET). However, the underlying molecular alterations within the skeletal muscle with respect to different exercise training modalities are largely unknown. Methods In patients with chronic heart failure with reduced ejection fraction (HFrEF) who participated in the SMART-EX skeletal muscle substudy needle biopsies from the vastus lateralis muscle were performed before and after 12 weeks of supervised HIIT, MCT, or recommendation of regular exercise (RRE) to allow molecular assessment of markers for muscle catabolism, inflammation and energy supply by RT-PCR and western blotting. Echocardiography and CPET were performed in all patients. Changes over time were tested within each group. Results Skeletal muscle biopsies at baseline and follow-up were available in 31 patients (HIIT n=9; MCT n=9; RRE n=13). The majority of patients were male (87%). Median left ventricular ejection fraction was 29%. Median improvement in peak VO2 was 2.0 (IQR -0.4-2.8) in HIIT vs. 1.4 (IQR -0.9-3.4) in MCT vs. 0.0 (IQR -2.9-2.1) ml/min/kg in RRE. This was statistically not significant. HIIT reduced mRNA levels of the E3 ligases of the ubiquitine proteasome system MuRF1 by -72% (p<0.01) and MafBx -45% (p=0.09) with no change in MCT (MuRF1 -31%, p=0.23; MafBx -47%, p=0.21) and RRE (MuRF1 -8%, p=0.20; MafBx -6%, p=0.46). There was no change in mRNA expression of the inflammatory markers interleukin 6 (HIIT 12%; MCT 29%; RRE -35%; n.s.) and TNFα (HIIT -9%; MCT 20%; RRE 27%; n.s.) in either group. The mRNA expression of the mitochondrial F1 subunit of complex V (ATP5F1) significantly increased in HIIT by 14% (p<0.05) with no change in MCT (-3%, p=0.75) and RRE (2%, p=0.76). The mRNA expression of mitochondrial complex I subunits NDUFB8 and NDUFB6 remained unchanged in all groups. Western blot analysis of porin expression, which is a marker of total mitochondrial content, revealed a significant increase in HIIT by 69% (p<0.05) whereas MCT (21%, p=0.18) and RRE (4%, p=0.79) remained unchanged. Conclusion High-intensity interval training in HFrEF for 12 weeks resulted in reduced markers of protein degradation via the ubiquitine proteasome system and increased markers of mitochondrial content and energy supply via mitochondrial complex V whereas moderate continuous exercise training had only minor (non-significant) effects. These molecular changes are probably one reason why exercise capacity improved in patients of the SMART-EX trail.

Moderate continuous or high intensity interval exercise in heart failure with reduced ejection fraction: Differences between ischemic and non-ischemic etiology

BackgroundExercise for heart failure (HF) with reduced ejection fraction (HFrEF) is recommended by guidelines, but exercise mode and intensities are not differentiated between HF etiologies. We, therefore, investigated the effect of moderate or high intensity exercise on left ventricular end-diastolic diameter (LVEDD), left ventricular ejection fraction (LVEF) and maximal exercise capacity (peak VO2) in patients with ischemic cardiomyopathy (ICM) and non-ischemic cardiomyopathy (NICM). MethodsThe Study of Myocardial Recovery after Exercise Training in Heart Failure (SMARTEX-HF) consecutively enrolled 231 patients with HFrEF (LVEF ≤ 35 %, NYHA II-III) in a 12-weeks supervised exercise program. Patients were stratified for HFrEF etiology (ICM versus NICM) and randomly assigned (1:1:1) to supervised exercise thrice weekly: a) moderate continuous training (MCT) at 60–70 % of peak heart rate (HR), b) high intensity interval training (HIIIT) at 90–95 % peak HR, or c) recommendation of regular exercise (RRE) according to guidelines. LVEDD, LVEF and peak VO2 were assessed at baseline, after 12 and 52 weeks. Results215 patients completed the intervention. ICM (59 %; n = 126) compared to NICM patients (41 %; n = 89) had significantly lower peak VO2 values at baseline and after 12 weeks (difference in peak VO2 2.2 mL/(kg*min); p < 0.0005) without differences between time points (p = 0.11) or training groups (p = 0.15). Etiology did not influence changes of LVEDD or LVEF (p = 0.30; p = 0.12), even when adjusting for sex, age and smoking status (p = 0.54; p = 0.12). Similar findings were observed after 52 weeks. ConclusionsEtiology of HFrEF did not influence the effects of moderate or high intensity exercise on cardiac dimensions, systolic function or exercise capacity. Clinical Trial Registration–URLhttp://www.clinicaltrials.gov. Unique identifier: NCT00917046.

Reduced LVEDD following a 12 week exercise training program in patients with symptomatic chronic heart failure is associated with reduction in serum levels of Troponin I

Abstract Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): Norwegian University of Science and Technology Danish Research Council Background Exercise training (ET) exerts many beneficial effects on the cardiovascular system, and longitudinal observational data from epidemiological studies suggest that higher physical activity is associated with lower concentrations of cardiac troponins. We have previously shown that ET can reduce Left Ventricle End-diastolic diameter (LVEDD), and improve exercise capacity. Purpose Our aim was to explore the relationship between changes in LVEDD and changes in high-sensitive plasma troponin I (hs-TnI) levels in patients with symptomatic heart failure undergoing a 12 week structured exercise training program in the randomized multicenter SMARTEX trial. Methods This was a post hoc analysis in 199 patients with symptomatic HF with LVEF &amp;lt;35% and NYHA II-III that were randomly assigned to High Intensity Interval Training (HIIT, n = 73), Moderate Continuous Training (MCT, n = 59) or Recommendation of Regular Exercise, (RRT, n = 67) for 12 weeks. Log-transformed Hs-TnI measurements and clinical data acquired before (BL) and after a 12 week exercise training intervention (12 weeks) and at 1 year follow-up (1 year) were analysed using a linear mixed model. For Troponin analysis the STAT Troponin-I from Abbott Diagnostics was used. Nakagawa’s marginal R2 and conditional R2 were used to evaluate variance explained by fixed effects only and by fixed and random effects together, respectively. Changes of LVEDD between baseline and 12 weeks and baseline and 52 weeks were evaluated using linear mixed model. The outcome variable were measures of LVEDD, while age, sex, visit and training group and their interaction [visit × training group] were included as fixed effects. Patient id and training center were random effects. Covariance structure was compound symmetry. Linear association between log-transformed TnI and LVEDD baseline was evaluated using Pearson correlation coefficient (R). Results Serum was available for hs-TnI analyses in 199 patients. In the HIIT group there was a sustained significant reduction in LVEDD at both 12 and 52 weeks. In the MCT group this reduction was statistically significant at 52 weeks only. Mixed model analysis predicts that each 1 mm decrease in LVEDD is associated with 1.2% decrease in TnI levels (95% CI: 0.6 – 1.9%, p &amp;lt;0.001). Neither time nor training group were associated with changes of TnI (overall test p = 0.739 and p = 0.987, respectively). Dynamics of TnI is highly patient-specific with Intraclass correlation coefficient (ICC) = 0.86. Mixed model explains 87% variation of the data (conditional R2), however, only 7% is attributed to the fixed effects (marginal R2). At baseline, TnI and LVEDD have modest but statistically significant correlation (R = 0.2, p= 0.004). Conclusions A reduction of LVEDD following a 12-week exercise-training program is associated with a reduction in plasma troponin levels, in patients with mild to moderate chronic heart failure. Abstract Figure.

Blood Lactate AUC Is a Sensitive Test for Evaluating the Effect of Exercise Training on Functional Work Capacity in Patients with Chronic Heart Failure.

Purpose Exercise training is an essential treatment option for patients with chronic heart failure (CHF). However, it remains controversial, which surrogate measures of functional work capacity are most reliable. The purpose of this paper was to compare functional capacity work measured as capillary lactate concentrations area under the curve (AUC) with standard cardiopulmonary exercise testing (CPET) with VO2peak and the 6-minute walk test (6 MWT). Methods Twenty-three patients in New York Heart Association (NYHA) class II/III with left ventricular ejection fraction (LVEF) <35% were randomised to home-based recommendation of regular exercise (RRE) (controls), moderate continuous training (MCT) or aerobic interval training (AIT). The MCT and AIT groups underwent 12 weeks of supervised exercise training. Exercise testing was performed as standard CPET treadmill test with analysis of VO2peak, the 6 MWT and a novel 30-minute submaximal treadmill test with capillary lactate AUC. Results All patients had statistically significant improvements in VO2peak, 6 MWT and lactate AUC after 12 weeks of exercise training: 6 MWT (p =0.035), VO2peak (p =0.049) and lactate AUC (p =0.002). Lactate AUC (p =0.046) and 6MWT (p =0.035), but not VO2peak revealed difference between the exercise modalities regarding functional work capacity. Conclusion 6-MWT and lactate AUC, but not VO2peak, were able to reveal a statistically significant improvement in functional capacity between different exercise modalities.

Exercise training and high-sensitivity cardiac troponin T in patients with heart failure with reduced ejection fraction.

AimsWhether an exercise training intervention is associated with reduction in long‐term high‐sensitivity cardiac troponin T (hs‐cTnT) concentration (a biomarker of subclinical myocardial injury) in patients with heart failure with reduced ejection fraction (HFrEF) is unknown. The aims were to determine (i) the effect of a 12 week endurance exercise training intervention with different training intensities on hs‐cTnT in stable patients with HFrEF (left ventricular ejection fraction ≤ 35%) and (ii) associations between hs‐cTnT and peak oxygen uptake (VO2peak).Methods and resultsIn this sub‐study of the SMARTEX‐HF trial originally including 261 patients from nine European centres, 213 eligible patients were included after withdrawals and appropriate exclusions [19% women, mean age 61.2 years (standard deviation: 11.9)], randomized to high‐intensity interval training (HIIT; n = 77), moderate continuous training (MCT; n = 63), or a recommendation of regular exercise (RRE; n = 73). Hs‐cTnT measurements and clinical data acquired before (BL) and after a 12 week exercise training intervention (12 weeks) and at 1 year follow‐up (1 year) were analysed using multivariable mixed models. Baseline hs‐cTnT was above the 99th percentile upper reference limit of 14 ng/L in 35 (48%), 35 (56%), and 49 (64%) patients in the RRE, MCT, and HIIT groups, respectively. Median hs‐cTnT was 16 ng/L at BL, 14 ng/L at 12 weeks, and 14 ng/L at 1 year. Hs‐cTnT was statistically significantly reduced at 12 weeks in a model adjusted for randomization group, centre and VO2peak, and after further adjustment in the final model that also included age, sex, creatinine concentrations, N‐terminal pro‐brain natriuretic peptide, smoking, and heart failure treatment. The mean reduction from BL to 12 weeks in the final model was 1.1 ng/L (95% confidence interval: 1.0–1.2 ng/L, P < 0.001), and the reduction was maintained at 1 year with a mean reduction from BL to 1 year of 1.1 ng/L (95% confidence interval: 1.0–1.1 ng/L, P = 0.025). Randomization group was not associated with hs‐cTnT at any time point (overall test: P = 0.20, MCT vs. RRE: P = 0.81, HIIT vs. RRE: P = 0.095, interaction time × randomization group: P = 0.88). Independent of time point, higher VO2peak correlated with lower hs‐cTnT (mean reduction over all time points: 0.2 ng/L per increasing mL·kg−1·min−1, P = 0.002), without between‐group differences (P = 0.19).ConclusionsIn patients with stable HFrEF, a 12 week exercise intervention was associated with reduced hs‐cTnT in all groups when adjusted for clinical variables. Higher VO2peak correlated with lower hs‐cTnT, suggesting a positive long‐term effect of increasing VO2peak on subclinical myocardial injury in HFrEF, independent of training programme.

Plasma levels of troponin I is reduced after a 12 week exercise training program in patients with uncomplicated heart failure. A substudy of the SMARTEX-HF study

Abstract Background Low-level elevation of cardiac troponins has been associated with adverse outcome, and concentrations even within the normal range provide independent information concerning risk in heart failure (HF). Exercise training exerts many beneficial effects on the cardiovascular system, and longitudinal observational data from epidemiological studies suggest that higher physical activity (PA) is associated with lower concentrations of cardiac troponins. Purpose Our aim was to compare changes in plasma troponin I (TnI) levels (Abbott Diagnostics) in patients with symptomatic heart failure undergoing a 12 week structured exercise training program (Intervention group, IG) with changes in controls on a recommendation of regular exercise (RRE); control group, (CG) in a randomized clinical trial. Methods This was a post hoc analysis of the SMARTEX-HF trial in 199 patients with symptomatic HF with LVEF &amp;lt;35% and NYHA II-III. The patients were randomly assigned to High Intensity Interval Training (HIIT, n=73), Moderate Continuous Training (MCT, n=59) or RRE, (n=67) for 12 weeks. HIIT and MCT groups constituted the intervention group (IG). Measurements and clinical data acquired before and after the 12-week exercise training intervention were analysed. Statistical analysis Changes of TnI levels from baseline to 12 weeks are presented as medians and interquartile ranges. One-sample Wilcoxon sign rank test was used to determine if for a specific group of patients, the median change of troponin levels was equal to zero. In addition, Mann-Whitney U test was used to compare reductions of TnI between two groups. Results After 12 weeks plasma levels of TnI were reduced for all patients (median 11.9 to 11.4 ng/L, p=0.032) and there was no difference between the study groups (p=0.072). However, when the groups were studied separately, reduction of plasma levels of TnI was statistically significant in the IG only (12.5 to 11.7 ng/L, p=0.011), (CG 11.4 to 10.7 ng/L, p=0.955). For the study cohort restricted to patients without additional complicating factors (i.e. no atrial fibrillation, no history of hypertension, diabetes or chronic obstructive pulmonary disease, n=77), difference in changes of plasma levels of TnI between IG (n=54) and CG (n=23) was found to be statistically significant (p=0.004). IG changed from 11.3 to 9.5 ng/L (p=0.002), (CG 12.6 to 12.7 ng/L, p=0.467). Conclusions A 12 weeks exercise-training program was associated with a reduction of plasma TnI levels in patients with mild to moderate HFrEF without additional complicating factors. Figure 1 Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): Western Norway Regional; Health Authority [Grant Number 911 715]. St. Olavs Hospital; Faculty of Medicine, Norwegian University of Science and Technology; Norwegian Health Association

Treatment of anxiety disorders in clinical practice: a critical overview of recent systematic evidence

The aim of this study was to review emerging evidence of novel treatments for anxiety disorders. We searched PubMed and EMBASE for evidence-based therapeutic alternatives for anxiety disorders in adults, covering the past five years. Eligible articles were systematic reviews (with or without meta-analysis), which evaluated treatment effectiveness of either nonbiological or biological interventions for anxiety disorders. Retrieved articles were summarized as an overview. We assessed methods, quality of evidence, and risk of bias of the articles. Nineteen systematic reviews provided information on almost 88 thousand participants, distributed across 811 clinical trials. Regarding the interventions, 11 reviews investigated psychological or nonbiological treatments; 5, pharmacological or biological; and 3, more than one type of active intervention. Computer-delivered psychological interventions were helpful for treating anxiety of low-to-moderate intensity, but the therapist-oriented approaches had greater results. Recommendations for regular exercise, mindfulness, yoga, and safety behaviors were applicable to anxiety. Transcranial magnetic stimulation, medication augmentation, and new pharmacological agents (vortioxetine) presented inconclusive benefits in patients with anxiety disorders who presented partial responses or refractoriness to standard treatment. New treatment options for anxiety disorders should only be provided to the community after a thorough examination of their efficacy.

High-Intensity Interval Training in Patients With Heart Failure With Reduced Ejection Fraction.

Small studies have suggested that high-intensity interval training (HIIT) is superior to moderate continuous training (MCT) in reversing cardiac remodeling and increasing aerobic capacity in patients with heart failure with reduced ejection fraction. The present multicenter trial compared 12 weeks of supervised interventions of HIIT, MCT, or a recommendation of regular exercise (RRE). Two hundred sixty-one patients with left ventricular ejection fraction ≤35% and New York Heart Association class II to III were randomly assigned to HIIT at 90% to 95% of maximal heart rate, MCT at 60% to 70% of maximal heart rate, or RRE. Thereafter, patients were encouraged to continue exercising on their own. Clinical assessments were performed at baseline, after the intervention, and at follow-up after 52 weeks. Primary end point was a between-group comparison of change in left ventricular end-diastolic diameter from baseline to 12 weeks. Groups did not differ in age (median, 60 years), sex (19% women), ischemic pathogenesis (59%), or medication. Change in left ventricular end-diastolic diameter from baseline to 12 weeks was not different between HIIT and MCT (P=0.45); left ventricular end-diastolic diameter changes compared with RRE were -2.8 mm (-5.2 to -0.4 mm; P=0.02) in HIIT and -1.2 mm (-3.6 to 1.2 mm; P=0.34) in MCT. There was also no difference between HIIT and MCT in peak oxygen uptake (P=0.70), but both were superior to RRE. However, none of these changes was maintained at follow-up after 52 weeks. Serious adverse events were not statistically different during supervised intervention or at follow-up at 52 weeks (HIIT, 39%; MCT, 25%; RRE, 34%; P=0.16). Training records showed that 51% of patients exercised below prescribed target during supervised HIIT and 80% above target in MCT. HIIT was not superior to MCT in changing left ventricular remodeling or aerobic capacity, and its feasibility remains unresolved in patients with heart failure. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00917046.

Exercise and Preexercise Nutrition as Treatment for McArdle Disease

McArdle disease is due to an inborn defect in the muscle isoform of glycogen phosphorylase (or "myophosphorylase"), the enzyme that catalyzes the first step of glycogenolysis. This condition is still not fully understood, and although advances in research would help patients immeasurably, these would also enhance our understanding of exercise metabolism. It has been 10 yr since the first published report demonstrating the benefits of regular aerobic exercise for these patients. However, misconceptions remain and the value of exercise prescription for patients with McArdle disease is still overlooked. Here, we review the role of exercise in McArdle disease with the aim to better inform health-care professionals and thus better serve the interests of patients. Recommendations for regular exercise together with preexercise nutrition in children and adult patients are also provided along with examples of exercise practice and its benefits.

From exercise to physical activity.

Recommendations for regular exercise have been evident in the nursing literature since the early 1900s. Health professionals and popular media have promoted vigorous exercise for positive health benefits since the 1960s. The concept of exercise as it appeared in the nursing literature during the early part of the 20th century is closer to the concept of physical activity of today--regular, moderate-intensity activities that become part of one's lifestyle. Nurses are in a unique position to counsel individuals, families, and communities on the importance of regular physical activity and to correct misconceptions that only vigorous exercise has health benefits.