Major increase in creatine kinase after intensive exercise. / Kraftig stigning i kreatinkinase etter intensiv trening.

BACKGROUND: Exercise-induced rhabdomyolysis is an increasingly frequent cause of hospitalisation and is much debated in the media. The real incidence of the condition is unknown. We wanted to investigate changes in creatine kinase (CK) levels in healthy students following intensive exercise and to look for a correlation between CK, pain and previous exercise history. METHOD AND MATERIAL: Twenty-four healthy students performed a single intensive workout and acted as their own controls with testing before and after the exercise session. RESULTS: All participants displayed an increase in CK levels after the workout, 58 % to above 5 000 IU/l. CK rose from a median of 104 IU/l (72-212) to a median of 6 071 IU/l (2 815-12 275) on day 4, p < 0.001. A negative Spearman's rank correlation was observed between the frequency of strength training prior to the experiment and the CK increase, rho = -0.477 (p = 0.021). INTERPRETATION: A major increase in CK levels is a normal phenomenon after intensive exercise, and the amount of the increase is related to previous exercise history. Further studies should evaluate whether patients with exercise-induced rhabdomyolysis should receive the same treatment as those with rhabdomyolysis caused by other mechanisms.

Exercise-Based Telerehabilitation for Heart Failure Patients Declining Outpatient Rehabilitation - A Randomized Controlled Trial.

ABSTRACT: Purpose: Cardiac rehabilitation participation rates are low despite strong recommendations, and many chronic heart failure patients remain physically inactive. Rural living, long travel distance, costs, age, and frailty might be factors explaining this. To increase cardiac rehabilitation uptake, we designed an exercise-based randomized controlled telerehabilitation trial enabling chronic heart failure patients unable or unwilling to participate in outpatient cardiac rehabilitation to exercise at home. Aim was to evaluate the long-term effects of telerehabilitation on physical activity levels.Methods and results: CHF patients (n = 61) with reduced (≤40%), mildly reduced (41-49%), or preserved ejection fraction (≥50%) were randomized (1:1) to telerehabilitation (n = 31) with an initial 3-month group-based high-intensity exercise telerehabilitation program or control (n = 30), with regular follow-up visits over a 2-year period. All participants attended a "Living with heart failure" course. Outcomes were measures of physical activity, peak oxygen uptake, 6-minute walk test distance, quality of life, morbidity, and mortality. We found no significant differences between groups for long-term changes in moderate to vigorous activity (MVPA) or peak oxygen uptake from baseline to the 2-year follow-up. Nor quality of life differed between groups, but both groups had significant within-group improvements in score on the Minnesota living with heart failure questionnaire (p = 0.000) and improvement in EQ-5D VAS score was significant (p = 0.05) in the telerehabilitation group.Conclusions: Telerehabilitation performed as home-based real-time high-intensity exercise sessions provided by videoconferencing for participants unable or unwilling to participate in standard outpatient cardiac rehabilitation did not affect long-term physical activity levels or physical capacity as expected. Still, a positive effect on health-related quality of life was seen in both groups.

Feasibility of telerehabilitation for heart failure patients inaccessible for outpatient rehabilitation.

AIMS: Despite strong recommendations, outpatient cardiac rehabilitation is underused in chronic heart failure (CHF) patients. Possible barriers are frailty, accessibility, and rural living, which may be overcome by telerehabilitation. We designed a randomized, controlled trial to evaluate the feasibility of a 3-month real-time, home-based telerehabilitation, high-intensity exercise programme for CHF patients who are either unable or unwilling to participate in standard outpatient cardiac rehabilitation and to explore outcomes of self-efficacy and physical fitness at 3 months post-intervention. METHODS AND RESULTS: CHF patients with reduced (≤40%), mildly reduced (41-49%), or preserved ejection fraction (≥50%) (n = 61) were randomized 1:1 to telerehabilitation or control in a prospective controlled trial. The telerehabilitation group (n = 31) received real-time, home-based, high-intensity exercise for 3 months. Inclusion criteria were (i) ≥18 years, (ii) New York Heart Association class II-III, stable on optimized medical therapy for >4 weeks, and (iii) N-terminal pro-brain natriuretic peptide >300 ng/L. All participants participated in a 2-day 'Living with heart failure' course. No other intervention beyond standard care was provided for controls. Outcome measures were adherence, adverse events, self-reported outcome measures, the general perceived self-efficacy scale, peak oxygen uptake (VO2peak ) and a 6-min walk test (6MWT). The mean age was 67.6 (11.3) years, and 18% were women. Most of the telerehabilitation group (80%) was adherent or partly adherent. No adverse events were reported during supervised exercise. Ninety-six per cent (26/27) reported that they felt safe during real-time, home-based telerehabilitation, high-intensity exercise, and 96% (24/25) reported that, after the home-based supervised telerehabilitation, they were motivated to participate in further exercise training. More than half the population (15/26) reported minor technical issues with the videoconferencing software. 6MWT distance increased significantly in the telerehabilitation group (19 m, P = 0.02), whereas a significant decrease in VO2peak (-0.72 mL/kg/min, P = 0.03) was observed in the control group. There were no significant differences between the groups in general perceived self-efficacy scale, VO2peak , and 6MWT distance after intervention or at 3 months post-intervention. CONCLUSIONS: Home-based telerehabilitation was feasible in chronic heart failure patients inaccessible for outpatient cardiac rehabilitation. Most participants were adherent when given more time and felt safe exercising at home under supervision, and no adverse events occurred. The trial suggests that telerehabilitation can increase the use of cardiac rehabilitation, but the clinical benefit of telerehabilitation must be evaluated in larger trials.

Indexing cardiac volumes for peak oxygen uptake to improve differentiation of physiological and pathological remodeling: from elite athletes to heart failure patients.

AIMS: Cardiovascular structures adapt to meet metabolic demands, but current methodology for indexing by body size does not accurately reflect such variations. Therefore, we aimed to investigate how left ventricular end-diastolic volume (LVEDV) and left atrial maximal volume (LAVmax) are associated with absolute (L/min) peak oxygen uptake (VO2peak) and fat-free mass (FFM) compared to body surface area (BSA). We subsequently assessed the impact of indexing by absolute VO2peak, FFM, and BSA to discriminate pathological from physiological remodeling. METHODS AND RESULTS: We used data from 1190 healthy adults to explore relationships for BSA, FFM, and absolute VO2peak with LVEDV and LAVmax by regression and correlation analyses. We then compared these indexing methods for classification to normalcy/pathology in 61 heart failure patients and 71 endurance athletes using the chi-squared and Fisher exact tests and the net reclassification and integrated discrimination indices. Absolute VO2peak correlated strongly with LVEDV, explaining 52% of variance vs. 32% for BSA and 44% for FFM. Indexing LVEDV for VO2peak improved discrimination between heart failure patients and athletes on top of indexing to BSA. Seventeen out of 18 athletes classified to pathology by BSA were reclassified to normalcy by VO2peak indexing (P < 0.001), while heart failure patients were reclassified to pathology (39-95%, P < 0.001). All indexing methods explained below 20% of the variance in LAVmax in univariate models. CONCLUSIONS: Indexing LVEDV to VO2peak improves the ability to differentiate physiological and pathological enlargement. The LVEDV to absolute VO2peak ratio may be a key index in diagnosing heart failure and evaluating the athlete's heart.

Cardiorenal syndrome and the association with fitness: Data from a telerehabilitation randomized clinical trial.

AIMS: To investigate the associations of cardiorespiratory fitness with cardiac, vascular, renal and cardiorenal characteristics in chronic heart failure in a telerehabilitation randomized clinical trial. Secondly, to evaluate the associations of cardiorenal syndrome with the effects of exercise. METHODS AND RESULTS: Sixty-nine heart failure patients attended baseline examination, and 61 patients were randomly assigned 1:1 to 3-month telerehabilitation or control. Data were collected at baseline and 3-month post-intervention, including echocardiography and vascular ultrasound, laboratory tests, exercise test with peak oxygen consumption (VO2peak ) measurement and 6-min walk test (6MWT). Baseline VO2peak and 6MWT distance was 0.85 mL*min-1 *kg-1 lower and 20 m shorter per 10 mL/min/1.73m2 lower estimated glomerular filtration rate (both P < 0.001). Heart failure patients with cardiorenal syndrome had 3.5 (1.1) mL*min-1 *kg-1 lower VO2peak and diastolic dysfunction grade 2-3, and elevated filling pressure was >50% more common compared with those without (all P < 0.05). At the 3-month post-intervention follow-up, only the non-CRS patients in the intervention group increased VO2peak (0.73 (0.51) mL*min-1 *kg-1 ), whereas VO2peak in the CRS subpopulation of controls decreased (-1.34 (0.43) mL*min-1 *kg-1 ). Cardiorenal syndrome was associated with a decrease in VO2peak in CRS patients compared with non-CRS patients, -0.91 (0.31) vs. 0.39 (0.35) mL*min-1 *kg-1 respectively, P = 0.013. CONCLUSIONS: Cardiorenal syndrome was negatively associated with VO2peak and 6MWT distance in chronic HF, and the associations were stronger than for heart failure phenotypes and other characteristics. The effect of exercise was negatively associated with cardiorenal syndrome. Exercise seems to be as important in heart failure patients with cardiorenal syndrome, and future studies should include CRS patients to reveal the most beneficial type of exercise.

Blood Volume, Hemoglobin Mass, and Peak Oxygen Uptake in Older Adults: The Generation 100 Study.

Purpose: To investigate the association between blood volume, hemoglobin mass (Hbmass), and peak oxygen uptake (VO2peak) in healthy older adults. Methods: Fifty fit or unfit participants from the prospective randomized Generation 100 Study (n = 1,566) were included (age- and sex-specific VO2peak above or below average values). Blood, plasma, and erythrocyte volume and Hbmass were tested using the carbon monoxide rebreathing method within 1 week after VO2peak testing. Results: Mean age, BMI, Hbmass, blood volume, and VO2peak were 73.0 ± 2.1 years, 24.8 ± 3.3 kg·m2, 10.0 ± 1.7 g·kg-1, 76.4 ± 11.8 mL·kg-1, and 33.5 ± 8.4 mL·kg-1·min-1. VO2peak in fit and unfit participants and women and men were 38.6 ± 6.5 and 25.8 ± 3.8 mL·kg-1·min-1, 30.7 ± 7.6 mL·kg-1·min-1, and 35.5 ± 8.5 mL·kg-1·min-1, respectively. Women were shorter (Δ14 cm), leaner (Δ13 kg), and with less muscle mass (Δ9%) than men (P < 0.05). Relative erythrocyte volume and Hbmass were lower in women, and blood and erythrocyte volume and Hbmass were higher in the fit participants (P < 0.05). Hbmass and erythrocyte volume explained 40 and 37%, respectively, of the variability in VO2peak, with a limited effect of physical-activity adjustment (40 and 38%, respectively). Blood and plasma volume explained 15 and 25%, respectively, of VO2peak variability, and the association was strengthened adjusting for physical activity (25 and 31%, respectively), indicating a training-dependent adaptation in plasma but not erythrocyte volume (p ≤ 0.006). Conclusions: Blood and plasma volumes were moderately associated with VO2peak in healthy older men and women, and the association was strengthened after adjustment for physical activity. Hbmass and erythrocyte volume were strongly associated with VO2peak but unrelated to physical activity.

Circulating microRNAs May Serve as Biomarkers for Hypertensive Emergency End-Organ Injuries and Address Underlying Pathways in an Animal Model.

There is an incomplete understanding of the underlying pathophysiology in hypertensive emergencies, where severely elevated blood pressure causes acute end-organ injuries, as opposed to the long-term manifestations of chronic hypertension. Furthermore, current biomarkers are unable to detect early end-organ injuries like hypertensive encephalopathy and renal thrombotic microangiopathy. We hypothesized that circulating microRNAs (c-miRs) could identify acute and chronic complications of severe hypertension, and that combinations of c-miRs could elucidate important pathways involved. We studied the diagnostic accuracy of 145 c-miRs in Dahl salt-sensitive rats fed either a low-salt (N = 20: 0.3% NaCl) or a high-salt (N = 60: 8% NaCl) diet. Subclinical hypertensive encephalopathy and thrombotic microangiopathy were diagnosed by histopathology. In addition, heart failure with preserved ejection fraction was evaluated with echocardiography and N-terminal pro-brain natriuretic peptide; and endothelial dysfunction was studied using acetylcholine-induced aorta ring relaxation. Systolic blood pressure increased severely in animals on a high-salt diet (high-salt 205 ± 20 mm Hg vs. low-salt 152 ± 18 mm Hg, p < 0.001). Partial least squares discriminant analysis revealed 68 c-miRs discriminating between animals with and without hypertensive emergency complications. Twenty-nine c-miRs were strongly associated with hypertensive encephalopathy, 24 c-miRs with thrombotic microangiopathy, 30 c-miRs with heart failure with preserved ejection fraction, and 28 c-miRs with endothelial dysfunction. Hypertensive encephalopathy, thrombotic microangiopathy and heart failure with preserved ejection fraction were associated with deviations in many of the same c-miRs, whereas endothelial dysfunction was associated with a different set of c-miRs. Several of these c-miRs demonstrated fair to good diagnostic accuracy for a composite outcome of hypertensive encephalopathy, thrombotic microangiopathy and heart failure with preserved ejection fraction in receiver-operating-curve analyses (area-under-curve 0.75-0.88). Target prediction revealed an enrichment of genes related to several pathways relevant for cardiovascular disease (e.g., mucin type O-glycan biosynthesis, MAPK, Wnt, Hippo, and TGF-beta signaling). C-miRs could potentially serve as biomarkers of severe hypertensive end-organ injuries and elucidate important pathways involved.