Exercise training improves exercise capacity and quality of life after transcatheter aortic valve implantation: A randomized pilot trial.

BACKGROUND: Transcatheter aortic valve implantation (TAVI) is increasingly applied for aortic stenosis in elderly patients with impaired mobility and reduced quality of life. These patients may particularly benefit from postinterventional exercise programs, but no randomized study has evaluated the safety and efficacy of exercise in this population. METHODS: In a prospective pilot study, 30 patients after TAVI (mean age, 81±6 years, 44% female, 83±34 days postintervention) were randomly allocated 1:1 to a training group (TG) performing 8 weeks of supervised combined endurance and resistance exercise or to usual care. The formal primary efficacy end point was between-group difference in change in peak oxygen uptake assessed by cardiopulmonary exercise testing; secondary end points included muscular strength, 6-minute walk distance, and quality of life (Kansas City Cardiomyopathy Questionnaire and Medical Outcomes Study 12-Item Short-Form Health Survey questionnaires). Safety was assessed by documenting training-related adverse events, prosthesis, and renal function. RESULTS: Significant changes in favor of TG were observed for peak oxygen uptake (group difference, 3.7 mL/min per kg [95% CI, 1.1-6.3; P=.007]), muscular strength (bench press, 6 kg [95% CI, 3-10; P=.002]; rowing, 7 kg [95% CI, 3-11; P<.001]; pulldown, 9 kg [95% CI, 4-14; P=.001]; shoulder press, 5 kg [95% CI, 1-8; P=.008]; leg press, 17 kg [95% CI 6-28; P=.005]), components of quality of life (Kansas City Cardiomyopathy Questionnaire physical limitation, 19.2 [95% CI, 4.1-34.2; P=.015]; symptom burden, 12.3 [95% CI, 0.5-24.0; P=.041]; clinical summary, 12.4 [3.4-21.4; P=.009]), but not for other questionnaire subscales and 6-minute walk distance (15 m [95% CI, -23 to 53; P=.428]). Three dropouts unrelated to exercise occurred (TG=2; usual care,=1); prosthesis and renal function were not affected by the exercise intervention. CONCLUSIONS: In patients after TAVI, exercise training appears safe and highly effective with respect to improvements in exercise capacity, muscular strength, and quality of life. CLINICAL TRIAL REGISTRATION: Clinicaltrials.govNCT01935297.

Decreased prevalence of cardiac arrhythmias during and after vigorous and prolonged exercise in healthy male marathon runners.

BACKGROUND: Vigorous exercise such as marathon running results in an increased risk of sudden cardiac death. Malignant arrhythmias seem to be the primary cause. However, continuous electrocardiographic monitoring for detection of arrhythmias during a marathon race has not been performed yet. METHODS: Twenty male marathon runners (age 45 ± 8 years) free of cardiovascular disease underwent 24-hour Holter monitoring 5 weeks before a marathon race (baseline). Subsequently, wireless Holter monitoring started immediately before the race, recorded up to 70 hours postrace. Electrocardiograms were analyzed for the presence of arrhythmias. Additionally, cardiac troponin, interleukin-6 (IL-6), and electrolytes were assessed prerace and postrace. RESULTS: At baseline Holter recordings, runners showed a median of 9 (interquartile range 3-25) atrial premature complexes (APCs) and 4 (2-16) ventricular premature complexes (VPCs) per 100,000 beats. Compared to baseline, the number of APCs decreased significantly during and 1 hour after the marathon race (0 [0-3] and 0 [0-0], all P < .001) as well as the number of VPCs during the race (0 [0-0], P = .008). No malignant arrhythmias occurred. Mean postrace levels for troponin and IL-6 were significantly augmented after the race (prerace to postrace: troponin 4 times, IL-6 17 times, all P < .001); however, no significant influence of these biomarkers or electrolytes on the prevalence of arrhythmias was observed (all P > .05). CONCLUSIONS: In this cohort of male runners free of cardiovascular disease, the prevalence of arrhythmias during and after a marathon race was decreased. Arrhythmogenic risk was independent of changes in biomarkers assessing cardiac injury, inflammation, and changes in electrolytes.

Rutoside and Hydrolytic Enzymes Do Not Attenuate Marathon-Induced Inflammation.

INTRODUCTION: Vigorous and prolonged exercise such as marathon running increases inflammatory markers and the risk of upper respiratory illness (URI) in athletes. Nutritional supplements are being tested as countermeasures of exercise-induced inflammation and immune dysfunction. METHODS: In this prospective randomized, double-blind, placebo-controlled phase I trial, healthy male runners (N = 138, age 42 ± 11 yr) were supplemented with rutoside (600-1200 mg·d) and hydrolytic enzymes (540-1080 mg·d bromelain, 288-576 mg·d trypsin) (WOB) or placebo (PL) for 1 wk before and 2 wk after the Munich Marathon 2013. Blood samples were collected 5 wk prerace and immediately, 24 h, and 72 h postrace and analyzed for inflammation biomarkers (interleukins [IL] 6 and 10, high-sensitivity C-reactive protein, and leukocytes). URI rates, assessed by the Wisconsin Upper Respiratory Symptom Survey, were compared between the study groups during the 2-wk period after the marathon race. URI was defined if the Wisconsin Upper Respiratory Symptom Survey score was equal or greater than seven, representing either one severe symptom or seven mild symptoms. RESULTS: Immediately postrace, the increase of IL-6 was not significantly different between the WOB and the PL groups (median [interquartile range]: WOB, 33.8 [22.5-58.8] ng·L; PL, 35.6 [24.8-61.29] ng·L; P = 0.758). No significant group differences were observed for increases of IL-10, high-sensitivity C-reactive protein, or leukocytes pre- to postrace (all P > 0.05). From race day until 2 wk after the marathon race, the percentage of individuals with at least one URI did not significantly differ between the groups (WOB, 50.0%; PL, 51.5%; P = 0.859). CONCLUSION: Supplementation with rutoside and hydrolytic enzymes before and after a marathon race did not attenuate postrace inflammation or decrease URI incidence in nonelite male marathon runners.

Changes of intima-media thickness in marathon runners: A mid-term follow-up.

Objective Carotid intima-media thickness (IMT) is used to assess cardiovascular risk and progression of atherosclerosis. It is known that regular physical activity of moderate intensity has beneficial effects on the vasculature. However, it is still discussed controversially whether prolonged exercise, including participation in exhaustive competitive sports such as long-distance races, has also beneficial effects or might even be harmful regarding the cardiovascular system. Patients and methods Thirty-eight male marathon runners (45.8 ± 7.3 years) were investigated twice (2009 and 2013) for their carotid IMT (using ultrasound techniques), anthropometrics and clinical chemistry. Additionally, training volume (running kilometres per year) and competition participation (half marathon, marathon and ultramarathon) within this follow-up period were assessed. Results During 3.8 ± 0.4 years of follow-up, runners performed 1587 (850-2500) training kilometres per year and participated in a total of 7 (4-12) long distance competitions. IMT increased in total by 0.05 ± 0.09 mm or annually by 0.013 ± 0.023 mm, respectively. Higher increase in IMT over that period was associated with higher fasting blood glucose (beta = .355, p = .045) at baseline examination. Effects of training volume and number of competitions on the progression of IMT could not be demonstrated in our longitudinal analysis. Conclusions Higher blood glucose levels are associated with detrimental effects on vasculature in otherwise healthy male marathon runners. Regular marathon training, including competition participation over at least several years, was not associated with detrimental effects on IMT or, vice versa, seems not to provide beneficial effects on vasculature.

Running multiple marathons is not a risk factor for premature subclinical vascular impairment.

Background In contrast to the well-accepted benefits of moderate exercise, recent research has suggested potential deleterious effects of repeated marathon running on the cardiovascular system. We thus performed a comprehensive analysis of markers of subclinical vascular damage in a cohort of runners having finished multiple marathon races successfully. Design This was a prospective, observational study. Methods A total of 97 healthy male Munich marathon participants (mean age 44 ± 10 years) underwent detailed training history, cardiopulmonary exercise testing for assessment of peak oxygen uptake, ultrasound for assessment of intima-media-thickness as well as non-invasive assessments of ankle-brachial index, augmentation index, pulse wave velocity and reactive hyperaemia index. Results Runners had previously completed a median of eight (range 1-500) half marathons, six (1-100) full marathons and three (1-40) ultramarathons; mean weekly and annual training volumes were 59 ± 23 and 1639 ± 979 km. Mean peak oxygen uptake was 50 ± 8 ml/min/kg, and the Munich marathon was finished in 3:45 ± 0:32 h. Runners showed normal mean values for intima-media-thickness (0.60 ± 0.14 mm), ankle-brachial index (1.2 ± 0.1), augmentation index (17 ± 13%), pulse wave velocity (8.7 ± 1.4 cm/s) and reactive hyperaemia index (1.96 ± 0.50). Age was significantly and independently associated with intima-media-thickness ( r = 0.531; p < 0.001), augmentation index ( r = 0.593; p < 0.001) and pulse wave velocity ( r = 0.357; p < 0.001). However, no independent associations of peak oxygen uptake, marathon finishing time, number of completed races or weekly and annual training km with any of the vascular parameters were observed. Conclusions In this cohort of healthy male runners, running multiple marathon races did not pose an additional risk factor for premature subclinical vascular impairment beyond age.

The effects of oral hydrolytic enzymes and flavonoids on inflammatory markers and coagulation after marathon running: study protocol for a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Regular moderate intensity physical activity positively influences the immune system with a lower incidence of upper respiratory tract infections (URTI) and lower levels of pro-inflammatory markers. However, marathon running due to its strenuous and prolonged nature results in immune perturbations with a major increase in pro-inflammatory markers and subsequent increased incidence of URTI. Furthermore, marathon running results in muscle damage and changes in hemostasis that promote a pro-thrombotic state.Naturally occurring hydrolytic enzymes and flavonoids have antioxidant, anti-inflammatory and fibrinolytic effects, and may serve as countermeasures to exercise-induced inflammation, immune dysfunction and URTI.The aim of this study is to determine whether the ingestion of oral hydrolytic enzymes and flavonoids before and after a marathon attenuates post-race muscle damage and inflammation, counters pro-thrombotic changes in hemostasis and decreases URTI incidence. METHODS/DESIGN: The Enzy-MagIC-study (Enzymes, Marathon runninG, Inflammation, Coagulation) is a randomized, double-blind, placebo-controlled, monocenter phase I trial. 160 healthy males (age 20-65 years) will be randomized to receive either placebo or treatment (Wobenzym, MUCOS Pharma, Berlin, Germany) which contains the hydrolytic enzymes (bromelain, trypsin) and the flavonoid rutoside. One week before the marathon race, participants will begin daily ingestion of the investigational product (3×4 tablets). Intake will be continued for two weeks after the race (3×2 tablets per day). Clinical and laboratory measures will be collected 5-weeks and 1-week before the race, and immediately-, 24-h, 72-h, and 2 weeks after the race. The primary endpoint is the influence of the treatment on the pre-to-post marathon race plasma concentration change of the inflammatory marker interleukin-6 (IL-6). Secondary endpoints include the effect of treatment on salivary IgA concentration and the frequency of upper respiratory tract infections (URTI) for two weeks post-marathon as determined by the Wisconsin Upper Respiratory Symptom Survey (WURSS-24). Furthermore, changes of muscular and rheological parameters will be measured before and after the marathon race. DISCUSSION: We hypothesize that marathon-induced inflammatory perturbations and the incidence of subsequent URTI, muscular damage, and changes of hemostasis can be positively influenced by the anti-edematous, anti-inflammatory, antioxidant, and fibrinolytic effects of oral hydrolytic enzymes and flavonoids (Wobenzym). TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01916408.