Physical exercise as a treatment for persisting symptoms post-COVID infection: review of ongoing studies and prospective randomized controlled training study.

BACKGROUND AND PURPOSE: No evidence-based treatment is available for patients with persisting symptoms post-COVID-19 infection. We hypothesized that physical exercise may represent a safe and effective treatment option for post-COVID. METHODS: We performed a systematic search of the literature that revealed a lack of randomized training studies in patients post-COVID. Based on these findings, a prospective randomized controlled study with open-label and blinded endpoint evaluation was designed. 272 patients with symptoms of fatigue persisting over 6 weeks post-COVID infection were screened. Patients with pathological cardiovascular findings were excluded. 57 patients consented and were randomized to 4 weeks of supervised personalized strength and endurance training or usual care. The follow-up period was 3 and 6 months. RESULTS: There were no adverse events related to the training. Spiroergometry of the training group showed a significantly higher increase in VO2peak (10.0 ± 12.7% vs. 0.1 ± 8.9%, p < 0.01, respectively) and oxygen pulse (9.8 ± 10.8% vs. 0.0 ± 13.9%, p < 0.05, respectively). Parameters of the Multidimensional Fatigue Inventory-20, McGill Quality of Life Questionnaire, and Post-COVID-19 Functional Status were improved after 4 weeks in both groups. In the follow-up period, the total physical activity per week was significantly greater in the exercise group than in controls (1280 ± 1192 min vs. 644 ± 554 min, p < 0.05, respectively). The improvements in fatigue and quality of life were not statistically different between the training and usual care groups. CONCLUSION: Exercise is safe and improves maximal exercise capacity in post-COVID patients. Fatigue and quality of life improve over time in individuals that are willing to participate in a training study irrespective of their allocation. REGISTRATION: German Clinical Trials Register: DRKS00026686. Date of registration: 27.09.2021.

Intensity-dependent cardiopulmonary response during and after strength training.

Whereas cardiopulmonary responses are well understood in endurance training, they are rarely described in strength training. This cross-over study examined acute cardiopulmonary responses in strength training. Fourteen healthy male strength training-experienced participants (age 24.5 ± 2.9 years; BMI 24.1 ± 2.0 kg/m2) were randomly assigned into three strength training sessions (three sets of ten repetitions) with different intensities (50%, 62,5%, and 75% of the 3-Repetition Maximum) of squats in a smith machine. Cardiopulmonary (impedance cardiography, ergo-spirometry) responses were continuously monitored. During exercise period, heart rate (HR 143 ± 16 vs. 132 ± 15 vs. 129 ± 18 bpm, respectively; p < 0.01; η2p 0.54) and cardiac output (CO: 16.7 ± 3.7 vs. 14.3 ± 2.5 vs. 13.6 ± 2.4 l/min, respectively; p < 0.01; η2p 0.56) were higher at 75% of 3-RM compared to those at the other intensities. We noted similar stroke volume (SV: p = 0.08; η2p 0.18) and end-diastolic volume (EDV: p = 0.49). Ventilation (VE) was higher at 75% compared to 62.5% and 50% (44.0 ± 8.0 vs. 39.6 ± 10.4 vs. 37.6 ± 7.7 l/min, respectively; p < 0.01; η2p 0.56). Respiration rate (RR; p = .16; η2p 0.13), tidal volume (VT: p = 0.41; η2p 0.07) and oxygen uptake (VO2: p = 0.11; η2p 0.16) did not differ between intensities. High systolic and diastolic blood pressure were evident (62.5% 3-RM 197 ± 22.4/108.8 ± 13.4 mmHG). During the post-exercise period (60 s), SV, CO, VE, VO2, and VCO2 were higher (p < 0.01) than during the exercise period, and the pulmonary parameters differed markedly between intensities (VE p < 0.01; RR p < 0.01; VT p = 0.02; VO2 p < 0.01; VCO2 p < 0.01). Despite the differences in strength training intensity, the cardiopulmonary response reveals significant differences predominantly during the post-exercise period. Intensity-induced breath holding induces high blood pressure peaks and cardiopulmonary recovery effects after exercise.

Effects of surgical and FFP2 masks on cardiopulmonary exercise capacity in patients with heart failure.

AIMS: Surgical and FFP2 masks are recommended to reduce transmission of SARS-CoV-2. The cardiopulmonary effects of facemasks in patients with chronic heart failure are unknown. This prospective, cross-over study quantified the effects of wearing no mask (nm), surgical mask (sm), and FFP2 mask (ffpm) in patients with stable heart failure. METHODS: 12 patients with clinically stable chronic heart failure (HF) (age 63.8±12 years, left ventricular ejection fraction (LVEF) 43.8±11%, NTProBNP 573±567 pg/ml) underwent spiroergometry with and without masks in a randomized sequence. Comfort/discomfort was assessed using a standardized questionnaire. RESULTS: Maximum power was reduced with both types of masks (nm: 108.3 W vs. sm: 101.2 W vs. ffpm: 95.6 W, p<0.01). Maximum respiratory oxygen uptake (1499ml/min vs. 1481 ml/min vs. 1300 ml/min, p = 0.95 and <0.01), peak ventilation (62.1 l/min vs. 56.4 l/min vs. 50.3 l/min, p = 0.15 and p<0.05) and O2-pulse (11.6 ml/beat vs. 11.8 ml/beat vs. 10.6 ml/beat, p = 0.87 and p<0.01) were significantly changed with ffpm but not sm. Discomfort was moderately but significantly increased (nm: 1.6 vs. sm: 3.4 vs. ffpm: 4.4, p<0.05). CONCLUSION: Both surgical and FFP masks reduce exercise capacity in heart failure patients, while FFP2 masks reduce oxygen uptake and peak ventilation. This reduction in cardiopulmonary performance should be considered in heart failure patients whose daily life activities are often just as challenging as exercise is for healthy adults.

Extracellular Inflammasome Particles Are Released After Marathon Running and Induce Proinflammatory Effects in Endothelial Cells.

Objectives: The intracellular NLRP3 inflammasome is an important regulator of sterile inflammation. Recent data suggest that inflammasome particles can be released into circulation. The effects of exercise on circulating extracellular apoptosis-associated speck-like protein (ASC) particles and their effects on endothelial cells are not known. Methods: We established a flow cytometric method to quantitate extracellular ASC specks in human serum. ASC specks were quantitated in 52 marathon runners 24-72 h before, immediately after, and again 24-58 h after the run. For mechanistic characterization, NLRP3 inflammasome particles were isolated from a stable mutant NLRP3 (p.D303N)-YFP HEK cell line and used to treat primary human coronary artery endothelial cells. Results: Athletes showed a significant increase in serum concentration of circulating ASC specks immediately after the marathon (+52% compared with the baseline, p < 0.05) and a decrease during the follow-up after 24-58 h (12% reduction compared with immediately after the run, p < 0.01). Confocal microscopy revealed that human endothelial cells can internalize extracellular NLRP3 inflammasome particles. After internalization, endothelial cells showed an inflammatory response with a higher expression of the cell adhesion molecule ICAM1 (6.9-fold, p < 0.05) and increased adhesion of monocytes (1.5-fold, p < 0.05). Conclusion: These findings identify extracellular inflammasome particles as novel systemic mediators of cell-cell communication that are transiently increased after acute extensive exercise with a high mechanical muscular load.

Effects of Medical Face Masks on Physical Performance in Patients With Coronary Artery Disease or Hypertension.

In this randomized, prospective monocentric study, 40 subjects with coronary artery disease or hypertension (cardiovascular disease [CVD] group) were assigned to either surgical mask (SM) or class 2 filtering facepiece mask (FFP2). They performed cycle ergometry exercise tests with progressive intensity until exhaustion with the assigned mask and another test with no mask (NM) in random order. A control group of 10 healthy subjects randomly performed 3 exercise tests with NM, SM, and FFP2, respectively. Blood pressure, heart rate, 12-lead electrocardiogram, exertion, shortness of breath, and capillary blood gases from the earlobe were documented. Across all groups, exercise testing with face masks resulted in a significantly reduced peak power output in watts compared with testing with NM (CVD group: SM vs NM: -5.0 ± 7.0%, p = 0.005; FFP2 vs NM: -4.7 ± 14%, p = 0.03; control group: SM vs NM: -6.8 ± 4.4%, p = 0.008; FFP2 vs NM: -8.9 ± 6.3%; p = 0.01) without differences in hemodynamic parameters, such as maximum heart rate and systolic blood pressure. Wearing an FFP2 compared with NM resulted in significant higher carbon dioxide partial pressure (CVD group: FFP2: 36.0 ± 3.2 mm Hg vs NM: 33.3 ± 4.4 mm Hg, p = 0.019; control group: FFP2: 32.6 ± 2.8 mm Hg vs NM: 28.1 ± 1.7 mm Hg, p <0.001) with corresponding differences in hydrogen carbonate and base excess, but not to a clinically critical extent. In conclusion, exercise testing with SM and FFP2 resulted in a significant reduction of peak power output without differences in hemodynamic parameters in subjects with preexisting CVD and in healthy subjects.

Analysis of left ventricular rotational deformation by 2D speckle tracking echocardiography: a feasibility study in athletes.

2D speckle tracking echocardiography (2DSTE) is established to analyse left ventricular (LV) longitudinal function. The analysis of LV rotational deformation is challenging and requires standardization of image acquisition as well as postprocessing analysis. The aim of this study was to test the feasibility to analyse LV rotational deformation using 2DSTE by introducing a novel algorithm for the detection of artefacts. The study was performed in 20 healthy subjects serving as a control group and in 53 competitive sportsmen. Circumferential, radial strain (CS, RS) and LV rotation were analysed by 2DSTE in parasternal short axis views. The stepwise algorithm to exclude potential artefacts starts with the visual estimation of the image quality with respect to complete visualization of all myocardial segments during the entire cardiac cycle followed by the exclusion of data sets in participants with conduction abnormalities. The next step is the optimization of tracking areas and a cross-check of implausible strain waveforms in multiple acquired comparable cineloops. The last step is the exclusion of strain curves with persisting implausible waveforms if standardization failures and incorrect LV wall tracking are fixed. Plausible physiological strain curves were observed in 89% (n = 65/73) of all subjects. In controls all implausible waveforms could be verified as artefacts. The algorithm was applied in 53 professional athletes to test and confirm its feasibility. Abnormal CS waveforms were documented in 25 athletes, verified as artefacts due to tracking failures in 22 athletes and due to incorrect image acquisition in 3 athletes. CS artefacts were mostly located in the basal posterior and lateral LV segments. (endocardial: 6%, n = 4/70; p < 0.05) and basal posterior (endocardial: 8%, n = 5/70; p < 0.05) segments were highly susceptible to artefacts. 2DSTE of parasternal short axis views to analyse circumferential and radial deformation as well as LV rotation is feasible in athletes. The proposed algorithm helps to avoid artefacts and might contribute to standardization of this technique. 2DSTE might provide an interesting diagnostic tool for the detection of viral myocarditis, e.g. in athletes.

Impact of COVID-19 lockdown on endurance capacity of elite handball players.

BACKGROUND: The lockdown due to the Coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 has far-reaching consequences for professional sports in Germany. The aim of the present study was to investigate the impact of the eight-week lockdown on endurance capacity of elite male handball players. METHODS: Ten male athletes (192±8 cm and 96±6 kg) from the first German handball league participated in the study. The effects of training on shuttle run tests between period 1 (P1: pre-season to mid-season) and period 2 (P2: mid-season to time after lockdown) were compared. The maximum oxygen uptake (VO2max) was assessed using an incremental exercise test (IET) (July 2019 and May 2020). RESULTS: During the COVID-19 lockdown, the athletes completed an instructed home-based strength and endurance program (52/48). The training effects were found to be reduced after the 8-weeks of COVID-19 lockdown (period 2) as compared to period 1 (mean difference 249±248 m, P=0.005). There was no significant difference in the running distance (2358±430 m vs. 2400±362 m, respectively, P=0.70) after the lockdown as compared to the pre-seasonal performance. VO2max (46.6±5.1 vs. 49.4±7.0 mL/kg/min, respectively, P=0.12) and the power output (3.13±0.36 vs. 3.13±0.43 W/kg, respectively, P=1.0) also did not differ between pre-season and after COVID-19 lockdown. CONCLUSIONS: The COVID-19 lockdown led to a reduction in endurance capacity of elite handball players without team training, despite a home-based strength and endurance program. Supervision of individual home-based training is highly recommended to avoid inadequate implementation of the training.

Effects of surgical and FFP2/N95 face masks on cardiopulmonary exercise capacity.

BACKGROUND: Due to the SARS-CoV2 pandemic, medical face masks are widely recommended for a large number of individuals and long durations. The effect of wearing a surgical and a FFP2/N95 face mask on cardiopulmonary exercise capacity has not been systematically reported. METHODS: This prospective cross-over study quantitated the effects of wearing no mask (nm), a surgical mask (sm) and a FFP2/N95 mask (ffpm) in 12 healthy males (age 38.1 ± 6.2 years, BMI 24.5 ± 2.0 kg/m2). The 36 tests were performed in randomized order. The cardiopulmonary and metabolic responses were monitored by ergo-spirometry and impedance cardiography. Ten domains of comfort/discomfort of wearing a mask were assessed by questionnaire. RESULTS: The pulmonary function parameters were significantly lower with mask (forced expiratory volume: 5.6 ± 1.0 vs 5.3 ± 0.8 vs 6.1 ± 1.0 l/s with sm, ffpm and nm, respectively; p = 0.001; peak expiratory flow: 8.7 ± 1.4 vs 7.5 ± 1.1 vs 9.7 ± 1.6 l/s; p < 0.001). The maximum power was 269 ± 45, 263 ± 42 and 277 ± 46 W with sm, ffpm and nm, respectively; p = 0.002; the ventilation was significantly reduced with both face masks (131 ± 28 vs 114 ± 23 vs 99 ± 19 l/m; p < 0.001). Peak blood lactate response was reduced with mask. Cardiac output was similar with and without mask. Participants reported consistent and marked discomfort wearing the masks, especially ffpm. CONCLUSION: Ventilation, cardiopulmonary exercise capacity and comfort are reduced by surgical masks and highly impaired by FFP2/N95 face masks in healthy individuals. These data are important for recommendations on wearing face masks at work or during physical exercise.

Possible new options and benefits to detect myocarditis, right ventricular remodeling and coronary anomalies by echocardiography in systematic preparticipation screening of athletes.

Exclusion of cardiac abnormalities should be performed at the beginning of the athlete's career. Myocarditis, right ventricular remodeling and coronary anomalies are well-known causes of life-threatening events of athletes, major cardiovascular events and sudden cardiac death. The feasibility of an extended comprehensive echocardiographic protocol for the detection of structural cardiac abnormalities in athletes should be tested. This standardized protocol of transthoracic echocardiography includes two- and three-dimensional imaging, tissue Doppler imaging, and coronary artery scanning. Post processing was performed for deformation analysis of all compounds including layer strain. During 2017 and 2018, the feasibility of successful image acquisition and post processing analysis was retrospectively analyzed in 54 male elite athletes. In addition, noticeable findings inside the analyzed cohort are described. The extended image acquisition and data analyzing was feasible from 74 to 100%, depending on the used modalities. One case of myocarditis was detected in the present cohort. Coronary anomalies were not found. Right ventricular size and function were within normal ranges. Isovolumetric right ventricular relaxation time showed significant regional differences. One case of hypertrophic cardiomyopathy and two subjects with bicuspid aortic valves were found. Due to the excessive cardiac stress in highly competitive sports, high-quality and precise screening modalities are necessary, especially with respect to acquired cardiac diseases like acute myocarditis and pathological changes of left ventricular and RV geometry. The documented feasibility of the proposed extended protocol underlines the suitability to detect distinct morphological and functional cardiac alterations and documents the potential added value of a comprehensive echocardiography.

Effects of cardioselective beta-blockade on plasma catecholamines and performance during different forms of exercise.

BACKGROUND: Beta-blockers are still frequently used in cardiovascular diseases but may negatively influence the exercise capacity. The aim of the study was to analyze the effect of beta-blockade on physical performance and plasma level of catecholamine during different forms of exercise. METHODS: Ten prehypertensive athletes (age: 25.1±2.5 years, BMI: 24.4±2.4 kg/m2) performed repeated incremental exercise and steady-state-tests without and with the cardioselective beta-blocker bisoprolol (5mg/day). The cardiopulmonary, metabolic and the catecholamine responses were monitored. RESULTS: Beta-blocker treatment had no effect on maximum power output (Pmax), lactate and the maximal oxygen uptake (VO2max) (Pmax: 269.0±41.5 vs. 269.0±41.5 W; lactate: 8.7±2.6 vs. 8.6±3.2 mmol/L and VO2max: 3110±482 vs. 3077±425 mL/min, respectively; P not significant). Epinephrine and norepinephrine showed a similar exponential increase to maximum load with and without beta-blockade (epinephrinemax 1.92±1.8 vs. 1.93±1.3 nmol/L; P not significant; norepinephrinemax 12.78±7.9 vs. 16.89±12.2 nmol/L; P not significant). Beta-blockade lowered heart rate (HR) and systolic blood pressure (SBP) at rest and under maximum load (ΔHRrest: 10.6±11.1 bpm, P<0.05, ΔHR-Max: 27.8±6.6 bpm, P<0.01; ΔSBPrest: 19.4±9.3 mmHg, P<0.05, ΔSBPmax: 17.7±15.3 mmHg, P<0.01). The maximum oxygen pulse was higher in the tests performed under beta-blockade (IET: ΔVO2/HR: 3.1±2.2 mL/beat, P<0.01; SST: ΔVO2/HR: 3.4±1.4 mL/beat, P<0.001). CONCLUSIONS: Despite beta blockade and resulting differences in cardiopulmonary regulation during the exercise tests, the maximal oxygen capacity and the catecholamine concentration was similar. Higher exercise intensities (>50% Pmax) are associated with a marked increase in plasma catecholamines, which are not influenced by treatment with bisoprolol 5 mg/day.

Unraveling the steroid hormone response in male marathon runners: Correlation of running time with aldosterone and progesterone.

Marathon running is a physical and psychological stressor. We aimed to characterize the response of nine steroid hormones, which include estradiol, progesterone, testosterone, cortisol, aldosterone, 17-hydroxyprogesterone, cortisone, androstenedione, and dehydroepiandrosterone sulfate, to marathon running and their association with performance. Blood samples of sixty men (age: 49.3 ± 5.9 years) who participated in the Berlin marathon were collected within 3 days before, within 30 min and within 58 h after the end of the marathon. The nine steroid hormones in serum were quantified using liquid chromatography-tandem mass spectrometry. The responses of nine steroid hormones to marathon running were characterized. Aldosterone (fold change: 8.5), progesterone (fold change: 6.6), and cortisol (fold change: 3.7) showed significant increases within 30 min after the marathon (all p < 0.0001). Estradiol but not testosterone increased in the male runners. Marathon running time was significantly related to aldosterone increase (beta=-0.238, p = 0.008) and progesterone increase (beta=-0.192, p = 0.036) in addition to body mass index, self-reported training distance, and age. Serum progesterone correlated with aldosterone and cortisol (r = 0.81 and r = 0.92, respectively, p < 0.001). Progesterone, as a precursor hormone, is increased after the completion of marathon running in association with the increase of aldosterone and cortisol. These findings reveal a contribution of progesterone during the response to the psycho-physical stress of marathon running in males.

Pain During "Noncomplex" Electrophysiological Studies and Cardiac Rhythm Device Surgery.

BACKGROUND: There are only limited data about peri-interventional pain during cardiac electrophysiological procedures without analgosedation. In this study, peri-interventional pain and recollection of it after the intervention were evaluated. METHODS: A total of 101 patients (43 electrophysiological/ablation procedures and 58 device surgeries) reported pain on a numerical rating scale (NRS; 0-10) before (pre), during (peri), and after (post) the intervention. Maximum pain (maxNRS) and the average of pain (meanNRS) were used for statistical analysis. Peri-interventional pain was compared with postinterventional data of the recollection of peri-interventional pain (peri-post). Patients were allocated into 2 groups (with 51 and 50 patients, respectively) to evaluate the mode of patient-staff interaction on pain recollection. Depressive, anxiety, and somatic symptom scales (Patient Health Questionnaire-15, Generalized Anxiety Disorder-7, and Patient Health Questionnaire-15) were used to analyze their influence on pain recollection. RESULTS: In total, 49.6% of patients (n = 50) complained of moderate to severe pain (maxNRS) at least once during the procedure. The comparison between peri and peri-post data revealed the following (median (range)-maxNRS, peri: 3 (0-10) versus peri-post: 4 (0-9) (ns), and meanNRS, peri: 1.4 (0-7) versus peri-post: 2.0 (0-6) (ns). The mode of patient-staff interaction had no influence on pain. No effect was found for psychosocial factor concerning pain and the recollection of pain. The results of the linear regression showed no influence of low-dose midazolam on recollection of pain. CONCLUSION: Half of the patients reported moderate to severe pain at least once during cardiac electrophysiological procedures without analgosedation. However, on average, patients reported only low pain levels. Postinterventional derived data on discomfort reflect the peri-interventional situation.

Acute cardiopulmonary responses to strength training, high-intensity interval training and moderate-intensity continuous training.

PURPOSE: Long-term effects of exercise training are well studied. Acute hemodynamic responses to various training modalities, in particularly strength training (ST), have only been described in a few studies. This study examines the acute responses to ST, high-intensity interval training (HIIT) and moderate-intensity continuous training (MCT). METHODS: Twelve young male subjects (age 23.4 ± 2.6 years; BMI 23.7 ± 1.5 kg/m2) performed an incremental exertion test and were randomized into HIIT (4 × 4-min intervals), MCT (continuous cycling) and ST (five body-weight exercises) which were matched for training duration. The cardiopulmonary (impedance cardiography, ergo-spirometry) and metabolic response were monitored. RESULTS: Similar peak blood lactate responses were observed after HIIT and ST (8.5 ± 2.6 and 8.1 ± 1.2 mmol/l, respectively; p = 0.83). The training impact time was 90.7 ± 8.5% for HIIT and 68.2 ± 8.5% for MCT (p < 0.0001). The mean cardiac output was significantly higher for HIIT compared to that of MCT and ST (23.2 ± 4.1 vs. 20.9 ± 2.9 vs. 12.9 ± 2.9 l/min, respectively; p < 0.0001). VO2max was twofold higher during HIIT compared to that observed during ST (2529 ± 310 vs. 1290 ± 156 ml; p = 0.0004). Among the components of ST, squats compared with push-ups resulted in different heart rate (111 ± 13.5 vs. 125 ± 15.7 bpm, respectively; p < 0.05) and stroke volume (125 ± 23.3 vs. 104 ± 19.8 ml, respectively; p < 0.05). CONCLUSIONS: Despite an equal training duration and a similar acute metabolic response, large differences with regard to the training impact time and the cardiopulmonary response give evident. HIIT and MCT, but less ST, induced a sufficient cardiopulmonary response, which is important for the preventive effects of training; however, large differences in intensity were apparent for ST.

Normal Values of Hemoglobin Mass and Blood Volume in Young, Active Women and Men.

Hemoglobin mass (Hbmass) and total blood volume (BV) determine the oxygen content in the blood. Varying anthropometric values are used to standardize blood volume and Hbmass. The aim of this study was to create normal values and to evaluate an anthropometric reference for Hbmass and BV. One hundred healthy young subjects participated in this study (50 women: 20.9±2.0 yr; 50 men: 23.2±2.9 yr). The Hbmass was measured twice by using a CO rebreathing method. The BV was calculated from the Hbmass, Hb concentration and hematocrit values. The lean body mass (LBM) was measured by a bio-impedance analysis. Women had a significant lower Hbmass per kg LBM compared with that of men (13.6±1.3 g vs. 16.1±1.7 g; p<0.0001). The BV per kg LBM tended to be lower in women than in men (105.3±8.4 ml vs. 108.7±9.0 ml; p=0.0548). LBM had the best correlation with Hbmass (r=0.9274) and BV (0.9233) when considering the entire study group. Normal values of Hbmass and BV could be potentially useful for fluid management and contribute to the diagnosis of blood disorders. For normalization and assessment of measured BV and Hbmass, lean body mass should be prioritized in future studies instead of body weight or body surface area.