Anaerobic Threshold Research Articles

Downhill running does not alter blood C1q availability or complement-dependent cytotoxicity of therapeutic monoclonal antibodies against haematological cancer cell lines in vitro.

Complement-dependent cytotoxicity (CDC) is a primary mechanism-of-action of monoclonal antibody (mAb) immunotherapies used to treat haematological cancers, including rituximab and daratumumab. However, mAb efficacy may be limited by reduced bioavailability of complement C1q - which activates the complement classical pathway following interactions with mAb-opsonised target cells. C1q is secreted by phagocytes upon recruitment to sites of muscle damage to facilitate muscular repair, hence we hypothesised that muscle damaging exercise may increase C1q 'spill-over' into blood. Additionally, other complement proteins (e.g., C1s) have been reported to increase following ultra-endurance and resistance exercise. Taken together, we hypothesised that muscle damaging exercise could be harnessed to enhance mAb-mediated CDC. In this study, n = 8 healthy males (28 ± 5-years) completed two 45-minute treadmill running protocols: (1) a flat running protocol at a speed 15% above anaerobic threshold, and (2) a downhill running protocol (- 10% slope) at the same speed. Blood samples were collected before, immediately after, and 1-hour, 24-hours, 2-days, and 4-days after exercise. Isolated serum was assessed for C1q by ELISA, and used to measure mAb (rituximab, daratumumab) mediated CDC against two haematological cancer cell lines (Raji, RPMI-8226) in vitro. Isolated plasma was assessed for markers of inflammation (C-reactive protein [CRP]), and muscle damage (creatine kinase [CK]) by turbidimetry. C1q and CDC activity were not different between running protocols and did not change over time (p > 0.05). Significantly greater perceived muscle soreness (p < 0.001) and fluctuations observed from baseline to 24-hours post-exercise in the downhill running trial in CK (+ 171%) and CRP (+ 66%) suggests some degree of muscle damage was present. It is possible that any increase in C1q post-exercise may have been masked by the increase and subsequent interaction with CRP, which utilises C1q to facilitate muscular repair. This is the first study to investigate whether exercise can increase circulating C1q and improve mAb-mediated CDC and our findings show that downhill running exercise does not increase circulating C1q nor improve CDC in vitro.

Six weeks of polarized functional interval training with large training load reductions does not affect performance gains compared to traditional workouts

PurposeHigh-intensity functional interval training (HIFT) is predominantly composed of high exercise training intensities (HiT) and loads. Both have been linked to a higher risk of overtraining and injuries in inexperienced populations. A polarized training approach is characterized by high amounts of low-intensity training (LiT) and only approximately 5%–20% HiT. Compared to HIT-based training, this approach can result in temporary training load and intensity reductions without diminishing training gains. Thus, we aimed to examine the effects of traditional (TRAD) HIFT vs. polarized (POL) HIFT on relevant performance parameters.MethodsThirty athletes (15 females, age: 26.6 ± 5.0 years, height: 1.76 ± 0.13 m, body mass: 79.6 ± 12.4 kg, prior experience: 2.3 ± 2.0 years, training volume: 6.1 ± 2.4 h/wk) were randomly assigned to 6 weeks of either POL (78% LiT, 22% threshold intensity training (ThT) to HiT) or TRAD (26% LiT, 74% ThT to HiT). HIFT performance testing focused on maximal strength (squat: SQ1RM, deadlift: DL1RM, overhead press: OHP1RM, high pull: HP1RM), endurance (peak oxygen uptake: V̇O2peak, lactate threshold: LT, peak power output (PPO), and benchmark HIFT workout (Jackie: 1000 m rowing, 50 thrusters, and 30 pull-ups for time).ResultsPOL (785 ± 71 au) completed significantly (p ≤ 0.001; SMD = 4.55) lower training load (eTRIMP) than TRAD (1,273 ± 126 au). rANCOVA revealed no statistical relevant group×time interaction effects (0.094 ≤ p ≤ 0.986; 0.00 ≤ ηp2 ≤ 0.09) for SQ1RM, DL1RM, OHP1RM, high pull, V̇O2peak, LT, PPO, and Jackie performance. Both groups revealed trivial to moderate but significant (rANCOVA time effects: p ≤ 0.02; 0.01 ≤ ηp2 ≤ 0.11; 0.00 ≤ SMD ≤ 0.65) performance gains regarding DL1RM, OHP1RM, HP1RM, and Jackie.ConclusionDespite a notably lower total training load, conditioning gains were not affected by a polarized functional interval training regimen.

Aerobic Energy Turnover and Exercise Economy Profile During Race Simulation in a World-Record-Breaking Male Full-Distance Triathlete.

To investigate metabolism and exercise economy during prolonged race simulation (>4h) in a world-class, full-distance triathlete to help guide/adjust strategies for training, nutrition, hydration, and thermoregulation. Two experimental race-simulation days, designed to mimic the demands of a full-distance triathlon, were executed by a world-class maletriathlete(MD; 25y, body weight 82kg, V˙O2max 6.2L·min-1, blood lactate threshold ∼410W, and 18km · h-1 in cycling and running) who at the time ranked second in the world. Race simulation was performed 23 and 10 days prior to competing in Challenge Roth 2023, where MD won in a new world record/best time (7:24:40h:min:s). Both test days lasted ∼4 to 5hours with physiologic testing every ∼45 to 60minutes in a "stationary" setting during cycling on a direct-mount trainer (∼320W) and treadmill running (16km · h-1), enabling gas exchange measurements (V˙O2 and respiratory exchange ratio) and other physiologic measurements of interest (ie,core temperature and heart rate). This was combined with "real activity" as repeated loops in an open-air field setting at expected race pace in swimming, biking, and running. V˙O2 was maintained at ∼4.2L·min-1, with carbohydrates being the dominant fuel for oxidation as respiratory exchange ratio values dropped from ∼1 at the start of cycling to ∼0.85 during running. Cycling economy was stable, whereas a slight impairment in running economy occurred over time. High aerobic energy turnover and stable exercise economy can be maintained in a world-class record-breaking triathlete for prolonged period of time (+4h), showcasing the importance of both for success in competition.

OGC SO28 - Predictors of Pulmonary Complications Following Thoracoscopic Oesophagectomy

Abstract Background Thoracoscopic oesophagectomy, a minimally invasive technique, is associated with less postoperative pain and reduced pulmonary dysfunction. There is a correlation between preoperative cardiopulmonary fitness and postoperative outcomes, with certain variables linked to a higher risk of complications following oesophagogastric cancer surgery. This review aims to identify variables that correlate with pulmonary complications after oesophagectomy. Method A retrospective review of patients undergoing thoracoscopic oesophagectomy between 2014 -2022 at a single oesophagogastric unit was performed. 96 patients were identified and separated into two groups (19 with serious complications (SC) (greater than Clavien Dindo 3b), and 77 without serious complications (Clavien Dindo 3a and below)(NC). The primary outcomes measured included FEV1, FVC, VE/VCO2, VO2 Peak, anaerobic threshold, Estimated Met Score (EMS). Secondary outcomes measured preexisting pulmonary complications, smoking status and operating (chest time, one lung ventilation time (OLVT)). Results Groups were similar in age, gender, BMI, ASA, and clinical stage. SC had a significantly less number of smokers (p=0.004) and less individuals with pulmonary disease (p=0.019). AT was higher in NC (14.15 vs 13.50, p=0.355) and VE/VCO2 was significantly greater in SC (28 vs 32, p=0.018). SC had a significantly lower FEV1 and FVC (2.12 vs 2.81, p=0.009 and 3.11 vs 3.80, p=0.010) and a trend towards a lower EMS (6.95 vs 7.25, p=0.245). There was no significant difference in chest time between NC and SC (295min vs 265min, p=0.151) and OLVT (270min vs 245min, p=0.381) in both groups. Conclusion VE/VCO2 ratio in thoracoscopic oesophagectomy patients is a significant predictor of postoperative complications and has increasing links to adverse outcomes. Smoking status and pulmonary history do not significantly correlate with pulmonary complications in our cohort. Lower EMS, FEV1, and FVC are significantly associated with complications. Although preoperative inspiratory muscle training has not broadly impacted postoperative outcomes, it may benefit specific groups. These variables are crucial for clinicians to consider when counselling patients and planning prehabilitation.

AHP SO01 - Establishing Physiotherapy led Prehabilitation for patients undergoing major hepatobiliary surgery in a Regional Centre - A Service Improvement

Abstract Background Prehabilitation is increasingly on the agenda for major surgical patients and will be an essential service in an ageing population with increasing cancer prevalence. By 2040 5.3 million people in the UK will be living with cancer physical fitness can have an impact on both treatment options and survival rates. Prehabilitation has been mentioned in both the Major Conditions Strategy and the Long-Term Plan. Currently within the trust, there are no established multiprofessional prehabilitation services. New funding allowed a service improvement project to develop a ‘model’ for a specialist physiotherapy prehabilitation pathway pilot in patients undergoing major hepatobiliary surgery. Method Patients undergoing major surgery complete Cardiopulmonary Exercise Testing, providing data indicating fitness levels and guides risk stratification. Patients deemed to be at high risk due to poor fitness, (anaerobic threshold 10.9 or below), were referred to the prehabilitation physiotherapist. Patients attended a 1:1 assessment with a Physiotherapist, were provided with an individualised home exercise programme, including cardio-vascular and muscle strengthening. Weekly follow up virtual follow was provided. Outcome measures taken at initial appointment included five sit to stand (5STS) time, Grip strength and EQ-5D. These were repeated before surgery, and after hospital discharge. Patients had the opportunity to provide feedback. Results Average improvement in all outcome measures was demonstrated. Outcome MeasuresPre-intervention averagePost intervention averageAverage changeEQ-5D Score8.17.30.8EQ-5D Health score687465 STS (seconds)14.711.5-3.1Grip (kg)29.831.31.5Sarcopenic 5 STS (seconds)20.913.1-7.9 Patient and staff feedback was positive, finding patients reported they felt prepared for the post operative period, and staff noted and increased in their patients preparedness. It is too early to say if Prehabilitation has had an impact on hospital length of stay or post operative complications, though early results are promising. Conclusion Physiotherapy led prehabilitation is beneficial for patients undergoing major HPB surgery, demonstrating improvements in physical strength and fitness following an individualised home exercise programme with regular virtual support, especially those who have sarcopenia.

OGC O02 - Measurement of functional, psychosocial, and quality of life impacts of Robotic versus Hybrid Oesophago-gastrectomy

Abstract Background Since the introduction of Robotic-Assisted Minimally-Invasive Oesophago-gastrectomy (RAMIO), comparisons to other surgical approaches have focussed primarily on peri-operative and oncological outcomes. Few studies have focused on quality-of-life measures once the patient has been discharged home. We sought to compare physical, psychosocial, sleep, pain and employment related measures at six weeks following discharge in patients undergoing RAMIO versus Hybrid Oesophago-gastrectomy. Method We performed a prospective cohort study comparing RAMIO and Hybrid Oesophago-gastrectomy. Twenty-five consecutive patients on a curative surgical pathway were recruited to each group. Participants were contacted via telephone pre-operatively and six weeks post-operatively. Parameters studied were: physical activity, social activity, sleep, pain control, and employment. Psychological wellbeing was measured using the Hospital Anxiety and Depression Scale, and quality of life with the European Organisation for Research and Treatment of Cancer questionnaires C30 (all cancer patients) and OG25 (patients undergoing oesophago-gastric cancer treatment). Results were analysed using Chi Square and Mann-Whitney-U statistical tests. Results There were no differences in age, ASA, or anaerobic threshold between study groups. At six weeks the RAMIO group was more likely than Hybrid to have returned to pre-operative physical and social activity (physical 7/25 vs. 1/25, p=0.04, social 13/25 vs. 5/25, p=0.03). The RAMIO group stopped regular analgesia earlier, and required fewer opiates. Patients were more likely to return to work in the RAMIO group (7/15 vs. 1/12,p=0.04). The RAMIO group had fewer cases of depression (2 vs. 9, p=0.03), lower QLQ C30 and OG25 scores, and reported higher overall health and quality of life scores (p=0.001). Conclusion We have demonstrated an improvement in physical and social activity, a faster return to work, a reduction in analgesia requirements, lower rates of depression and improved health and quality of life, six weeks post-operatively when comparing RAMIO to hybrid oesophago-gastrectomy. This study has highlighted additional considerations for the selection of surgical modality in oesophago-gastrectomy beyond peri-operative outcomes. Further investigation across a larger sample size and longer time frame to quantify the full spectrum of potential benefits of robotic oesophago-gastric surgery is warranted.

Abstract 4122543: Can We Diagnose Ticagrelor-induced Dyspnea After Urgent Percutaneous Coronary Intervention with Cardiopulmonary Exercise Testing?

Background: Ticagrelor has been reported to cause shortness of breath (SOB) in 6 to 9 % of patients. Precise mechanisms are not enirely understood. We hypothesize that cardiopulmonary exercise testing (CPET) may be helpful in clinical assessment of patients reporting SOB on ticagrelor. Case presentation: 66-yo female with history of arterial hypertension, DM type 2 and prior MI presented with STEMI and successfully underwent urgent PCI of RCA and LAD. The patient received ticagrelor in loading dose followed by 90 mg b.i.d plus low-dose aspirin. Just after PCI she developed SOB with no evidence of acute cardiac or respiratory compromise. After discharge the patient continued to experience SOB impairing daily activities. In 6 months she was re-assessed. Clinical investigation (physical exam, blood tests, echo, CXR, spirometry) showed no abnormalities that could explain SOB. CPET despite good effort showed low VO 2 peak (7,8 ml*min/kg; 49% from predicted), undetectable anaerobic threshold (AT), severely impaired ventilatory efficacy (VE/VCO 2 =50,1) and marked hyperventilation (resting RER=1,0; PetCO 2 =18,0 mmHg at rest and 22,4 mmHg at peak load). Exercise EKG, blood pressure response, SpO 2 and breathing reserve were normal. Once the patient was switched from ticagrelor to clopidogrel she reported significant improvement. CPET one week after showed increase in VO 2 peak up to 12,5 ml/kg/min., AT of 11,1 ml*min/kg, better ventilatory efficacy (VE/VCO 2 =37,1) and less hyperventilation (PetCO 2 28,1 mmHg at rest and 28,8 mmHg at peak load). CPET performed one month later showed further improvement in VO 2 peak to 13,2 ml*min/kg, normal VE/VCO 2 and no signs of hyperventilation. Discussion: it is believed that ticagrelor-induced dyspnea can be driven by 2 potential mechanisms, first related to inhibition of adenosine reuptake, second - to sensory neuron P2Y12 inhibition. It occurs early after starting the medication and is not associated with structural cardiopulmonary abnormalities. Previous small data showed evidence of Cheyne-Stokes respiration during both night and day related to ticagrelor. Symptoms usually are dose-dependent and disappear after discontinuation of ticagrelor. In our case the patient demonstrated reversible hyperventilation and reduced exercise capacity associated with ticagrelor that was confirmed with CPET. Conclusion: CPET allows differentiating SOB in patients treated with ticagrelor. Further investigations are required to confirm this hypothesis.

Abstract 4137985: Impaired Skeletal Muscle Condition and Stroke Volume Reserve Characterize Poor Exercise Performance in Childhood Cancer Survivors

Background: Childhood cancer survivors (CCS) frequently show poor exercise performance, but its pathophysiology and clinical significance are poorly understood. Methods: Poor exercise performers, defined as peak oxygen consumption (VO2)/kg &lt; 80% of predicted maximum VO2/kg, were enrolled, including 40 CCS (20 males, 20 females) and 32 controls (15 males, 17 females) from 79 CCS and 147 age-matched controls, respectively. Peak and submaximal CPET parameters were compared between CCS and controls with poor exercise performance. Submaximal slope parameters represent a trend up to anaerobic threshold (AT). Results: Ages and anthropometric measurements (weight, height, and body mass index) were comparable between CCS and controls in both sexes (Table 1). Both resting and peak heart rate (HR) were significantly higher in CCS than in controls in males. There was no significant difference in peak VO2/kg, peak oxygen pulse (OP)/kg, peak respiratory exchange ratio, or VO2/kg at AT (VAT/kg) between CCS and controls in both sexes. Peak work rate (WR/kg) was significantly lower in CCS compared with that in controls in both sexes, suggesting reduced muscle strength in CCS. Figure 1 demonstrates decreased muscle mass/strength in CCS than in controls. In males, Δ[VO2/kg]/ ΔHR was significantly lower in CCS than in controls, indicating limited stroke volume reserve (SVR) in male CCS. In female, although there was no significant difference in Δ[VO2/kg]/ΔHR between CCS and controls, HR-dependency expressed by ΔHR/Δ[WR/kg] was significantly higher in CCS than in controls, suggesting impaired SVR. ΔVO2/ΔWR, a marker for physical conditioning, was comparable between CCS and controls in both sexes. Conclusions: Poor exercise performance in CCS is characterized mainly by decreased muscle mass/strength and impaired SVR for both sexs. Impaired SVR may be an early sign of subclinical cardiotoxicity. Poor exercise performance in CCS should be improved to prevent future cardiovascular complications.

Cigarette Smoking Impairs Cardiorespiratory and Metabolic Response at Peak Incremental Exercise and during Recovery in Young, Physically Active Adults

ABSTRACT Purpose: Cigarette smoking (CS) induces systemic changes that impair cardiorespiratory and muscular function both at rest and during exercise. Although these abnormalities are reported in sedentary, middle-aged smokers (SM) with pulmonary disease, few and controversial studies focused on young, physically active SM at the early stage of smoking history. This study aimed at assessing the impact CS on cardiorespiratory and metabolic response during an incremental test and the subsequent recovery in young, physically active SM without known lung or cardiovascular disease. Methods: After pulmonary function evaluation, 12 SM (age: 22±2 yr; body mass: 75±8 kg; stature: 1.78±0.06 m; 12±4 cigarette/day for 6±2 years; mean±SD) and 12 non-smokers (CTRL; age: 23±1 yr; body mass: 76±8 kg; stature: 1.79±0.08 m) matched for age and exercise habits, underwent an exhaustive incremental step test (25 W/2 min) on a cycle ergometer. Pulmonary O2 uptake (V’O2), expiratory ventilation (V’E), heart rate (f H) responses and lactate concentration were assessed during the test and subsequent recovery. Results: Despite similar static lung volumes, SM reported lower peak expiratory flow (-23%; P = 0.003) and maximal voluntary ventilation (-10%; P = 0.003). At submaximal exercise, no differences in the cardiorespiratory and metabolic were noted between the two groups. However, SM exhibited ventilatory (P &lt; 0.01) and lactate thresholds at lower work rates (P = 0.01). At peak exercise, SM exhibited lower V’O2 (-8%; P = 0.02), mechanical power (-11%; P = 0.02) and V’E (-9%; P = 0.01). During recovery, SM showed longer time constants (τ) in V’O2 (+52%; P = 0.002), V’E (+19%; P = 0.027) and f H (+21%; P = 0.022) and smaller f H at 30 s of recovery (HRR30; -31%; P = 0.032). Conclusions: These results are compatible with an early CS-related impairment of the cardiorespiratory and metabolic function even in young individuals with relatively short smoking history.

Hemodynamic responses at anaerobic threshold during exercise in preload insufficiency.

Preload insufficiency is an underrecognized cause of exercise intolerance identified during invasive cardiopulmonary exercise testing, and defined hemodynamically by decreased biatrial filling pressures, cardiac output, and oxygen consumption (V̇O2) at peak effort. Patients with preload insufficiency, however, typically present with symptoms of dyspnea on exertion, and/or exercise intolerance at submaximal efforts, particularly when performing activities of daily living. The cardiopulmonary hemodynamics and physiology at submaximal work levels of preload insufficiency have not been previously investigated. We hypothesized that preload insufficiency hemodynamics exist along a continuum, with submaximal exercise values reflecting peak exercise cardiopulmonary hemodynamics. We compared submaximal cardiopulmonary hemodynamics, measured at anaerobic threshold, between preload insufficiency patients and age-matched controls referred for dyspnea but with normal exercise responses. Our study included 66 patients: 41 with preload insufficiency and 25 controls. Preload insufficiency patients exhibit significantly reduced V̇O2, watts, and METS at submaximal levels compared to controls, alongside earlier anaerobic threshold achievement and similar heart rates at anaerobic threshold. These findings underscore the profound impact of preload insufficiency on submaximal exercise capacity, emphasizing the importance of its recognition and management. This insight sets the stage for further investigations into interventions targeting preload insufficiency at submaximal exercise levels to enhance both exercise performance and quality of life.

Prescribing submaximal training based on the lactate threshold improved aerobic fitness in dogs with preclinical myxomatous mitral valve disease

Abstract Exercise intolerance may be a primary symptom of myxomatous mitral valve disease (MMVD) and a significant factor in reducing the quality of a dog’s life. Aerobic training effectively improves oxygen uptake and life expectancy in human patients with chronic heart failure. Lactate threshold (LT) is used to prescribe training programs. We conducted a study with dogs diagnosed with asymptomatic MMVD (stage B1), using the velocity corresponding to the visual lactate threshold (VLTv) and an eight-week submaximal training program (STP), three times a week, with each session lasting 30 min, to improve their aerobic fitness. The dogs were assigned into two groups: a healthy control group and a MMVD group (stage B1). The treadmill-based graded exercise test (GXT) was used to determine the lactate-velocity curve (LVC) inflexion point. We utilised the velocity corresponding to 70% VLTv as the external load STP, representing a training zone between 145 and 157 bpm. Before the STP, VLTv and maximum velocity (Vmax) were lower in B1 dogs compared with the healthy group. The VLTv increased in the B1 dogs, resulting in rightward shifts of the LVC. The VLT values for healthy dogs were 3.62 ± 0.90 m/s and 4.75 ± 0.6 m/s; for B1 dogs were 3.03 ± 0.6 m/s and 3.8 ± 0.75 m/s in the pre-STP and post-STP. The Vmax values were 4.50 ± 0.70 m/s and 4.75 ± 1.04 m/s for healthy dogs, and 4.0 ± 0.53 m/s and 4.66 ± 0.74 m/s for B1 dogs. In both groups, changes in the relationship between lactatemia and exercise work may indicate improvements in aerobic and anaerobic capacities. VLTv, as an external training loading, should be considered when prescribing tailored training programs for dogs with asymptomatic myxomatous mitral valve disease to improve their muscular and cardiovascular function and exercise tolerance.

Old and new equations for maximal and anaerobic threshold heart rate prediction in coronary heart disease in Chinese population

BackgroundThe prediction of maximal heart rate (MHR) and anaerobic threshold heart rate (HRAT) in patients with coronary heart disease (CHD), particularly among the Chinese population, remains a significant challenge. Existing equations for MHR prediction are primarily designed for healthy individuals not on medication for optimized β-blocker (BB) therapy, showing limited efficacy for individuals on various drug regimens. Moreover, the prediction of HRAT lacks established formulas. This study aims to develop equations for MHR and HRAT, assess the accuracy of historical MHR formulas, and examine their correlation with HR measurements at the anaerobic threshold (AT).MethodsAmong 2021 to 2023, 170 CHD patients were recruited. Patients were categorized into groups based on BB usage. BB dose was transformed into carvedilol dose. Multiple linear stepwise regression analysis was employed to identify predictors of MHR and HRAT, incorporating key patient variables according to prior studies (age, sex, height, weight, carvedilol dose, HRrest). The mean absolute percentage errors (MAPEs) were calculated and compared among abovementioned MHR and HRAT prediction formulas. Besides, the percentages of MHR in predicting HRAT among different formulas were calculated.ResultsFor the patients with BB medication, the simplified equations derived for MHR and HRAT were 176 − 1.2*age + 0.7*HRrest − 0.4*weight and 98 − 0.6*age + 0.7*HRrest − 0.3*weight, respectively. For those without BB medication, the derived equations for MHR and HRAT were 200 − 1.1*age and 91 − 0.5*age + 0.5*HRrest, respectively. There are significant differences between the results predicted by the new formula and the prior formulas. The new formulas are helpful for predicting the MHR of patients during exercise more accurately and guiding exercise training more scientifically.ConclusionsThe new equations for estimating MHR and HRAT in CHD patients enhance the accuracy of prior formulas. Given the BB impact on sympathetic nerve activity, the predictive formulas for MHR and HRAT were significantly improved.

Exercise in Pediatric COVID-19: A Randomized Controlled Trial.

Purpose: This study assessed the impact of a 12-week, home-based exercise training (HBET) program on health-related quality of life (HRQOL, primary outcome), cardiovascular and metabolic parameters in pediatric COVID-19 patients.Methods: In this single-center, randomized controlled trial conducted in Sao Paulo (Brazil) from October 2020 to January 2022, 32 patients (mean age 12 ± 3.3 years; median 4 months [range: 0.7-6.6] between COVID-19 diagnosis [n = 25 mild, n = 4 moderate, n = 3 severe illness] and study entry) from a tertiary hospital were randomly assigned to either HBET or standard of care (CONTROL) in a 2:1 ratio. The HBET group underwent supervised and unsupervised sessions 3 times/week for 12 weeks emphasizing aerobic and bodyweight exercises and the CONTROL group received standard care which included general advice for a healthy lifestyle with no prescribed exercise intervention. HRQOL (Pediatric Quality of Life Inventory [PedsQL], cardiopulmonary exercise test (CPET), brachial flow-mediated dilation (b-FMD) and echocardiography assessments were conducted in both groups. Statistical analysis was performed using an intention-to-treat approach (ITT) for the primary analysis and complete-case (per-protocol) as sensitivity analysis and significance was set at P ≤ 0.05 (P ≤ 0.10 were considered as trend).Results: There was no difference in HRQOL between groups. Intention-to-treat analysis showed a trend toward increased VO2 at anaerobic threshold at post-intervention for the HBET group. Additionally, a sensitivity analysis showed significant changes in peak HR, HRR1min, RER and chronotropic response and tendency towards significance in VE/MVV and chronotropic response for the HBET group. No other between-group differences were detected for CPET, b-FMD and echocardiography variables (all p > 0.05).Conclusions: In this RCT, a 12-week HBET intervention did not impact HRQOL in pediatric COVID-19 patients. However, HBET led to greater improvements in VO2 VAT, heart rate peak and one-minute recovery and in chronotropic response with no changes in other cardiovascular parameters. Further studies are needed to explore the effects of exercise on the recovery of pediatric COVID-19 patients with persistent COVID-19 symptoms.

Ketogenic diet in adult patients with mitochondrial myopathy

BackgroundThis study aimed to explore the feasibility, safety and efficacy of a Modified Atkins Diet (MAD) in patients with mitochondrial myopathy (MM). MethodsPatients with genetically proven mitochondrial disorder and exercise intolerance or muscle weakness followed a twelve week MAD. Feasibility was measured by diet duration and ketone levels. Safety was assessed by monitoring adverse events (AE). Efficacy was assessed by a maximal incremental test and a muscle performance test. ResultsEight out of twenty patients completed the twelve week intervention. Reasons to discontinue were the occurrence of AE: rhabdomyolysis (n = 3), vomiting (n = 1), fatigue (n = 6), constipation (n = 1), in combination with a lack of improvement and adherence difficulties. On an individual level, various positive effects were reported including improvements in VO2peak (n = 6), anaerobic threshold (n = 9), muscle fatigue resistance (n = 5), muscle strength (n = 7), fatigue (n = 6), glucose tolerance (n = 7), migraine (n = 3), sleep (n = 3), and gastrointestinal complaints (n = 2). Lipid profile improved and thirteen patients lost weight. All patients with mitochondrial DNA (mtDNA) deletions, experienced muscle related AE. The five patients with the m.3243A>G mutation achieved the longest diet duration. Discussion/conclusionMAD feasibility, safety and efficacy is variable in MD patients. MAD appears to be unsuitable for MD patients with mtDNA deletions. All patients should be monitored closely for adverse events when initiating the diet. Further research should focus on predictive factors to consider the diet, effectiveness of less stringent carbohydrate restricted diets.

Carbon monoxide supplementation: evaluating its potential to enhance altitude training effects and cycling performance in elite athletes.

Altitude training is a cornerstone for endurance athletes for improving blood variables and performance, with optimal effects observed at ∼2,300-2,500 meters above sea level (m.a.s.l.). However, elite cyclists face challenges such as limited access to such altitudes, inadequate training facilities, and high expenses. To address these issues, a novel method involving daily exposure to carbon monoxide (CO) has been proposed to amplify altitude training adaptations at suboptimal altitudes. Thirty-one male cyclists were assigned to three groups: Live-High Train-High with CO inhalation (LHTHCO), Live-High Train-High (LHTH), and Live-Low Train-Low (LLTL). The LHTHCO group underwent CO inhalation twice daily in the afternoon/evening to elevate carboxyhemoglobin concentration to ∼10%. Hematological variables, in vivo muscle oxidative capacity, and physiological indicators of cycling performance were assessed before and after a 3-week altitude training camp at 2,100 m.a.s.l. LHTHCO demonstrated a larger increase in hemoglobin mass (Hbmass) compared to both LHTH and LLTL. Although there were no statistical differences between LHTHCO and LHTH in submaximal and maximal performance measures, LHTHCO displayed greater improvements in 1-min maximal power output during incremental testing (Wmax), power output at lactate threshold, and maximal oxygen consumption (V̇o2max) compared to LLTL. LHTH demonstrated a larger improvement than LLTL in Wmax and V̇o2max, with no group differences in Hbmass or submaximal measures. Muscle oxidative capacity did not differ between groups. These findings suggest that combining moderate-altitude training with daily CO inhalation promotes hematological adaptations more effectively than moderate altitude alone and enhances cycling performance metrics in cyclists more than sea-level training.NEW & NOTEWORTHY Three weeks of training at moderate altitude with exposure to low doses of CO can significantly enhance hematological adaptations in elite cyclists compared to moderate-altitude training alone. Cycling performance determinants improved more with CO inhalation at moderate altitude compared to sea-level training, whereas there were no differences in submaximal and maximal performance measures compared to moderate-altitude training alone. This study highlights the potential of CO supplementation as an effective adjunct to altitude training regimens.

The ventilatory efficiency parameters outperform peak oxygen consumption in monitoring the therapy effects on the right ventricular load in patients with hypertrophic cardiomyopathy

Abstract Aim We sought the cardiopulmonary exercise testing (CPET) parameter that is the most reflective of right ventricular (RV) load and its coupling with pulmonary artery (PA) in patients diagnosed with hypertrophic cardiomyopathy (HCM) undergoing medical therapy. Methods CPET on recumbent bike was performed in adult patients with symptomatic non-obstructive HCM with NYHA class I–III, during phase II, randomised, open-label multicentre study, before and after diverse medical treatment for 16 weeks. Endpoints were the changes in: 1) peak oxygen consumption (peak VO2); 2) minute ventilation (VE)/carbon-dioxide (CO2) production slope during the whole CPET; 3) VE/VCO2 slope before anaerobic threshold (AT); 4) VE/VCO2 slope after AT; 5) VE/VCO2 nadir; 6) VE/VCO2 at AT; and 7) VE/VCO2 intercept. Standard ehocardiography at rest was performed concomitantly with CPET to assess tricuspid annular plane systolic excursion (TAPSE), pulmonary artery systolic pressure (PASP), severity of mitral regurgitation (MR) and TAPSE/PASP ratio as a measure of RV-PA coupling. Results Of 115 screened patients, 61 (mean age 52 years [SD 14], 43% women) met the study inclusion criteria and underwent CPET. On regression analysis, among all CPET end-point variables, the best independent predictor of the change in PASP, TAPSE and MR severity after 16 weeks of medical treatment was VE/VCO2 below AT (B=-0.28, -0.01,-0.11; SE=0.10, 0.05, 0.01; CI=-0.48 to -0.08, -0.22 to -0.01; -0.02 to 0.01; p=0.007, 0.035, 0.004, respectively), whereas the best predictor of TAPSE/PASP ratio was intercept of the VE/VCO2 curve (B=0.014, CI=0.01to 0.03, p=0.005). Conclusion The changes in VE/VCO2 slope below anaerobic threshold, and intercept of the VE/VCO2 curve outperform peak VO2 in the monitoring of therapy effects on the right heart load and RV-PV coupling in patients with hypertrophic cardiomyopathy.

Quality of muscle in the thigh predicts the prognosis in patients with non-ischemic cardiomyopathy

Abstract Background Skeletal muscle atrophy is an independent prognostic predictor for patients with chronic heart failure, and the concept of sarcopenia has garnered scientific attention. Furthermore, the importance of not only muscle mass but also quality of muscle has been pointed out. And a sarcopenia diagnosis is confirmed by the presence of low quality of muscle. However, there is a lack of consensus on the implications of ectopic fat as a quality of muscle for the prognosis in patients with non-ischemic cardiomyopathy. Purpose We investigated whether intramuscular fat (IMF) in the thigh affects the prognosis in patients with non-ischemic cardiomyopathy. Methods We recruited 250 patients who were diagnosed with non-ischemic cardiomyopathy by cardiac catheterization and echocardiographic date between September 2017 and November 2022. Finally, 223 patients enrolled in this prospective study conducted at a single center. Functional status was evaluated by using cardiopulmonary exercise test at baseline. All patients were measured quantity of the percentage of IMF (%IMF) in the thigh using computed tomography scan. Demographic, laboratory and echocardiographic date were collected from the patients’ medical records. Patients were followed up for up to 3 years. Clinical endpoints were cardiovascular death or unexpected rehospitalization because of cardiac events. Results During the follow-up 58 patients had cardiac events. The %IMF was significantly higher in the group with adverse events than without (4.49 ± 4.21 and 3.06 ± 2.39%, respectively; p = 0.001). Spearman correlation coefficient analysis showed a modest correlation between %IMF and exercise tolerance such as anaerobic threshold (Spearman r = -0.367; p &amp;lt; 0.001) and peak oxygen uptake (Spearman r = -0.382; p &amp;lt; 0.001). Patients were divided into 2 groups according to the median values of %IMF. Kaplan-Meier analysis demonstrated that events were significantly higher in the high %IMF group (log-rank p = 0.008). Furthermore, subgroup with left ventricular ejection fraction ≦ 40% or BMI ≧ 22 had a significantly greater frequency of adverse events in the high %IMF group. However, there was no significant difference in %IMF between the groups when divided into two groups at the mean age of this study. Multivariate Cox regression analysis adjusted for left ventricular ejection fraction, estimated glomerular filtration rate, hemoglobin and body mass index found %IMF as an independent factor of adverse events (hazard ratio 1.088; 95% confidential interval 1.024-1.156; p = 0.007). Conclusions In patients with non-ischemic cardiomyopathy, quality of muscle represented by %IMF in the thigh is an independent factor for predicting adverse cardiac events.

Cardiopulmonary exercise testing in long-term calcium channel blockers responders, does it normalize in the same way as pulmonary vascular resistance?

Abstract Background and aims Long-term calcium channel blockers (CCB) responders represent &amp;lt;10% of pulmonary arterial hypertension (PAH) patients and are known to have an excellent prognosis on high dose CCB. The few reports of lung histology of these patients suggest a predominant muscular thickening of the precapillary arterioles. Nevertheless, the classic intimal proliferation characteristic of PAH has also been reported, although to a lesser extent. Hence, we hypothesized that long-term CCB responders are likely to exhibit some degree of ventilatory inefficiency as a result of their impaired alveolo-capillary membrane. In this study, we aimed to evaluate the exercise performance of a contemporary cohort of long-term responders to CCB in terms of both exercise capacity and ventilatory efficiency, and whether there are differences depending on the haemodynamic severity. Methods We evaluated all long-term CCB responders with regular follow-up at our institution between 1996 to 2024 with at least one cardiopulmonary exercise test (CPET) and a right heart catheterization (RHC) within a three-year period, provided they had remained clinically stable without changes in pulmonary vasodilator treatment. Patients with additional PAH specific treatment were excluded. For data analysis purposes, the population was divided into 2 groups according to pulmonary vascular resistance (PVR). The cut-off point for PVR was set at ≥3. Results Twenty-four patients (91,6% female) with complete data were retrospectively enrolled. Baseline characteristics were as follows: median age 45.5 years (59-33) median mean pulmonary artery pressure of 26 mmHg (29-24) and median PVR of 3 WU (3-2.6). Regarding the whole cohort, peak oxygen consumption (pVO2) revealed mild impairment of functional capacity (mean pVO2: 1281 ± 245 ml/kg – 75 ± 15% of predicted). Ventilatory efficiency parameters were also mildy affected with low end-tidal carbon dioxide pressure at the anaerobic threshold (PETCO2@AT) (33.7±3.6mmHg), and increased minute ventilation (VE)/carbon dioxide output (VCO2) slope (33.5±4.5). The subgroup analysis depending on PVR showed no significant differences between groups in terms of pVO2 (1291.9 ±240 Vs. 1150 ±350 ml/kg, p:0.29 / 79%±16 vs 67%±12, p:0.8), VE/VCO2 slope (33 Vs. 34, p:0.21), or PETC02@AT (35 Vs. 33 mmHg, p:0.25). All CPET parameters by subgroups are displayed in Table 1. Conclusions Long-term CCB responders exhibit mildly reduced functional capacity. Moreover, they often fail to normalize the ventilatory efficiency parameters in most of the cases, even when PVR reaches close to normal values, suggesting persistent endothelial impairment.Results according to PVR

Relationship between six-minute walk distance and cardiopulmonary exercise testing in non-obstructive hypertrophic cardiomyopathy

Abstract Background Recent studies have shown the promise of new approaches to the management of hypertrophic cardiomyopathy (HCM) symptoms. However, as HCM is a chronic disorder that evolves slowly over decades with low annual event rates, therapeutic trials in the disease rely on surrogate measures of disease severity and progression rather than hard endpoints such as mortality. Exercise capacity is one potential surrogate endpoint. Purpose To examine the relationship between peak oxygen uptake (VO2) and six-minute walk test distance (6MWD) in patients with non-obstructive hypertrophic cardiomyopathy (nHCM) and describe the association with clinical parameters and quality of life. Methods We examined baseline data from patients with nHCM enrolled in a randomised placebo-controlled trial of trimetazidine therapy. The study was conducted in a single European centre. Cardiopulmonary exercise testing (CPET) was performed to assess peak oxygen consumption (pVO2), ventilatory anaerobic threshold (VAT) and ventilatory equivalent for carbon dioxide (minute ventilation to carbon dioxide production (VEVCO2). Health related quality of life was assessed with the Minnesota Living with Heart Failure Questionnaire (MLHFQ). ECG and echocardiography were performed on the same day and biomarkers (NT-proBNP and cardiac Troponin T, cTnT) were measured prior to exercise testing. Results In 51 patients (age 50 ± 13 years; 71% male) with nHCM, pVO2 ranged from 10 to 24.3 ml/kg/min and 6MWD from 188 to 650 metres. 6MWD correlated with peak VO2 (Pearson r=0.41, 95% CI 0.15 to 0.67, p=0.003) and anaerobic threshold (r=0.32, 95%CI 0.04 to 0.55, p=0.024). After adjusting for age and sex, NT-proBNP concentration correlated with peak VO2 (radi=-0.35, 95% CI -0.69 to -0.01, p=0.042) but not 6MWD (radj=-0.05, 95% CI -0.42 to 0.32, p=0.779). Health related quality of life assessed by the Minnesota Living with Heart Failure Questionnaire (MLHFQ) correlated moderately with 6MWD (radi=-0.54, 95% CI -0.79 to -0.29, p&amp;lt;0.001) but weakly with peak VO2 (radi 0.28, 95% CI -0.55 to -0.01, p=0.042). I Conclusions There is a modest correlation between peak VO2 and 6MWD in nHCM. The pVO2 correlates more strongly with NT-proBNP whereas 6MWD better reflects quality of life. These data suggest pVO2 and 6MWD provide complementary information about health status in nHCM.Relationship between 6MWD and CPETCharacteristics of study cohort

Obesity and its impact on functional capacity: understanding the interplay for health management

Abstract Background Cardiopulmonary exercise testing (CPET) plays a significant role in evaluating obese individuals due to the unique physiological challenges they face during exercise. As diastolic function is impaired in majority of morbidly obese pts, combination of CPET with diastolic stress echocardiography may add more information to objective assessment Objective To assess the value of combined stress echo CPET (ESE-CPET) in assessment of diastolic function in morbidly obese pts. Methods We studied 400 pts (74% female, age 39.2±9.9 years) referred for bariatric surgery. Echocardiographic measurements have been performed before CPET and immediately after the test. CPET was performed on treadmill (maximal Bruce) with breath-by-breath gas analysis. We measured both peak oxygen consumption (peakVO2) and VO2 at anaerobic threshold (AT), as well as other ventilatory and hemodynamic parameters. Results Mean BMI was 44± kg/m2. Left ventricular ejection fraction was 63.5±5.6%. Mean VO2 at AT was 17±2 ml/kg/min, mean Peak VO2 was 19±4 ml/kg/min. Resting eho : mitral E to A wave (E/A),deceleration time ( Dt) and mitral E to mitral anular E’ (E/E’) values did not correlate significantly with parameters of CPET. However, there was significant correlation between maximal E/ E’ with PeakVO2 and VO2 at AT (p&amp;lt;0.001), , Pet CO2 (p=0.0001) as well as with myocardial performance index as a parameter of global left ventricular function (p&amp;lt;0.001) However, VE/VCO2 was the strongest predictor of increase in E/ E’≥ 15 indicating the importance of ventilatory parameters and dynamic tests. Conclusions Assessment of diastolic function in morbid obese patients represents a great challenge to cardiologists because obesity contributed significantly to deterioration of diastolic function. Combined stress echo CPET showed the advantage and benefit of integrated evaluation of both pulmonary and cardiovascular function representing as a significant step forward in assessment of diastolic function overcoming the limitations of resting echocardiography and CPET performed as a single test.