Submaximal Exercise Research Articles

Effect of menstrual cycle phase on physiological responses in healthy women at rest and during submaximal exercise at high altitude.

As more women engage in high-altitude activities, understanding how ovarian hormone fluctuations affect their cardiorespiratory system is essential for optimizing acclimatization to these environments. This study investigates the effects of menstrual cycle (MC) phases on physiological responses at rest, during and after submaximal exercise, at high-altitude (barometric pressure 509 ± 6 mmHg; partial pressure of inspired oxygen 96 ± 1 mmHg; ambient temperature 21 ± 2°C and relative humidity 27 ± 4%) in 16 eumenorrheic women. Gas exchange, hemodynamic responses, heart rate variability and heart rate recovery (HRR) were monitored at low altitude, and then at 3375m on the Mont Blanc (following nocturnal exposure) during both the early-follicular (EF) and mid-luteal (ML) phases. Significant differences were observed between low and high-altitude in ventilation, heart rate and cardiac output. Resting ventilation (15.2 ± 1.9 vs. 13.2 ± 2.5L.min-1; p = 0.039) and tidal volume (812 ± 217 vs. 713 ± 190 mL; p = 0.027) were higher during EF than ML at high-altitude. These differences between EF and ML were no longer evident during exercise, with comparable responses in oxygen uptake kinetics, cycling efficiency and HRR. The MC had negligible effects on physiological responses to high-altitude. An individualized approach, tailored to each woman's specific responses to hypoxia across the MC, may be more beneficial in optimizing high-altitude sojourns than general guidelines.

Abstract 4118444: Right Ventricular Contractile Reserve and Right Ventricular-Pulmonary Arterial Coupling Are Impaired in Long-Term Survivors of Childhood Cancers

Background: Childhood cancer survivors are at risk of right ventricular (RV) dysfunction in relation to cardiac toxicity due to chemotherapy and radiation therapy. This study tested the hypothesis that RV contractile reserve and RV-pulmonary arterial (PA) coupling are altered in long-term survivors of childhood cancers. Methods: Thirty survivors (60% men) aged 24.3 ± 5.2 years at 15.3 ± 6.3 years after completion of chemotherapy and thirty healthy control subjects (47% men) were studied. Resting and submaximal supine bicycle stress echocardiography was performed for assessment of RV fractional area change (FAC), tricuspid annular plane systolic excursion (TAPSE), left ventricular (LV) and RV longitudinal strain, mitral and tricuspid annular velocities and myocardial acceleration during isovolumic contraction (IVA). The slope of the RV force-frequency relationship was derived from the change in IVA with the change in heart rate during exercise (△IVA/△heart rate), while RV-PA coupling was determined by the ratio between TAPSE and pulmonary arterial acceleration time indexed to RV ejection time (PAATi). Results: At rest, tricuspid annular systolic velocity and RV systolic strain were significantly lower in survivors ( P < 0.05 for both), while RV FAC, TAPSE and IVA were similar between the two groups ( P > 0.05 for all). During submaximal exercise testing, all RV systolic functional indices were significantly lower in survivors than controls ( P < 0.05 for all). The slope of the RV force-frequency relationship was significantly flatter in survivors compared to controls (0.038 ± 0.002 vs 0.059 ± 0.003 m/sec 2 beats/min, P < 0.001). For RV-PA coupling, TAPSE/PAATi was similar between survivors and controls at baseline but became significantly lower in survivors during submaximal exercise ( P = 0.002). Conclusions: The RV contractile reserve and RV-PA coupling are impaired during exercise in long-term survivors of childhood cancers. Future studies aimed at determining the clinical and prognostic significance of these impairments are warranted.

Abstract 4136159: Determinants of Exercise Intolerance in Postural Orthostatic Tachycardia Syndrome: a Systematic Review

Background: Postural Orthostatic Tachycardia Syndrome (POTS) is a syndrome of an exaggerated heart rate (HR) response with standing, disproportionately affecting young women associated with exercise intolerance due to dizziness, palpitations, and/or chest pain. Research question: How does the exaggerated increase in HR with standing translate into impaired exercise tolerance in subjects with POTS? Aims: To systematically analyze determinants of exercise intolerance in subjects with POTS. Methods: We searched the National Library of Science and identifed 11 cohorts with a diagnosis of POTS and an assessment of exercise capacity. We abstracted the information including type of exercise testing, hemodynamics and gas exchange parameters (peak oxygen consumption [VO 2 ]) with exercise, and effect of interventions (if present). Results: We identified 849 subjects with POTS, female:male ratio of 8.5:1, 25±8 years, and 365 age-and sex-matched controls. A cycle ergometer was used in 8 studies (574 subjects, 68%) and a treadmill in 3 (275 subjects, 32%). Peak VO 2 was measured in 10 studies (836 subjects, 98%), and exercise hemodynamics in 9 (593 subjects, 70%). All 11 (100%) studies described a higher HR at rest and during submaximal exercise in subjects with POTS, with a similar slope of HR/load, and shorter time to peak HR. Of the 9 studies with hemodynamics, 6 (67%) reported a reduction in stroke volume (SV) with standing and with exercise, but only 1 (11%) documented a reduction in cardiac output (CO). Two studies (22%) enrolling teenagers showed a variable increase in SV and CO in POTS. Peak VO 2 was reduced in 8 (80%) studies when compared with predicted values, but only in 4 (40%) when compared with controls matched for deconditioning. Intravenous fluid administration in two studies did not affect HR, SV, CO or peak VO 2 . Exercise training in one study (19 subjects) and propranolol 20 mg in another study (11 subjects) led to improving peak VO 2 . Conclusions: An exaggerated HR response with standing and with exercise is a hallmark of POTS, a mechanism by which subjects reach a higher HR at lower workloads. While the increase in HR is associated with a reduction in SV, CO is typically maintained and occasionally increased, therefore making it an unlikely mechanism responsible for the peculiar exertional symptoms of POTS. Strategies that result in a reduction in HR may, on the other hand, translate in improved exercise capacity in subjects with POTS.

The whole-body and skeletal muscle metabolic response to 14 days of highly controlled low energy availability in endurance-trained females.

This study investigated the effects of 14 days low energy availability (LEA) versus optimal energy availability (OEA) in endurance-trained females on substrate utilization, insulin sensitivity, and skeletal muscle mitochondrial oxidative capacity; and the impact of metabolic changes on exercise performance. Twelve endurance-trained females (V̇O2max 55.2 ± 5.1 mL × min-1 × kg-1) completed two 14-day randomized, blinded, cross-over, controlled dietary interventions: (1) OEA (51.9 ± 2.0 kcal × kg fat-free mass (FFM)-1 × day-1) and (2) LEA (22.3 ± 1.5 kcal × kg FFM-1 × day-1), followed by 3 days OEA. Participants maintained their exercise training volume during both interventions (approx. 8 h × week-1 at 79% heart rate max). Skeletal muscle mitochondrial respiratory capacity, glycogen, and maximal activity of CS, HAD, and PFK were unaltered with LEA. 20-min time trial endurance performance was impaired by 7.8% (Δ -16.8 W, 95% CI: -23.3 to -10.4, p < .001) which persisted following 3 days refueling post-LEA (p < .001). Fat utilization was increased post-LEA as evidenced by: (1) 99.4% (p < .001) increase in resting plasma free fatty acids (FFA); (2) 270% (p = .007) larger reduction in FFA in response to acute exercise; and (3) 28.2% (p = .015) increase in resting fat oxidation which persisted during submaximal exercise (p < .001). These responses were reversed with 3 days refueling. Daily glucose control (via CGM), HOMA-IR, HOMA-β, were unaffected by LEA. Skeletal muscle O2 utilization and carbohydrate availability were not limiting factors for aerobic exercise capacity and performance; therefore, whether LEA per se affects aspects of training quality/recovery requires investigation.

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.

Abstract 4145857: The effect of homebase exercise training on single ventricle heart (SVH) function, exercise performance, body composition and quality of Life in children and adolescents living with a Fontan circulation

Objectives: Fontan patients have impaired exercise capacity. Exercise training has been shown to improve exercise performance. We aim to determine the effect of exercise training on SVH function, and its correlation with exercise capacity, body composition and self-reported QOL. Methods: 31 paediatric Fontan patients were prospectively recruited to complete 3x30 minute homebased HIIT sessions per week for 20 weeks. Baseline physical activity levels, including structured sports participation, daily step-counts and active-zone-minutes (AZM) were recorded by accelerometer (Fitbit inspire3). Patients were considered active if they met 2 of the 3 criteria: 1/Structured sports training ≥ 2 per week (moderate-vigorous intensity &gt;30 minutes) 2/Daily steps ≥ 10k 3/AZM ≥60 minutes per day Bio-impedance-analysis, cardiopulmonary exercise tests, echocardiography including deformation imaging and PedQL questionnaires were performed at baseline and upon completion. Results: 28 participants completed the programme. 86% had good compliance (completed &gt;45/60 sessions). 17 male (60.7%), mean age 14.3±2.03 years, 14 LV-dominant, 14 non-LV dominant (9RV, 5BiV). No serious adverse events reported. The exercise duration improved from 7.56±2.6 to 9.16±2.5 minutes, p&lt;0.001 and peak workload from 110±43.6 to 129±45.8 watts, p&lt;0.001. Indexed oxygen consumption (VO 2 /kg peak) improved from 30.9±7.1 to 32.2±7ml/min/kg, p=0.003 and oxygen pulse, O 2 pulse peak from 9.1±2.6 to 9.7±3 mL/beat, p&lt;0.001. Submaximal analysis showed normal %predicted VO2 (&gt;40%) and improvement of O 2 pulse, p=0.024. LV systolic function showed improved MAPSE from 1.65±0.2 to 1.86±0.2, p=0.017, and improved apical rotation from 2.3±3.8 to 5.9±3.1, p=0.043. RV systolic function showed improved TAPSE of 1.4±0.2 to 1.6±0.3, p=0.032 and FAC of 44±5.6% to 49±10.5%, p=0.170. Self-reported QOL scores were higher in Fontan children who were physically active at baseline, with a downward trend noted when poor compliance was evident (Child’s QOL V3.0 91.21±0.7 to 86.1±5.2, p=0.018 (Table 2). Although no significant change in body composition, a higher appendicular skeletal muscle mass, SMMa% and lower body fat% were noted pre and post exercise training in the active Fontan group (Table 3), Conclusions: We observed significant improvements in both the submaximal and peak exercise performance in paediatric Exercise training associated with improvement of single ventricle longitudinal systolic function and ventricular mechanics.

Abstract 4137678: Maximal Oxygen Uptake Prediction From Resting and Submaximal Variables of Cardiopulmonary Exercise Testing by Using Machine Learning Methods

Background: Cardiorespiratory fitness, as measured by maximal oxygen consumption (VO2max) during a cardiopulmonary exercise test (CPET), is a prognostic indicator for longevity and adverse cardiovascular event prevention. This study aims to formulate a regression model utilizing resting and submaximal variables during CPET evaluation in the general population to predict VO2max. Methods: We used 13,535 CPET results on cycle ergometer collected by the UCLA Exercise Physiology Research Laboratory over eight years. Patients were divided into a normal group (NG; n=1,400) and an other group (OG; n=12,135). The inclusion criteria for the NG were: the absence of any known clinical diagnosis, BMI &lt;30, no current use of beta blocker, and VO2max &gt;85% of the predicted value for age and sex (Wasserman equation). OG refers to all other patients not in NG. Models were trained and evaluated for each group using stratified 5-fold cross-validation. We also trained different models using only resting variables (R-VARS) and resting and submaximal exercise variables (R+S-VARS). Feature importance was assessed using Shapely additive explanations (SHAP) values to identify how the feature related to the VO2max prediction. Results: The regression models were trained on the NG, OG, and total (N+OG) groups. The optimal models were Bayesian Ridge for the NG and Light Gradient Boosting Machine for the other two groups. The mean (standard deviation) R2 when using only R-VARS was 0.67(0.037) for the NG, 0.54 (0.014) for the OG, and 0.55 (0.009) for the N+OG. When using R+S-VARS, performance increased to 0.82 (0.014) for the NG, 0.80 (0.010) for the OG, and 0.8 (0.008) for the N+OG. Chronotropic index (ci), body mass index (BMI), VO2 at the first ventilatory threshold (VO2h1kg), minute ventilation at the second ventilatory threshold (VEH2), and forced expiratory volume (FEV1) were important features across the models trained with R+S-VARS. CI, BMI, and VEH2 had a negative effect, while VO2h1kg, FEV1 had positive effect on VO2max prediction. Conclusion: Our VO2max prediction model demonstrated remarkable accuracy in this dataset representing a generally healthy, non-athlete population using R+S-VARS. Particularly noteworthy was the enhanced performance within subgroups exhibiting a lower VO2max. This methodology offers a means to assess VO2max for individuals who might not achieve maximal exhaustion during CPET due to non-cardiopulmonary reasons.

Abstract 4147647: Effects on Cognition, Sleep, Quality of life and Exercise Capacity of a 12-week Tele-yoga Intervention in Persons with Heart Failure - Results from 3 and 6 Months Follow-up

Background and Objectives: Yoga may be a promising form of mind-body rehabilitation for patients with long term illness. Digitally delivered yoga increases access to participation but has not previously been evaluated in the heart failure population. The aim of this study was to examine the effects of tele-yoga on cognition, sleep, health-related quality of life and exercise capacity in persons with heart failure. Methods: The Tele-yoga study (ClinicalTrials.gov, ID: NCT 03703609) was a parallel two-arm randomised controlled trial (RCT) with 1:1 distribution to an intervention and control group. Study participants were randomised to tele-yoga including live-streamed group-yoga for 60 minutes twice weekly during 12 weeks and yoga individually for 10 minutes/day using an app, or to a control group receiving individual exercise advice. Cognition (Montreal Cognitive Assessment: MoCA), sleep (minimal insomnia symptom scale; MISS), health-related quality of life (EQ-5D VAS) and sub-maximal exercise capacity (6 minute walk test; 6MWT) were assessed at baseline, after 3 and 6 months. Linear mixed model with random intercept for patients as the random effect and group-time interaction along with age was taken as the fixed effects to analyse outcomes. Results: A total of 311 participants were included (tele-yoga n=156 and active controls n=155), mean age 66 years, 70% men. Adherence to the group yoga was very good. The linear mixed models showed a significant change in cognition, health-related quality of life and exercise capacity favouring the tele-yoga group. No significant differences between the groups were seen regarding sleep. When analysing the fixed effects of all outcomes, age, group assignment and time-points interaction had significant effects on EQ-5D VAS score, 6MWT distance and MoCA scores. For EQ-5D VAS the tele-yoga group performed significantly better than the control group at 3 months, but not at 6 months. For the 6MWT distance, the tele-yoga group performed better than the control group at 3 months, but not at 6 months. The tele-yoga group had significantly higher MoCA scores than the control group at both 3 and 6 months. Conclusion: This adequately powered RCT showed that digitally delivered mind-body training in the format of group and individual yoga during 12 weeks lead to an improvement in cognition, quality of life and exercise capacity at the end of the intervention. The effect was sustained for cognition also after 6 months.

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.

Impact of Right Ventricular Function on Cardiopulmonary Exercise Capacity in Mitral Regurgitation Patients Undergoing Transcatheter Mitral Valve Intervention

Transcatheter mitral valve interventions (TMVI) has been proven to reduce symptom burden and improve outcome in patients with severe mitral regurgitation (MR). However, the impact of right ventricular function (RVF) on exercise capacity in MR patients is less well understood. Cardiopulmonary exercise testing (CPET) is the most comprehensive approach to assess maximum exercise capacity. Submaximal exercise capacity (SEC), assessed by constant work rate exercise time testing (CWRET), is presumed to be relevant in daily life activities, and gives a more differentiated physiological insight into the nature of exercise intolerance. Thus, 28 MR patients underwent CPET and CWRET (at 75% of maximum work rate in the initial incremental exercise test) prior to TMVI and 3-months post-procedurally. Patients´ mean age was 75.0±8.7 years and 32.1% were female. One patient presented with a MR reduction of less than 2 grades. RVF was at least moderately impaired in 25% of the patients. SEC of these patients was lower, but did not significantly differ (416.4s±359.6 vs. 296.1±216.5s; p=) from patients without RVF-deterioration. At follow up, the SEC improved significantly (from 337.4±262.2s to 517.4±393.5s; p=0.006). Maximum oxygen uptake (peakVO2) showed a positive trend, but no statistically significant difference (10.3±3.1ml/min/kg vs. 11.3±3.4ml/min/kg; p=0.06). RVF improved in 35.7% of the patients and these patients showed a significantly higher SEC increase (471.7±153.9s vs. 82.7±47.0s, p=0.003). SEC is significantly increased in MR patients undergoing TMVI, reflecting an improvement especially regarding daily life activities. This may be related to TMVI´s beneficial effect on right ventricular remodeling.

Oxygen consumption, locomotory-respiratory coupling and exercise-induced pulmonary hemorrhage in horses during the Paso Fino gait.

Workload associated with the high frequency Colombian Paso Fino gait has not been evaluated. To determine the oxygen consumption (V̇O2), heart rate (HR), stride frequency: breathing ratio, and hematology associated with the Paso Fino gait, including whether exercise-induced pulmonary hemorrhage (EIPH) occurs. Eleven Paso Fino horses. Prospective cohort study. Horses performed a standardized Paso Fino gait test across a wooden sounding board, simulating competition. V̇O2 and ventilatory parameters (tidal volume [VT]; peak inspiratory and expiratory airflows [PkV̇I, PkV̇E]; respiratory rate [RR], minute ventilation [V̇E]) were measured using a portable ergospirometry facemask. Heart rate was measured using electrocardiograms. Post-exercise lactate, hematocrit, bicarbonate, pH, electrolytes, and biochemistry concentrations were measured. EIPH was assessed via tracheobronchoscopy. Four horses completed a secondary high-intensity gallop to elicit peak V̇O2 for comparative purposes. Median [IQR] mean individual HR during the Paso Fino gait was 190 [178, 201] bpm. Relative V̇O2 measured 49.8 [48.4, 59.5] mL/(kg min; VT = 8.6 [8.0, 10.7] L; RR = 87.1 [75.4, 99.5] bpm; V̇E = 869 [740, 902] L/min; PkV̇I = 33.4 [32.7, 37.2] L/s; PkV̇E = 44.2 [40.3, 46.0] L/s). Horses took 2.8 [2.7, 2.9] strides/second and had a stride frequency: breathing ratio of 2.0 [1.8, 2.3]. Post-exercise blood lactate concentration and hematocrit measured 2.7 mmol/L and 50% respectively. Three horses showed endoscopic evidence of Grade-1 EIPH. The Paso Fino gait V̇O2 and HR equaled 79% V̇O2pk and 91% maximal HR, respectively, based on the high-intensity gallop. The Paso Fino gait represents submaximal exercise based on V̇O2 < V̇O2pk and blood lactate.

Predictive Role of Atrial Strain, Aortic Stiffness, and Muscle-Related Factors for Maximal and Submaximal Exercise Capacity in Fontan Patients.

Fontan patients' exercise capacity and associated risks of morbidity and mortality necessitate a comprehensive study. We aim to explore maximal and submaximal exercise capacity, assessing the impact of cardiovascular and peripheral factors, including atrial strain, aortic stiffness, and muscle-related factors. Fontan patients and matched controls were examined. Clinical details were recorded, and atrial strain and aortic stiffness were measured using echocardiography. Hand grip and knee extensor strength were assessed, and muscle oxygenation was recorded. Cardiopulmonary exercise test determined exercise capacity, with peak oxygen uptake/kg (VO2/kg) and oxygen uptake efficiency slope/kg (OUES/kg) as markers for maximal and submaximal capacity, respectively. Thirty-one Fontan patients (median age = 18, range = 7-31years) and 30 controls (median age = 18, range = 7-32years) were studied. No significant differences in body composition and muscle strength were observed between Fontan patients and controls (p > 0.05). Fontan patients exhibited lower peak VO2/kg and OUES/kg (p < 0.001 for both), along with decreased atrial strain and increased aortic stiffness compared to controls (p < 0.001). Aortic pulse wave velocity (PWV), left atrial strain contractile phase (LASct), and knee extensor strength independently predicted peak VO2/kg (R2 = 0.514) and OUES/kg (R2 = 0.486) in Fontan patients; age was a predictor for peak VO2/kg. Atrial contractile strain, aortic stiffness, and knee extensor muscle strength are predictors of submaximal exercise capacity; furthermore, age, along with these variables, serves as predictors of maximal exercise capacity in Fontan patients. Evaluating hemodynamic, vascular, and muscular parameters, in conjunction with assessing both maximal and submaximal exercise capacities, is crucial for optimizing disease management in Fontan patients. Clinicaltrials.gov registration: NCT05011565.

Exaggerated blood pressure response to submaximal exercise must be considered relative to fitness: strong associations with hypertensive target organ damage

Abstract Exaggerated systolic blood pressure (SBP) during submaximal exercise is associated with increased cardiovascular (CV) risk. However, findings are mixed and new evidence indicates that cardiorespiratory fitness should be considered for proper clinical interpretation of exercise SBP responses. This study aimed to determine the relationship between SBP response to submaximal effort corrected for fitness and abnormalities of cardiac structure and function. Methods Each of 231 participants (age 54±12 years; 53% females) with controlled clinic BP, no evidence for ischemic heart disease, valvular heart disease or heart failure underwent cardiopulmonary exercise testing (Bruce protocol), resting and exercise echocardiography and 24h ABPM. Submaximal exercise SBP (measured at the 2nd stage of Bruce protocol) was corrected for two fitness variables: 1) peak VO2 and 2) maximal workload in METs (SBP/peakVO2 and SBP/METs). Results There were no, or weak, associations with exercise SBP and target organ damage. However, there was a progressive deterioration of cardiac function and structure parameters across the exercise SBP tertiles corrected for fitness (Table 1). Both SBP/peakVO2 and SBP/METs significantly correlated with left ventricular (LV) mass, LV diastolic and systolic, and left atrial parameters (Table 2). ROC analysis revealed good performance of corrected SBP response to submaximal exercise in detection of LV hypertrophy and diastolic dysfunction (AUC 0.792 and 0.808, and 0.771 and 0.802 for SBP/peakVO2 and SBP/METs, respectively; Figure). Conclusions Fitness-corrected SBP responses to submaximal exercise can identify more profound target organ damage with respect to cardiac function and structure even among patients with controlled clinic BP. Exaggerated BP response to exercise must be considered relative to fitness for proper clinical interpretation of BP responses to exercise testing.Figure

The added value of deep learning to submaximal exercise electrocardiogram for the 10-year prediction of major adverse cardiovascular and cerebrovascular events

Abstract Background The added value of exercise ECG data to traditional risk factors in predicting cardiovascular events remains unclear. Deep learning of ECG signals has demonstrated state-of-the-art performance in detecting subtle abnormalities indicative of cardiovascular disease. We investigated whether deep learning analysis of exercise ECGs could improve the prediction of major cardiovascular and cerebrovascular events (MACCE) with respect to established risk models in a large population-based cohort. Purpose To assess the added value of submaximal exercise ECG measurements to established cardiovascular risk prediction models. Methods We obtained ECG recordings from 41,076 UK Biobank participants without cardiovascular disease (CVD) who underwent a submaximal exercise ECG test. We obtained ECG recordings from 41,076 UK Biobank participants without cardiovascular disease (CVD) who underwent a submaximal exercise ECG test. We created two deep neural network ECG risk scores: one derived from conventional ECG parameters, measured at rest, peak exercise and late-stage recovery, and another based on the complete ECG (Q-ECG). We assessed the added value of conventional ECG parameters and Q-ECG risk scores to the UK's current prediction algorithm (QRISK3). We estimate the association between ECG parameters and MACCE, using Cox Proportional hazard models, following adjustment for traditional risk factors. All models were internally validated via 5-fold cross-validation and 1000 bootstrap iterations. Predictive performance was evaluated using Harrel's C-index, Net Reclassification Index (NRI) and net benefit. Findings: Incident MACCE was reported in 4,082 (9.9%) individuals in the study population and 3,463(9.7%) individuals with valid ECG parameters over a median follow-up period of 12.5 years. We found combined conventional ECG and Q-ECG scores were independently associated with MACCE, following adjustment for multiple testing: adjusted hazard ratio [HZ] = 1.76 (95% CI:1.63-1.91); HZ = 1.14 (95% CI:1.10-1.18), respectively, per standard deviation increase. Both conventional ECG parameters and Q-ECG were predictive of MACCE, independent of clinical risk factors, C-index = 0.64 (95%CI 0.63-0.65); net benefit = 0.09(95% CI 0.07 - 0.11) and C-index = 0.56 (95% CI 0.55-0.57); net benefit = 0.07(95% CI 0.05 - 0.09). ECG measurement's modestly improved model discrimination over the bassline QRISK3 risk score when combined with QRISK3 risk factors for conventional markers and Q-ECG score, respectively; ΔC-index 0.03 (95% CI: 0.02 – 0.04) and ΔC-index 0.03 (95% CI: 0.02 – 0.03); However, we observed no significant improvements in classification at the current recommended threshold of 10%. Conclusion In individuals without a history of prior cardiovascular disease, ECG measures independently predict the risk of MACCE. When combined with QRISK3, neural-network-derived ECG risk scores marginally improve cardiovascular risk prediction over QRISK3.

Skeletal and respiratory muscle weakness contributes to decreased exercise capacity in hypertrophic cardiomyopathy

Abstract Background and Aims Although decreased exercise capacity (due to dyspnea or angina-like symptoms) constitutes the fundamental characteristics of hypertrophic cardiomyopathy (HCM), the pathophysiology of these symptoms remains only partly understood. We investigated clinical and functional determinants of decreased exercise capacity in a broad range of HCM patients irrespective of primary disease aetiology (either genetic disorder or e.g. infiltrative phenocopies in the course of cardiac amyloidosis), overt heart failure (HF) and the presence of haemodynamically significant left ventricular outflow tract obstruction (LVOTO). Further, we deterimined the contribution of skeletal and respiratory muscle weakness to decresed exercise capacity. Methods We analyzed clinical data and functional assessments (skeletal and respiratory muscle strength, physical fitness) in relation to symptomatology and sub-maximal exercise capacity in 82 clinically stable patients with HCM (females: 32 %; age: 62±16 years; left ventricular ejection fraction [LVEF] 59±7%; intraventricular septum wall thickness [IVS] 19±4 mm; median plasma N-terminal pro-B-type natriuretic peptide [NT-proBNP]: 818 pg/mL [lower and upper quartile: 208-1917]; New York Heart Association [NYHA] class 0/I/II/III: 38/18/33/11 % [0 indicates no HF]; significant LVOTO: 29%). Results HCM patients with more severe symptomatology (NYHA class II-III vs 0-I) were older, had more frequently significant LVOTO and greater comorbidity burden, and had higher NT-proBNP and worse estimated renal function (all p≤0.03). Gender distribution, percentage of beta-blocker therapy and implanted device, body mass index, major echocardiography parameters (including LVEF, left ventricular end-diastolic diameter and IVS), high-sensitive (hs) cardiac troponin type I and hs-C-reactive protein were comparable in these 2 groups of subjects (all p&amp;gt;0.05). In multivariable linear regression models more advanced age, higher circulating natriuretic peptides (NT-proBNP) and previous coronary revascularization were independent predictors of more advanced NYHA class (standardized β-coefficient=0.30, p&amp;lt;0.01; β=0.27, p&amp;lt;0.01; and β=0.22, p&amp;lt;0.05; respectively). Similarly, more advanced age, female sex and higher NT-proBNP were independent correlates of shorter distance in 6-minute walking test (6MWT) (β=-0.46, p&amp;lt;0.001; β=-0.26, p&amp;lt;0.001; and β=-0.36, p&amp;lt;0.001; respectively). All analyzed muscle parameters (including respiratory muscle strength parameters) and objective measures of physical fitness (Functional Fitness Test for older adults) remained independently associated with 6MWT distance (all p&amp;lt;0.001) when adjusted for aforementioned clinical and laboratory correlates of 6MWT. Conclusions Muscle weakness and low physical fitness are related to decreased exercise capacity in HCM and may be potential therapeutic targets to alleviate disease symptoms also in non-obstructive HCM phenotype.

Improving exercise cardiac reserve assessment using a novel cardiopulmonary and echocardiography testing protocol (CPET-ESE) based on individualised exercise intensity domains

Abstract Background Functional exercise stress echocardiography (ESE) is used to quantify changes in cardiac reserve and can improve early cardiac dysfunction diagnosis and follow-up.[1.2] Current ESE protocols do not account for individual variations in fitness and heart rate response, leading to difficulties in defining normal reference values.[2,3] Physiologically defined exercise intensity domains could be implemented as part of combined cardiopulmonary and ESE testing (CPET-ESE) to address this problem. Purpose We propose that using exercise intensity domains as part of CPET-ESE will result in cardiac reserve values not influenced by individual cardiorespiratory fitness or physical activity (PA) levels. We also hypothesise by matching work-rates and heart rates (HR), respectively, cardiac reserve will be higher in those exercising at the higher exercise intensity domain. Methods A total of 45 healthy adults (mean age 43.8 ± 14.2, range 18-65 y) underwent a CPET followed by a CPET-ESE consisting of two 6-minute stages: 1. Moderate intensity (MOD) at 90% of the work-rate at the gas exchange threshold (GET) and 2. High intensity (HIGH) at 40% of the difference between GET and peak. Global left ventricular and right ventricular free wall (LV and RV) longitudinal strain (Sl), RV fractional area change (RV-FAC), peak LV and RV TDI derived systolic (S’) and diastolic velocities (E’) were measured at each step, including rest. HIGH steps were matched 1-to-n with MOD steps from other participants based on work-rate and HR, respectively. Questionnaire derived PA was classified as low, moderate, and high active. Cardiorespiratory fitness was measured as peak oxygen uptake relative to body mass (mL·kg-1·min-1). Results After adjusting for age and sex, neither higher PA nor peak VO2 were associated with higher cardiac function parameters at either intensity (Table 1). Higher peak VO2 was associated with higher work-rate for HIGH only, while higher PA was associated with lower HR for MOD only (interaction term p&amp;lt;0.05). When paired by matching HR and work-rate, respectively, HIGH was associated with higher cardiac function parameters compared to MOD (all except for LV-S’ and RV-FAC when HR matched, Table 2), despite those matched from HIGH being older, less physically active and having lower peak VO2 (p&amp;lt;0.05 for all). Conclusions Current ESE protocols, which define submaximal exercise intensity using arbitrary work-rate or HR targets,[3] do not account for the complex differences in exercise response between healthy individuals. Cardiac function augmentation during exercise is likely a response to VO2 kinetics and this is not accurately described by either HR or work-rate alone. We derived normal reference values for cardiac reserve from implementing physiologically defined exercise intensity domains within the combined CPET-ESE testing frameworks. These values could be more appropriately used when comparing diverse clinical populations using CPET-ESE.

Clinical and Functional Outcomes Associated with Quality of Life in Patients with Lymphangioleiomyomatosis: A Cross-Sectional Study.

Lymphangioleiomyomatosis (LAM) is a rare (twenty-one per million female inhabitants) neoplastic cystic lung disease that impairs health-related quality of life (HRQoL). However, the factors associated with impaired quality of life in patients with LAM are poorly understood. To assess the clinical, psychosocial, and functional characteristics associated with impaired quality of life in patients with LAM. This was a cross-sectional study performed on two nonconsecutive days. HRQoL (SF-36 and CRQ), lung function tests, anxiety and depression symptoms (HADS), maximal (CPET and ISWT), and submaximal exercise capacity (6MWT) were assessed. Linear associations among outcomes were assessed using Pearson's correlation and multivariate tests. Forty-five women with LAM (46 ± 10.years; FEV1,74%pred) were evaluated. The lowest SF-36 scores were observed for general health and vitality and the highest for the physical and social domains. The lowest CRQ scores were observed for dyspnea and fatigue, and the highest were for the emotional function and self-control domains. Sixteen (35%) women had anxiety, and 8 (17%) had depression symptoms. Most of the SF-36 and CRQ domains were associated with anxiety and depression symptoms (from r = 0.4 to r = 0.7; p < 0.05) and exercise capacity (from r = 0.3 to r = 0.5; p < 0.05). Lung function parameters were weakly or not associated with quality of life domains. After multiple linear regression, HRQoL was independently associated with depression symptoms and physical capacity but not with lung function. Our results show that aerobic capacity and depression symptoms are the main factors, rather than lung function, related to quality of life in patients with LAM.

Exercise testing in patients with tricuspid regurgitation undergoing transcatheter tricuspid valve intervention.

Transcatheter tricuspid valve intervention (TTVI) has shown promising results with persistent reduction of tricuspid regurgitation (TR) and improvements in functional class and quality of life (QOL). To analyze the impact of TTVI on maximal and submaximal exercise capacity (SEC). Constant work-rate exercise-time (CWRET) testing reflects SEC, which is more likely to be relevant for daily life activities and provides more differentiated physiological insight into the nature of exercise intolerance. Thus, 30 patients undergoing TTVI (21 direct annuloplasty and 9 edge-to-edge repair) received cardiopulmonary exercise testing (CPET) and CWRET (at 75% of maximum work rate in the initial CPET) before and 3months after TTVI. Patients' age was 80.5 [74.8-82.3] years and 53.3% were female. TR reduction ≥ 2 grades was achieved in 93.3% (TR grade ≤ moderate in 83.3%). Echocardiography revealed improved right ventricular (RV) characteristics with decreased RV basal diameter (47.0mm [43.0-54.3] vs. 41.5mm [36.8-48.0]; p < 0.001) and decreased inferior caval vein diameter. CWRET testing showed a significantly improved SEC (246.5s [153.8-416.8] vs. 338.5s [238.8-611.8] p = 0.001). Maximum oxygen uptake showed a positive trend without statistically significant differences (9.9ml/min/kg [8.6-12.4] vs. 11.7ml/min/kg [9.7-13.3]; p = 0.31). In contrast to the six-minute-walking distance (6MWD), SEC correlated moderately with effective regurgitation orifice area reduction (r = 0.385; p = 0.036), increased cardiac output (r = 0.378; p = 0.039), and improved QOL (r = 387; p = 0.035). Improvements in exercise capacity after TTVI mainly occur in the submaximal rather than in the maximal exercise range and correlate with hemodynamic effects and QOL. This may have a methodological impact on assessment of exercise capacity in these patients.

Effect of a Ketogenic Diet on Submaximal Exercise Capacity and Efficiency in Runners-Erratum.

Effect of a Ketogenic Diet on Submaximal Exercise Capacity and Efficiency in Runners-Erratum.

Cardiorespiratory Responses to Exercise in Hypobaric versus Normobaric Hypoxia: A Randomized, Single-Blind, Crossover Study.

There is controversy whether there are meaningful physiological differences between hypobaric (HH) and normobaric hypoxia (NH). This study aimed to compare the cardiorespiratory responses to acute HH and NH under strictly controlled conditions. We hypothesized no differences at rest and during submaximal exercise, whereas during maximal exercise, a higher maximal ventilation (V̇Emax), peripheral oxygen saturation (SpO2) and maximal oxygen consumption (V̇O2max) in HH than in NH. In a randomized, single-blind, crossover design, eight young healthy subjects (three females) were studied in an environmental chamber in which either the barometric pressure (HH) or the inspired oxygen fraction (NH) was reduced to the equivalent of ~4000 m altitude. Measurements were taken at rest, during submaximal (moderate and high intensity) and maximal cycling exercise. All resting parameters were similar between HH and NH, except for a lower root mean square of the successive R-R interval differences in HH (p < 0.05). SpO2 was 2% higher in HH at all exercise intensities (p < 0.05). During submaximal exercise, minute ventilation was similar between HH and NH. However, HH yielded a 7% lower tidal volume during moderate-intensity exercise (p < 0.05) and a lower respiratory exchange ratio during high-intensity exercise (p < 0.01). V̇Emax and V̇O2max were 11% and 6% higher in HH, respectively (p < 0.01 for both). SpO2 at maximal exercise was positively correlated with V̇Emax, V̇Emax/V̇O2max and V̇O2max. The higher V̇O2max found in HH than in NH can be attributed to the higher V̇Emax counteracting desaturation at maximal exercise. Conversely, submaximal SpO2 improved in HH through mechanisms other than increased ventilation. These findings are likely due to respiratory muscle unloading in HH, which operated through different mechanisms depending on exercise intensity.