Submaximal Cardiopulmonary Exercise Research Articles

Comparison of Cardiopulmonary Exercise Test Variables to Predict Adverse Events in Patients with Heart Failure.

Given the rising burden of heart failure (HF), stratification of patients at increased risk for adverse events is critical. We aim to compare the predictive value of various maximal and submaximal cardiopulmonary exercise test (CPET) variables for adverse events in patients with HF. 237 patients with HF (66 [58-73] years, 30% women, 70% HF with reduced ejection fraction) completed a CPET and had five years of follow-up. Baseline characteristics and clinical outcomes (all-cause mortality, major adverse cardiovascular events, and cardiovascular-related hospitalization) were extracted from electronic patient files. Receiver operating characteristics curves for maximal (e.g. peak VO2) and submaximal CPET variables (e.g. VE/VCO2 slope, cardiorespiratory optimal point (COP), VO2 at anaerobic threshold) were compared using the Akaike Information Criterion (AIC) method, whereas their calibration was assessed. 103 participants (43%) reached the composite endpoint, and 55 (23%) died. Percent predicted peak VO2 was the best predictor for adverse outcomes (AIC: 302.6) followed by COP (AIC: 304.3), and relative peak VO2 (mL/(kg·min), AIC: 304.4). Relative peak VO2 (AIC: 217.1) and COP (AIC: 224.4) were also among the three best predictors for mortality, together with absolute peak VO2 (ml/min, AIC: 220.5). A good calibration between observed and predicted event rate was observed for these variables. Percent predicated and relative peak VO2 had the best predictive accuracy for adverse events and mortality, but the submaximal COP had a non-inferior predictive accuracy for adverse events in patients with HF. These findings highlight the potential of submaximal exercise testing in patients with HF.

The effect of 12 weeks supervised exercise-based cardiac rehabilitation on resting and exercise blood pressure in males and females

Abstract Background Exercise is key in the prevention and management of hypertension. It remains unclear to what extent sex differences exist with regard to changes in blood pressure (BP) in patients following an exercise-based cardiac rehabilitation (CR) program. Purpose To investigate the effect of a 12 week supervised exercise-based CR program on resting BP (BPrest), peak exercise BP (BPmax) and systolic BP (SBP)/metabolic equivalents (MET)-slope and compare sex differences. Methods Of 2963 patients referred for CR at a singular test centre in Belgium during the years 2010-2019, those with missing BP data or with a submaximal (RER<1.1) cardiopulmonary exercise test (CPET) were excluded. Reasons for referral included post myocardial infarction, percutaneous coronary intervention, coronary artery bypass surgery and valve surgery. Patients underwent a bicycle CPET with BP measured at rest seated on the bike (BPrest) and throughout the test using an automated auscultatory BP machine at baseline and after 12 weeks of CR. BPrest, BPmax, peak oxygen uptake (VO2peak), peak workload (Wattpeak), resting heart rate (HRrest), maximal HR (HRmax) and the SBP/MET-slope were recorded from each test. CR incorporated 3 sessions of supervised aerobic and resistance exercise per week. Results A final sample of 2500 patients (20.4% females) were included for analysis with similar age (62±11 for males vs 61±11years for females, P=0.142). More males were on an ACE-inhibitor (55 vs 46% females, P<0.001) with a comparable prevalence of beta-blocker usage between sexes (75 vs 71% females, P=0.053). At both baseline and 12 weeks, females had a significantly lower body mass index, VO2peak, Wattpeak, BPmax and HRmax compared to males (P<0.001 for all) but a higher HRrest (P<0.001). However, both sexes had similar BPrest and SBP/MET-slope at baseline and 12 weeks. After 12 weeks of CR both males and females had a comparable mean±SD improvement in VO2peak (+4.1±3.2 and +3.1±2.6mL/kg/min), and Wattpeak (+33±22 and +22±15Watts), respectively (P<0.001 for all). This was associated with an increased SBPmax for males (171±30 to 181±30mmHg, P<0.001) and for females (159±29 to 167±30mmHg, P<0.001) from baseline to 12 weeks respectively. No change was seen in SBPrest between baseline and 12 weeks for males (128±20 to 128±19mmHg, P=0.39) and females (129±21 to 128±19mmHg, P=0.21) respectively. The SBP/MET-slope also remained unchanged after 12 weeks CR for males (8.97±5.48 to 9.04±4.81mmHg/MET, P=0.63) and for females (8.68±7.11 to 9.19±6.16mmHg/MET, P=0.13) respectively. Conclusion Twelve weeks of exercise-based CR was associated with an increase in SBPmax, although this was largely proportional to the improvement in exercise capacity demonstrated by the unchanged SBP/MET-slope and this was similar in both sexes. These routine clinical markers require further interrogation as to whether they parallel improvements in vascular health associated with exercise training.

Periodized Aerobic Training between Thresholds Improves Submaximal Cardiorespiratory Parameters in Octogenarians.

The worldwide aging population is expanding, with more individuals living into their 80s. Physiological functions decline gradually with age, compounded by sedentary lifestyles. Incorporating physical activity into daily routine is crucial for maintaining independence. This study aimed to assess a periodized high-intensity aerobic training program (PEZO-BT) in octogenarians, focusing on submaximal ergospirometry effects. A total of 48 non-frail octogenarian subjects (12 females, 36 males) were randomized into control and intervention groups. All subjects underwent submaximal cardiopulmonary exercise testing with gas analysis at baseline, stopping after the respiratory compensation point (RCP). Our intervention group completed a 14-week PEZO-BT aerobic training program. The outcomes were oxygen consumption at first ventilatory threshold (VO2AT), ventilatory efficiency slope (VE/VCO2), oxygen uptake efficiency slope (OUES), cardiorespiratory optimal point (COP), oxygen pulse change (ΔVO2/HR) from anaerobic threshold (AT) to respiratory compensation point (RCP), and power output at anaerobic threshold (POAT). Mixed ANOVA examined time and treatment effects. If significance emerged, post hoc t-tests were used to compare significances between groups. The homogeneity of variance was assessed using Levene's test. Chi-square tests compared ergospirometry criteria and ventilatory performance within groups. The mean differences at post intervention were significant in VO2AT (p < 0.001), VE/VCO2 (p < 0.001), ΔVO2/HR (p < 0.05), and POAT (p < 0.001), while OUES and COP were not significant (p > 0.05). However, clinical effects were observed in the entire intervention group. Training improved exercise capacity and workload. Overall, this periodic aerobic and high-intensity interval training (HIIT) program yielded significant improvements in cardiorespiratory fitness (CRF) in previously untrained octogenarians with and without comorbidities. The findings suggest implications for promoting long-term healthy aging.

OUES from submaximal cardiopulmonary exercise

Abstract Introduction Cardiopulmonary exercise testing (CPEX) provides valuable diagnostic and prognostic cardiopulmonary function data. However, in clinical setting a maximal test is not always achievable. The Oxygen Efficiency Uptake Slope (OUES) has been proposed as a possible submaximal measure of cardiopulmonary function as it remains relatively stable during the final quartile of the exercise test. This study explored the validity of OUES as a surrogate marker for cardiopulmonary function in the event of a submaximal test. Methods Four groups of subjects [128 healthy controls (73 M), 44 asymptomatic hypertensive (HT) patients (26 M), 67 adult cardiac congenital heart disease (ACHD) patients (44 M) and 35 Heart Failure with preserved Ejection Fraction (HFpEF) (10M) patients] were recruited after informed consent. All subjects underwent clinical assessment, resting ECG, blood pressure and spirometry prior to a treadmill CPEX to volitional exhaustion and a respiratory exchange ratio (RER) of at least 1.1 using the same testing protocol. Peak VO2 (ml/min) was recorded from the last 5s of the maximal test (RER=1.1) and OUES was calculated from complete (RER=1.1) and truncated (RER=0.9) gas exchange data. The linear relationships between absolute peak VO2 and OUES from complete and truncated gas exchange data were assessed using Pearson's correlation coefficient. Subsequently, the two correlations obtained in each patient group were compared. Statistical significance was set at p&amp;lt;0.01. Results Mean and 95% confidence intervals of the peak VO2 for males and females in each decile of life examined in the 4 subject groups are shown in the Figure. Peak VO2 values achieved in each of the patient groups were significantly lower when matched for age and sex compared to healthy participants (HT p=0.006, ACHD patients p&amp;lt;0.001 and HFpEF patients p&amp;lt;0.001). In all 4 groups there was a good correlation between absolute peak VO2 and the OUES at RER 1.1 (healthy volunteers r=0.910, p&amp;lt;0.001, HT r=0.899, p&amp;lt;0.001, ACHD r=0.816, p&amp;lt;0.001 and HFpEF r=0.846, p&amp;lt;0.001). Correlations were inferior for absolute peak VO2 and OUES at RER 0.9 (healthy volunteers r=0.74, p&amp;lt;0.001, HT r=0.780, p&amp;lt;0.001, ACHD r=0.651, p&amp;lt;0.001 and HFpEF r=0.817, p&amp;lt;0.001). Correlations between absolute peak VO2 vs OUES at RER of 1.1 and 0.9 were significantly different only for healthy controls (p=0.001, Z-score = −4.649), but not for HT (p=0.05, Z-score = −1.909), ACHD (p=0.04, Z-score = −2.080) or HFpEF (p=0.7, Z-score = −0.377) patients. Conclusion Our data support the use of submaximal OUES at an RER of 0.9 as a surrogate marker for absolute peak VO2 obtained at an RER of 1.1, especially in patients, in whom it can often be difficult to achieve maximal exercise. Funding Acknowledgement Type of funding sources: None.

Value of cardiopulmonary exercise test submaximal parameters in the assessment of aortic stenosis patients

Abstract Background Exercise test is recommended for risk stratification of asymptomatic patients with severe aortic stenosis (AS), although a significant number of patients can't perform a maximal exercise test, increasing the potential value of sub-maximal parameters for the assessment of these patients. Aim To assess which parameters could be useful for risk stratification in case of a submaximal Cardiopulmonary Exercise Testing (CPET) in asymptomatic patients with severe AS. Methods Retrospective evaluation of adult patients with asymptomatic severe AS, in a single center, who underwent CPET between December 2016 and November 2021. All patients underwent a treadmill CPET using an exercise protocol with progressive increase in workload. Patients were divided in group A (maximal CPET) or group B, respectively, if respiratory exchange ratio (RER) was &amp;gt;1.10 at peak exercise or below this value. Known parameters accessed in a submaximal CPET were evaluated: mean minute ventilation/carbon dioxide production slope (VE/VCO2), VO2 value in first ventilatory threshold (VT1), peak circulatory power, and oxygen uptake efficiency slope (OUES). Results CPET was performed in 25 patients with severe asymptomatic AS (80 years ± 7 years, 56% male), median AVA was 0.86 cm2 [IQR 0.65–0.95 cm2] and transaortic pressure gradient was 46 mmHg [IQR 41–55 mmHg]. The most used protocol was a ramp slope. Nineteen patients (76%) didn't reach a RER&amp;gt;1.10 (group B) due to respiratory (26%) or peripheral limitation (53%). Comparing both groups, group B patients showed a shorter duration of exercise of (8±3 min vs. 9±4 min, p=0.422), and a lowest mean peak VO2 (16.3±3.6 vs. 20.5±6.9 ml/kg/min, p=0.207). In our population, bivariate analyses demonstrated that OUES was the only submaximal parameter that could discriminate both groups: Group B patients had the lowest values (1.53 [IQR 1.47–1.70] vs. 1.94 [IQR 1.56–2.11], p=0.042). ROC curve analysis of OUES values revealed an AUC of 0.78 (p=0.042) for maximal CPET prediction. The cut-off point with most sensitivity (S) and specificity (E) obtained using the Youden index (0.62) was 1.9 (S≈67%; E≈95%) (Figure 1). Conclusions In our cohort of asymptomatic AS patients, even with submaximal CPET, OUES accurately identify patients with higher degrees of functional limitation. Whether OUES is useful as prognostic marker to the workflow treatment of AS it's worth to be assessed prospectively. Funding Acknowledgement Type of funding sources: None.

Intraocular Pressure Fluctuation during Aerobic Exercise at Different Exercise Intensities.

Few studies have examined the effects of different aerobic-exercise intensities on intraocular-pressure (IOP) changes. This may be important for eye diseases that are impacted by IOP or its fluctuation, including glaucoma, and diabetes that is complicated by diabetic retinopathy. We investigated the effects of low-, moderate-, and high-intensity exercise on IOP in healthy subjects. A submaximal cardiopulmonary exercise test was performed in 18 healthy male subjects, and the maximal oxygen uptake was calculated. The subjects then exercised for 20 min at 30%, 50%, and 70% ·VO2 of maximal oxygen uptake, and their IOP was measured at rest and every 5 min during exercise. Oxygen uptake was monitored using an expiratory gas analyzer during exercise to maintain accurate exercise intensity and adjust exercise load. Oxygen uptake during exercise was significantly higher at all intensities from 5 to 20 min than at rest. IOP was significantly lower at 70% exercise intensity from 5 to 20 min than at rest. A negative correlation existed between IOP and ·VO2. IOP remained unchanged during low- and moderate-intensity exercise but significantly declined during high-intensity exercise compared with that at rest. Although various factors, such as β-blockers, are involved in IOP decline at rest, a different mechanism is involved in IOP decline during exercise.

Abnormal Maximal and Submaximal Cardiopulmonary Exercise Capacity in Pediatric Stem Cell Transplant Recipients Despite Normal Standard Echocardiographic Parameters: A Pilot Study

Left ventricular systolic dysfunction is a known complication of stem cell transplantation (SCT). There has been minimal research to determine whether subclinical cardiac dysfunction exists in SCT patients using tools other than standard echocardiography, such as maximal and submaximal effort cardiopulmonary exercise testing (CPET) and vascular function studies. The objective of this study was to determine the rate of subclinical cardiac dysfunction in patients with normal ejection fraction after SCT, identified by abnormal values by CPET, tissue-Doppler imaging, and arterial stiffness measurements and to further describe submaximal exercise test measures in this population. A prospective cohort study of SCT survivors who were at least 3 years after SCT without prior anthracycline or radiation exposure and with preserved systolic function (left ventricular ejection fraction > 50%) was performed to evaluate for abnormalities in exercise, vascular function, and diastolic function in an effort to detect subclinical dysfunction in SCT patients. Eleven patients (12.4 ± 3.8 years old) were included in the study. No patients had diastolic dysfunction. All patients completed a maximal effort exercise test, and 73% (8/11) had abnormal peak oxygen consumption (Vo2 peak), which is a measure of aerobic fitness. However, during submaximal effort CPET, 45% (5/11) had an abnormal Vo2 at anaerobic threshold (i.e., the point in exercise where aerobic transitions to anaerobic metabolism and fatigue starts), and 64% (7/11) had an abnormal oxygen uptake efficiency slope (a measure that relates Vo2 peak to total ventilation). Eighty-six percent (6/7) of the patients with an abnormal oxygen uptake efficiency slope ultimately had an abnormal Vo2 peak. There were no vascular function abnormalities. Pediatric survivors of SCT often have abnormal maximal and submaximal exercise capacity without vascular or cardiac dysfunction.

Abnormal whole-body energy metabolism in iron-deficient humans despite preserved skeletal muscle oxidative phosphorylation

Iron deficiency impairs skeletal muscle metabolism. The underlying mechanisms are incompletely characterised, but animal and human experiments suggest the involvement of signalling pathways co-dependent upon oxygen and iron availability, including the pathway associated with hypoxia-inducible factor (HIF). We performed a prospective, case–control, clinical physiology study to explore the effects of iron deficiency on human metabolism, using exercise as a stressor. Thirteen iron-deficient (ID) individuals and thirteen iron-replete (IR) control participants each underwent 31P-magnetic resonance spectroscopy of exercising calf muscle to investigate differences in oxidative phosphorylation, followed by whole-body cardiopulmonary exercise testing. Thereafter, individuals were given an intravenous (IV) infusion, randomised to either iron or saline, and the assessments repeated ~ 1 week later. Neither baseline iron status nor IV iron significantly influenced high-energy phosphate metabolism. During submaximal cardiopulmonary exercise, the rate of decline in blood lactate concentration was diminished in the ID group (P = 0.005). Intravenous iron corrected this abnormality. Furthermore, IV iron increased lactate threshold during maximal cardiopulmonary exercise by ~ 10%, regardless of baseline iron status. These findings demonstrate abnormal whole-body energy metabolism in iron-deficient but otherwise healthy humans. Iron deficiency promotes a more glycolytic phenotype without having a detectable effect on mitochondrial bioenergetics.

Impact of high-flow oxygen therapy during exercise in idiopathic pulmonary fibrosis: a pilot crossover clinical trial

BackgroundSupplemental oxygen delivered with standard oxygen therapy (SOT) improves exercise capacity in patients with idiopathic pulmonary fibrosis (IPF). Although high-flow nasal cannula oxygen therapy (HFNC) improves oxygenation in other respiratory diseases, its impact on exercise performance has never been evaluated in IPF patients. We hypothesized that HFNC may improve exercise capacity in IPF subjects compared to SOT.MethodsThis was a prospective, crossover, pilot randomized trial that compared both oxygenation methods during a constant submaximal cardiopulmonary exercise test (CPET) in IPF patients with exertional oxygen saturation (SpO2) ≤ 85% in the 6-min walking test. The primary outcome was endurance time (Tlim). Secondary outcomes were muscle oxygen saturation (StO2) and respiratory and leg symptoms.ResultsTen IPF patients [71.7 (6) years old, 90% males] were included. FVC and DLCO were 58 ± 11% and 31 ± 13% pred. respectively. Tlim during CPET was significantly greater using HFNC compared to SOT [494 ± 173 vs. 381 ± 137 s, p = 0.01]. HFNC also associated with a higher increase in inspiratory capacity (IC) [19.4 ± 14.2 vs. 7.1 ± 8.9%, respectively; p = 0.04], and a similar trend was observed in StO2 during exercise. No differences were found in respiratory or leg symptoms between the two oxygen devices.ConclusionsThis is the first study demonstrating that HFNC oxygen therapy improves exercise tolerance better than SOT in IPF patients with exertional desaturation. This might be explained by changes in ventilatory mechanics and muscle oxygenation. Further and larger studies are needed to confirm the benefits of HFNC in IPF patients and its potential usefulness in rehabilitation programs.

Cardiorespiratory optimal point during exercise testing and sudden cardiac death: A prospective cohort study

BackgroundCardiorespiratory optimal point (COP) during exercise, a potentially useful submaximal cardiopulmonary exercise testing (CPET) variable, may be an independent risk factor for cardiovascular disease outcomes. However, the relationship of COP with risk of sudden cardiac death (SCD) has not been previously investigated. We sought to evaluate the association between COP during exercise and SCD risk and determine whether COP improves SCD risk prediction. MethodsCOP, the minimum value of the ventilatory equivalent for oxygen (VE/VO2) in a given minute of a CPET, was ascertained in 2190 men who underwent clinical exercise testing. Hazard ratios (HRs) (95% confidence intervals [CIs]) and measures of risk discrimination for SCD were calculated. ResultsA total of 240 SCDs death occurred during a median follow-up of 28.8 years. COP was linearly associated with SCD in a dose-response manner. In a multivariable model comprising several established and emerging CVD risk factors, the HR (95% CI) for SCD was 2.51 (1.36–4.62) per standard deviation increase in COP. This was minimally attenuated to 2.36 (1.27–4.37) on further adjustment for high sensitivity C-reactive protein. The association did not vary importantly in several relevant clinical subgroups. Addition of COP to a SCD risk score was associated with a C-index change of 0.0086 (0.0005 to 0.0167; p = .038) and difference in −2 log likelihood (p = .017). ConclusionsCOP during exercise is strongly, inversely and independently associated with SCD in a graded fashion. COP during exercise may potentially be used for the prediction of the long-term risk for SCD beyond established CVD risk factors.

Facemasks and Walk Distance in Pulmonary Arterial Hypertension Patients.

Little is known about the effect of wearing a facemask on the physiological and perceptual responses to exercise in patients with pulmonary arterial hypertension (PAH). We performed a single-center retrospective study to evaluate whether facemask wearing impacted distanced covered, rating of perceived exertion (RPE), and arterial oxygen saturation (SpO2) during a 6-minute walk test (6MWT) in PAH patients. Forty-five patients being treated for group 1 PAH and who performed a 6MWT before and after implementation of a facemask mandate were included in the analysis. Each included patient performed a 6MWT without (test 1) and with (test 2) a facemask between October 1, 2019, and October 31, 2020. At both time points, all patients also underwent a submaximal cardiopulmonary exercise test, echocardiogram, and blood laboratory tests, with a Registry to Evaluate Early and Long-Term PAH Disease Management Lite 2.0 score calculated. The two 6MWTs were performed 81±51 days apart, and all patients were clinically stable at both testing timepoints. Six-minute walk test distance was not different between test 1 and test 2 (405±108 m vs 400±103 m, P=.81). Similarly, both end-test RPE and lowest SpO2 during the 6MWT were not different in test 1 and test 2 (RPE: 2.5±1.7 vs 2.5±2.1, P=.91; SpO2 nadir: 92.8±3.4% vs 93.3±3.3%, P=.55). Our findings show that wearing a facemask has no discernable impact on the arterial oxygen saturation and perceptual responses to exercise or exercise capacity in patients with moderate-to-severe PAH. This study reinforces the evidence that wearing a facemask is safe in PAH patients, even during exercise.

Two-minute exercise testing is sufficient to estimate maximal cardiorespiratory fitness in people with epilepsy

We aimed to examine the agreement between submaximal cardiopulmonary exercise testing (CPET) measures and peak oxygen consumption (VO2peak) in adults with epilepsy. Data from a randomized controlled trial with adults with epilepsy (N = 21) were analyzed. VO2peak was assessed using indirect calorimetry during a treadmill graded maximal CPET. Oxygen uptake efficiency slope (OUES) was calculated from the relationship between oxygen uptake and minute ventilation during the entire test (OUESpeak) and the first 2 (OUES2min), 3 (OUES3min), and 4 (OUES4min) minutes of the CPET. The strength of the association between measures was tested by Pearson correlation. Linear regression models were used to predict VO2peak based on OUES from the different testing durations. Agreement between measured and predicted maximal values was tested using intraclass correlation coefficient (ICC) and Bland-Altman plots. OUES2min, OUES3min, and OUES4min were highly associated with absolute (r = 0.84, r = 0.76, r = 0.75, respectively) and relative (r = 0.84, r = 0.78, r = 0.78, respectively) VO2peak. Agreement (ICC = 0.83) between CPET-measured and OUES-predicted VO2peak values was stronger with OUES2min than the other time-based OUES markers. Bland-Altman plot showed satisfactory agreement between predicted and measured CPET measures with the narrowest limits of agreement observed with the OUES2min. No potential bias was identified between these two measurements (p = 0.33). Changes in absolute (r = 0.77) and relative (r = 0.88) VO2peak were highly associated with the change in OUES2min. OUES2min can be used as a surrogate for maximal cardiorespiratory fitness in adults with epilepsy. Studies with larger samples size are encouraged to confirm our findings in a more heterogeneous population.

Cardiac autonomic associations on exercise and ambulatory capacity in individuals with lower-extremity artery disease

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): This work was in part supported by Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP #2019/19596-7), and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq #303399/2018-0). OnBehalf Exercise and Chronic Disease Research Laboratory - Bauru, Brazil; Research Group for Cardiovascular Rehabilitation - Leuven, Belgium. INTRODUCTION Lower-extremity artery disease (LEAD) characterized by progressive atherosclerotic build-up in leg arteries is becoming increasingly prevalent, affecting more than 200 million people worldwide. In line with other atherosclerotic disorders, LEAD is often associated with autonomic dysfunction as evidenced by a reduced heart rate variability (HRV). To date, little is known on the impact of cardiac autonomic function on exercise and ambulatory capacity. PURPOSE We aimed to investigate whether autonomic function is associated with ambulatory capacity and exercise capacity in patients with LEAD. METHODS Thirty-four patients (age≥17 years) diagnosed with LEAD (ankle brachial index: ABI ≤ 0.9 and/or 20% decrease after a maximal treadmill test) suffering from intermittent claudication (Rutherford I-III) were recruited in the PROSECO-IC trial. Patients were grouped based on beta-blocker medication (β-blocker and non β-blocker). Intervals between R waves (i-RR) obtained by heart rate (HR) signal were acquired beat-to-beat via a digital telemetry system (Polar®️ H10) during 15 min of supine rest and were used for 5-minute HRV analysis. Time domain indexes (mean i-RR, SNDD, pNN50%), and frequency domains (high frequency band (HF), low frequency (LF, very LF (VLF)) and the ratio (LF/HF). HRV was analyzed in absolute (abs), normalized (nu) and log units (log). Ambulatory capacity was assessed by means of a submaximal treadmill test, graded maximal treadmill test using Gardner protocol (GTM) and 6 minutes walking test (6MWT); exercise capacity was assessed by means of a graded maximal cardiopulmonary exercise test (HR, blood pressure (BP) and peak oxygen uptake (VO2peak)) at resting, 2 minutes, and peak of exercise. RESULTS Pearson test showed that sympathetic modulation indexes were moderate associated with pain free distance in GTM (LF/HF: r = 0.52, p = 0.04), and pain free time in 6MWT (LFlog: r=-0.62, p = 0.01; VLF: r=-0.52, p = 0.04), respectively, in patients without β-blocker. Similar HR associations with HRV (time and frequency domain) were observed during submaximal treadmill test and cardiopulmonary exercise test (p ≤ 0.05). Test-t demonstrated a significantly increased response intra-groups in HR and BP during both tests (p ≤ 0.05). Average BP were positive associated with the earlier stages of the cardiopulmonary test (resting to 2 min) with LFlog (r = 0.70, p= &amp;lt;0.001) in β-blocker while non-β-blocker were associated from 2 min to peak with LFabs (r = 0.67, p= &amp;lt;0.001) and LF/HF (r = 0.52, p = 0.03). CONCLUSION Sympathetic modulation was correlated with a longer pain free walking capacity in non-β-blockers. Yet, individuals treated by -β-blockers showed an earlier sympathetic modulation through exercise pressor response during the first stages of cardiopulmonary exercise compared to non-β-blockers with LEAD.

Are There Associations Between Submaximal and Maximal Aerobic Power and International Ski Federation World Cup Ranking in Elite Alpine Skiers?

To analyze the predictive value of parameters of submaximal and maximal cardiopulmonary exercise performance on International Ski Federation (Fédération Internationale de Ski) World Cup ranking (FIS ranking) in elite Austrian Alpine skiers. Over 7 World Cup seasons (2012-2018), exercise data (maximal oxygen uptake and maximum power output, lactate threshold 2, and ventilatory threshold 2, based on stepwise cycle spiroergometry) were analyzed to determine whether there was a correlation between world FIS ranking and exercise capacity of male and female elite Alpine skiers. The data of 39 male skiers (age: 27.67 [4.20]y, body mass index: 26.03 [1.25]kg/m2) and 36 female skiers (age: 25.49 [3.18]y, body mass index: 22.97 [1.71]kg/m2) were included in this study. The maximum oxygen uptake and maximum power output ranged from 4.37 to 4.42W/kg and 53.41 to 54.85mL/kg/min in men and from 4.17 to 4.30W/kg and 45.96 to 49.16mL/kg/min in women, respectively, over the 7 seasons; the yearly mean FIS ranking ranged from 17 to 24 in men and 9 to 18 in women. In a fixed-effects model used for the subsequent panel regression analysis, no statistically significant effect on FIS ranking was found for the exercise parameters of interest. Neither maximal aerobic tests nor maximum power output significantly predicted competitive performance, as indexed by the FIS ranking. This reinforces the assumption that no single parameter determines competition performance in this complex sport. Therefore, identifying the optimum amount of endurance training remains a major challenge for athletes and coaches, as does identifying and improving the factors that determine performance.

The physiological effect of early pregnancy on a woman's response to a submaximal cardiopulmonary exercise test.

Given all its systemic adaptive requirements, pregnancy shares several features with physical exercise. In this pilot study, we aimed to assess the physiological response to submaximal cardiopulmonary exercise testing (CPET) in early pregnancy. In 20 healthy, pregnant women (<13 weeks gestation) and 20 healthy, non‐pregnant women, we performed a CPET with stationary cycling during a RAMP protocol until 70% of the estimated maximum heart rate (HR) of each participant. Hemodynamic and respiratory parameters were non‐invasively monitored by impedance cardiography (PhysioFlow®) and a breath‐by‐breath analyzer (OxyconTM). To compare both groups, we used linear regression analysis, adjusted for age. We observed a similar response of stroke volume, cardiac output (CO) and HR to stationary cycling in pregnant and non‐pregnant women, but a slightly lower 1‐min recovery rate of CO (−3.9 [−5.5;‐2.3] vs. −6.6 [−8.2;‐5.1] L min−1 min−1; p = .058) and HR (−38 [−47; −28] vs. −53 [−62; −44] bpm/min; p = .065) in pregnant women. We also observed a larger increase in ventilation before the ventilatory threshold (+6.2 [5.4; 7.0] vs. +3.2 [2.4; 3.9] L min−1 min−1; p < .001), lower PETCO2 values at the ventilatory threshold (33 [31; 34] vs. 36 [34; 38] mmHg; p = .042) and a larger increase of breathing frequency after the ventilatory threshold (+4.6 [2.8; 6.4] vs. +0.6 [−1.1; 2.3] breaths min−1 min−1; p = .015) in pregnant women. In conclusion, we observed a slower hemodynamic recovery and an increased ventilatory response to exercise in early pregnancy.

Cardiac autonomic dysfunction in survivors of childhood acute lymphoblastic leukemia: The St. Jude Lifetime Cohort Study.

Cardiac autonomic dysfunction (CAD) is possible following treatment for childhood cancer. The aims of our analyses were to compare the prevalence of CAD between adult survivors of childhood acute lymphoblastic leukemia and controls, compare exercise response among survivors with and without CAD, and identify treatment-related risk factors for CAD. Participants were treated for childhood acute lymphoblastic leukemia at St. Jude Children's Research Hospital between 1980 and 2003 (N=338). A comparison group matched for race/ethnicity, age, and sex was also recruited (N=325). Resting heart rate (HR) was assessed via electrocardiogram, and heart rate recovery (HRR) and exercise capacity were evaluated with submaximal cardiopulmonary exercise testing. CAD was present in 33.7% of survivors and 27.6% of controls (P=0.09). Although mean resting HR did not differ between survivors and controls (74 ± 12 vs 72 ± 12 beats per minute (bpm), P=0.07), survivors had lower mean HRR than controls (22 ± 9 vs 25 ± 10bpm; P<0.001). Survivors with CAD had lower peak exercise tolerance (25.7 ± 6.5 vs 21.2 ± 4.9mL/kg/min, P<0.001) than those without. Survivors treated with cyclophosphamide in combination with vincristine ≥38mg/m2 and/or glucocorticoids ≥10000mg/m2 were 1.56 (95% CI 1.09-2.24) times more likely to have CAD than those without this treatment. Obese survivors were 1.78 (95% CI: 1.31-2.40) times more likely to have CAD than nonobese survivors (P<0.001). CAD was present in over one third of survivors and was associated with lower exercise capacity. Obese survivors and those exposed to cyclophosphamide with high doses of vincristine and/or corticosteroids were at greatest risk.

65-LB: Sweet Performance: Associations of Maximum Physiological Performance and Diabetes in a Group of World Class Road Cyclists with Type 1 Diabetes

Aim: This study investigated whether markers related to type 1 diabetes (T1D) influence cardiopulmonary exercise (CPX) test performance in a group of world class road cyclists with T1D. Methods: Fifteen elite male road cyclists with T1D (age 27±4 years, T1D duration 11±5 years, BMI 21.6±1.5 kg·min-2, HbA1c 6.8±0.6%) performed a ramped (10 W per min) CPX test to exhaustion. Adjusted stepwise linear regression analysis was performed to investigate relationships between markers of T1D control and absolute maximum markers of performance, maximum oxygen consumption (V O2max), maximum power output (Pmax) and maximum heart rate (HRmax). Associations between submaximal CPX parameters and V O2max, Pmax and HRmax were also investigated. Results: Starting-CPX blood glucose (BG), post-CPX BG, ΔBG, T1D duration, HbA1c and BMI were not associated with V O2max (r2=0.51, P=0.32) and Pmax (r2=0.48, P=0.37) during CPX testing. However, HRmax was associated with T1D duration (r2=0.31, P=0.03). CO2 expiration at the lactate turn point 2 (V CO2LTP2) and power at the heart rate turn point (PHRTP) were associated with V O2max (r2=0.87, P&amp;lt;0.0001). These results were also associated when adjusted for T1D parameters (r2=0.95, p=0.002). Pmax was solely associated with V O2HRTP (r2=0.71, P&amp;lt;0.0001). Also, this association remained significant when adjusted for T1D parameters (r2=0.86, P=0.03). HRmax was associated with ventilation at the LTP2 (VELTP2), LactateLTP1, VCO2LTP2 and PLTP2 (r2=0.91, P=0.002). When this result was adjusted for T1D parameters the association was significant (r2=0.93, P=0.05). Conclusion: This is the first dataset presenting CPX data from a world class cycle team with T1D. The study shows that not all markers of maximum physiological performance are influenced by T1D, solely HRmax by T1D duration. Yet, maximum performance is dependent on several submaximal cardiopulmonary markers of performance. Disclosure M.L. Eckstein: Research Support; Self; Novo Nordisk A/S. O. Moser: Research Support; Self; Abbott, Dexcom, Inc., Novo Nordisk A/S. O. McCarthy: None. S.N. Scott: None. M. Riddell: Advisory Panel; Self; Xeris Pharmaceuticals, Inc. Consultant; Self; Lilly Diabetes. Research Support; Self; Dexcom, Inc., Insulet Corporation, Novo Nordisk Inc., Sanofi. Speaker’s Bureau; Self; Medtronic MiniMed, Inc., OmniPod. Stock/Shareholder; Self; Zucara Therapeutics Inc. F.Y. Fontana: None. K. Skroce: None. M.P. Christiansen: Research Support; Self; Abbott, Biolinq, Dexcom, Inc., Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Medtronic MiniMed, Inc., Novo Nordisk A/S, Sanofi-Aventis, Xeris Pharmaceuticals, Inc. L. Festa: None. M. Fisher: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Mylan, NAPP Pharmaceuticals Limited, Novo Nordisk A/S. Speaker’s Bureau; Self; Eli Lilly and Company, Sanofi. C.A. Hayes: Other Relationship; Self; Novo Nordisk A/S. P. Southerland: Other Relationship; Self; Novo Nordisk Inc. C. Stettler: None. P.H. Lagrou: None. B.W. Bode: Consultant; Self; ADOCIA, Lexicon Pharmaceuticals, Inc., Novo Nordisk Inc. Research Support; Self; Becton, Dickinson and Company, Dexcom, Inc., Diasome Pharmaceuticals, Inc., Eli Lilly and Company, Eyenuk Inc., Insulet Corporation, National Institutes of Health, Novo Nordisk Inc., Sanofi Research &amp; Development, Senseonics, Xeris Pharmaceuticals, Inc. Speaker’s Bureau; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Janssen Pharmaceuticals, Inc., Novo Nordisk Inc., Sanofi US, Senseonics. Stock/Shareholder; Self; AgaMatrix, Glytec, LLC. R.M. Bracken: None. Funding Novo Nordisk A/S

Clinical Surrogates of Right Ventricular-Pulmonary Arterial Uncoupling

Purpose Right ventricular (RV) function is best represented by the ratio of RV contractility to pulmonary arterial (PA) load (RV-PA coupling). Gold standard measurement of RV-PA coupling, using multi-beat pressure-volume (P-V) loop to obtain the ratio of end-systolic elastance (Ees) to effective arterial elastance (Ea), is costly and invasive. Therefore, we sought to identify clinical surrogates of reduced Ees/Ea and RV-PA uncoupling. Methods We prospectively studied 35 patients suspected to have pulmonary hypertension (PH) with same day echocardiography, cardiac magnetic resonance imaging (CMR), right heart catheterization, and supine bicycle submaximal cardiopulmonary exercise testing. Multi-beat RV P-V loop measurements were also performed. Ees/Ea Results Of 35 patients, 26 had resting PH while 9 did not (20/26 had group I PH). Average age was 57±13 years; 30 were women. Compared with baseline Ees/Ea ≥ 1.0, Ees/Ea Conclusion Readily attainable clinical variables correspond to the gold standard Ees/Ea. We identified a novel parameter, exercise change in ΔESV/ΔESP, a marker of RV reserve, which had the best ability to predict RV-PA uncoupling. Future studies will investigate RV ΔESV/ΔESP and other markers of RV reserve.

Abnormal submaximal cardiopulmonary exercise parameters predict impaired peak exercise performance in sickle cell anemia patients.

Sickle cell anemia (SCA) patients frequently have many comorbidities, including diastolic dysfunction (DD) and exercise intolerance. SCA patients often cannot reach maximal effort on exercise testing; little is known regarding whether submaximal exercise parameters can predict abnormal maximal exercise results in SCA patients and if there are any possible associations with DD. A prospective longitudinal study was performed in SCA patients. All patients had a resting cardiac MRI (CMR), cardiopulmonary exercise test (CPET) with cycle ergometry using a ramp protocol, and an echocardiogram. Exercise data were compared with age-, gender-, and size-matched normal controls. Compared with normal controls, the SCA group (n=19) had lower mean max oxygen consumption (VO2 ; 1378 ± 412mL/min vs 2237 ± 580, P<0.01) and workload (117 ± 37.6 watts vs 175 ± 50.5 watts, P=0.0003). When evaluating the submaximal exercise parameters, there was lower VO2 at the anaerobic threshold (AT; 950 ± 311.7vs 1460 ± 409.9, P<0.01) and oxygen uptake efficiency slope (OUES) at AT (1512 ± 426.2vs 2080 ± 339, P<0.01). The max VO2 strongly correlated with VO2 at AT (r=0.9, P<0.01) and OUES (r=0.83, P<0.01) at AT. The VO2 at AT correlated with hematocrit (r=0.77, P<0.05). The OUES correlated with left ventricular ejection fraction by CMR (r=0.55, P=0.01), hematocrit (r=0.52, P=0.02), and lateral E/e' (r=-0.54, P=0.01). SCA patients have abnormal submaximal exercise measures compared with controls, which is strongly associated with abnormal maximal exercise results. The degree of submaximal abnormality correlates with DD abnormalities by echocardiography. These data expand the scope of functional cardiovascular abnormalities in SCA.

Abstract 16697: Predictive Value of Cardiopulmonary Exercise Testing Parameters for 1-Year Adverse Outcomes in Ambulatory Advanced Heart Failure

Introduction: Maximal and submaximal cardiopulmonary exercise (CPX) parameters predict heart failure (HF) outcomes, yet the best predictors in advanced ambulatory HF are not known. Hypothesis: We examined the discriminative value of maximal CPX parameters including peak oxygen consumption (peak VO2), VO2 pulse, circulatory power (CP, peak systolic BP x peak VO2), and end tidal pressure CO2 (PetCO2), as well as submaximal parameters of ventilatory efficiency (VE/VCO2 slope), VO2 at anaerobic threshold (VO2AT) and oxygen uptake efficiency slope (OUES) on the combined outcome of LVAD, UNOS 1 transplant or death at 1 year. Methods: REVIVAL enrolled systolic HF pts in INTERMACS profiles 4-7 despite optimal medical therapy and CRT, of whom 273 performed CPX; 64 did not exercise (26 too ill, 38 for non-cardiac issues). ROC curves display the discriminative power of each parameter using censored c-statistics. The best multivariable model was identified by Cox regression. Results: At 1 year, there were 53 events (10 transplants,19 deaths; 24 LVADs). Pts with and without events were comparable for age (61 vs 60 yrs), LVEF (27 vs 29%), and BMI (31 vs 32 kg/m 2 ).) Peak VO2, VO2AT, OUES, PetCO2, and CP were higher in the no event group (all p &lt;0.001), whereas VE/VCO2 slope was lower (p&lt;0.0001); respiratory exchange ratio was not different. Among the 26 pts too sick for exercise, the event rate was 15/26 (58%) compared to 38/273 (14%) in those exercising (HR=6.7, p&lt;0.0001). Figure displays ROC curves and c-indices for CPX parameters. VO2 pulse (HR 1.18, p=0.017), CP (HR 0.86, p=0.005) and VE/VCO2 slope (HR 1.1, p=0.0001) were significant predictors in the multivariable analysis (model c-statistic=0.80). Conclusions: In ambulatory advanced HF, the inability to perform exercise due to being too ill predicts adverse outcome and for those who can exercise, VE/VCO2 slope is the most robust submaximal CPX parameter, while CP was the strongest maximal parameter to predict death, transplant or LVAD at 1 year.