Peak Respiratory Exchange Ratio Research Articles

Hypertension and Ventilatory Ineffciency During Exercise in the Fitness Registry and the Importance of Exercise National Database (FRIEND)

Background: Ventilatory ineffciency (high minute ventilation/rate of carbon dioxide production [V̇E/V̇CO2] slope) during exercise is more common in patients with metabolic syndrome and cardiovascular disease, and is prognostic of cardiovascular mortality. Interestingly, new data suggest that adults with controlled or untreated, but not uncontrolled, primary hypertension (HTN) have ventilatory ineffciency during exercise. However, the sample sizes were modest (n=~20/group). Therefore, we used a large database to test the hypothesis that adults with controlled or untreated, but not uncontrolled, primary HTN have higher V̇E/V̇CO2 slope than adults with no HTN. Methods: We used American Heart Association guidelines for HTN as systolic blood pressure [BP] ≥130mmHg, diastolic BP ≥80, or anti-HTN medication in the Fitness Registry and the Importance of Exercise National Database (FRIEND). To isolate primary HTN, we excluded those with any disease other than HTN, any medication use other than anti-HTN medication(s), current smoking status, and/or obesity (body mass index [BMI]≥30). The V̇E/V̇CO2 slope was determined from a peak cycling exercise test. We excluded adults with a peak respiratory exchange ratio <1.00 during exercise. All data are presented as median[IQR]. We compared groups using linear regression unadjusted and adjusted for sex, fitness, and age. Results: The sample (n=4,659) characteristics were age: 42[18] years old (range 18-91 years); 52% with HTN; 18% female; BMI: 26.0[4.0] kg/m2; cardiorespiratory fitness: 28.5[11.0] mL O2/kg/min; race/ethnicity: <1% American Indian, 3% Asian, 12% Black, 8% Hispanic, 4% Other, & 73% White. The V̇E/V̇CO2 slope during exercise was higher in adults without HTN (n=2,410; 24.9[3.8]) compared to those with uncontrolled HTN (n=252; 24.7[3.0]; standard error of the estimate[SE]: -0.20, 95% confidence interval[CI]: -0.33 to -0.07, p=0.003), but not controlled HTN (n=132; 24.4[3.4]; SE: -0.14, 95%CI: -0.31 to 0.04, p=0.12) or untreated HTN (n=1,865; 24.7[3.7]; SE: -0.05, 95%CI: -0.11 to 0.009, p=0.09) (model: R2=0.002, F3,4655=3.83, p=0.009). However, no pairwise differences were observed after covariate adjustment (model: R2=0.117, F6,4652=103, p<0.001). Conclusion: In contrast to our hypothesis, these data from the FRIEND indicate that primary HTN is not associated with ventilatory ineffciency (i.e., higher V̇E/V̇CO2 slope). National Institutes of Health K01HL160772 (JCW), American Heart Association 23CDA1037938 (JCW). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Cardiopulmonary Exercise Testing in a Prospective Multicenter Cohort of Older Adults.

Cardiorespiratory fitness (CRF) measured by peak oxygen consumption (VO 2 peak) declines with aging and correlates with mortality and morbidity. Cardiopulmonary Exercise Testing (CPET) is the criterion method to assess CRF, but its feasibility, validity and reliability in older adults is unclear. Our objective was to design and implement a dependable, safe and reliable CPET protocol in older adults. VO 2 peak was measured by CPET, performed using treadmill exercise in 875 adults ≥70 years in the Study of Muscle, Mobility and Aging (SOMMA). The protocol included a symptom-limited peak (maximal) exercise and two submaximal walking speeds. An adjudication process was in place to review tests for validity if they met any prespecified criteria [VO 2 peak < 12.0 ml/kg/min; maximum heart rate (HR) <100 bpm; respiratory exchange ratio (RER) <1.05 and a rating of perceived exertion <15]. A subset (N = 30) performed a repeat test to assess reproducibility. CPET was safe and well tolerated, with 95.8% of participants able to complete the VO 2 peak phase of the protocol. Only 56 (6.4%) participants had a risk alert and only two adverse events occurred: a fall and atrial fibrillation. Mean ± SD VO 2 peak was 20.2 ± 4.8 mL/kg/min, peak HR 142 ± 18 bpm, and peak RER 1.14 ± 0.09. Adjudication was indicated in 47 tests; 20 were evaluated as valid, 27 as invalid (18 data collection errors, 9 did not reach VO 2 peak). Reproducibility of VO 2 peak was high (intraclass correlation coefficient = 0.97). CPET was feasible, effective and safe for older adults, including many with multimorbidity or frailty. These data support a broader implementation of CPET to provide insight into the role of CRF and its underlying determinants of aging and age-related conditions.

A COMPARISON OF GUIDELINES FOR HEART TRANSPLANT CONSIDERATION BASED ON CPET DATA

BACKGROUND The International Society for Heart and Lung Transplantation (ISHLT) recommends using peak oxygen uptake (VO2≤12 mL/kg/min), percent predicted peak VO2 (ppVO2≤50%), or the ventilation to carbon dioxide slope (VE/VCO2 slope&amp;gt;35) to guide listing for heart transplantation (HTx) in patients with heart failure with reduced ejection fraction (HFrEF). Data comparing the mortality rates between each of these thresholds is lacking. The purpose of this retrospective cohort study was to describe the 3-year mortality rate among patients with HFrEF based on the ISHLT recommendations. METHODS This was a secondary analysis of a combined cohort of patients (≥18 years) with HFrEF from Henry Ford Hospital (n=1,063) and the HF-ACTION study (n=1,772). The cohort was limited to patients who completed a cardiopulmonary exercise test on a treadmill and were prescribed a beta-adrenergic blockade at the time of the test. The primary outcome was probability of all-cause mortality at 3 years based on Kaplan-Meier estimates. Patients were censored at the date of HTx, left ventricular assist device implant, or last known alive. Mortality rates were calculated for patients with a peak VO2≤12 mL/kg/min, ppVO2≤50%, and VE/VCO2 slope&amp;gt;35. The cohort was stratified by sex, age, obesity (body mass index [BMI]&amp;gt; 30 kg/m2), and peak respiratory exchange ratio (RER). Mortality rates were compared to the 3-year mortality post HTx reported by ISHLT. RESULTS In our combined cohort (n=2,775; age=57±13 y; 19% women; 48% non-white), 3-year mortality for peak VO2≤12 mL/kg/min, ppVO2≤50%, and VE/VCO2 slope&amp;gt;35 was 30%, 31%, and 28%, respectively. Each of these are higher than the 3-year mortality post HTx (20%). Similar results were observed by age below/above 50 y, BMI &amp;lt; versus &amp;gt; 30 kg/m2, RER ≤ versus &amp;gt;1.05, and within men. However, among women the 3-year mortality was 18% for peak VO2≤12 mL/kg/min, 25% for ppVO2≤50%, and 21% for VE/VCO2 slope&amp;gt;35. CONCLUSIONS ISHLT recommendations to guide listing for HTx for peak VO2≤12 mL/kg/min, ppVO2≤50%, and VE/VCO2 slope&amp;gt;35 are associated with a higher 3-year mortality than patients post HTx irrespective of age, obesity, and RER. However, among women only ppVO2≤50% and VE/VCO2 slope&amp;gt;35 identify patients with 3-year mortality that is higher than HTx.

A Reference Equation for Peak Oxygen Uptake for Pediatric Patients Who Undergo Treadmill Cardiopulmonary Exercise Testing

Pediatric patients are often referred to cardiopulmonary exercise testing (CPET) laboratories for assessment of exercise-related symptoms. For clinicians to understand results in the context of performance relative to peers, adequate fitness-based prediction equations must be available. However, reference equations for prediction of peak oxygen uptake (VO2peak) in pediatrics are largely developed from field-based testing, and equations derived from CPET are primarily developed using adult data. Our objective was to develop a pediatric reference equation for VO2peak. Clinical CPET data from a validation cohort of 1,383 pediatric patients aged 6 to 18years who achieved a peak respiratory exchange ratio ≥1.00 were analyzed to identify clinical and exercise testing factors that contributed to the prediction of VO2peak from tests performed using the Bruce protocol. The resultant prediction equation was applied to a cross-validation cohort of 1,367 pediatric patients. Exercise duration, gender, weight, and age contributed to the prediction of VO2peak, generating the following prediction equation: (R2=0.645, p <0.001, standard error of the estimate=6.19ml/kg/min): VO2peak (ml/kg/min) =16.411+ 3.423 (exercise duration [minutes]) - 5.145 (gender [0=male, 1=female]) - 0.121 (weight [kg])+0.179 (age [years]). This equation was stable across the age range included in the present study, with differences ≤0.5ml/kg/min between mean measured and predicted VO2peak in all age groups. In conclusion, this study represents what we believe is the largest pediatric CPET-derived VO2peak prediction effort to date, and this VO2peak prediction equation provides clinicians who perform and interpret exercise tests in pediatric patients with a resource with which to better quantify fitness when CPET is not available.

Surveillance cardiopulmonary exercise testing can risk-stratify childhood cancer survivors: underlying pathophysiology of poor exercise performance and possible room for improvement

BackgroundAsymptomatic childhood cancer survivors (CCS) frequently show decreased exercise performance. Poor exercise performance may indicate impaired future cardiovascular health.MethodsCardiopulmonary exercise testing (CPET) was performed in asymptomatic off-treatment CCS (age ≥ 10 years). Patients were divided into Normal and Poor performance groups by %predicted maximum VO2 at 80%. Both peak and submaximal CPET values were analyzed.ResultsThirty-eight males (19 Normal, 19 Poor) and 40 females (18 Normal, 22 Poor) were studied. Total anthracycline dosage was comparable among 4 groups. The body mass index (BMI), although normal, and weight were significantly higher in Poor groups. Peak heart rate (HR) and peak respiratory exchange ratio (RER) were comparable in all four groups. Peak work rate (pWR)/kg, peak oxygen consumption (pVO2)/kg, peak oxygen pulse (pOP)/kg, and ventilatory anaerobic threshold (VAT)/kg were significantly lower, whereas heart rate (HR) increase by WR/kg (ΔHR/Δ[WR/kg] was significantly higher in Poor groups. Simultaneously plotting of weight & pVO2 and ΔHR/ΔWR & ΔVO2/ΔHR revealed a distinct difference between the Normal and Poor groups in both sexes, suggesting decreased skeletal muscle mass and decreased stroke volume reserve, respectively, in Poor CCS. The relationship between VAT and pVO2 was almost identical between the two groups in both sexes. Ventilatory efficiency was mildly diminished in the Poor groups.ConclusionsDecreased skeletal muscle mass, decreased stroke volume reserve, and slightly decreased ventilatory efficiency characterize Poor CCS in both sexes. This unique combined CPET analysis provides useful clinical biomarkers to screen subclinical cardiovascular abnormality in CCS and identifies an area for improvement.

Validation of the maximal cardiopulmonary exercise test in adolescents with major depressive disorder and comparison of cardiorespiratory fitness with sex- and age-related control values

Endurance training has been shown to be effective in treating adolescents with major depressive disorder (MDD). To integrate endurance training into the therapeutic setting and the adolescents' daily lives, the current performance status of the adolescents should be accurately assessed. This study aims to examine adolescents with MDD concerning exhaustion criteria during a cardiopulmonary exercise test (CPET), as well as to compare the values obtained thereon with sex- and age-related control values. The study included a retrospective examination of exhaustion criteria ((i) oxygen consumption (V̇O2) plateau, (ii) peak respiratory exchange ratio (RERpeak) > 1.0, (iii) peak heart rate (HRpeak) ≥ 95% of the age-predicted maximal HR, and (iv) peak blood lactate concentration (BLCpeak) > 8.0 mmol⋅L−1) during a graded CPET on a cycle ergometer in adolescents with MDD (n = 57). Subsequently, maximal V̇O2, peak minute ventilation, V̇O2 at the first ventilatory threshold, and peak work rate of participants who met at least two of four criteria were compared with published control values using an independent-sample t-test. Thirty-three percent of the total population achieved a V̇O2 plateau and 75% a RERpeak > 1.0. The HR and BLC criteria were met by 19% and 22%, respectively. T-test results revealed significant differences between adolescents with MDD and control values for all outcomes. Adolescents with MDD achieved between 56% and 83% of control values. Conclusions: The study shows that compared with control values, fewer adolescents with MDD achieve the exhaustion criteria on a CPET and adolescents with MDD have significantly lower cardiorespiratory fitness. Clinical trial registration: No. U1111-1145–1854.What is Known:• It is already known that endurance training has a positive effect on depressive symptoms.What is New:• A relevant proportion of adolescents with major depressive disorder do not achieve their V̇O2max during a graded cardiopulmonary exercise test.• Adolescents with major depressive disorder have significantly lower cardiorespiratory fitness compared to sex- and age-related control values.

Short vs. Long Bouts of All-Out Rope Skipping: Effects on Metabolic and Perceptual Responses

Rope skipping has been well documented for eliciting positive effects on various health outcomes and contributing to overall physical activity levels. However, the specific health benefits may depend on the duration and intensity of the exercise bouts. This study aimed to compare the (1) metabolic and (2) perceptual responses between short (30 s) and long (3 min) bouts of all-out rope skipping, and to (3) evaluate the reliability and validity of a newly invented electronic rope (E-rope). A total of 23 young adults (13 males and 10 females; aged 23.23 ± 2.62 y) repeated short and long skipping bouts on two testing days. The oxygen consumption (V·O2), peak respiratory exchange ratio (RER), heart rate (HR), rate of perceived exertion (RPE), and post-exercise muscle soreness were assessed during each trial. Longer skipping bouts (148.33 skips·min−1) resulted in significantly greater metabolic responses (p &lt; 0.01, d = 1.00–3.27), higher rates of perceived exertion (p &lt; 0.01, d = 2.28), and more post-exercise muscle soreness (p &lt; 0.01, d = 0.66–1.49) compared to shorter bouts (165.83 skips·min−1). The E-rope demonstrated sufficient concurrent validity (r &gt; 0.9) and between-day reliability (ICC3,1 = 0.89–0.95) but slightly overestimated the number of skips. Both long and short all-out skipping bouts were considered moderate-to-vigorous exercise, but longer bouts resulted in higher metabolic and perceptual demands. These findings may be useful for practitioners to strategically apply different skipping bouts to improve physical activity levels and facilitate training adaptation. The E-rope could serve as a self-monitoring and self-evaluating tool.

Prognostic Significance of Peak Workload-to-Weight Ratio by Cardiopulmonary Exercise Testing in Chronic Heart Failure

The prognostic impact of peak workload-to-weight ratio (PWR) during cardiopulmonary exercise testing (CPET) and its determinants in patients with chronic heart failure (CHF) are not well understood. Consecutive 514 patients with CHF referred for CPET at the Hokkaido University Hospital between 2013 and 2018 were identified. The primary outcome was a composite of hospitalization because of worsening heart failure and death. PWR was calculated as peak workload normalized to body weight (W/kg) by CPET. Patients with low PWR (cut-off median 1.38 [W/kg], n=257) were older and more anemic than those with high PWR (n=257). In CPET, patients with low PWR displayed reduced peak oxygen consumption and impaired ventilatory efficiency compared with those with high PWR, whereas the peak respiratory exchange ratio was not significantly different between the 2 groups. There were 89 patients with events over a median follow-up period of 3.3 (interquartile range 0.8 to 5.5) years. The incidence of composite events was significantly higher in patients with low PWR than in those with high PWR (log-rank p <0.0001). In the multivariable Cox regression, lower PWR was associated with adverse events (hazard ratio 0.31, 95% confidence interval 0.13 to 0.73, p=0.008). Low hemoglobin concentration was strongly related to impaired PWR (βcoefficient=0.43, per 1g/100ml increased, p <0.0001). In conclusion, PWR was associated with worse clinical outcomes, where blood hemoglobin was strongly related to PWR. Further study is required to identify therapies targeting peak workload achievements in exercise stress tests to improve the outcome in patients with CHF.

Moderators of peak respiratory exchange ratio during exercise testing in children and adolescents with Fontan physiology.

Many patients with Fontan physiology are unable to achieve the minimum criteria for peak effort during cardiopulmonary exercise testing. The purpose of this study is to determine the influence of physical activity and other clinical predictors related to achieving peak exercise criteria, signified by respiratory exchange ratio ≥ 1.1 in youth with Fontan physiology. Secondary analysis of a cross-sectional study of 8-18-year-olds with single ventricle post-Fontan palliation who underwent cardiopulmonary exercise testing (James cycle protocol) and completed a past-year physical activity survey. Bivariate associations were assessed by Wilcoxon rank-sum test and simple regression. Conditional inference forest algorithm was used to classify participants achieving respiratory exchange ratio > 1.1 and to predict peak respiratory exchange ratio. Of the n = 43 participants, 65% were male, mean age was 14.0 ± 2.4 years, and 67.4% (n = 29) achieved respiratory exchange ratio ≥ 1.1. Despite some cardiopulmonary exercise stress test variables achieving statistical significance in bivariate associations with participants achieving respiratory exchange ratio > 1.1, the classification accuracy had area under the precision recall curve of 0.55. All variables together explained 21.4% of the variance in respiratory exchange ratio, with peak oxygen pulse being the most informative. Demographic, physical activity, and cardiopulmonary exercise test measures could not classify meeting peak exercise criteria (respiratory exchange ratio ≥ 1.1) at a satisfactory accuracy. Correlations between respiratory exchange ratio and oxygen pulse suggest the augmentation of stroke volume with exercise may affect the Fontan patient's ability to sustain high-intensity exercise.

Effects of Mavacamten on Measures of Cardiopulmonary Exercise Testing Beyond Peak Oxygen Consumption

Mavacamten, a cardiac myosin inhibitor, improved peak oxygen uptake (pVO2) in patients with symptomatic obstructive hypertrophic cardiomyopathy (HCM) in the EXPLORER-HCM study. However, the full extent of mavacamten's effects on exercise performance remains unclear. To investigate the effect of mavacamten on exercise physiology using cardiopulmonary exercise testing (CPET). Exploratory analyses of the data from the EXPLORER-HCM study, a randomized, double-blind, placebo-controlled, phase 3 trial that was conducted in 68 cardiovascular centers in 13 countries. In total, 251 patients with symptomatic obstructive HCM were enrolled. Patients were randomly assigned in a 1:1 ratio to mavacamten or placebo. The following prespecified exploratory cardiovascular and performance parameters were assessed with a standardized treadmill or bicycle ergometer test protocol at baseline and week 30: carbon dioxide output (VCO2), minute ventilation (VE), peak VE/VCO2 ratio, ventilatory efficiency (VE/VCO2 slope), peak respiratory exchange ratio (RER), peak circulatory power, ventilatory power, ventilatory threshold, peak metabolic equivalents (METs), peak exercise time, partial pressure of end-tidal carbon dioxide (PETCO2), and VO2/workload slope. Two hundred fifty-one patients were enrolled. The mean (SD) age was 58.5 (11.9) years and 59% of patients were male. There were significant improvements with mavacamten vs placebo in the following peak-exercise CPET parameters: peak VE/VCO2 ratio (least squares [LS] mean difference, -2.2; 95% CI, -3.05 to -1.26; P < .001), peak METs (LS mean difference, 0.4; 95% CI, 0.17-0.60; P < .001), peak circulatory power (LS mean difference, 372.9 mL/kg/min × mm Hg; 95% CI, 153.12-592.61; P = .001), and peak PETCO2 (LS mean difference, 2.0 mm Hg; 95% CI, 1.12-2.79; P < .001). Mavacamten also improved peak exercise time compared with placebo (LS mean difference, 0.7 minutes; 95% CI, 0.13-1.24; P = .02). There was a significant improvement in nonpeak-exercise CPET parameters, such as VE/VCO2 slope (LS mean difference, -2.6; 95% CI, -3.58 to -1.52; P < .001) and ventilatory power (LS mean difference, 0.6 mm Hg; 95% CI, 0.29-0.90; P < .001) favoring mavacamten vs placebo. Mavacamten improved a range of CPET parameters beyond pVO2, indicating consistent and broad benefits on maximal exercise capacity. Although improvements in peak-exercise CPET parameters are clinically meaningful, the favorable effects of mavacamten on submaximal exertional tolerance provide further insights into the beneficial impact of mavacamten in patients with obstructive HCM. ClinicalTrials.gov Identifier: NCT03470545.

Peak Work Rate Increases With Lower Extremity-Focused Exercise Training in Adolescents With Fontan Circulation.

Background Skeletal muscle deficits are associated with worse exercise performance in the Fontan circulation and may be improved by exercise training. We aimed to assess the change in leg lean mass (a marker of skeletal muscle), exercise performance, and functional health status after a lower extremity-focused exercise intervention in adolescents with Fontan circulation. Methods and Results Densitometry for measurement of leg lean mass, cardiopulmonary exercise test, exercise cardiac magnetic resonance, peripheral vascular testing, physical activity questionnaire, and quality of life assessment were performed at baseline and after a 24-week, hybrid center- and home-based training program. Leg lean mass Z-scores were generated, and exercise parameters were expressed as percentage expected based on reference data. The effect of training was assessed by paired t-tests and simple linear regression. Twenty participants (15.6±1.7 years, 50% male) demonstrated low baseline leg lean mass Z-scores with no significant improvement with training (-1.38±1.02 pre versus -1.31±1.06 post, P=0.33). Maximum and percent predicted work increased from 121.9±29.8 (0.66±0.12) to 131.3±35.1 (0.70±0.15) watts (P=0.02). Peak respiratory exchange ratio increased (1.19±0.02 versus 1.25±0.01, P=0.02) but percent predicted oxygen consumption was unchanged, suggesting higher anaerobic activity after training. Physical activity questionnaire score positively associated with peak work at baseline (ß=18.13 [95% CI, 0.83-35.44], R2=0.21; P=0.04) but physical activity questionnaire, quality of life scores, exercise cardiac magnetic resonance performance, and peripheral vascular function were unchanged with training. Conclusions Peak work rate and anaerobic activity increased with lower extremity-focused training in adolescents with Fontan circulation. Larger studies should test the impact of these changes on functional status and quality of life.

Abstract 11959: Cardiopulmonary Exercise Testing Delineates Multiple Contributing Factors to Poor Exercise Performance in Childhood Cancer Survivors

Background: Childhood cancer survivors (CCS) show decreased exercise performance despite normal ventricular function at rest. Multiple underlying mechanisms are considered. Methods: Cardiopulmonary exercise testing (CPET) was performed in asymptomatic off-treatment CCS. Patients were divided into four groups by their peak oxygen consumption (pVO2) at 35 and 25 ml/kg/min in males and females, respectively (“Good” and “Poor” performance groups). * denotes weight-indexed values. Data are shown as mean ± standard deviation. Results: Demographic and CPET data are presented in Table 1. There was no notable correlation between total anthracycline dosage and CPET values. Weight, body mass index, and peak respiratory exchange ratio were significantly higher in “Poor” groups in both sexes. Peak oxygen pulse (pOP*) and ventilatory anaerobic threshold (VAT*) were significantly lower whereas heart rate (HR) dependency on work rate (WR*) (= ΔHR/ΔWR*) was significantly higher in “Poor” groups than in “Good” groups. There was no difference in ventilatory efficiency presented as a slope of ventilation (VE)/carbon dioxide output (VCO2)(ΔVE/ΔVCO2). Figure 1 demonstrated the relationship between weight and pVO2 (L/min) and between ΔHR/ΔWR* and pOP*, showing distinct difference between “Good” and “Poor” performers in both sexes; “Poor” performers revealed lower skeletal mass and stroke volume effects. Conclusions: Treatment-mediated cardiotoxicity is not the only cause of poor exercise performance in CCS. In addition to limited stroke volume indicated by lower pOP* with higher HR dependency, skeletal muscle loss and increased BMI mitigated the overall exercise performance.

Abstract 10985: Cardiopulmonary Assessment of COVID-19 Survivors Stratified by Acute Disease Severity and Post-Acute Symptoms

Introduction: Studies have demonstrated a reduction in peak oxygen consumption (VO 2 ) post-acute COVID-19. We sought to determine the association between acute COVID-19 severity, post-acute symptoms and peak VO 2 after recovery. Methods: This study analyzed data from patients who recovered from COVID-19 and underwent cardiopulmonary exercise testing (CPET) as part of prospective studies in 5 centers across UK and Europe. Patients were asked to report current symptoms. Peak VO 2 , lung volumes, gas exchange, ventilatory efficiency, heart rate and O 2 pulse were measured in a standard symptom-limited incremental cycle ergometer CPET. Results: Among 417 patients examined 136±63 days after recovery from COVID-19, 164 (39%) were female. Mean age was 56.9±13.3 years. The spectrum of acute COVID-19 severity included critical (N=47; 11.3%), severe (180; 43.2%), moderate (75; 18.0%) and mild (115; 27.5%) illness. The most common post-acute symptom was dyspnea (200; 48%), followed by muscle pain (173; 41%). Mean peak respiratory exchange ratio was 1.13±0.1, and did not vary across acute disease severity or post-acute symptom status. There was no significant difference in peak VO 2 as % from predicted in mild to critical acute disease: 84.0±2.1%, 91.4±2.6%, 82.9±1.7% and 83.7±3.2%, respectively (p=0.06). Patients with dyspnea or muscle pain had each lower peak VO 2 as % from predicted, compared to patients free of the specific symptom (81.3±21.2% vs. 88.1±22.9%, p=0.002 and 78.6±19.1% vs. 88.2±22.0%, p&lt;0.0001, respectively). Both dyspnea and muscle pain were each associated with significantly lower peak heart rate and peak O 2 pulse, as well as lower lung volumes and gas exchange capacity, compared to patients free of the specific symptom. Conclusions: Common post-acute COVID-19 symptoms, and not acute disease severity, are associated with lower peak VO2 in CPET. Parameters related to both cardiac and pulmonary function seem to play a role in this reduced physical performance.

Prognostic value of cardiopulmonary exercise testing in a European cohort with cardiovascular risk factors absent of a cardiovascular disease diagnosis

IntroductionCardiorespiratory fitness (CRF) is now considered a vital sign. Cardiopulmonary exercise testing (CPET) is the gold-standard assessment of CRF; peak oxygen consumption (VO2) and the minute ventilation/carbon dioxide production (VE/VCO2) slope are considered primary CPET measures of CRF. More work is needed to determine the role of this exercise assessment in the primary care setting. Methods695 subjects (mean age: 62 ± 13 years, body mass index: 28.9 ± 5.3 kg/m2, 375 female and 320 male) underwent CPET using a cycle ergometer. 95% of the cohort had one or more major cardiovascular risk factor (i.e., obesity, smoking, dyslipidemia, hypertension, diabetes); no subject was diagnosed with cardiovascular disease (CVD) at the time of CPET. Subjects were tracked for the composite endpoint of cardiovascular mortality or hospital admission. ResultsMean peak VO2, VE/VCO2 slope and peak respiratory exchange ratio were 17.8 ± 5.8 mlO2•kg−1•min−1, 26.7 ± 4.1, and 1.18 ± 0.13, respectively. There were 42 composite events during the 64 ± 18 month tracking period. Both peak VO2 (Chi-square 16.3, p < 0.001) and the VE/VCO2 slope (Chi-square 14.9, p < 0.001) were significant univariate predictors of the composite endpoint. The VE/VCO2 slope added significant predictive value to peak VO2 and was retained in the multivariate regression (residual Chi-square 7.0, p = 0.008). DiscussionThese results support the prognostic value of CPET prior to a CVD diagnosis. The prognostic value of the VE/VCO2 slope, not commonly the focus of CPET trials in patients with one or more major cardiovascular risk factors but without a confirmed CVD diagnosis, is a particularly novel finding in the current study.

Cardiopulmonary Exercise Testing Characterizes Silent Cardiovascular Abnormalities in Asymptomatic Pediatric Cancer Survivors.

Late-onset cardiovascular complications are serious concerns for pediatric cancer survivors (PCS) including those who are asymptomatic. We investigated whether cardiopulmonary exercise testing (CPET) can delineate the underlying pathophysiology of preclinical cardiovascular abnormalities in PCS. We examined CPET data via cycle ergometer in asymptomatic PCS with normal echocardiogram and age-matched controls. Peak and submaximal parameters were analyzed. Fifty-three PCS and 60 controls were studied. Peak oxygen consumption (VO2), peak work rate (WR), and ventilatory anaerobic threshold (VAT) were significantly lower in PCS than controls (1.86 ± 0.53 vs. 2.23 ± 0.61 L/min, 125 ± 45 vs. 154 ± 46W, and 1.20 ± 0.35 vs. 1.42 ± 0.43 L/min, respectively; all p < 0.01), whereas peak heart rate (HR) and ventilatory efficiency (a slope of minute ventilation over CO2 production or ∆VE/∆VCO2) were comparable. Peak respiratory exchange ratio (RER) was significantly higher in PCS (p = 0.0006). Stroke volume (SV) reserve was decreased in PCS, indicated by simultaneous higher dependency on HR (higher ∆HR/∆WR) and lower peak oxygen pulse (OP). Twelve PCS with high peak RER (≥ 1.3) revealed lower pVO2 and VAT than the rest of PCS despite higher ventilatory efficiency (lower ∆VE/∆VCO2), suggesting fundamental deficiency in oxygen utilization in some PCS. Poor exercise performance in PCS may be mainly attributed to limited stroke volume reserve, but the underlying pathophysiology is multifactorial. Combined assessment of peak and submaximal CPET parameters provided critical information in delineating underlying exercise physiology of PCS.

Physiological Response to the 6-Minute Frame Running Test in Children and Adults With Cerebral Palsy.

To determine the physiological response and association to peak oxygen uptake of the 6-minute Frame Running test (6-MFRT) in persons with cerebral palsy (CP). Twenty-four participants with CP, Gross Motor Function Classification System II/III/IV, performed the 6-MFRT. Distance, peak heart rate (HR peak ), peak respiratory exchange ratio (RER peak ), and peak oxygen uptake ( O 2peak ) were measured. HR peak ranged from 146 to 201 beats per minute, RER peak from 0.94 to 1.49, 6-MFRT distance from 179 to 1220 m and O 2peak from 0.62 to 2.18 L/min. HR peak was achieved in 63%, RER peak in 71%. A strong correlation was observed between 6-MFRT and O 2peak . The 6-MFRT represented a (near) maximum effort for 75% of the participants and the 6-MFRT can be used to estimate oxygen consumption on an individual basis.

Revisiting a Prognosticating Algorithm from Cardiopulmonary Exercise Testing in Chronic Heart Failure (from the MECKI Score Population)

Cardiopulmonary exercise testing is a prognostic tool in heart failure with reduced left ventricular ejection fraction (HFrEF). Prognosticating algorithms have been proposed, but none has been validated. In 2017, a predictive algorithm, based on peak oxygen consumption (VO2), ventilatory response to exercise (ventilation [VE] carbon dioxide production [VCO2], the VE/VCO2 slope), exertional oscillatory ventilation (EOV), and peak respiratory exchange ratio, was recommended, according treatment with β blockers: patients with HFrEF registered in the metabolic exercise test data combined with cardiac and kidney indexes (MECKIs) database were used to validated this algorithm. According to the inclusion/exclusion criteria, 4,683 MECKI patients with HFrEF were enrolled. At 3years follow-up, the end point was cardiovascular death and urgent heart transplantation (cardiovascular events [CV]). CV events occurred in 25% in patients without β blockers, whereas those with β-blockers had 11% (p <0.0001). In patients without β blockers, 36%, 24%, and 7% CV events were observed in those with peak VO2 ≤10, with peak VO2 >10 <18, and with peak VO2 ≥18ml/kg/min (p=0.0001), respectively; in MECKI patients with peak VO2 ≤10 and patients with intermediate exercise capacity, a peak respiratory exchange ratio (≥1.15) and VE/VCO2 slope (≥35) were diriment, respectively (p=0.0001). EOV, when occurred, increased risk. In MECKI patients on β blockers, 29%, 17%, and 8% CV events were noticed in those with a peak VO2 ≤8, with peak VO2=8 to 12, and patients with peak VO2 ≥12ml/kg/min, respectively (p=0.0000); when EOV was monitored an increment of risk was witnessed. In conclusion, the outcome of this algorithm was confirmed with the MECKI cohort.

Evaluation of maximal exercise capacity through the incremental shuttle walking test in lymphangioleiomyomatosis

BackgroundThe cardiopulmonary exercise test (CPET) is the gold standard for assessing aerobic fitness; however, it is expensive, not widely available, and requires specialized equipment and staff. The incremental shuttle walking test (ISWT) is an exercise field test used to evaluate exercise capacity and may be an alternative to CPET in patients with lymphangioleiomyomatosis (LAM). ObjectiveTo investigate whether the ISWT can be used to assess maximal aerobic capacity in patients with LAM. MethodsForty-five women were evaluated on two days, and they randomly performed the CPET and ISWT. The maximum oxygen uptake (peak VO2) was evaluated using gas analyzers in both tests. The carbon dioxide production (VCO2), respiratory exchange ratio (RER), and heart rate (HR) were compared during peak exercise. Pearson's correlation and Bland-Altman assessed the association and agreement, respectively. The intraclass correlation coefficient (ICC) was used to assess the reliability of the data. ResultsAll patients (46.1 ± 10.2 years) presented similar peak VO2, RER, and peak HR during the CPET and ISWT (15.6 ± 4.6 vs. 15.7 ± 4.4 ml·kg−1·min−1; 1.15±0.09 vs. 1.17±0.12; and 142.2 ± 18.6 vs. 141.5 ± 22.2 bpm, respectively; p>0.05). A good linear correlation (r = 0.79; p<0.001) and ICC (0.86; 95%CI 0.74−0.93) were observed between the peak VO2 in both tests. Predictive peak VO2 equations based on the ISWT performance are also presented. ConclusionOur results suggest that the ISWT can be used to assess maximal exercise performance in patients with LAM, and it is a valuable option to be used as an alternative to the CPET and predict maximal exercise capacity.

Age-Related Differences for Cardiorespiratory Fitness Improvement in Patients Undergoing Cardiac Rehabilitation.

ObjectiveWe investigated age-related differences for peak oxygen uptake (peak VO2) improvement with exercise training during cardiac rehabilitation (CR).Patients and MethodsThis was a retrospective cohort study of the Mayo Clinic Rochester CR program including adult patients who attended CR (≥1 session) for any eligible indication between 1999 and 2017 and who had a cardiopulmonary exercise test pre and post CR with VO2 data (peak respiratory exchange ratio ≥1.0). Younger (20–49 yrs), midlife (50–64 yrs), and older adults (≥65 yrs) were compared using ANOVA for delta and percent change in peak VO2; and percentage of peak VO2 responders (>0% change).Results708 patients (age: 60.8 ± 12.1 years; 24% female) met inclusion criteria. Delta and percent change in peak VO2 was lower for older adults (1.6 ± 3.2 mL.kg.min−1; 12 ± 27%) compared with younger (3.7 ± 4.0 mL.kg.min−1, p < 0.001; 23 ± 28%, p = 0.002) and midlife adults (2.8 ± 3.8 mL.kg.min−1, p < 0.001; 17 ± 28%, p = 0.04). For midlife, delta change, but not percent change in peak VO2 was significantly lower (p = 0.02) compared with younger. Percentage of responders was only different between older and younger (72 vs. 86%; p = 0.008). Sensitivity analyses in non-surgical patients showed similar differences for delta change, and differences in percent change remained significant between older and younger adults (10 ± 20% vs. 16 ± 18%; p = 0.04).ConclusionsIn CR patients, older adults had lower improvement in cardiorespiratory fitness than younger and midlife adults. While excluding surgical patients reduced age-related differences, older adults still had lower cardiorespiratory fitness improvement during CR. These findings may have implications for individualizing CR programming in aging populations to reduce future cardiovascular risk.

Overshoot of the Respiratory Exchange Ratio during Recovery from Maximal Exercise Testing in Kidney Transplant Recipients.

The overshoot of the respiratory exchange ratio (RER) during recovery from exercise has been found to be reduced in magnitude among patients with heart failure. The aim of this study is to investigate whether this phenomenon could also be present in patients with peripheral, and not cardiac, limitations to exercise such as kidney transplant recipients (KTRs). In this retrospective cross-sectional study, KTRs were evaluated with maximal cardiopulmonary exercise testing (CPET) assessing the RER overshoot parameters during recovery: the RER at peak exercise, the maximum RER value reached during recovery, the magnitude of the RER overshoot (RER mag = (RER max-peak RER)/peak RER%) and the linear slope of the RER increase after the end of exercise. A total of 57 KTRs were included in the study (16 females), all of them showing a significant RER overshoot (RER mag: 28.4 ± 12.7%). Moreover, the RER mag showed significant correlations with the fitness of patients (peak VO2: ρ = 0.57, p < 0.01) and cardiorespiratory efficiency (VE/VCO2 slope: r = −0.32, p < 0.05; oxygen uptake efficiency slope (OUES): r = 0.48, p < 0.01). Indeed, the RER mag was significantly different between the subgroups stratified by Weber’s fitness class or a ventilatory efficiency class. Our study is the first to investigate recovery of the RER in a population of KTRs, which correlates well with known prognostic CPET markers of cardiorespiratory fitness, determining the RER mag as the most meaningful RER overshoot parameter. Thus, the RER recovery might be included in CPET evaluations to further improve prognostic risk stratifications in KTRs and other chronic diseases.