Ventilatory Anaerobic Threshold Research Articles

Health-related quality of life in children and adolescents with Marfan syndrome or related disorders: a controlled cross-sectional study

BackgroundThis cross-sectional controlled study aims to assess health-related quality of life (HRQoL) of children and adolescents with a molecular diagnosis of Marfan syndrome (MFS) or related disorders and to evaluate the factors associated with HRQoL in this population. Sixty-three children with MFS and 124 age- and sex-matched healthy children were recruited. HRQoL was assessed using the Pediatric Quality of Life Inventory (PedsQL™) generic questionnaire. The correlation between HRQoL scores and the different continuous parameters (age, body mass index, disease severity, systemic score, aortic sinus diameter, and aerobic physical capacity) was evaluated using Pearson’s or Spearman’s coefficient. A multiple linear regression analysis was performed on the two health summary self-reported PedsQL™ scores (physical and psychosocial) to identify the factors associated with HRQoL in the MFS group.ResultsExcept for emotional functioning, all other domains of HRQoL (psychosocial and physical health, social and school functions) were significantly lower in children with MFS compared to matched healthy children. In the MFS group, the physical health summary score was significantly lower in female than in male patients (self-report: absolute difference [95%CI] = -8.7 [-17.0; -0.47], P = 0.04; proxy-report: absolute difference [95%CI] = -8.6 [-17.3; 0.02], P = 0.05) and also negatively correlated with the systemic score (self-report: R = -0.24, P = 0.06; proxy-report: R = -0.29, P = 0.03) and with the height Z-score (proxy-report: R = -0.29, P = 0.03). There was no significant difference in the physical health summary scores between the different genetic subgroups. In the subgroup of 27 patients who performed a cardiopulmonary exercise test, self- and proxy-reported physical health summary scores were highly correlated with their aerobic physical capacity assessed by peak oxygen consumption (VO2max) and ventilatory anaerobic threshold (VAT). In the multivariate analysis, the most important independent predictors of decreased physical health were increased height, decreased body mass index, decreased VAT and use of prophylactic therapy.ConclusionsThis study reports an impaired HRQoL in children and adolescents with MFS or related conditions, in comparison with matched healthy children. Educational and rehabilitation programs must be developed and evaluated to improve exercise capacity and HRQoL in these patients.Trial registrationClinicalTrials.gov, NCT03236571. Registered 28 July 2017.

Borg's exertion scale did not coincide with ventilatory anaerobic threshold in atrial fibrillation patients with restored sinus rhythm after ablation.

The determination of precise exercise intensity is essential for effective exercise rehabilitation. The Borg rating of perceived exertion category ratio (CR) scale is utilized to prescribe an appropriate level of exertion intensity. A Borg CR of approximately 13 coincides with the ventilatory aerobic threshold (VAT). Patients with atrial fibrillation (AF) exhibit various symptoms. We hypothesized that the workload at Borg CR13 (Borg CR13-Watt) differs from the workload at the VAT level (VAT-Watt) in AF patients with restored sinus rhythm (SR) following ablation. Accordingly, the relationship between Borg CR13-Watt and VAT-Watt was studied in patients with restored SR. Cardiopulmonary exercise testing (CPET) was performed at 101±88 days after ablation in 150 patients using a bicycle ergometer. No adverse events were observed during CPET. Borg CR13-Watt was significantly higher than VAT-Watt (67.2±27.8 Watt vs. 54.7±17.6 Watt, P<0.0001). Borg CR13-Watt showed significant linear regression with VAT-Watt (regression coefficient, 0.49, P<0.01; correlation coefficient, 0.80, P<0.01). Higher Borg CR13-Watt was associated with greater differences between Borg CR13-Watt and VAT-Watt (ΔWatt). The Bland-Altman plot showed nonconcordance between the two. Male sex, use of antiarrhythmic drugs, and smoking had contributed to the increased ΔWatt. Duration from ablation to time of CPET did not correlate with ΔWatt. Therefore, Borg CR13-Watt did not coincide with VAT-Watt in patients with restored SR. Higher Borg CR13-Watt was associated with greater ΔWatt. Prescribing exertion intensity as determined solely by perceived exertion is inadequate. CPET is required to determine the precise exercise intensity in AF patients with restored SR after ablation.

Partial Pressure of End-Tidal Oxygen and Blood Lactate During Cardiopulmonary Exercise Testing in Healthy Older Participants and Patients at Risk of Cardiac Disease.

The partial pressure of end-tidal oxygen (PETO2) and end-tidal oxygen concentration (ETO2) are among the indices that can be measured by exhaled gas analysis. Several observational studies have shown that skeletal muscle function is impaired in patients with cardiac disease; thus, the assessment of skeletal muscle function is important. Additionally, although it has recently been suggested that the difference in PETO2 from rest to the ventilatory anaerobic threshold (VAT) reflects oxygen availability in peripheral factors, primarily skeletal muscle, the evidence for this is not well established. Therefore, we hypothesized and investigated whether increased blood lactate (BLa) levels, resulting from decreased skeletal muscle and mitochondrial oxygen availability, and PETO2 dynamics during cardiopulmonary exercise testing (CPET) would be related. All participants performed the symptomatic limited CPET, and their BLa levels were measured. The difference in PETO2 and ETO2 from rest to VAT determined by the V-slope method (ΔPETO2 and ΔETO2) was calculated and compared with the increase in BLa due to exercise testing. We recruited 22 healthy older participants (nine males; 69.4 ± 6.8 years) and 11 patients with cardiovascular risk (eight males; 73.0 ± 8.8 years). ΔPETO2 and ΔETO2 did not differ between the two groups (P = 0.355 and P = 0.369, respectively), showing no correlation between increase in BLa from rest to VAT, but were significantly correlated with an increase in BLa from rest to the end of exercise (ΔPETO2, P = 0.030; ΔETO2, P = 0.029). The correlation was particularly pronounced among those at cardiovascular risk (ΔPETO2, P = 0.012; ΔETO2, P = 0.011). ΔPETO2 and ΔETO2 from rest to VAT during CPET may be useful as indices reflecting skeletal muscle oxygen utilization capacity.

Preoperative aerobic fitness and perioperative outcomes in patients undergoing cystectomy before and after implementation of a national lockdown

BackgroundLower fitness is a predictor of adverse outcomes after radical cystectomy. Lockdown measures during the COVID-19 pandemic affected daily physical activity. We hypothesised that lockdown during the pandemic was associated with a reduction in preoperative aerobic fitness and an increase in postoperative complications in patients undergoing radical cystectomy. MethodsWe reviewed routine preoperative cardiopulmonary exercise testing (CPET) data collected prior to the pandemic (September 2018 to March 2020) and after lockdown (March 2020 to July 2021) in patients undergoing radical cystectomy. Differences in CPET variables, Postoperative Morbidity Survey (POMS) data, and length of hospital stay were compared. ResultsWe identified 267 patients (85 pre-lockdown and 83 during lockdown) who underwent CPET and radical cystectomy. Patients undergoing radical cystectomy throughout lockdown had lower ventilatory anaerobic threshold (9.0 [7.9–10.9] vs 10.3 [9.1–12.3] ml kg−1 min−1; P=0.0002), peak oxygen uptake (15.5 [12.9–19.1] vs 17.5 [14.4–21.0] ml kg−1 min−1; P=0.015), and higher ventilatory equivalents for carbon dioxide (34.7 [31.4–38.5] vs 33.4 [30.5–36.5]; P=0.030) compared with pre-lockdown. Changes were more pronounced in males and those aged >65 yr. Patients undergoing radical cystectomy throughout lockdown had a higher proportion of day 5 POMS-defined morbidity (89% vs 75%, odds ratio [OR] 2.698, 95% confidence interval [CI] 1.143–6.653; P=0.019), specifically related to pulmonary complications (30% vs 13%, OR 2.900, 95% CI 1.368–6.194; P=0.007) and pain (27% vs 9%, OR 3.471, 95% CI 1.427–7.960; P=0.004), compared with pre-lockdown on univariate analysis. ConclusionsLockdown measures in response to the COVID-19 pandemic were associated with a reduction in fitness and an increase in postoperative morbidity among patients undergoing radical cystectomy.

The oxygen uptake efficiency slope in adults with CHD: group validity.

The maximal oxygen uptake (V02 max) is a well-validated measure of cardiorespiratory function that is calculated during a maximal cardiopulmonary exercise test. V02 max enables physicians to objectively assess cardiopulmonary function to aid in decision-making for patients with CHD. A significant proportion of these patients however are unable to achieve a maximal exercise test, and as such, there is a need for reliable submaximal predictors of cardiorespiratory reserve.The oxygen uptake efficiency slope represents a measure of how effectively oxygen is extracted from the lungs and taken into the body and can be calculated from a submaximal exercise test. Its reliability as a predictor of cardiorespiratory reserve has been validated in various patient populations, but there is limited evidence for its validity in adult patients with CHD.Retrospective analysis of cardiopulmonary exercise test data in 238 consecutive patients with CHD who completed a maximal cardiopulmonary exercise test at our tertiary cardiology centre demonstrated a strong correlation between peak V02 and the oxygen uptake efficiency slope (0.936). A strong correlation with peak V02 was also demonstrated when oxygen uptake efficiency slope was calculated at ventilatory anaerobic threshold (OUESVAT), 75% (OUES75), and 90% (OUES90) of the test (0.833, 0.905, 0.927 respectively).In adult patients with CHD who are unable to complete a maximal cardiopulmonary exercise test, the oxygen uptake efficiency slope is a reliable indicator of cardiopulmonary fitness which correlates strongly with peak V02 at or beyond the ventilatory anaerobic threshold. Further research is required to validate the findings in patients with less common anatomies and to assess the relationship between the oxygen uptake efficiency slope and mortality.

‘Effects of a home-based bimodal lifestyle intervention in frail patients with end-stage liver disease awaiting orthotopic liver transplantation’: study protocol of a non-randomised clinical trial

IntroductionPatients with end-stage liver disease awaiting orthotopic liver transplantation (OLT) are generally classified as frail due to disease-related malnutrition and a progressive decline in musculoskeletal and aerobic fitness, which is...

Cardiac and intramuscular adaptations following short-term exercise prehabilitation in unfit patients scheduled to undergo hepatic or pancreatic surgery: study protocol of a multinuclear MRI study

IntroductionShort-term exercise prehabilitation programmes have demonstrated promising results in improving aerobic capacity of unfit patients prior to major abdominal surgery. However, little is known about the cardiac and skeletal muscle...

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.

Effect of High-Intensity Interval Training and Moderate-Intensity Continuous Training in People With Poststroke Gait Dysfunction: ARandomized Clinical Trial.

Background The exercise strategy that yields the greatest improvement in both cardiorespiratory fitness () and walking capacity poststroke has not been determined. This study aimed to determine whether conventional moderate-intensity continuous training (MICT) or high-intensity interval training (HIIT) have different effects on and 6-minute walk distance (6MWD). Methods and Results In this 24-week superiority trial, people with poststroke gait dysfunction were randomized to MICT (5 days/week) or HIIT (3 days/week with 2 days/week of MICT). MICT trained to target intensity at the ventilatory anaerobic threshold. HIIT trained at the maximal tolerable treadmill speed/grade using a novel program of 2 work-to-recovery protocols: 30:60 and 120:180 seconds. V̇O2 and heart rate was measured during performance of the exercise that was prescribed at 8 and 24 weeks for treatment fidelity. Main outcomes were change in and 6MWD. Assessors were blinded to the treatment group for but not 6MWD. Secondary outcomes were change in ventilatory anaerobic threshold, cognition, gait-economy, 10-meter gait-velocity, balance, stair-climb performance, strength, and quality-of-life. Among 47 participants randomized to either MICT (n=23) or HIIT (n=24) (mean age, 62±11 years; 81% men), 96% completed training. In intention-to-treat analysis, change in for MICT versus HIIT was 2.4±2.7 versus 5.7±3.1 mL·kg-1·min-1 (mean difference, 3.2 [95% CI, 1.5-4.8]; P<0.001), and change in 6MWD was 70.9±44.3 versus 83.4±53.6 m (mean difference, 12.5 [95% CI, -17 to 42]; P=0.401). HIIT had greater improvement in ventilatory anaerobic threshold (mean difference, 2.07 mL·kg-1·min-1 [95% CI, 0.59-3.6]; P=0.008). No other between-group differences were observed. During V̇O2 monitoring at 8 and 24 weeks, MICT reached 84±14% to 87±18% of while HIIT reached 101±22% to 112±14% of (during peak bouts). Conclusions HIIT resulted in more than a 2-fold greater and clinically important change in than MICT. Training to target (ventilatory anaerobic threshold) during MICT resulted in ~3 times the minimal clinically important difference in 6MWD, which was similar to HIIT. These findings show proof of concept that HIIT yields greater improvements in cardiorespiratory fitness than conventional MICT in appropriately screened individuals. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03006731.

Abstract 12288: Sex Differences in Cardiac Adaptation to Obesity During Adolescence: A Role of Cardiopulmonary Exercise Testing

Introduction: Heart size is known to increase in obese individuals as a physiological adaptation. Cardiac hypertrophy is also regarded as a risk factor for future adult cardiovascular disease. Sex differences of cardiac adaptation to obesity during adolescence are poorly understood. Hypothesis: Physiological cardiac responses to obesity are different between male and female adolescents. Methods: Anthropometric measurements, left ventricular mass index (LVMI; g/m 2.7 ), and cardiopulmonary exercise testing parameters were analyzed. Peak oxygen consumption (VO2), ventilatory anaerobic threshold (VAT), and submaximal sloop parameters including ΔVO2/Δheart rate (HR) and ΔHR/Δwork rate (WR) were obtained. Data are shown as mean ± standard deviation. * denotes weight-indexed value. Results: Table 1 showed enrolled obese adolescents (19 males and 40 females). ΔVO2/ΔHR and ΔHR/ΔWR are surrogates of stroke volume and HR-dependency, respectively. Males showed significantly higher pVO2, pVO2*, VAT*, ΔVO2/ΔHR, and ΔVO2*/ΔHR but lower ΔHR/ΔWR and ΔHR/ΔWR* than females, suggesting males had higher peak exercise performance, higher stroke volume, and lower HR-dependency than females. Significant correlation was noted between LVMI and VAT* only in males (p = 0.045) and between LVMI and body mass index (BMI) only in females (p = 0.006), suggesting cardiac hypertrophy may not effectively contribute to exercise performance in females (Figure 1). Cardiac hypertrophy assessed by LVMI presented different physiological significance between obese males and females. Conclusions: Cardiac adaptation to obesity occurs differently between males and females during adolescence.

Impaired cardiorespiratory fitness and endothelial function after SARS-CoV-2 infection in a sample of mainly immunocompromised youth.

This study aimed to compare cardiopulmonary fitness and endothelial function 6 months after hospital diagnosis in a sample mainly comprising immunocompromised patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection versus noninfected controls. Youth (n = 30; age: 14 yr; 60% females) with confirmed SARS-CoV-2 seen in a tertiary hospital of Sao Paulo, Brazil, were matched by propensity score based on BMI, age, sex, and pre-existing diseases with a control group who had not been tested positive for SARS-CoV-2 infection (n = 30; age: 15 yr; 50% females). Cardiopulmonary fitness (by means of a cardiopulmonary exercise test: CPET) and brachial flow-mediated dilation (%b-FMD) were assessed 3-6 mo after diagnosis. Patients were matched by propensity score based on BMI, age, sex and pre-existing diseases, if any, with a control group who had not been tested positive for SARS-CoV-2. Compared with controls, patients with COVID-19 showed reduced ventilatory anaerobic threshold (VAT) and peak exercise time and minute ventilation/maximum voluntary ventilation (V̇e/MVV) (all P < 0.01). Brachial endothelial function variables were all adjusted for body surface area (BSA). Patients with COVID-19 had decreased %b-FMD (3.6 vs. 5.4; P = 0.03) mean and positive flow (P = 0.02 and P = 0.03, respectively) versus controls. Adjusted linear regression models exploring associations between CPET variables, %b-FMD and the potential predictors post-COVID-19 syndrome, number of symptoms, hospitalization, and COVID severity did not detect significant associations, except for total shear rate in hospitalization (coefficient: -65.07 [95%CI -119.5;-10.5], P = 0.02). Immunocompromised and previously healthy children and adolescents with COVID-19 presented with impaired exercise capacity and endothelial dysfunction when compared with their noninfected counterparts, but the mechanisms remain unknown.NEW & NOTEWORTHY COVID-19 appeared to impair recovery of exercise capacity and endothelial function in a sample mainly comprising immunocompromised patients, but the mechanisms are unknown. These findings support the need for preventive measures against COVID-19 in this vulnerable population and suggest the necessity of proper monitoring and treatment for these patients.

The Effect of Udenafil on Heart Rate and Blood Pressure in Adolescents With the Fontan Circulation

The Fontan Udenafil Exercise Longitudinal (FUEL) trial showed that treatment with udenafil was associated with improved exercise performance at the ventilatory anaerobic threshold in children with Fontan physiology. However, it is not known how the initiation of phosphodiesterase 5 inhibitor therapy affects heart rate and blood pressure in this population. These data may help inform patient selection and monitoring after the initiation of udenafil therapy. The purpose of this study is to evaluate the effects of udenafil on vital signs in the cohort of patients enrolled in the FUEL trial. This international, multicenter, randomized, double-blind, placebo-controlled trial of udenafil included adolescents with single ventricle congenital heart disease who had undergone Fontan palliation. Changes in vital signs (heart rate [HR], systolic [SBP] and diastolic blood pressure [DBP]) were compared both to subject baseline and between the treatment and the placebo groups. Additional exploratory analyses were performed to evaluate changes in vital signs for prespecified subpopulations believed to be most sensitive to udenafil initiation. Baseline characteristics were similar between the treatment and placebo cohorts (n=200 for each). The groups demonstrated a decrease in HR, SBP, and DBP 2 hours after drug/placebo administration, except SBP in the placebo group. There was an increase in SBP from baseline to after 6-min walk test in the treatment and placebo groups, and the treatment group showed an increase in HR (87.4 ± 15.0 to 93.1 ± 19.4 beats/min, p <0.01) after exercise. When comparing changes from baseline to the 26-week study visit, small decreases in both SBP (-1.9 ± 12.3 mm Hg, p=0.03) and DBP (-3.0 ± 9.6 mm Hg, p <0.01) were seen in the treatment group. There were no clinically significant differences between treatment and placebo group in change in HR or blood pressure in the youngest age quartile, lightest weight quartile, or those on afterload-reducing agents. In conclusion, initiation of treatment with udenafil in patients with Fontan circulation was not associated with clinically significant changes in vital signs, implying that for patients similar to those enrolled in the FUEL trial, udenafil can be started without the requirement for additional monitoring after initial administration.

Remote ischaemic conditioning for fatigue after stroke (RICFAST): A pilot randomised controlled trial

BackgroundPost stroke fatigue (PSF) affects 50 % of stroke survivors, and can be disabling. Remote ischaemic conditioning (RIC), can preserve mitochondrial function, improve tissue perfusion and may mitigate PSF. This pilot randomised controlled trial evaluates the safety and feasibility of using RIC for PSF and evaluated measures of cellular bioenergetics. Methods24 people with debilitating PSF (7 item Fatigue Severity Score, FSS-7 > 4) were randomised (1:1) in this single-centre phase 2 study to RIC (blood pressure cuff inflation around the upper arm 200 mmHg for 5 min followed by 5 min of deflation), or sham (inflation pressure 20 mmHg), repeated 4 cycles, 3 times per week for 6 weeks. Primary outcomes were safety, acceptability, and compliance. Secondary outcomes included FSS-7, 6 min walking test (6MWT), peak oxygen consumption (V̇O2peak), ventilatory anaerobic threshold (VAT), and muscle adenosine triphosphate (ATP) content measured using 31-phosphorous magnetic resonance spectroscopy of tibialis anterior. ResultsRIC was safe (no serious adverse events, adverse events mild) and adherence excellent (91 % sessions completed). Exploratory analysis revealed lower FSS-7 scores in the RIC group compared to sham at 6 weeks (between group difference FSS-7 -0.7, 95 %CI -2.0 to 0.6), 3 months (-1.0, 95 %CI -2.2 to 0.2) and 6 months (-0.9, 95 %CI -2.0 to 0.2). There were trends towards increased VAT, increased muscle ATP content and improved 6MWT in the RIC group. DiscussionRIC is safe and acceptable for people with PSF and may result in clinically meaningful improvements in fatigue and muscle bioenergetics that require further investigation in larger studies.

FRI607 SGLT2 Inhibition Improves Muscle Oxidative Capacity And Its Relationship With Cardiac Performance In Patients With T2D And Heart Failure

Abstract Disclosure: Y. Qin: None. N.D. Sanchez: None. A.J. Moody: None. F.M. Acosta: None. S. Neppala: None. M. Brown: None. H. Honka: None. B. Todd: None. L.A. Cruz Moreno: None. A.R. Stepanenko: None. S.E. Espinoza: None. N. Musi: None. C. Triplitt: None. G. Clarke: None. E. Cersosimo: None. R.A. DeFronzo: None. C. Solis-Herrera: None. Cardioprotective benefits of SGLT2 inhibitors (SGLT2i) have been largely thought to be coupled to a physiologic increase in plasma ketones, with much interest in the role of adaptive changes in cardiac fuel source in subjects with T2D and HF. Given the changes in the global dynamics of bioenergetics with SGLT2i, and the proven pleiotropic effects of ketone bodies, suggest that, in addition to their cardioprotective function, SGLT2i may influence other organ systems. In particular, how skeletal muscle (SkM), or cardiopulmonary function, respond to these global bioenergetics changes remains largely unknown. A pilot randomized-controlled clinical study was designed to examine the effects of SGLT2i on SkM bioenergetics (31P MRS), &amp; cardiopulmonary function (CPET), and its association with left ventricular cardiac function (MRI). Six subjects (Age=59±2.6, BMI=33.3±1.1, A1c=7.1±0.3) with T2D and HF (&amp;lt;50%) were randomized empagliflozin 25mg/day (SGLT2i) vs. placebo (control) in a 2:1 fashion for 12 weeks. Imaging and clinical evaluations were performed pre- and post-intervention. The SGLT2i group improved EF (28.7 vs. 38.8, p=0.1). SkM 31P MRS at rest, measuring the relative intracellular concentrations of high-energy metabolites of phospholipid breakdown, reduced with SGLT2i, suggesting better energy utilization by the SkM. 31P MRS-after exercise, showed significant improvements in SkM oxidative capacity (KPCR*[PCr], 0.6 to 0.8, p=0.03), with SGLT2i.During CPET testing, the ventilatory anaerobic threshold (VT), with SGLT2i, showed a significant (p=0.05) increase in VT time, suggesting an increase in the time in aerobiosis in these subjects. The minute ventilation-to-carbon dioxide output slope (a strong predictor of cardiopulmonary complications/death) was improved in the SGLT2i group vs. placebo, which could be associated with the CV benefit observed with these agents. Additionally, patient self-reported outcomes (Promis) showed a trend of improvement in the SGLT2i group. In summary, we demonstrate novel and exciting preliminary findings that in patients with T2D &amp; HF, SGLT2i-associated benefits are not isolated to the heart and may also expand to the SkM, including improved oxidative capacity, energy utilization, and SkM recovery post-exercise. With improvements in HF prognostic markers and patient self-reported outcomes. These original findings may represent novel mechanisms contributing to the cardiac benefits of SGLT2i. Presentation: Friday, June 16, 2023

Supervised Home-Based Exercise Prehabilitation in Unfit Patients Scheduled for Pancreatic Surgery: Protocol for a Multicenter Feasibility Study.

Morbidity rates in pancreatic surgery are high, and frail patients with low aerobic capacity are especially at risk of complications and require prophylactic interventions. Previous studies of small patient cohorts receiving intra-abdominal surgery have shown that an exercise prehabilitation program increases aerobic capacity, leading to better treatment outcomes. In this study, we aim to assess the feasibility of a home-based exercise prehabilitation program in unfit patients scheduled for pancreatic surgery on a larger scale. In this multicenter study, adult patients scheduled for elective pancreatic surgery with a preoperative oxygen uptake (VO2) at the ventilatory anaerobic threshold ≤13 mL/kg/min or a VO2 at peak exercise ≤18 mL/kg/min will be recruited. A total of 30 patients will be included in the 4-week, home-based, partly supervised exercise prehabilitation program. The program comprises 25-minute high-intensity interval training on an advanced cycle ergometer 3 times a week. Training intensity will be based on steep ramp test performance (ie, a short-term maximal exercise test on a cycle ergometer), aiming to improve aerobic capacity. Twice a week, patients will perform functional task exercises to improve muscle function and functional mobility. A steep ramp test will be repeated weekly, and training intensity will be adjusted accordingly. Next to assessing the feasibility (participation rate, reasons for nonparticipation, adherence, dropout rate, reasons for dropout, adverse events, and patient and therapist appreciation) of this program, individual patients' responses to prehabilitation on aerobic capacity, functional mobility, body composition, quality of life, and immune system factors will be evaluated. Recruitment for this study began in January 2022 and is expected to be completed in the summer of 2023. Results of this study will provide important clinical and scientific knowledge on the feasibility of a partly supervised home-based exercise prehabilitation program in a vulnerable patient population. This might ease the path to implementing prehabilitation programs in unfit patients undergoing complex abdominal surgery, such as pancreatic surgery. ClinicalTrials.gov NCT05496777; https://classic.clinicaltrials.gov/ct2/show/NCT05496777. DERR1-10.2196/46526.

Reference Values of Cardiopulmonary Exercise Test Parameters in the Contemporary Paediatric Population

BackgroundThe evaluation of health status by cardiopulmonary exercise test (CPET) has shown increasing interest in the paediatric population. Our group recently established reference Z-score values for paediatric cycle ergometer VO2max, applicable to normal and extreme weights, from a cohort of 1141 healthy children. There are currently no validated reference values for the other CPET parameters in the paediatric population. This study aimed to establish, from the same cohort, reference Z-score values for the main paediatric cycle ergometer CPET parameters, apart from VO2max.ResultsIn this cross-sectional study, 909 healthy children aged 5–18 years old underwent a CPET. Linear, quadratic, and polynomial mathematical regression equations were applied to identify the best CPET parameters Z-scores, according to anthropometric parameters (sex, age, height, weight, and BMI). This study provided Z-scores for maximal CPET parameters (heart rate, respiratory exchange ratio, workload, and oxygen pulse), submaximal CPET parameters (ventilatory anaerobic threshold, VE/VCO2 slope, and oxygen uptake efficiency slope), and maximum ventilatory CPET parameters (tidal volume, respiratory rate, breathing reserve, and ventilatory equivalent for CO2 and O2).ConclusionsThis study defined paediatric reference Z-score values for the main cycle ergometer CPET parameters, in addition to the existing reference values for VO2max, applicable to children of normal and extreme weights. Providing Z-scores for CPET parameters in the paediatric population should be useful in the follow-up of children with various chronic diseases. Thus, new paediatric research fields are opening up, such as prognostic studies and clinical trials using cardiopulmonary fitness outcomes.Trial registration NCT04876209—Registered 6 May 2021—Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT04876209.

The Fontan Udenafil Exercise Longitudinal Trial: Subgroup Analysis.

The Pediatric Heart Network's Fontan Udenafil Exercise Longitudinal (FUEL) Trial (Mezzion Pharma Co. Ltd., NCT02741115) demonstrated improvements in some measures of exercise capacity and in the myocardial performance index following 6months of treatment with udenafil (87.5mg twice daily). In this post hoc analysis, we evaluate whether subgroups within the population experienced a differential effect on exercise performance in response to treatment. The effect of udenafil on exercise was evaluated within subgroups defined by baseline characteristics, including peak oxygen consumption (VO2), serum brain-type natriuretic peptide level, weight, race, gender, and ventricular morphology. Differences among subgroups were evaluated using ANCOVA modeling with fixed factors for treatment arm and subgroup and the interaction between treatment arm and subgroup. Within-subgroup analyses demonstrated trends toward quantitative improvements in peak VO2, work rate at the ventilatory anaerobic threshold (VAT), VO2 at VAT, and ventilatory efficiency (VE/VCO2) for those randomized to udenafil compared to placebo in nearly all subgroups. There was no identified differential response to udenafil based on baseline peak VO2, baseline BNP level, weight, race and ethnicity, gender, or ventricular morphology, although participants in the lowest tertile of baseline peak VO2 trended toward larger improvements. The absence of a differential response across subgroups in response to treatment with udenafil suggests that the treatment benefit may not be restricted to specific sub-populations. Further work is warranted to confirm the potential benefit of udenafil and to evaluate the long-term tolerability and safety of treatment and to determine the impact of udenafil on the development of other morbidities related to the Fontan circulation.Trial Registration NCT0274115.

97-LB: Empagliflozin Improves Cardiopulmonary Function and VE/VCO2 in Patients with T2D and HFrEF

Background: Cardioprotective benefits of SGLT2 inhibitors (SGLT2i) are well established. However, their effects on cardiopulmonary function measured by CPET in patients with T2D and HFrEF continue to be largely unknown. Objective: Examine the effects of SGLT2i on cardiopulmonary function measured by cardiopulmonary exercise test (CPET) &amp; 6MWT in patients with T2D &amp; HFrEF. Methods: Six subjects with T2D with HFrEF (&amp;lt;40%) (Age=59±2.6, BMI=33.3±1.1, A1c=7.1±0.3, EF 28±4%) were randomized to empagliflozin 25mg (SGLT2i) vs. placebo in a 2:1 fashion for 12 weeks. Cardiac MRI, 6MWT, and CPET were performed pre- and post-intervention. Results: SGLT2i group showed an increase in EF. All subjects reached submaximal cardiovascular effort (RER≤1.10). The Ventilatory Anaerobic Threshold (VT, submaximal index of exercise capacity) showed a significant increase in VT time with SGLT2i (p=0.05). The rest of the parameters trended toward improvement including Ve/VCO2 slope and 6MWT. Conclusion: Subjects with T2D and HFrEF, treated with an SGLT2i had improved EF, a decrease in the worsening of the Ve/VCO2 slope (a predictor of mortality in HF patients), an increase in 6MWT, and significantly improved VT time (aerobic metabolism) compared to placebo. These findings may represent a novel mechanism of CV protection and warrants further investigation. Disclosure Y. Qin: None. C. L. Triplitt: Speaker's Bureau; Novo Nordisk. G. D. Clarke: None. E. Cersosimo: None. S. E. Espinoza: None. R. A. Defronzo: Advisory Panel; AstraZeneca, Bayer Inc., Boehringer-Ingelheim, Novo Nordisk, Research Support; AstraZeneca, Boehringer-Ingelheim, Merck &amp; Co., Inc., Speaker's Bureau; AstraZeneca. C. Solis-herrera: None. F. M. Acosta: None. S. Neppala: None. T. M. Cortes: None. A. Stepanenko: None. A. Moody: None. N. D. Sanchez: None. M. Brown: None. L. A. Cruz moreno: None. Funding Doris Duke Charitable Foundation; Voelcker Foundation; National Institutes of Health

Machine Learning for Prediction of Adverse Cardiovascular Events in Adults With Repaired Tetralogy of Fallot Using Clinical and Cardiovascular Magnetic Resonance Imaging Variables

Background: Existing models for prediction of major adverse cardiovascular events (MACE) after repair of tetralogy of Fallot have been limited by modest predictive capacity and limited applicability to routine clinical practice. We hypothesized that an artificial intelligence model using an array of parameters would enhance 5-year MACE prediction in adults with repaired tetralogy of Fallot. Methods: A machine learning algorithm was applied to 2 nonoverlapping, institutional databases of adults with repaired tetralogy of Fallot: (1) for model development, a prospectively constructed clinical and cardiovascular magnetic resonance registry; (2) for model validation, a retrospective database comprised of variables extracted from the electronic health record. The MACE composite outcome included mortality, resuscitated sudden death, sustained ventricular tachycardia and heart failure. Analysis was restricted to individuals with MACE or followed ≥5 years. A random forest model was trained using machine learning (n=57 variables). Repeated random sub-sampling validation was sequentially applied to the development dataset followed by application to the validation dataset. Results: We identified 804 individuals (n=312 for development and n=492 for validation). Model prediction (area under the curve [95% CI]) for MACE in the validation dataset was strong (0.82 [0.74–0.89]) with superior performance to a conventional Cox multivariable model (0.63 [0.51–0.75]; P =0.003). Model performance did not change significantly with input restricted to the 10 strongest features (decreasing order of strength: right ventricular end-systolic volume indexed, right ventricular ejection fraction, age at cardiovascular magnetic resonance imaging, age at repair, absolute ventilatory anaerobic threshold, right ventricular end-diastolic volume indexed, ventilatory anaerobic threshold % predicted, peak aerobic capacity, left ventricular ejection fraction, and pulmonary regurgitation fraction; 0.81 [0.72–0.89]; P =0.232). Removing exercise parameters resulted in inferior model performance (0.75 [0.65–0.84]; P =0.002). Conclusions: In this single-center study, a machine learning-based prediction model comprised of readily available clinical and cardiovascular magnetic resonance imaging variables performed well in an independent validation cohort. Further study will determine the value of this model for risk stratification in adults with repared tetralogy of Fallot.

Comparison of telehealth and supervised phase III cardiac rehabilitation in regional Australia: protocol for a non-inferiority trial

IntroductionExercise-based cardiac rehabilitation programmes (ExCRP) promote recovery and secondary prevention for individuals with cardiovascular disease (CVD). Despite this, enrolment and adherence to ExCRP in rural locations is low. Telehealth programmes...