• Stevens JL; Department of Anaesthesia, Royal Sussex County Hospital,  Brighton and Hove, United Kingdom.; and other UK centgres
• McKenna HT; Minnion M; Murray AJ; Feelisch M; Martin DS;

Experimental biology and medicine (Maywood, N.J.) [Exp Biol Med (Maywood)] 2025 Feb 21; Vol. 250, pp. 10254.
Date of Electronic Publication: 2025 Feb 21

Abstract

• More complex surgeries are being performed in increasingly sicker patients, resulting in a greater burden of postoperative morbidity. Delineating the metabolic and bioenergetic changes that occur in response to surgical stress may further our understanding about how humans respond to injury and aid the identification of resilient and frail phenotypes.
  Skeletal muscle biopsies were taken from patients undergoing hepato-pancreatico-biliary surgery at the beginning and end of the procedure to measure mitochondrial respiration and thiol status. Blood samples were taken at the same timepoints to measure markers of inflammation and systemic redox state. A sub-group of patients underwent cardiopulmonary exercise testing prior to surgery, and were assigned to two groups according to their oxygen consumption at anaerobic threshold (≤10 and >10 mL/kg/min) to determine whether redox phenotype was related to cardiorespiratory fitness.
  No change in mitochondrial oxidative phosphorylation capacity was detected. However, a 26.7% increase in LEAK (uncoupled) respiration was seen after surgery (P = 0.03). Free skeletal muscle cysteine also increased 27.0% (P = 0.003), while S-glutathionylation and other sulfur and nitrogen-based metabolite concentrations remained unchanged. The increase in LEAK was 200% greater in fit patients (P = 0.004). Baseline plasma inflammatory markers, including TNF-⍺ and IL-6 were greater in unfit patients, 96.6% (P = 0.04) and 111.0% (P = 0.02) respectively, with a 58.7% lower skeletal muscle nitrite compared to fit patients.
  These data suggest that oxidative phosphorylation is preserved during the acute intraoperative period. Increase in free cysteine may demonstrate the muscle’s response to surgical stress to maintain redox balance. The differences in tissue metabolism between fitness groups suggests underlying metabolic phenotypes of frail and resilient patients. For example, increased LEAK in fitter patients may indicate mitochondrial adaptation to stress. Higher baseline measurements of inflammation and lower tissue nitrite in unfit patients, may reflect a state of frailty and susceptibility to postoperative demise.

• Miao G; China Institute of Sport Science, Beijing, China.;  Shijiazhuang, Hebei, China.
• Yan Q; Zhu H;

Frontiers in physiology [Front Physiol] 2024 Dec 24; Vol. 15, pp. 1437962. Date of Electronic Publication: 2024 Dec 24

• Objective: To explore the feasibility of post-exercise heart rate recovery indicators for predicting maximum oxygen uptake (VO2max) in healthy adults aged 30-60 years.
• Methods: 260 healthy adults who did not perform regular exercise were randomly recruited and divided into a model group (n = 200) and a verification group (n = 60). Measure body fat percentage, weight, height and other indicators, and complete a cardiopulmonary exercise test as required to measure VO2max and heart rate recovery (HRR1, HRR2) in the first and second minutes after exercise. Equations are established through stepwise regression method, and the selected optimal equation is tested for back substitution.
• Results: The optimal equation is: Absolute VO 2 ⁡ max = – 0.528 + 0.039 * weight – 3.463 * body fat rate + 0.042 * HRR 2 – 0.180 * gender male = 1 , female = 2 . Analysis of variance, goodness-of-fit test, VIF test, Shapiro-Wilk test, and Durbin-Watson test indicate that the equation is more reliable; Pearson product-moment correlation analysis, paired t test, and Bland-Altman consistency test indicate that the equation is more valid good.
• Conclusion: The regression equation established through heart rate recovery after exercise can be used to predict VO2max in healthy adults aged 30-60 years.

Badiani, Sveeta; St Bartholomew’s Hospital, Barts Health NHS Trust, London,
van Zalen, Jet; Alborikan, Sahar; Althunayyan, Aeshah; et al

Echo research and practice,2025 Mar 05

• Background: Patients with moderate aortic stenosis (AS) may experience symptoms and adverse outcomes. The aim of this study was to determine whether patients with moderate AS exhibited objective evidence of exercise limitation, compared with age and sex matched controls and if so, to determine which echocardiographic parameters predicted exercise ability.
• Methods: This was a prospective case control study of patients with moderate AS (peak velocity (Vmax) 3.0-3.9 m/s, mean gradient (MG) 20-39mmHg, aortic valve area (AVA)1.1-1.5cm ² ) and left ventricular ejection fraction (LVEF) ≥ 55%. All patients underwent cardiopulmonary stress echocardiography.
• Results: 25 patients with moderate AS (Vmax 3.5 ± 0.2mmHg, mean gradient 28 ± 5mmHg, AVA 1.2 ± 0.1cm ² , LVEF 61 ± 4%) were compared with 25 controls. % predicted oxygen uptake efficiency slope (OUES), % predicted O ₂ pulse and VO ₂ at anaerobic threshold (AT) were significantly lower in patients compared with controls (OUES 79 ± 15 vs. 89 ± 15%, p = 0.013). VO ₂ did not significantly differ between cases and controls.
• Conclusion: Objective measures of exercise capacity including OUES, O ₂ pulse and VO ₂ at AT are significantly lower in patients with moderate AS compared with controls, suggesting that these parameters may be more useful than VO ₂ where patients may be unable to complete a maximal exercise test. Risk stratification using cardiopulmonary exercise echocardiography may help to identify patients with moderate AS who are at increased risk of cardiovascular events and should be considered for more intensive surveillance and intervention.
• Trial Registration: Clinical trial number MRC 0225 IRAS 207395.

Genecand, Léon; Service de Pneumologie,  Hôpitaux Universitaires de Genève, Genève, Switzerland.;
Jaksic, Cyril; Desponds, Roberto; Simian, Gaëtan; et al

Physiological reports,2025 Mar

• he dispersion of the tidal volume and of the breathing frequency have been used to diagnose dysfunctional breathing during cardio-pulmonary exercise testing. No validated methods to objectively describe this dispersion exist. We aimed to validate such a method. We used simulations based on real-life parameters. Moving standard deviation (MSD) and residuals from locally estimated scatterplot smoothing (LOESS) were evaluated. The precision and the bias of each tested method at rest and during exercise simulations, with and without sighs, were measured. For LOESS, a 2nd degree polynomial was used, and different spans were tested (LOESS ₁ , LOESS _0.75 , and LOESS _0.5 ). For MSD, different number of points used for the calculation were tested (MSD ₇ , MSD ₁₁ , MSD ₁₅ , and MSD19). The LOESS method was globally more precise, had less bias, and was less influenced by the trend as compared to MSD in almost all simulations except for extremely low dispersion combined with extreme trends. LOESS _0.75 had intermediate bias and precision between LOESS _0.5 and LOESS ₁ in all simulations. LOESS _0.75 is a method that combines high precision, low bias, and low influenceability of trends. It could be considered as the method of choice to evaluate the dispersion of breathing parameters during cardiopulmonary exercise testing.
• (© 2025 The Author(s). Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

Souilla, Luc; Department of Pediatric and Congenital Cardiology, Montpellier University Hospital, France
Werner, Oscar; Huguet, Helena; et al

JAMA Network Open,25/02/2025

• Key Points: Question: What are the levels of cardiopulmonary fitness among children and adolescents with inherited cardiac disease compared with healthy controls and the factors associated with maximum oxygen uptake (V̇o₂ max) in young patients? Findings: This cross-sectional study with 207 participants showed lower levels of cardiopulmonary fitness among youths with inherited cardiac disease. The multivariable model explained 80% of V̇o₂ max, including clinical, functional, sociodemographic, and behavioral parameters. Meaning: This study suggests that assessing cardiopulmonary fitness among children with inherited cardiac disease can be incorporated into the shared decision-making process for sports participation and may help identify eligible patients for early preventive cardiac rehabilitation programs. Importance: Historical restrictions on children with inherited cardiac arrhythmia or cardiomyopathy have been implemented to mitigate the potential risk of sudden death, but these limitations can be detrimental to overall health and cardiopulmonary fitness.
  Objectives: To evaluate cardiopulmonary fitness and physical activity among children with inherited cardiac disease and identify the factors associated with maximum oxygen uptake (V̇o₂ max) in this population.
  Design, Setting, and Participants: This cross-sectional, multicenter, prospective controlled study was conducted in 7 tertiary care expert centers for inherited cardiac disease in France from February 1, 2021, to June 20, 2023, with a 2-week follow-up. Participants included 100 children and adolescents aged 6 to 17 years with inherited cardiac arrhythmia or cardiomyopathy who were compared with 107 sex- and age-matched controls.
  Main Outcomes and Measures: Maximum oxygen uptake was assessed using cardiopulmonary exercise testing, and results were expressed using pediatric reference z score values. The main determinants of V̇o₂ max included clinical (New York Heart Association [NYHA] functional class, treatment, echocardiographic, and electrocardiogram variables), functional (cardiopulmonary exercise test parameters), sociodemographic (sex, schooling, and parents’ education), and behavioral (physical activity and motivation) characteristics. Results: A total of 100 patients (mean [SD] age, 12.7 [3.1] years; 52 boys [52.0%]) and 107 controls (mean [SD] age, 11.7 [3.3] years; 54 boys [50.5%]) were included. The V̇o₂ max was lower in patients than controls, expressed as z scores (mean [SD] score, −1.49 [1.48] vs −0.16 [0.97]; P <.001) or raw values (mean [SD] value, 32.2 [7.9] vs 40.2 [8.5] mL/kg/min; P <.001). Moderate to vigorous physical activity levels were lower in patients than in controls (mean [SD] level, 42.0 [23.6] vs 48.2 [20.4] min/d; P =.009). The final multivariable model explained 80% of the V̇o₂ max by integrating clinical (lower NYHA functional class, absence of ventricular dilatation, and absence of implantable cardioverter-defibrillator), functional (higher forced vital capacity and ventilatory anaerobic threshold), sociodemographic (male sex, normal progression of schooling, and higher maternal educational level), and behavioral (higher self-reported physical activity and motivation toward physical activity) parameters.
  Conclusions and Relevance: This cross-sectional study suggests that levels of cardiopulmonary fitness and physical activity were lower in children and adolescents with inherited cardiac disease than in healthy controls, even after adjusting for use of β-blockers and using modern pediatric reference models. Assessing cardiopulmonary fitness among children with inherited cardiac disease can contribute to engaging in a shared decision-making process for sports participation and preventive interventions, such as early cardiac rehabilitation programs. This cross-sectional study evaluates cardiopulmonary fitness and physical activity among children with inherited cardiac disease vs controls and identifies the factors associated with maximum oxygen uptake in this population.

Joosen, Renée S; Department of Pediatric Cardiology, University Medical Center Utrecht,  the Netherlands.
Voskuil, Michiel;de Pater, Wieke G;Wijk, Sebastiaan W H van;

International journal of cardiology. Congenital heart disease,2025 Feb 15

• Background: Patients with transposition of the great arteries (TGA) experience reduced exercise capacity after the arterial switch operation (ASO), possibly due to limited stroke volume. This study evaluates the role of stroke volume in reduced exercise capacity in these patients.
• Methods: A retrospective analysis was conducted on TGA patients who underwent a transthoracic echocardiogram (TTE), cardiac magnetic resonance (CMR) and cardiopulmonary exercise test (CPET) within one year between September 2009 and February 2024 at the University Medical Center Utrecht. Excluding those with submaximal CPET results, the remaining patients were divided into <18 and ≥ 18 years old groups. Reduced exercise capacity was defined as a peak oxygen uptake (VO ² peak) with a Z-score < -2. Left and right ventricular (LV and RV) data including volumes, function, strain and RV outflow tract obstructions were collected from TTE and CMR.
• Results: A total of 126 patients (72 % male, mean age 19 ± 8 years) were included. Left ventricular function, RV volumes, function and strain were relatively preserved on CMR. Reduced VO ² peak was seen in 55 % of patients ≥18 years, significantly more than those <18 years (23 %, p < 0.001). Reduced VO ² peak was independently associated with time since ASO, body mass index, peak heat rate (HRpeak), and O ² pulse. VO ² peak showed weak to moderate correlations with time after ASO (R = -0.295,p < 0.001), body mass index (R = -0.468,p < 0.001) and HRpeak (R = 0.270,p = 0.002) and a strong correlation with O ² pulse (R = 0.621,p < 0.001).
• Conclusion: Exercise capacity in TGA patients after ASO might be limited by an impaired ability to increase stroke volume.
• Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: J.M.P.J. Breur reports financial support was provided by Netherlands Heart Foundation. J.M.P.J. Breur reports financial support was provided by Stichting Hartekind. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Bomma, Meghana; Department of Physiology and Aging, University of Florida, Gainesville, FL, USA.
Lott, Donovan;Forbes, Sean;Shih, Renata; et al

Journal of neuromuscular diseases,2025 Mar 04

• Background: Cardiopulmonary exercise testing (CPET) is the gold-standard for quantification of peak oxygen uptake (VO ₂ ) and cardiorespiratory and muscle responses to exercise. Its application to Duchenne muscular dystrophy (DMD) has been scarce due to the notion that muscle weakness inherent to disease restricts the cardiorespiratory system from reaching maximal capacity.
• Objective: To investigate the utility of CPET in DMD by 1) establishing whether patients can perform maximal-effort exercise for valid VO ₂ peak assessment; 2) quantifying VO ₂ peak repeatability; 3) characterizing muscle and cardiorespiratory responses; 4) comparing VO ₂ peak to 6-min walk distance (6MWD).
• Methods: Twenty-seven DMD and eight healthy boys (6 years and older) underwent CPET using an incremental work-rate protocol for leg (ambulatory) or arm (non-ambulatory) cycling with measurement of heart rate (HR) and gas-exchange variables from rest to maximal-effort. The oxygen cost of work (ΔVO ₂ /Δwork-rate) was calculated, and peak exercise parameters (VO ₂ , HR, O ₂ pulse, ventilation (VE) and ventilatory threshold (VT)) were considered valid if the respiratory exchange ratio ≥1.01.
• Results: VO ₂ peak was valid (81.5% of patients), repeatable (intraclass correlation coefficient = 0.998) and low in ambulatory and non-ambulatory DMD compared to controls (19.0 ± 6.0; 10.7 ± 2; 35.2 ± 4.5 mL/kg/min respectively). VT was low (30.8 ± 10.7; 19.4 ± 3.0; 61.2 ± 6.9% VO ₂ peak) reflecting significant muscle metabolic impairment. Peak HR in ambulatory-DMD (172 ± 14 bpm) was similar to controls (183 ± 8.3 bpm), but O ₂ pulse was low (3.4 ± 1.0; 6.5 ± 1.1 mL/beat). Peak VE/VO ₂ (ambulatory = 42.1 ± 6.8; non-ambulatory = 42.2 ± 7.8; controls = 34.3 ± 4.6) and ΔVO ₂ /Δwork-rate were elevated (ambulatory = 12.4 ± 4.9; non-ambulatory = 19.0 ± 9.7; controls = 10.1 ± 0.8) revealing ventilatory and mechanical inefficiency. Despite strong correlation between VO ₂ peak and 6MWD, severity of impairment was discordant.
• Conclusion: Valid CPET is feasible in DMD, revealing low VO ₂ peak due to abnormal muscle metabolic and cardiorespiratory responses during dynamic exercise. CPET reveals cardiorespiratory limitations in DMD boys with unremarkable 6MWD, and should be considered an integrative approach in clinical care and assessment of emerging therapeutics.

Marra, Alberto Maria; Department of Internal Medicine, Naples, Italy
D’Assante, Roberta; De Luca, Mariarosaria, et al.

JACC. Heart failure [JACC Heart Fail] 2025 Feb 18.
Date of Electronic Publication: 2025 Feb 18.

• Background: Growing evidence suggests that reduced activity of the growth hormone (GH)/insulin-like growth factor (IGF)-1 axis is common and associated with poor clinical status and outcome in heart failure (HF). In addition, preliminary results of growth hormone deficiency (GHD) correction in HF showed an improvement in quality of life, cardiac structure and function, and cardiovascular performance.
• Objectives: The aim of the present double-blind, randomized, placebo-controlled trial was to evaluate the cardiovascular effects of 1 year of GH replacement therapy in a cohort of patients with heart failure and reduced ejection fraction (HFrEF).
• Methods: Consecutive patients with HFrEF in NYHA functional class I/II/III and concomitant GHD were recruited. GHD patients were randomized to receive GH (0.012 mg/kg every second day ∼2.5 IU), or placebo, on top of background therapy. The primary endpoint was peak oxygen consumption (VO ₂ ). Secondary endpoints included hospitalizations, end-systolic left ventricular volumes, N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels, health-related quality of life score, and muscle strength (handgrip).
• Results: A total of 318 consecutive patients were screened, with 86 (27%) fulfilling the criteria for GHD. Of these, 22 subjects refused to participate in the study. The final study groups consisted of 64 patients, 30 randomized in the active treatment group and 34 in the control group. After 1 year, 45 patients completed the study (21 in the control group and 24 in the active group). A statistically significant improvement of peak VO ₂ was reached in the active group (from 12.8 ± 3.4 mL/kg/min to 15.5 ± 3.15 mL/kg/min; P < 0.01; delta peak VO ₂ between groups: +3.1 vs -1.8; P < 0.01). Other cardiopulmonary exercise test parameters (ie, peak workload, VO ₂ at the aerobic threshold, O ₂ pulse and VE/VCO ₂ slope; P < 0.05) also improved, paralleled by an increase in 6-minute walking test distance (P < 0.05) and handgrip strength (P < 0.01). GH improved right ventricular function (ie, TAPSE and TAPSE/pulmonary artery systolic pressure ratio; P < 0.01), leading to an amelioration of clinical status (NYHA functional class; P < 0.05) and health-related quality of life (Minnesota Living With Heart Failure Questionnaire; P < 0.05). A significant decrease of NT-proBNP was also found (P < 0.05).
• Conclusions: This randomized, double-blind, placebo-controlled trial demonstrates that GH replacement therapy in HFrEF patients with GHD improves exercise performance, and left ventricular and right ventricular structure and function, leading to an amelioration of clinical status and health-related quality of life. (Treatment of GHD Associated With CHF; NCT03775993).
• Competing Interests: Funding Support and Author Disclosures This study was supported by Merck’s Grant for Growth Innovation 2016. Drs Crisci and Giardino have received a research grant from the CardioPath program from Federico II University of Naples, Italy. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

E. Kleinhendler, Division of Pulmonary Medicine, Tel-Aviv Sourasky Medical Center, Tel Aviv, Israel.
A. Pinkhasov, S. Hayek, A. Man, O. Freund, T. M. Perluk, et al.

Expert Rev Respir Med 2025 Pages 1-8

BACKGROUND: Cardiopulmonary exercise testing (CPET) is used in the evaluation of unexplained dyspnea. However, its interpretation requires expertise that is often not available. We aim to evaluate the utility of ChatGPT (GPT) in interpreting CPET results.
RESEARCH DESIGN AND METHODS: This cross-sectional study included 150 patients who underwent CPET. Two expert pulmonologists categorized the results as normal or abnormal (cardiovascular, pulmonary, or other exercise limitations), being the gold standard. GPT versions 3.5 (GPT-3.5) and 4 (GPT-4) analyzed the same data using pre-defined structured inputs.
RESULTS: GPT-3.5 correctly interpreted 67% of the cases. It achieved a sensitivity of 75% and specificity of 98% in identifying normal CPET results. GPT-3.5 had varying results for abnormal CPET tests, depending on the limiting etiology. In contrast, GPT-4 demonstrated improvements in interpreting abnormal tests, with sensitivities of 83% and 92% for respiratory and cardiovascular limitations, respectively. Combining the normal CPET interpretations by both AI models resulted in 91% sensitivity and 98% specificity. Low work rate and peak oxygen consumption were independent predictors for inaccurate interpretations.
CONCLUSIONS: Both GPT-3.5 and GPT-4 succeeded in ruling out abnormal CPET results. This tool could be utilized to differentiate between normal and abnormal results.

Zamodics M, Heart and Vascular Center, Faculty of Medicine, Semmelweis University, Budapest, Hungary
Babity M, Schay G, Leel-Ossy T, Bucsko-Varga A, Kulcsar P, Benko R, Boroncsok D, Fabian A, Ujvari , Ladanyi Z, Balla D, Vago H, Kovacs A, Hosszu E, Meszaros S, Horvath C, Merkely B, Kiss O:

Sports (Basel). 2025 Feb 10;13(2):51

AIMS
Body composition and cardiopulmonary exercise testing (CPET) are vital for optimizing sports performance, but the correlations between them are still underexplored. Our study aimed to investigate the relationships between body composition and specific CPET variables describing physical fitness in young athletes, also adjusting for age and height, in a less-studied, female population.
METHODS
Seventy players participated in our study (age: 16.10 ± 1.63 y). After determining body composition using dual-energy X-ray absorptiometry, we conducted treadmill-based maximal-intensity CPET. Data were analyzed in R using multivariate linear regression, accounting for age and height as confounders.
FINDINGS
Lean body mass (LBM), body fat mass (BFM), and bone mineral content (BMC) showed no effect on resting, maximum, or recovery heart rates and no correlation with resting or maximal lactate values. LBM positively correlated with maximum ventilation (VE-max) (Est: 1.3 × 10-3; SE: 6.1 × 10-4; p < 0.05) and maximum absolute oxygen consumption (VO2abs-max) (Est: 7.710-5; SE: 6.9 × 10-6; p < 0.001)-with age as an influencing factor for VE-max and height as an influencing factor for VO2abs-max. Conversely, BFM showed a negative correlation with maximum relative oxygen consumption (VO2rel-max) (Est: -4.8 × 10-4; SE: 1.2 × 10-4; p < 0.001). Moreover, BFM and BMC were also negatively correlated with maximal exercise duration (Est: -2.2 × 10-4; SE: 8.0 × 10-5; p < 0.01; Est: -3.2 × 10-3; SE: 1.4 × 10-3; p < 0.05) with height as an influencing factor.
CONCLUSION
Our findings indicate complex correlations between body composition and CPET parameters, providing important information for the analysis of individual ergospirometric data. Our results draw attention to the fact that body composition is more precise than weight and height in the evaluation of athletes’ physical fitness.