Papic V; Department of Sport, Exercise and Health, University of Basel, Basel, Switzerland.
Ledergerber R; Roth R; Knaier R;

Pediatric research [Pediatr Res] 2025 Jun 19.
Date of Electronic Publication: 2025 Jun 19.

Background: Physiological responses to exercise differ between children and adults, but achieving maximal exertion in children complicates the interpretation of VO _2max . This study, therefore, examines age- and sex-related physiological differences in submaximal parameters during incremental exercise.
Methods: In this cross-sectional study, 24 children (7-11 years), 20 moderately trained adults (MTA), and 20 well-trained adults (WTA; 20-30 years) completed a maximal incremental exercise test on a cycle ergometer with continuous respiratory measurement. Linear regression models analysed age and sex differences in ventilatory thresholds (VT1, VT2) and oxygen uptake efficiency slope and plateau (OUES), with Cohen’s d effect sizes reported.
Results: Children showed higher body mass-adjusted VO ₂ at VT1 and VT2 (d = 0.58-0.66) compared to MTA, and slightly lower VT2 values than WTA (d = 0.35). Adults had higher absolute OUES (d = 0.37-1.45) and OUEP (d = 0.60-0.81), while children exhibited higher body mass-adjusted OUES (d = 0.87 - 1.80). Males had higher VO ₂ at VT2, OUES, and OUEP (d = 0.41-0.81), while females showed higher relative VO ₂ at VT1 and VT2 (d = 0.44-0.59) compared to males.
Conclusions: Children rely more on oxidative metabolism than adults. Maturation influences exercise efficiency more than body mass, underscoring physiological differences. These age- and sex-specific patterns call for longitudinal studies to further explore the roles of growth and training.
Impact: This study identifies clear physiological differences in submaximal CPET parameters between children and adults. It adds novel insight by including both ventilatory thresholds and oxygen uptake efficiency, adjusted for body mass and training status. The findings suggest children rely more on oxidative metabolism, emphasizing the importance of maturation on exercise efficiency and informing age- and sex-specific assessment protocols in pediatric exercise physiology.

Lewsey SC; Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore,
Samuel TJ; Schär M; Sourdon J; Goldenberg JR; Yanek LR; Lai S; Steinberg AM; Bottomley PA; Gerstenblith G; Weiss RG;

Circulation. Heart failure [Circ Heart Fail] 2025 Jun 19, pp. e012512.
Date of Electronic Publication: 2025 Jun 19.

Background: Heart failure with preserved ejection fraction (HFpEF) is a systemic process with contributions from peripheral factors, including skeletal muscle (SM). Age-associated SM loss and impaired energy metabolism occur without heart failure, but the relative importance of changes in SM quantity versus metabolic quality in patients with HFpEF for exercise intolerance (EI) or outcomes has not been studied. We hypothesized that EI and subsequent clinical outcomes across the adult lifespan in patients with HFpEF are related to impaired SM energy metabolism rather than age-associated SM loss.
Methods: Patients with HFpEF (n=64; aged 34-86 years) with left ventricular ejection fraction ≥50% were stratified by age in a prospective study. They underwent 3T magnetic resonance imaging to measure calf muscle quantity and ³¹ P magnetic resonance spectroscopy to measure muscle high-energy phosphate metabolism during plantar flexion exercise.
Results: Older patients with HFpEF exhibited more severe EI, less calf muscle, faster exercise-induced high-energy phosphate decline, and worse SM energetics at fatigue than younger patients. EI correlated closely with muscle metabolic quality, not quantity. Neither magnetic resonance imaging exercise time, 6-minute walk distance, nor peak oxygen uptake at cardiopulmonary exercise testing on cardiopulmonary bicycle exercise testing correlated with calf SM area. In contrast, the 6-minute walk distance and peak oxygen uptake at cardiopulmonary exercise testing were inversely related to rapid exercise-induced high-energy phosphate decline and worse SM energetic profile at fatigue. Rapid exercise-induced high-energy phosphate decline and lower ATP at fatigue were associated with increased cardiovascular death and heart failure hospitalizations in univariate analysis over a median of 39.3 months.
Conclusions: EI in older patients with HFpEF is closely linked to age-associated abnormalities in SM energy metabolism, namely, rapid exercise-induced energetic decline and worse energetic profile at fatigue, and not SM quantity. Abnormal SM energy metabolism is associated with worse outcomes in patients with HFpEF in unadjusted analysis. These findings support SM energy metabolism as a barometer of systemic HFpEF severity and the pursuit of new SM metabolic modulators to reduce disabling EI and possibly adverse outcomes in patients with HFpEF.

Kramer M; Division of Pediatric Cardiology and Intensive Care, University Hospital, LMU Munich, 81377, Munich, Germany.
Li P; Langer M; Vilsmaier T; Sciuk F; Kolbinger B; Jakob A; Rogenhofer N; Dalla-Pozza R;Thaler C; Haas NA; Oberhoffer FS;

European journal of pediatrics [Eur J Pediatr] 2025 Jun 21; Vol. 184 (7), pp. 431.
Date of Electronic Publication: 2025 Jun 21.

Children conceived through assisted reproductive technologies (ART) potentially display an increased cardiovascular morbidity. Despite cardiorespiratory fitness (CRF) and muscle strength being key indicators of cardiovascular outcomes, they have not been investigated in ART offspring yet. This observational pilot cohort study aimed to evaluate CRF and muscle strength in ART participants and spontaneously conceived controls.
Anthropometric variables, diet quality, level of physical activity, and sedentary behavior were evaluated. Participants performed a 6-min walking test (6MWT) and a 20-m shuttle run test (20mSRT). 6MWT distance and the number of archived laps were assessed, the maximal oxygen uptake (V̇O2 _max ) was estimated, and pulse rate recovery was calculated. Maximal hand grip strength (HGS) was determined as a marker of muscle strength. Generalized linear models were used to adjust data for age, birthweight, and gestational age. Sixty-seven ART participants and 86 spontaneously conceived peers were included. Both groups did not differ significantly in age (11.3 (IQR 8.1-18.2) vs. 11.9 (IQR 8.7-18.3) years), gender ratio, anthropometric variables, diet quality, level of physical activity and sedentary behavior. The amount of 20mSRT laps (P _adj =0.02), estimated VO2 _max (45.0 (IQR 37.9-47.1) vs. 45.8 (IQR 43.1-48.0) ml·kg⁻ ¹ ·min⁻ ¹ , P _adj =0.04), and pulse rate recovery (P _adj =0.03) were significantly lower in ART participants after adjustment. HGS did not differ between groups.
Conclusion: This study indicates a significantly lower CRF in ART participants. Significant differences in muscle strength were not demonstrated between groups. Future studies should validate these results by using cardiopulmonary exercise testing for VO2 _max assessment.

Castiglione A; Department of Cardiology, Center for Congenital Heart Diseases, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
& many other centres in Switzerland
Schwerzmann M; Bouchardy J; Buechel RR; Engel R; Freese M; Gabriel H; Greutmann M; Heg D; Possner M; Ruperti-Repilado FJ; Rutz T; Schwitter J; Thomet C; Tobler D; Wilhelm M; Wustmann K; Schwitz F;

CJC pediatric and congenital heart disease [CJC Pediatr Congenit Heart Dis] 2024 Dec 12; Vol. 4 (2), pp. 81-91.
Date of Electronic Publication: 2024 Dec 12 (Print Publication: 2025).

Background: Adults with a transposition anatomy and a systemic right ventricle (RV) face long-term complications that may impact their quality of life (QoL). Few data are available regarding the QoL in this patient group and its evolution over time.
Methods: This study was performed in the SERVE trial’s (identifier: NCT03049540) prospective cohort of patients (n = 100) with congenitally corrected transposition of the great arteries (TGA) or dextro-TGA after the atrial switch procedure and a longitudinal follow-up of 3 years. We aimed to describe the longitudinal QoL levels and their predictors. QoL was assessed using the Linear Analog Scale. QoL parameters were collected at baseline, after 12 months, and after 36 months, together with clinical parameters and a questionnaire assessing general self-efficacy (GSE).
Results: The mean QoL on the Linear Analog Scale was 79.1 ± 13.6 at baseline, 75.5 ± 14.8 at 1 year, and 79.2 ± 13.6 at 3-year follow-up ( P  = 0.900). No significant differences in QoL were observed between congenitally corrected TGA or dextro-TGA patients. Cardiopulmonary exercise testing maximum work rate and maximum oxygen uptake, New York Heart Association class, end-diastolic RV volumes, N-terminal pro-B-type natriuretic peptide concentration, and GSE showed significant correlations with QoL levels. Multivariable regression analysis identified GSE value and New York Heart Association class ( r²  = 0.283, P < 0.001) as independent predictors of QoL at baseline.
Conclusions: Patients with a systemic RV reported a stable good QoL during 3 years of follow-up. Exercise capacity and self-efficacy were the only independent predictors of QoL.

Griffith GJ; Northwestern University Feinberg School of Medicine, Department of Physical Therapy and Human Movement Sciences, USA

International journal of cardiology [Int J Cardiol] 2025 May 31; Vol. 437, pp. 133445.
Date of Electronic Publication: 2025 May 31.

Chronotropic incompetence (CI) is characterized by an inadequate or blunted heart rate (HR) response to exercise, [1] and the clinical and prognostic importance of CI is being increasingly recognized. Associations between CI and mortality [2,3] and exercise capacity [4] have been demonstrated in a variety of cardiovascular disease patient populations. In this issue of the International Journal of Cardiology, the original research article by Smarz and colleagues further established the importance of CI to a population of post-myocardial infarction (MI) patients with preserved or mildly reduced ejection fraction. [5] This compelling research article provides important insight into the prognostic benefit of identification of CI and importantly highlights that methodological considerations relating to the assessment of CI are of the utmost importance. Firstly, there exists a general lack of universal agreement regarding the mathematical and functional definition of CI. Secondly, implementation of cardiopulmonary exercise testing (CPET) is oftentimes underutilized, and the multitude of variables obtained from it are rarely optimized in the characterization of patient prognosis following maximal exercise testing. The aims of this article are to 1) provide insight into best methodological practices surrounding CI as identified via CPET, 2) contextualize the importance of CI in MI patients, and 3) provide recommendations for future avenues of research to continue to build the body of evidence surrounding the importance of CPET and CI.

Möbus SF; School of Clinical Medicine, University of Cambridge, Cambridge, UK.
Harding CJ; Taylor CL; Sylvester KP; Fuld JP;

Physiological reports [Physiol Rep] 2025 Jun; Vol. 13 (11), pp. e70388.

Cardiopulmonary exercise testing (CPET) is emerging as a useful tool in the identification of dysfunctional breathing (DB). We aimed to evaluate the prevalence and functional impact of different patterns of DB in 628 adult patients referred for CPET due to unexplained dyspnoea (August 2019-December 2023). Patients were assigned to four groups following CPET interpretation: normal, breathing pattern disorder (BPD), hyperventilation (HV), and combined BPD with HV (BPDHV). Demographic and CPET performance data were analyzed using non-parametric tests as appropriate. 94 (15.0%) patients had normal CPETs and 267 (42.5%) were identified as having DB. The remaining 267 were excluded as having alternative diagnoses. Of those with DB, 145 (54.3%) had BPD, 41 (15.4%) had HV, and 81 (30.3%) had BPDHV. VE/VCO ₂ was significantly increased in HV or BPDHV only (p < 0.001). Patients in all three DB groups exhibited significantly impaired peak VO ₂ compared to those with normal CPETs (p < 0.001). These CPET findings highlight DB as a common driver of symptoms in unexplained dyspnoea. Over half of patients with DB had isolated BPD, which requires visual inspection of relevant CPET plots to diagnose. Those identified with DB had significantly reduced peak VO ₂ , which may be a useful classifier of functional severity in DB.

Wang X; Department of Biostatistics Boston University School of Public Health Boston MA USA.
Zhang Y; Pathiravasan CH; Spartano NL; Benjamin EJ; McManus DD;Lewis GD; Larson MG;Vasan RS; Murabito JM; Liu C; Nayor M;

Journal of the American Heart Association [J Am Heart Assoc] 2025 Jun 03; Vol. 14 (11), pp. e039457.
Date of Electronic Publication: 2025 Jun 03.

Background: Abnormal exercise blood pressure (BP) responses are associated with hypertension and cardiovascular disease, but their relationship with home BP over a mid- to long-term time span is unknown.
Methods: At an FHS (Framingham Heart Study) research examination (2016-2019), participants underwent maximum incremental ramp cycle ergometry cardiopulmonary exercise testing with BP measured every 2 minutes. At the same exam, English-speaking participants enrolled in the electronic FHS with an iPhone were provided with a digital BP cuff to measure home BP weekly for 1 year. Linear regression models examined associations of exercise BP with average home systolic BP (SBP), home-based hypertension, and week-to-week average real variability of home SBP, over 1-year follow-up. Participants with <3 weeks of BP return were excluded.
Results: Among 808 participants (mean age, 53 years; 58% women; 92% White individuals; 47% hypertension), higher exercise BP responses (peak SBP, SBP at 75 W, SBP/workload slope, peak diastolic BP, and diastolic BP at 75 W) were associated with higher average home SBP. Higher peak diastolic BP was associated with a greater risk for home hypertension. Additionally, higher SBP/workload slope and peak diastolic BP were associated with elevated average real variability of home SBP only in participants without antihypertensive use.
Conclusions: Higher exercise BP responses were associated with higher average home-based BP, greater home-based hypertension risk, and increased home-based BP variability over a mid- to long-term time span. However, these associations may vary by antihypertensive medication use. Exercise BP may play an important role in hypertension prevention and treatment.

Turquetto ALR; Instituto do Coração do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP, Brazil.
Amato LP; Thorup L; Kelly B; Hjortdal VE; de Souza FR;Canêo LF; Machado DS; Filho ACB; Ligeiro MG; Mohanakumar S; Rondon E; Binotto MA; Jatene MB; Jatene FB;

International journal of cardiology [Int J Cardiol] 2025 Jun 05, pp. 133480.
Date of Electronic Publication: 2025 Jun 05.

Introduction: Survival rates for post-Fontan patients have improved, allowing many to reach adulthood with better quality of life (QOL). However, they remain at risk for reduced functional capacity (FC), skeletal muscle loss, and lymphatic dysfunction, which negatively affect clinical outcomes. This study evaluated the feasibility of an online rehabilitation program for adult Fontan patients in the late postoperative period and its effects on FC, peripheral lymphatic function (PLF), and QOL.
Methods: This prospective, non-randomized, controlled clinical trial evaluated the impact of a fitness center’s 36-session online aerobic and resistance training program. Participants were divided into a control group (CG), continuing usual activities, and an exercise group (EG). Outcomes included QOL (Short Form-36 questionnaire: SF-36), FC via cardiopulmonary exercise testing (CPET), and PLF assessed using near-infrared fluorescence imaging and venous occlusion plethysmography.
Results: A total of 26 participants (13 EG,13 CG), with a median age of 30 (25-35) years, and follow-up time after Fontan of 19 (15-21) years, were enrolled. The EG showed significant improvements in peak VO2 (ml/kg/min), predicted peak VO2 (%), peak ventilation (L/min), and oxygen pulse (mL/beat), indicating enhanced cardiovascular efficiency. Additionally, 62 % of SF-36 domains improved in the EG, while no changes were observed in the CG. However, the program did not produce significant modifications in PLF.
Conclusions: The proposed online rehabilitation program proved to be feasible and effectively improved FC and quality of life in adults after Fontan surgery; however, this training model did not significantly influence peripheral lymphatic function.

Dudek M; 1 st Department of Cardiology, Poznan University of Medical Sciences, Poznan, Poland.
Górecki M; Marszałek S; Kufel-Grabowska J; Litwiniuk M; et al

European journal of applied physiology [Eur J Appl Physiol] 2025 Jun 05.
Date of Electronic Publication: 2025 Jun 05.

Purpose: Younger women are diagnosed more often with aggressive breast cancer (BC) subtypes, the treatment of which usually incorporates chemotherapy. Physical training plays a significant role in mitigating the adverse effects of systemic cancer therapy, improving quality of life, and potentially enhancing treatment efficacy. High-intensity interval training (HIIT) emerged as a promising intervention to counteract the fatigue induced by chemotherapy, which in younger women often causes depression and disruption of employment. This study aimed to investigate whether supervised HIIT employed concurrently with chemotherapy impacts the cardiorespiratory fitness of young BC patients.
Methods: Twenty-six young (18-40 years old) BC patients scheduled for chemotherapy were randomised to intervention comprising supervised HIIT employed concurrently with chemotherapy or no supervised training (control) for 6 months. Outcomes measured using cardiopulmonary exercise testing (CPET) and non-invasive cardiac output testing were cardiorespiratory fitness and cardiac output.
Results: Compared to control, employment of HIIT mitigated the decrease in relative peakVO ₂ from 33.630 to 29.540 ml/kg/min for HIIT group and from 29.679 to 22.571 ml/kg/min for control group (ANCOVA p = 0.018, ES = 0.469), and also a mitigated the decrease in exercise time from 685.600 to 666.500 s for HIIT group and from 703.357 to 555.500 s for control group (ANCOVA p = 0.008, ES = 0.815) measured during CPET.
Conclusions: Supervised HIIT implemented alongside chemotherapy can mitigate the decline in cardiorespiratory fitness caused by BC chemotherapy in young patients.

Carr ZJ; Yale University, School of Medicine, New Haven, CT, USA.; Department of Anesthesiology, Yale New Haven Hospital, New Haven, CT, USA.
Charchaflieh J; Brenes-Bastos A; He H;  Lin HM; Jankelovits A; Gu E; Zafar J; Ghali F; Tan WS; Heerdt P;

BJA open [BJA Open] 2025 Apr 24; Vol. 14, pp. 100407.
Date of Electronic Publication: 2025 Apr 24 (Print Publication: 2025).

Background: Early postoperative complication risk prediction would enhance perioperative surveillance and resource allocation. Reports have described brief submaximal cardiopulmonary exercise testing (CPET) for the routine assessment of cardiopulmonary disease. Compared with conventional CPET, it can be performed in 6 min and is used to predict peak CPET measurements. We aimed to determine whether submaximal CPET-derived measures outperform structured surveys in early postoperative complication detection.
Methods: An institutional review board-approved, single-centre, open-label, clinical device trial was conducted. A total of 101 participants undergoing noncardiac surgery, aged >60 yr, with revised cardiac risk index ≤2, self-reported metabolic equivalents >4 (METs in ml O ₂ kg ^-1 min ^-1 ; self-endorsed reliably climbing two flights of stairs), were enrolled. Participants completed a subjective METs assessment, Duke Activity Status Index, and submaximal CPET that derived peak oxygen uptake (VO ₂ , ml O ₂ kg ^-1 min ^-1 ), METs, and gas exchange-derived pulmonary capacitance (GXCAP, in ml O ₂ beat ^-1 kPa ^-1 ). Elastic net regularisation machine learning identified feature importance among study measures for the primary endpoint (Postoperative Morbidity Survey [POMS] ≥1), secondary endpoints (cardiac, pulmonary and renal domains of the POMS [POMS-CPR ≥1]), and length of stay. Adjusted multivariable regression models were used to identify significance.
Results: Of 101 participants, 53 (52.4%) had POMS ≥1. GXCAP to peak VO ₂ slope (GXCAP-VO ₂ ) was associated with POMS ≥1 (OR _adj 0.94; 95% CI 0.89-0.99; P =0.011) and increasing length of stay (OR _adj 0.98; 95% CI 0.96-0.99; P =0.01). GXCAP-VO ₂ slope (OR _adj 0.93; 95% CI 0.88-0.99; P =0.015) was associated with POMS-CPR ≥1.
Conclusions: Compared with structured surveys (subjective METs or Duke Activity Status Index) or conventional peak CPET values (VO ₂ or METs), a novel measure, GXCAP-VO ₂ slope, offered superior early postoperative complication discrimination in low-morbidity subjects. These preliminary findings support GXCAP-VO ₂ slope as a compelling investigational target for early postoperative complication risk, supporting the use of CPET to enhance early postoperative complication prediction.
Competing Interests: ZJC declares partial research funding from Shape Medical Systems, Inc (MN, USA). PMH declares consulting for Cardiage LLC and Baudax Bio, consulting and sponsored research for Edwards Lifesciences, and equity interest in emka Medical.