Schwantje M; Wilhelmina Children’s Hospital, University Medical Center Utrecht, Utrecht, the Netherlands.
van Brussel M; Takken T; Langeveld M; Visser G; Fuchs SA;

Journal of inherited metabolic disease [J Inherit Metab Dis] 2025 Sep; Vol. 48 (5), pp. e70070.

Long-chain fatty acid oxidation disorders are characterized by rhabdomyolysis, often provoked by physical exercise. For the newborn screening (NBS) cohort, it remains uncertain to what extent they will develop the myopathic phenotype. This study assesses physiological responses to exercise, muscle symptoms, and activity levels in 14 adolescent lcFAOD patients (VLCADD (n = 8), LCHADD (n = 4), CPT2D (n = 1) and LCKATD (n = 1); ages 9.9-17.8 years). Analyses of incremental and prolonged cardiopulmonary exercise tests, a symptom-based questionnaire, and the Short Questionnaire to Assess Health-enhancing physical activity were performed. The results revealed a decreased ventilatory anaerobic threshold compared to control data (z-score - 0.5 (0.8) [median (interquartile range (IQR))], p = 0.001) and, on average, a decreased relative peak oxygen uptake (z-score - 1.3 (2.8), p = 0.005) and relative peak work rate (z-score - 0.7 (1.3), p = 0.03). There were no adverse events during and following prolonged exercise under well-fed circumstances (based on symptoms and post-exercise creatine kinase). The symptom-based questionnaire revealed that the presence of provoking factors (e.g., infection, inadequate intake) increased the risk of rhabdomyolysis during/after exercise. Screening (n = 11) and symptomatically (n = 3) diagnosed patients showed normal levels of physical activity (medians: 3.5 h per week) compared to their healthy peers (3.2 h), despite debilitating muscle pain in 46% of the by screening and all of the symptomatically diagnosed patients. In conclusion, patients with seemingly normal exercise patterns reported debilitating muscle symptoms and rhabdomyolysis, especially when additional provoking factors were present. Exercise tests may provide a valuable tool to monitor and guide exercise potential in these new NBS cohorts.

Waite, R; Royal Infirmary of Edinburgh, NHS Lothian, Edinburgh, UK.
Hargreaves, D

British journal of hospital medicine (London, England : 2005) [Br J Hosp Med (Lond)] 2025 Jul 25; Vol. 86 (7), pp. 1-4.
Date of Electronic Publication: 2025 Jul 04.

Perioperative functional assessment is used to inform perioperative risk estimation and to target interventions such as prehabilitation, particularly in higher-risk cohorts. There are a variety of measures used and practice is variable. UK national guidance recommends cardiopulmonary exercise testing (CPET) or alternative objective measures when reduced functional capacity is identified on screening.

Xu F; Department of Functional Testing Center, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, Beijing, China.
Sun XG; Liu F; Zhai WX; Song Y; Tai WQ; Wang JN; Zhang YF;Zhou QQ; Shi C; Xie B; Chen JH; Huang J; Zhang ZF; Xiang MJ; Ye SD; Li L;

Journal of thoracic disease [J Thorac Dis] 2025 Jun 30; Vol. 17 (6), pp. 3863-3872.
Date of Electronic Publication: 2025 Jun 26.

Background: Gas exchange measurements, such as oxygen uptake ( INLINEMATH ) and carbon dioxide output ( INLINEMATH ), of cardiopulmonary exercise testing (CPET), are the key and gold standard for human cardiopulmonary functional evaluation. However, in terms of quality control, they are unstable and inaccurate. We used a metabolic simulator (MS) to detect measurement errors and enhance quality control.
Methods: In the Fuwai CPET laboratory, we performed CPET after systems had: (I) passed all the steps of regular system calibrations for flow and the partial pressure of O ₂ and CO ₂ ; and (II) passed the MS validation of INLINEMATH and INLINEMATH at low, medium, and high metabolic rates (MRs) daily from 2014 to 2023 for eight different CPET carts/systems. The absolute percentage difference of the 1 ^st validation of both INLINEMATH and INLINEMATH was calculated as follows: |[(measured – ideal) / ideal] × 100%|. A difference of <10% was set as the 1 ^st validation pass standard to run the laboratory, while a difference of ≥10% was classified as a 1 ^st validation failure. The absolute percentage difference of the 1 ^st validation among the eight carts/systems was compared using the Kruskal-Wallis H test. The rate of the 1 ^st validation failure, the number of validation days, and the median absolute percentage difference of the 1 ^st validation among the different CPET carts/systems were clustered using the hierarchical clustering method.
Results: In total, we completed 1,810 validation days for the eight CPET carts/systems, and found a 10,860 absolute percentage difference of the 1 ^st validation of INLINEMATH and INLINEMATH . The number of validation days completed by each cart/system and the 1 ^st validation failure rates were as follows: 8 (87.50%), 10 (90.00%), 54 (48.15%), 349 (43.27%), 20 (45.00%), 759 (21.21%), 525 (29.52%), and 85 (22.35%), respectively. The overall absolute percentage difference of the 1 ^st validation of each cart/system was 7.32% (P ₂₅ , P ₇₅ : 3.67%, 13.82%), 9.12% (P ₂₅ , P ₇₅ : 3.33%, 30.4%), 6.82% (P ₂₅ , P ₇₅ : 4.31%, 9.06%), 5.40% (P ₂₅ , P ₇₅ : 2.60%, 8.26%), 4.90% (P ₂₅ , P ₇₅ : 2.21%, 9.68%), 4.32% (P ₂₅ , P ₇₅ : 2.17%, 6.78%), 5.62% (P ₂₅ , P ₇₅ : 2.96%, 8.19%), and 5.35% (P ₂₅ , P ₇₅ : 2.55%, 7.81%), respectively. The Kruskal-Wallis H test results revealed significant differences among the eight carts/systems (H=274.86, P<0.001), and the pairwise comparisons showed that cart/system F had the lowest absolute percentage difference of 4.32% (P ₂₅ , P ₇₅ : 2.17%, 6.78%). The hierarchical cluster classified carts/systems A and B as one cluster, carts/systems C, E, and H as another cluster, and carts/systems D, F, and G as yet another cluster.
Conclusions: Using an MS can decrease measurement errors and variability for CPET. It can also improve the quality control of CPET.

Ghio S; Division of Cardiology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.;
S. Ghio and M.M. Moschella contributed equally as joint first authors.
Moschella MM; Division of Cardiology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.; authors.
Baccelli A; Department of Respiratory Medicine, Royal Brompton Hospital, Guy’s and St Thomas’ NHS Foundation Trust, London, UK.
Savonitto G; Maldera M; Haji G; Davies R; Howard L; DLo Giudice F;

Aim: The clinical and prognostic role of tricuspid regurgitation (TR) in patients with pulmonary arterial hypertension (PAH) is still underappreciated. The main objective of the present study was to assess the prognostic value of TR in incident PAH patients.
Methods: Consecutive incident PAH patients were enrolled from 2011 to 2021. Patients underwent right heart catheterisation (RHC), cardiopulmonary exercise test (CPET), echocardiography including the degree of TR, tricuspid annular plane systolic excursion (TAPSE), ratio of TAPSE to systolic pulmonary artery pressure (sPAP), right ventricular (RV) areas and right atrial area. The primary end-point of survival analysis was all-cause death.
Results: Compared with patients with mild TR or no TR, those with TR of moderate degree or more had a worse TAPSE and TAPSE/sPAP, similar RV areas at echocardiography, worse peak oxygen consumption at CPET, and higher right atrial pressure and pulmonary vascular resistance at RHC. TR of a moderate degree or more was the only echocardiographic parameter associated with poor survival on Cox regression analyses (hazard ratio 3.34, 95% CI 1.73-6.45; p<0.001). The assessment of TR severity was crucial to determine the prognosis of patients who would have been categorised as low risk based on normal values of TAPSE or TAPSE/sPAP values.
Conclusion: In treatment-naive PAH patients, TR is an important echocardiographic prognostic indicator. In particular, as an emerging concept, assessment of severity of TR is critical to stratify the prognosis of patients who would have been considered at low risk based on normal values of TAPSE or of TAPSE/sPAP.

Kler A; University of Liverpool, UK.; Countess of Chester Hospital NHS Foundation Trust, UK.& other Trusts
Tay J; Slawinski C; Welch C; Moug S;Blackwell S; Arnott R; Mitchell P; Heywood N;

nnals of the Royal College of Surgeons of England [Ann R Coll Surg Engl] 2025 Jul 15.
Date of Electronic Publication: 2025 Jul 15.

Introduction: Surgical resection is the main treatment for non-metastatic colorectal cancer (CRC). However, 6% of patients do not undergo surgery owing to frailty, according to the National Bowel Cancer Audit (NBOCA). The impact of preoperative evaluation and decision making on outcomes in frail patients is underexplored. This study examines variation in decision making for frail, older patients and the availability/use of resources by colorectal multidisciplinary teams (MDTs) across United Kingdom (UK) hospitals.
Methods: A UK-wide questionnaire was distributed to colorectal MDTs via the NBOCA newsletter and social media (18 May to 30 June 2021). Part A assessed MDT structure and resource use; Part B explored MDT decisions for two simulated 75-year-old patients with colonic and rectal cancer.
Results: Twenty MDTs responded. Decisions were MDT-driven in 55% ( n = 11) and surgeon-driven in 45% ( n = 9). Clinical examination (85%) and performance status (90%) were most used. Resource utilisation during MDT meetings varied across sites; for example, echocardiogram results were available and considered in MDT decision making in only 15% of centres. Cardiopulmonary exercise testing was used in 75%, anaesthetic assessment in 80%, frailty scoring in 25%, and preoperative geriatric assessment in 5%. Management of right-sided cancer was more consistent; rectal cancer decisions were more variable.
Conclusions: Variation exists across MDTs in the availability and use of resources when managing frail CRC patients. There is less consensus for rectal than caecal cancer. These findings highlight the need for standardised MDT protocols to support equitable, patient-centred care in complex cases.

Mapelli M; Centro Cardiologico Monzino, IRCCS, Milan, Italy.;
Salvioni E; Mattavelli I; Grilli G; Zerboni G; Nava A; Capra N; Galotta A;Biroli M; Bellini G; Dall’Asta M;Pasini E; De Paola A; Torzolini L; Mani N; Turri S; Campodonico J; Agostoni P;

PloS one [PLoS One] 2025 Jul 16; Vol. 20 (7), pp. e0326661.
Date of Electronic Publication: 2025 Jul 16 (Print Publication: 2025).

Background: Nasal and oral exclusive breathing modes have benefits and drawbacks during submaximal exercise. It is less known whether these responses would extend to anaerobic work performed at high intensity. The purpose of this study is to find the most efficient mode of breathing during different phases of a maximal exercise at cardiopulmonary exercise test (CPET).
Methods: Healthy subjects were recruited to perform 4 maximal CPETs (standard conditions (STD), exclusively nasal breathing (eNAS), exclusively oral breathing (eOR), partial nasal breathing (pNAS) with just one blocked nostril) using the same ramp protocol on an electronically braked cycle ergometer. Before the exercise a standard spirometry was executed in the same order. Twelve healthy subjects (28.6 ± 5.2 y, 50% males) performed the 4 CPETs within one month. Variables were analysed at rest, at anaerobic threshold (AT), at intermediate exercise steps, and at peak.
Results: Compared to STD, eOR, and pNAS conditions, eNAS was associated with a significant lower peakVO2, peakVCO2, peak ventilation, respiratory rate, VE/VCO2 slope, respiratory exchange ratio, and workload (p < 0.05 for all). Moreover, peak inspiration and peak expiration time were augmented, while forced expiratory volume and vital capacity at rest were reduced. Only minor differences were detected at rest or AT. eNAS breathing Borg scale was higher in all phases of the exercise.
Conclusions: In young healthy subjects, an exclusively nasal respiration induces significant impairment on peak exercise capacity at CPET due to ventilatory limitation, with only minor effects on metabolic parameters at rest and in submaximal effort.

Phinicarides R; University Hospital Düsseldorf, Medical Faculty, Division of Cardiology, Düsseldorf, Germany.
Reuter I ; Wolff G; Karathanos A;Heidari H; Masyuk M; Pillekamp F; Kelm M;, Zeus T;, Klein K;

Diagnostics (Basel). 2025 Jun 30;15(13):1672.

Background: Congenital heart disease (CHD) affects approximately 9 per 1000 live births worldwide, with increasing prevalence due to improved survival. Today, over 90% of individuals with CHD reach adulthood, resulting in a growing population of adults with congenital heart disease (ACHD). Despite its clinical relevance, iron deficiency (ID) and anemia have been insufficiently studied in this group.
Objectives: To evaluate the prevalence and clinical impact of iron deficiency and anemia in ACHD, particularly their relationship with exercise capacity. Methods: We retrospectively analyzed 310 ACHD patients at University Hospital Düsseldorf between January 2017 and January 2019. Iron status was assessed using serum ferritin, transferrin saturation (TSAT), and hemoglobin levels. Exercise capacity was measured by cardiopulmonary exercise testing (VO2 max). Prevalence and clinical associations were compared with those reported in heart failure populations, using ESC guideline criteria. Analyses were adjusted for age, sex, and defect complexity.
Results: Iron deficiency (ID) was present in 183 patients (59.0%). Anemia was observed in 13 patients (4.2%), with 6 (46.2%) classified as microcytic and 5 (38.5%) as normocytic. Reduced exercise capacity, defined as VO2 max <80% of predicted, was present in 51 patients (16.5%), occurring more frequently in those with complex CHD (31.3% vs. 11.3%, p < 0.001). ID was associated with a trend toward lower VO2 max (21.3 vs. 23.5 mL/min/kg, p = 0.068), while anemia correlated with significantly reduced performance (19.8 ± 4.1 vs. 22.9 ± 6.3 mL/min/kg, p = 0.041).
Conclusions: Iron deficiency is highly prevalent, and anemia-though less common-was consistently associated with reduced functional capacity in ACHD. These findings highlight the need for targeted screening and management strategies in this growing patient population.

Seese L; Faculty Pavilion, Suite FP5210, UPMC Children’s Hospital of Pittsburgh, 4401 Penn Avenue, Pittsburgh, PA 15224-1334, USA.
Schiff M; Olivieri L; Da Fonseca Da Silva L;  Da Silva JP; Christopher A; Harris TH; Morell V;Castro Medina M; Rathod RH; Kreutzer J; Diaz Castrillon C; Viegas M; Alsaied T; The Force Investigators;

Journal of clinical medicine [J Clin Med] 2025 Jun 09; Vol. 14 (12).
Date of Electronic Publication: 2025 Jun 09.

Background: To explore the differences in exercise capacity between the extracardiac conduit (ECC) and lateral tunnel (LT) Fontan.
Methods: 2169 patients (36% LT ( n = 774); 64% ECC ( n = 1395)) underwent a Fontan operation between 2000 to 2023 in a multi-institutional Fontan registry. LT patients were age-matched to ECC patients, and cardiopulmonary exercise test (CPET) results were compared. Following age-matching and exclusion of those without CPET data, 470 patients emerged with 235 LT and 235 ECC patients.
Results: ECC achieved higher peak heart rates (174 vs. 169 bpm, p = 0.0008) and heart rates at ventilatory anaerobic threshold (VAT) (130 vs. 119 bpm p = 0.0005). Oxygen saturations at peak (93.0 vs. 90.0%, p = 0.0003) and baseline (95 vs. 92.5%, p &lt; 0.0001) were higher in the ECC group. The VO ₂ at VAT was higher in the ECC (17.8 vs. 16.4 mL/kg/min p = 0.0123). Baseline pre-exercise heart rate, peak oxygen pulse, VE/VCO ₂ slope, peak VO ₂ , peak % of predicted VO ₂ , peak work rate, and peak % of predicted work rate were similar (all, p &gt; 0.05). Notably, less than 35% of the cohort had a documented CPET.
Conclusions: We found that the ECC performed statistically better on many parameters of exercise capacity, including the ability to increase heart rate, have higher peak and baseline saturations, and to achieve superior VO ₂ at VAT. However, the magnitude of difference was small, suggesting that the translational value into the clinical realm may be limited. With a minority of the registry patients having CPET completed, this illuminates the need for the implementation of CPET surveillance for Fontan patients.

Blumberg Y; Division of Cardiovascular Medicine, Department of Medicine, Stanford University, Stanford, CA 94305, USA.
de Monts C; Montalvo S; Tang WJ; Hageman N;   Sanchis-Gomar F; Ashley EA; Amar D; Myers J; Wheeler MT; Day JW; Duong T; Christle JW;

Journal of clinical medicine [J Clin Med] 2025 Jun 12; Vol. 14 (12).
Date of Electronic Publication: 2025 Jun 12.

Background: Individuals with neuromuscular diseases (NMDs) have low physical activity levels and an increased risk of cardiovascular and pulmonary diseases. Respiratory gas kinetics obtained during cardiopulmonary exercise testing (CPET) may provide valuable insights into disease mechanisms and cardiorespiratory fitness in individuals with NMD. Recovery from exercise is an important marker of exercise performance and overall physical health, and impaired recovery is strongly associated with poor health outcomes. This study evaluates recovery metrics in individuals with NMD after performing maximal exertion during CPET.
Methods: A total of 34 individuals with NMD and 15 healthy volunteers were recruited for the study. CPET was performed using a wearable metabolic system and a wheelchair-accessible total body trainer to peak exertion. Recovery metrics assessed were (i) the time to reach 50% O ₂ recovery compared with peak exercise and (ii) the ratios of ventilation and respiratory gases between peak exercise and the highest values observed during recovery (overshoot).
Results: The NMD group had a significantly longer time to reach 50% O ₂ recovery (T1/2 VO ₂ : 105 ± 43.4 vs. 76 ± 36.4 s, p = 0.02), lower respiratory overshoot (17.1 ± 13.0% vs. 28.8 ± 9.03%), and lower ventilation/VO ₂ (31.9 ± 28.3 vs. 52.2 ± 23.5) compared to the control group.
Conclusions: This study observes significantly impaired recovery metrics following peak exercise in individuals with NMD compared to controls. These insights may improve the understanding of exercise recovery and mechanics, thus improving prognostication and optimizing exercise prescriptions for individuals with NMD.

Ferguson C; The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA.
Furrer R; Murach KA; Hepple RT; Rossiter HB;

Medicine and science in sports and exercise [Med Sci Sports Exerc] 2025 Jun 23.
Date of Electronic Publication: 2025 Jun 23.

Abstract: Introduction. Peak neuromuscular power and endurance are distinct qualities of dynamic exercise performance. Dynamometry is used to assess peak neuromuscular power, often during performance across a single joint e.g., isotonic or isokinetic torque, while aptitude for endurance exercise may be inferred by measurement of critical power/speed or cardiopulmonary exercise testing to determine e.g., gas exchange threshold (GET), maximum oxygen uptake (V̇O2max) and exercise economy. Specificity is a critical component of any training program, but oversimplification of the specificity principle has contributed to the view that training adaptations to increase peak neuromuscular power or the ability to endure high power outputs are mutually exclusive, due to: (i) differences in the types of motor units recruited and their patterns of activation; and (ii) induction of distinct, antagonistic molecular signaling pathways in response to resistance and endurance exercise training (the “interference effect”).
Methods, Results and Conclusion. This review explores evidence for reciprocation between peak neuromuscular power and endurance performance in sport, aging and among general and clinical populations. We also review the molecular events that mediate peak neuromuscular power and endurance training adaptations and their interactions. Finally, we describe the musculo-cardio-pulmonary exercise test (mCPET) to demonstrate that peak neuromuscular power and aerobic mediators of endurance performance are less polar opposites and more willing partners.
Competing Interests: Conflict of Interest and Funding Source: Carrie Ferguson is supported by a grant from NIH (R01HL166850; 5UH3HL155798). She is involved in contracted clinical research with United Therapeutics, Genentech, Regeneron, Respira Therapeutics and Mezzion. She reports consulting fees from Respira Therapeutics. Kevin Murach is supported by NIH R00 AG063994 and R01 AG080047. Russell Hepple is supported by grants from NIH (R21AR084591, R01AG059416, and R01AG076490). Harry Rossiter is supported by grants from NIH (R01HL151452, R01HL166850, R01HL153460, P50HD098593, R01DK122767), Tobacco Related Disease Research Program (T31IP1666) and Department of Defense / USAMRAA (HT9425-24-1-0249). He reports consulting fees from the NIH RECOVER-ENERGIZE working group (1OT2HL156812), and is involved in contracted clinical research with Astellas, GlaxoSmithKline, Genentech, Intervene Immune, Mezzion, Regeneron, Respira, Roche, and United Therapeutics.