Arena R; Department of Physical Therapy, College of Applied Science, University of Illinois, Chicago, IL, USA;
Myers J; Pronk NP;

Current problems in cardiology [Curr Probl Cardiol] 2025 Aug 05; Vol. 50 (10), pp. 103144.
Date of Electronic Publication: 2025 Aug 05.

A human’s ability to transfer oxygen from the environment to skeletal muscle and conversely remove carbon dioxide from skeletal muscle back to the environment during physical exertion is a critical representation of healthy longevity and functional capacity. Cardiorespiratory fitness (CRF) is the accepted construct for the assessment of oxygen consumption (VO ₂ ) and carbon dioxide production (VCO ₂ ) – CRF is most accurately quantified through cardiopulmonary exercise testing (CPET) in the clinical setting. All pharmacological interventions, from experimental to approved and on the market, are meant to impact one or more human physiological processes. In this context, the graphical primer on the physiological process of VO ₂ and VCO ₂ presented herein should facilitate the thought process on how pharmacology interacts with the factors that influence the capacity for physical exertion. Exercise is medicine and CRF is a vital sign and as such, the former should be prescribed to all capable individuals, and the latter should be considered a primary efficacy outcome measure in clinical and research settings. There is an opportunity to synergize and further enhance patient outcomes when pharmacologic and exercise interventions are considered integrated and in combination- a concept recently defined as pharma-cise – the graphical primer is proposed to facilitate application of this concept.

Silva RN; Division of Respiratory and Critical Care Physiology and Medicine, Harbor-UCLA Medical Center, Torrance, CA, USA.
Porszasz J; Ferguson C; Rehder-Santos P;Roscani MG; de Oliveira CR; Catai AM; Stringer WW; Borghi-Silva A;

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

Exercise intolerance is a cardinal symptom in patients with heart failure (HF), and cardiopulmonary exercise testing (CPET) is the gold standard method for its assessment. The treadmill and cycle ergometers (upright and recumbent) are used in clinical practice for tracking disease progression and risk stratification, therefore, understanding the physiological differences related to ergometer is important. The aim of this study was to compare the physiological responses to exercise on treadmill and recumbent cycle ergometer in patients with HF with reduced ejection fraction (HFrEF) using a linear ramp protocol matched with controlled work rate (WR) profiles. Thirteen patients with HFrEF (left ventricular ejection fraction: 34.5% [28.7-47%]) were included. They performed two randomized ramp-incremental CPETs, on recumbent cycle and treadmill, both with incrementation rates of 10 watts per minute (W/min). The cardiorespiratory data obtained in both tests were WR-aligned and iso-WR responses were compared. Patients reached similar WR peak on both exercise modalities (84 ± 23 vs 91 ± 26 watts, P = 0.133, for recumbent cycle and treadmill, respectively) with no differences in ventilatory efficiency ( INLINEMATH / INLINEMATH CO ₂ slope) (30.8 ± 4.7 vs 30.9 ± 7.3, P = 0.981). However, exercising on recumbent cycle resulted in lower peak oxygen uptake ( INLINEMATH O ₂ ) (13.4 [11.3-15.9] vs 15.8 [14.7-18.4] mL/kg/min, p = 0.002) and higher Weber HF severity classification (p = 0.034). Considering the higher INLINEMATH O ₂ peak reached and its role in clinical decision-making-despite similar INLINEMATH / INLINEMATH CO ₂ slope between ergometers-treadmill should be considered the optimal ergometer for exercise intolerance and risk stratification assessment in patients with HFrEF, since it reflects a more accurate exercise capacity and disease severity.

Competing Interests: Declarations. Conflict of interest: The authors declare no conflicts of interest. Financial support: Rebeca Nunes Silva reports financial support for the present study from Coordination for the Improvement of Higher Educational Personnel (CAPES), Brazil (CAPES 001 – PhD Scholarship; CAPES PrInt – Program #6685). Janos Porszasz receives royalty payments from a CPET book from Wolters Kluwer. Carrie Ferguson is supported by grants 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.  She is a visiting Associate Professor at the University of Leeds, UK. Patrícia Rehder-Santos has no research funding to declare. Meliza Goi Roscani reports financial support from São Paulo Research Foundation (FAPESP) (Grants #2021/05231–7 and #2023/04876–0). Claudio Ricardo Oliveira has no research funding to declare. Aparecida Maria Catai is supported by the National Council for Scientific and Technological Development (CNPq – level 1A Research Fellow, #310,612/2019–5) and receives financial support from FAPESP (#2016/22215-7). William Stringer is involved in contracted clinical research with Genentech, Regeneron, Roche, AstraZeneca and the NIH Recover-Vital and Recover-Neuro clinical trials. He performs CPET Data Center activities for the NIH funded PETRACT study (UG3HL155798-01A1). He is a co-investigator on an NIH Small Business Innovation Award (1R43HL167289-01) and has been a site PI for the NIH RETHINC (5U01HL128954‐04) and BLOCK-COPD (W81XWH-15–1-0705) studies. He performs Data Safety Monitoring Board activities for SYNEOS and CAPRICOR. He receives royalty payments from a CPET book from Wolters Kluwer. He is a paid consultant for Genentech, Verona and Regeneron. He owns stock in HIA. Audrey Borghi-Silva is involved in research grants from FAPESP (Grant #2015/26/501–1), CAPES-Brazil (CAPES-001), and CNPq-Brazil (Grant #201,157/2024–1) with national and international collaboration. Audrey Borghi-Silva is an established Investigator (level 1B) of CNPq. Currently, she is advisor of the scientific board of FAPESP.

Smyth E; Discipline of Physiotherapy, School of Medicine, Trinity College Dublin, Ireland.; Trinity St. James’s Cancer Institute, Ireland.
Kearney N; Sheill G; Wade S; Brennan L; Grehan S; Begic S; Egaña M; Ryan R; Fitzmaurice GJ; Murphy R; McKittrick M; Doyle SL; Walsh C; Ravi N;
Donohoe CL; Reynolds JV; Hussey J;Guinan EM;

Annals of surgery [Ann Surg] 2025 Aug 06.
Date of Electronic Publication: 2025 Aug 06.

Objective: This randomised controlled trial (RCT) compared the impact of high-intensity interval training (HIIT) versus standard care (SC) on preoperative cardiopulmonary fitness in patients prior to esophageal or lung cancer surgery.
Summary of Background Data: Exercise prehabilitation aims to optimise preoperative condition and attenuate postoperative risks. Although intuitive, defining the optimal training parameters to impact physiologically prior to surgery with attendant clinical benefit remains challenging.
Methods: Utilising a parallel, two-armed RCT design, n=79 participants ((mean age (SD) 64 (9.3), 67% males) scheduled for curative resection for lung (50.6%) or esophageal (49.6%) cancer with ≥2-weeks preoperative lead-in, were recruited and randomised to HIIT (n=41) or SC (n=38). HIIT was completed on an electronically braked cycle ergometer consisting of 30-minutes of 15-seconds intervals at 100% peak power output alternating with 15-second active recovery for five days/week. The SC arm was offered moderate-intensity exercises 2-3 days/week. The primary outcome was peak oxygen consumption (VO2peak), measured by cardiopulmonary exercise testing. Secondary outcomes included lower limb strength and physical functioning.
Results: Baseline cardiopulmonary fitness was predominantly very poor (n=75 (95%)). Adjusting for baseline in a linear model, VO2peak increased significantly (P=0.05) in the HIIT group vs SC (6.6% between-group difference). HIIT increased VO2peak from 18.7 (5.0) to 21.7 (5.7) ml/kg/min while with SC it remained unchanged at 19.6 (5.4) to 20.1 (5.7) ml/kg/min) from pre- to post-intervention. Sit-to-stand scores were significantly (P=0.02) improved with HIIT.
Conclusion: HIIT is effective for eliciting meaningful gains in preoperative fitness in a deconditioned cohort within short timeframes.

O’Connor FK; School of Health Sciences and Social Work, Griffith University, Southport, Qld, Australia.
Chen D; Sharma P; Adsett J; Hwang R; Roberts L; Bach A; Louis M; Morris N;

Heart, lung & circulation [Heart Lung Circ] 2025 Aug; Vol. 34 (8), pp. 789-797.
Date of Electronic Publication: 2025 Jun 20.

Background: Short-duration sit-to-stand tests are utilised in rehabilitation settings to alleviate logistical challenges associated with the six-minute walk test (6MWT). We assessed the utility of the 30-second sit-to-stand (30-STST) and 60-second sit-to-stand (60-STST) tests as surrogate measures of the 6MWT.
Method: On separate days, 16 male participants (71 [7] years) with stable heart failure with reduced ejection fraction (36.9 [4.9] %) completed two 6MWT and the 30-STST and 60-STST. Pulmonary gas exchange (oxygen consumption, carbon dioxide production [V˙CO ₂ ], ventilation [V˙ _E ], respiratory exchange ratio, ventilatory equivalent for CO ₂ [V˙ _E /V˙CO ₂ ] and partial pressure of end-tidal CO ₂ [P _ET CO ₂ ]) was measured using a portable metabolic system. Non-invasive haemodynamics (cardiac output, stroke volume, arteriovenous oxygen difference) were measured using impedance cardiography. Mean arterial pressure, heart rate, oxygen saturation and dyspnoea (0-10 scale, arbitrary units) were also monitored. Mixed-effects models (Bonferroni corrected) accounting for time (pre-exercise rest, end-exercise) and test (6MWT, 30-STST, and 60-STST) were used to assess the relation between results observed during each testing modality.
Results: While P _ET CO ₂ (mean difference [95% confidence interval], -4.9 [-8.9 to -0.8] mmHg), and dyspnoea (1 [0-2] arbitrary units) differed between the 6MWT and 60-STST, no other differences were observed between these tests. In contrast, oxygen consumption (-0.5 [-0.6 to -0.3] L.min ^-1 ), V˙CO ₂ (-0.5 [-0.7 to -0.4] L.min ^-1 ), V˙ _E (-18.3 [-26.0 to -10.0] L.min ^-1 ), P _ET CO ₂ (-5.1 [-9.6 to -0.7] mmHg), cardiac output (-2.4 [-4.9 to -0.3] L.min ^-1 ), heart rate (-20 [-33 to -7] beats/min) differed between the 6MWT and the 30-STST, however, no other differences were observed between the 6MWT and the 30-STST.
Conclusions: Cardiopulmonary, non-invasive haemodynamic and dyspnoea responses differed between the 30-STST and the 6MWT. However, the lack of test-specific differences between the 6MWT and the 60-STST highlights the strong physiological stimulus elicited by this short-duration test modality. The 60-STST has promising utility as a functional measure of heart and lung capacity within cardiac rehabilitation programs.

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.