Author Archives: Paul Older

Exploring the association between socioeconomic status and cardiopulmonary exercise testing measures: A cohort study based on routinely collected data.

Shrestha, D; Lancaster Medical School, Lancaster University, Lancaster, United Kingdom.;
Wisely, N; Bampouras, T; Subar, D et al

PloS one,2025 Aug 12

  • Background: Cardiopulmonary exercise testing (CPET) provides objective measures of cardiorespiratory fitness and can support surgical risk stratification. As socioeconomic status is a factor known to influence patient health and outcomes, we analysed how CPET-derived measures vary across levels of socioeconomic status in patients being considered for elective surgery.
  • Methods: A database of patients who underwent CPET between 2011 and 2024 was analysed. Measures including oxygen consumption (V̇O₂) at gas exchange threshold (GET), peak V̇O₂, and ventilatory equivalent for carbon dioxide (VE/V̇CO₂) were compared across socioeconomic deprivation quintiles. Multivariable linear and logistic regression models assessed the effects of age, sex, body mass index (BMI), Revised Cardiac Risk Index (RCRI), and deprivation quintiles on CPET measures. Hierarchical regression models incorporating the Indices of Deprivation (IoD) domains and Access to Healthy Assets and Hazards (AHAH) scores determined whether wider social determinants of health explained the variance in CPET measures.
  • Results: A total of 3344 patients (2476 male) were included, referred prior to procedures in vascular (2006), colorectal (650), upper GI (267), urology (205), and other (216) surgical specialties. Lower socioeconomic status was associated with younger age (p < 0.001), higher BMI (p = 0.022), higher smoking prevalence (p < 0.001), and RCRI ≥3 (p = 0.013). CPET measures were lower in the most deprived quintile (Q1) compared to the least (Q5): mean GET was 11.0 vs. 11.5 ml·kg-1·min-1 and peak V̇O2 was 14.8 vs. 16.3 ml·kg-1·min-1 (p < 0.05). Deprivation remained an independent predictor of lower GET and peak V̇O2, even after adjustment. Several IoD and AHAH domains explained small but significant variance in CPET measures.
  • Conclusion: Patients from more deprived areas exhibit risk factors for poor health and lower cardiorespiratory fitness as measured by CPET. These findings add to our understanding of socioeconomic disparities in physiological reserve among surgical patients and may support the need for more holistic approaches to peri-operative care.

Cardiopulmonary exercise testing in hypertrophic cardiomyopathy: the role of reduced O2 pulse and chronotropic incompetence in myocardial adaptation.

Willixhofer, R; Centro Cardiologico Monzino, IRCCS, Via Parea 4, Milan 20138, Italy.;
Mapelli, M; Baracchini, N; Campana, N; et al

European journal of preventive cardiology,2025 Aug 07

  • Aims: Hypertrophic cardiomyopathy (HCM) is associated with functional limitations during exercise. We aimed to evaluate oxygen pulse (O2p) as a stroke volume (SV) surrogate and to propose a new HCM classification (RoMa) based on haemodynamic profiles during exercise: predicted peak O2p (O2pp) and peak heart rate (HRpp).
  • Methods and Results: This multicentre, prospective study included 90 clinically stable HCM patients who underwent cardiopulmonary exercise testing with simultaneous impedance cardiography (PhysioFlow®). We assessed the relationship between SV and O2p. Patients were stratified into four groups based on HRpp (≥80% predicted) and O2pp (≥100% predicted): RoMa I (high HRpp-high O2pp), RoMa II (high HRpp-low O2pp), RoMa III (low HRpp-high O2pp), and RoMa IV (low HRpp-low O2pp). Oxygen uptake (VO2), minute ventilation-to-carbon dioxide production (VE/VCO2) slope, SV, and mitral regurgitation (MR) were analysed. Patients (80% male, 53 [42-64] years) had preserved left ventricular ejection fraction (62 [58-68]%) and peakVO2 (23.1 ± 7.8 mL/min/kg = 81 ± 21% predicted). SV correlated with O2p (r = 0.48, P < 0.001; β = 3.59, P < 0.001). Resting moderate to severe MR was more prevalent in RoMa class IV (41%) vs. RoMa I (18%, P = 0.038). PeakVO2 declined across groups, from 29.7 ± 8.3 (RoMa I) to 16.2 ± 5.1 mL/min/kg (RoMa IV, P < 0.001). VE/VCO2 slope increased from 26.4 ± 4.5 (RoMa I) to 38.6 ± 6.0 (RoMa IV, P = 0.002). Peak SV decreased from 128.7 ± 24.8 (RoMa I) to 104.7 ± 28.0 mL (RoMa IV, P = 0.019), while rest to peak SV difference dropped from 38.6 (30.4-52.8) to 15.8 (8.2-27.9) mL (P = 0.002).
  • Conclusion: SV and O2p are significantly related, and the RoMa classification effectively distinguished HCM patients.
  • Key Findings: O2p is a reliable indicator of SV, helping to better understand exercise limitations in HCM patients.The newly introduced RoMa classification effectively distinguishes different levels of exercise impairment in HCM, linking poorer heart function to lower oxygen uptake and higher breathing inefficiency.

An update on clinical recommendations for cardiopulmonary exercise testing in children with respiratory diseases.

Takken, T; Wilhelmina Children’s Hospital, University Medical Center Utrecht, Utrecht, the Netherlands.
Ruuls, T; Van der Kamp, M;Thio, B; et al

Expert review of respiratory medicine,2025 Aug 14

  • Introduction: Cardiopulmonary exercise testing (CPET) is a diagnostic-integrated tool for evaluating cardiovascular, ventilatory, and metabolic functional limitations in children with respiratory diseases. Recently, novel applications have emerged, revealing dynamic abnormalities that may go unnoticed in standard static cardiac and pulmonary function tests. Given its clinical importance and novel research findings, updated recommendations are warranted.
  • Areas Covered: We conducted a narrative review based on a literature search up to April 2025. This review provides an update on the application of CPET in pediatric respiratory diseases, covering physiological differences to adults, non-traditional CPET metrics such as the oxygen uptake efficiency slope (OUES), tidal volume to inspiratory time ratio (VT/Ti), and recent reference values. Indications, contraindications, and standardized protocols are discussed, alongside emerging trends in CPET technology.
  • Expert Opinion: CPET is a potent tool for assessing, evaluating, and diagnosing pediatric respiratory diseases. Standardized protocols, age-specific reference values, and novel CPET parameters enhance clinical utility. Future research should refine interpretation, integrate artificial intelligence for data analysis, and facilitate CPET for younger children.

 

Expanding the concept of pharma-cise: A graphical primer for clinicians, researchers and industry.

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.

Physiological responses to matched ramp-incremental exercise on recumbent cycle ergometer and treadmill in patients with heart failure.

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.

Preoperative Exercise to Improve Fitness in Patients Undergoing Complex Surgery for Cancer of the Lung or Esophagus (PRE-HIIT): A Randomised Controlled Trial.

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.

Physiological Responses to Sit-to-Stand and Six-Minute Walk Tests in Heart Failure: A Randomised Trial.

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.

Myopathic Symptoms and Exercise Tolerance in Adolescent Patients With Long-Chain Fatty Acid Oxidation Disorders.

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.

Perioperative Functional Assessment.

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.