Leonardi B; Department of Pediatric Cardiology, Cardiac Surgery and Heart Lung Transplantation, Bambino Gesù Children’s Hospital, IRCCS, 00165 Rome, Italy.
Sollazzo F; Gentili F; Bianco M; Pomiato E; Kikina SS; Wald RM;Palmieri V; Secinaro A; Calcagni G; Butera G; Giordano U; Cafiero G; Drago F;

Journal of clinical medicine [J Clin Med] 2024 Feb 20; Vol. 13 (5). Date of Electronic Publication: 2024 Feb 20.

Background: Despite a successful repair of tetralogy of Fallot (rToF) in childhood, residual lesions are common and can contribute to impaired exercise capacity. Although both cycle ergometer and treadmill protocols are often used interchangeably these approaches have not been directly compared. In this study we examined cardiopulmonary exercise test (CPET) measurements in rToF.
Methods: Inclusion criteria were clinically stable rToF patients able to perform a cardiac magnetic resonance imaging (CMR) and two CPET studies, one on the treadmill (incremental Bruce protocol) and one on the cycle ergometer (ramped protocol), within 12 months. Demographic, surgical and clinical data; functional class; QRS duration; CMR measures; CPET data and international physical activity questionnaire (IPAQ) scores of patients were collected.
Results: Fifty-seven patients were enrolled (53% male, 20.5 ± 7.8 years at CPET). CMR measurements included a right ventricle (RV) end-diastolic volume index of 119 ± 22 mL/m ² , a RV ejection fraction (EF) of 55 ± 6% and a left ventricular (LV) EF of 56 ± 5%. Peak oxygen consumption (VO₂ )/Kg (25.5 ± 5.5 vs. 31.7 ± 6.9; p < 0.0001), VO ₂ at anaerobic threshold (AT) (15.3 ± 3.9 vs. 22.0 ± 4.5; p < 0.0001), peak O₂ pulse (10.6 ± 3.0 vs. 12.1± 3.4; p = 0.0061) and oxygen uptake efficiency slope (OUES) (1932.2 ± 623.6 vs. 2292.0 ± 639.4; p < 0.001) were significantly lower on the cycle ergometer compared with the treadmill, differently from ventilatory efficiency (VE/VCO₂ ) max which was significantly higher on the cycle ergometer (32.2 ± 4.5 vs. 30.4 ± 5.4; p < 0.001). Only the VE/VCO₂ slope at the respiratory compensation point (RCP) was similar between the two methodologies ( p = 0.150).
Conclusions: The majority of CPET measurements differed according to the modality of testing, with the exception being the VE/VCO₂ slope at RCP. Our data suggest that CPET parameters should be interpreted according to test type; however, these findings should be validated in larger populations and in a variety of institutions.

Hijleh AA;  Department of Medicine, Queen’s University, Kingston, Ontario, Canada.
Wang S; Berton DC; Neder-Serafini I;Vincent S; James M; Domnik N; Phillips D; Nery LE; O’Donnell DE; Neder JA

Scandinavian journal of medicine & science in sports [Scand J Med Sci Sports] 2024 Apr; Vol. 34 (4), pp. e14625.

Heightened sensation of leg effort contributes importantly to poor exercise tolerance in patient populations. We aim to provide a sex- and age-adjusted frame of reference to judge symptom’s normalcy across progressively higher exercise intensities during incremental exercise. Two-hundred and seventy-five non-trained subjects (130 men) aged 19-85 prospectively underwent incremental cycle ergometry. After establishing centiles-based norms for Borg leg effort scores (0-10 category-ratio scale) versus work rate, exponential loss function identified the centile that best quantified the symptom’s severity individually. Peak O ₂ uptake and work rate (% predicted) were used to threshold gradually higher symptom intensity categories. Leg effort-work rate increased as a function of age; women typically reported higher scores at a given age, particularly in the younger groups (p < 0.05). For instance, “heavy” (5) scores at the 95th centile were reported at ~200 W (<40 years) and ~90 W (≥70 years) in men versus ~130 W and ~70 W in women, respectively. The following categories of leg effort severity were associated with progressively lower exercise capacity: ≤50th (“mild”), >50th to <75th (“moderate”), ≥75th to <95th (“severe”), and ≥ 95th (“very severe”) (p < 0.05). Although most subjects reporting peak scores <5 were in “mild” range, higher scores were not predictive of the other categories (p > 0.05). This novel frame of reference for 0-10 Borg leg effort, which considers its cumulative burden across increasingly higher exercise intensities, might prove valuable to judging symptom’s normalcy, quantifying its severity, and assessing the effects of interventions in clinical populations.

Hamilton B; School of Sport and Health Sciences, University of Brighton, Brighton, UK.;
Brown A; Montagner-Moraes S; Comeras-Chueca C; Bush PG; Guppy FM; Pitsiladis YP;

British journal of sports medicine [Br J Sports Med] 2024 Apr 10.
Date of Electronic Publication: 2024 Apr 10.

Objective: The primary objective of this cross-sectional study was to compare standard laboratory performance metrics of transgender athletes to cisgender athletes.
Methods: 19 cisgender men (CM) (mean±SD, age: 37±9 years), 12 transgender men (TM) (age: 34±7 years), 23 transgender women (TW) (age: 34±10 years) and 21 cisgender women (CW) (age: 30±9 years) underwent a series of standard laboratory performance tests, including body composition, lung function, cardiopulmonary exercise testing, strength and lower body power. Haemoglobin concentration in capillary blood and testosterone and oestradiol in serum were also measured.
Results: In this cohort of athletes, TW had similar testosterone concentration (TW 0.7±0.5 nmol/L, CW 0.9±0.4 nmol/), higher oestrogen (TW 742.4±801.9 pmol/L, CW 336.0±266.3 pmol/L, p=0.045), higher absolute handgrip strength (TW 40.7±6.8 kg, CW 34.2±3.7 kg, p=0.01), lower forced expiratory volume in 1 s:forced vital capacity ratio (TW 0.83±0.07, CW 0.88±0.04, p=0.04), lower relative jump height (TW 0.7±0.2 cm/kg; CW 1.0±0.2 cm/kg, p<0.001) and lower relative V̇O ₂ max (TW 45.1±13.3 mL/kg/min/, CW 54.1±6.0 mL/kg/min, p<0.001) compared with CW athletes. TM had similar testosterone concentration (TM 20.5±5.8 nmol/L, CM 24.8±12.3 nmol/L), lower absolute hand grip strength (TM 38.8±7.5 kg, CM 45.7±6.9 kg, p = 0.03) and lower absolute V̇O ₂ max (TM 3635±644 mL/min, CM 4467±641 mL/min p = 0.002) than CM.
Conclusion: While longitudinal transitioning studies of transgender athletes are urgently needed, these results should caution against precautionary bans and sport eligibility exclusions that are not based on sport-specific (or sport-relevant) research.
Competing Interests: Competing interests: YPP is a member of the IOC Medical and Scientific Commission, which recently published articles and framework documents on the topic. BH and FMG have recently published articles on the topic on behalf of the International Federation of Sports Medicine (FIMS). All authors declare no further conflict of interest or competing interests.
(© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Wolf C;  University of Pittsburgh & other American Universities
Blackwell TL; Johnson E;Glynn NW; Nicklas B; Kritchevsky SB; Carnero EA; Cummings SR;Toledo FGS; Newman AB; Forman DE; Goodpaster BH;

Medicine and science in sports and exercise [Med Sci Sports Exerc] 2024 Apr 11.
Date of Electronic Publication: 2024 Apr 11.

Purpose: Cardiorespiratory fitness (CRF) measured by peak oxygen consumption (VO 2 peak) declines with aging and correlates with mortality and morbidity. Cardiopulmonary Exercise Testing (CPET) is the criterion method to assess CRF, but its feasibility, validity and reliability in older adults is unclear. Our objective was to design and implement a dependable, safe and reliable CPET protocol in older adults.
Methods: VO 2 peak was measured by CPET, performed using treadmill exercise in 875 adults ≥70 years in the Study of Muscle, Mobility and Aging (SOMMA). The protocol included a symptom-limited peak (maximal) exercise and two submaximal walking speeds. An adjudication process was in place to review tests for validity if they met any prespecified criteria [VO 2 peak < 12.0 ml/kg/min; maximum heart rate (HR) <100 bpm; respiratory exchange ratio (RER) <1.05 and a rating of perceived exertion <15]. A subset (N = 30) performed a repeat test to assess reproducibility.
Results: CPET was safe and well tolerated, with 95.8% of participants able to complete the VO 2 peak phase of the protocol. Only 56 (6.4%) participants had a risk alert and only two adverse events occurred: a fall and atrial fibrillation. Mean ± SD VO 2 peak was 20.2 ± 4.8 mL/kg/min, peak HR 142 ± 18 bpm, and peak RER 1.14 ± 0.09. Adjudication was indicated in 47 tests; 20 were evaluated as valid, 27 as invalid (18 data collection errors, 9 did not reach VO 2 peak). Reproducibility of VO 2 peak was high (intraclass correlation coefficient = 0.97).
Conclusions: CPET was feasible, effective and safe for older adults, including many with multimorbidity or frailty. These data support a broader implementation of CPET to provide insight into the role of CRF and its underlying determinants of aging and age-related conditions.
Competing Interests: Conflict of Interest and Funding Source: None of the authors have conflicts of interest to report. The Study of Muscle, Mobility and Aging is supported by funding from the National Institute on Aging, grant number AG059416. Study infrastructure support was funded in part by NIA Claude D. Pepper Older American Independence Centers at University of Pittsburgh (P30AG024827) and Wake Forest University (P30AG021332) and the Clinical and Translational Science Institutes, funded by the National Center for Advancing Translational Science, at Wake Forest University (UL1 0TR001420).

Carrick L; Centre of Metabolism, Ageing & Physiology (COMAP),  Department of Surgery and Anaesthetics Royal Derby Hospital UK.
Doleman B; Wall J; Gates A; Lund JN; Williams JP; Phillips BE;

Aging medicine (Milton (N.S.W)) [Aging Med (Milton)] 2023 Dec 26; Vol. 7 (1), pp. 60-66.
Date of Electronic Publication: 2023 Dec 26 (Print Publication: 2024).

Objectives: Cardiorespiratory fitness (CRF) declines with advancing and has also, independent of age, been shown to be predictive of all-cause mortality, morbidity, and poor clinical outcomes. In relation to the older patient, there is a particular wealth of evidence highlighting the relationship between low CRF and poor surgical outcomes. Cardiopulmonary exercise testing (CPET) is accepted as the gold-standard measure of CRF. However, this form of assessment has significant personnel and equipment demands and is not feasible for those with certain age-associated physical limitations, including joint and cardiovascular comorbidities. As such, alternative ways to assess the CRF of older patients are very much needed.
Methods: Sixty-four participants (45% female) with a median age of 74 (65-90) years were recruited to this study via community-based advertisements. All participants completed three tests of physical function: (1) a step-box test; (2) handgrip strength dynamometry; and (3) a CPET on a cycle ergometer; and also had their muscle architecture (vastus lateralis) assessed by B-mode ultrasonography to provide measures of muscle thickness, pennation angle, and fascicle length. Multivariate linear regression was then used to ascertain bedside predictors of CPET parameters from the alternative measures of physical function and demographic (age, gender, body mass index (BMI)) data.
Results: There was no significant association between ultrasound-assessed parameters of muscle architecture and measures of CRF. VO _2peak was predicted to some extent from fast step time during the step-box test, gender, and BMI, leading to a model that achieved an R ² of 0.40 ( p  < 0.001). Further, in aiming to develop a model with minimal assessment demands (i.e., using handgrip dynamometry rather than the step-box test), replacing fast step time with non-dominant HGS led to a model which achieved an R ² of 0.36 ( p  < 0.001). Non-dominant handgrip strength combined with the step-box test parameter of fast step time and BMI delivered the most predictive model for VO _2peak with an R ² of 0.45 ( p  < 0.001).
Conclusions: Our findings show that simple-to-ascertain patient characteristics and bedside assessments of physical function are able to predict CPET-derived CRF. Combined with gender and BMI, both handgrip strength and fast step time during a step-box test were predictive for VO _2peak . Future work should apply this model to a clinical population to determine its utility in this setting and to explore if simple bedside tests are predictive of important clinical outcomes in older adults (i.e., post-surgical complications).

Fleurent-Grégoire C;  Montreal, Canada & Melbourne, Australia & Manchester and Southampton UK
Burgess N; Denehy L; Edbrooke L; Engel D; Dario Testa G; Fiore JF Jr;McIsaac DI;Chevalier S; Moore J; Grocott MP;Copeland R;
Levett D; Scheede-Bergdahl C; Gillis C;

British journal of anaesthesia [Br J Anaesth] 2024 Apr 02.
Date of Electronic Publication: 2024 Apr 02.

Background: Heterogeneity of reported outcomes can impact the certainty of evidence for prehabilitation. The objective of this scoping review was to systematically map outcomes and assessment tools used in trials of surgical prehabilitation.
Methods: MEDLINE, EMBASE, PsychInfo, Web of Science, CINAHL, and Cochrane were searched in February 2023. Randomised controlled trials of unimodal or multimodal prehabilitation interventions (nutrition, exercise, psychological support) lasting at least 7 days in adults undergoing elective surgery were included. Reported outcomes were classified according to the International Society for Pharmacoeconomics and Outcomes Research framework.
Results: We included 76 trials, mostly focused on abdominal or orthopaedic surgeries. A total of 50 different outcomes were identified, measured using 184 outcome assessment tools. Observer-reported outcomes were collected in 86% of trials (n=65), with hospital length of stay being most common. Performance outcomes were reported in 80% of trials (n=61), most commonly as exercise capacity assessed by cardiopulmonary exercise testing. Clinician-reported outcomes were included in 78% (n=59) of trials and most frequently included postoperative complications with Clavien-Dindo classification. Patient-reported outcomes were reported in 76% (n=58) of trials, with health-related quality of life using the 36- or 12-Item Short Form Survey being most prevalent. Biomarker outcomes were reported in 16% of trials (n=12) most commonly using inflammatory markers assessed with C-reactive protein.
Conclusions: There is substantial heterogeneity in the reporting of outcomes and assessment tools across surgical prehabilitation trials. Identification of meaningful outcomes, and agreement on appropriate assessment tools, could inform the development of a prehabilitation core outcomes set to harmonise outcome reporting and facilitate meta-analyses.

Waxman AB; Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA (A.B.W., D.M.S.).
Systrom DM; Manimaran S; Lu J; Rischard FP;

Circulation. Heart failure [Circ Heart Fail] 2024 Apr 04, pp. e011227.
Date of Electronic Publication: 2024 Apr 04.

Background: This study aims to assess the impact of sotatercept on exercise tolerance, exercise capacity, and right ventricular function in pulmonary arterial hypertension.
Methods: SPECTRA (Sotatercept Phase 2 Exploratory Clinical Trial in PAH) was a phase 2a, single-arm, open-label, multicenter exploratory study that evaluated the effects of sotatercept by invasive cardiopulmonary exercise testing in participants with pulmonary arterial hypertension and World Health Organization functional class III on combination background therapy. The primary end point was the change in peak oxygen uptake from baseline to week 24. Cardiac magnetic resonance imaging was performed to assess right ventricular function.
Results: Among the 21 participants completing 24 weeks of treatment, there was a significant improvement from baseline in peak oxygen uptake, with a mean change of 102.74 mL/min ([95% CIs, 27.72-177.76]; P =0.0097). Sotatercept demonstrated improvements in secondary end points, including resting and peak exercise hemodynamics, and 6-minute walk distance versus baseline measures. Cardiac magnetic resonance imaging showed improvements from baseline at week 24 in right ventricular function.
Conclusions: The clinical efficacy and safety of sotatercept demonstrated in the SPECTRA study emphasize the potential of this therapy as a new treatment option for patients with pulmonary arterial hypertension. Improvements in right ventricular structure and function underscore the potential for sotatercept as a disease-modifying agent with reverse-remodeling capabilities.

Juarez M; Department of Internal Medicine, Texas Tech University Health Sciences Center, USA.
Castillo-Rodriguez C; Soliman D; Del Rio-Pertuz G; Nugent K;

Publisher: MDPI AG Country of Publication: Switzerland NLM ID: 101651414 Publication Model: Electronic Cited Medium: Internet ISSN: 2308-3425 (Electronic) Linking ISSN: 23083425 NLM ISO Abbreviation: J Cardiovasc Dev Dis Subsets: PubMed not MEDLINE

Cardiopulmonary exercise testing (CPET) provides important information for the assessment and management of patients with heart failure. This testing measures the respiratory and cardiac responses to exercise and allows measurement of the oxygen uptake (V˙O ₂ ) max and the relationship between minute ventilation (V˙E) and carbon dioxide excretion (V˙CO ₂ ). These two parameters help classify patients into categories that help predict prognosis, and patients with a V˙O ₂ < 14 mL/kg/min and V˙E/V˙CO ₂ slope >35 have a poor prognosis. This testing has been used in drug trials to determine complex physiologic responses to medications, such as angiotensin-converting enzyme inhibitors. For example, a study with enalapril demonstrated that the peak V˙O ₂ was 14.6 ± 1.6 mL/kg/min on placebo and 15.8 ± 2.0 mL/kg/min on enalapril after 15 days of treatment. The V˙E/V˙CO ₂ slopes were 43 ± 8 on placebo and 39 ± 7 on enalapril. Chronic heart failure and reduced physical activity measured by cardiopulmonary exercise testing are associated with increases in BNP, and several studies have demonstrated that cardiac rehabilitation is associated with reductions in BNP and increases in V˙O ₂ . Therefore, BNP measurements can help determine the benefits of cardiac rehabilitation and provide indirect estimates of changes in V˙O ₂ . In addition, measurement of microRNAs can determine the status of skeletal muscle used during physical activity and the changes associated with rehabilitation. However, CPET requires complicated technology, and simpler methods to measure physical activity could help clinicians to manage their patients. Recent advances in technology have led to the development of portable cardiopulmonary exercise testing equipment, which can be used in various routine physical activities, such as walking upstairs, sweeping the floor, and making the bed, to provide patients and clinicians a better understanding of the patient’s current symptoms. Finally, current smart watches can provide important information about the cardiorespiratory system, identify unexpected clinical problems, and help monitor the response to treatment. The organized use of these devices could contribute to the management of certain aspects of these patients’ care, such as monitoring the treatment of atrial fibrillation. This review article provides a comprehensive overview of the current use of CPET in heart failure patients and discusses exercise principles, methods, clinical applications, and prognostic implications.

Ait Ali L; Institute of Clinical Physiology, National Research Council, Pisa, Italy. & other Italian centres
Martini N;Listo E; Valenti E; Sotelo J; Salvadori S; Passino C; Monteleone A; Stagnaro N; Trocchio G; o, Italy.Marrone C; Raimondi F; Catapano G;

Pediatric cardiology [Pediatr Cardiol] 2024 Mar 22.
Date of Electronic Publication: 2024 Mar 22.

We sought to evaluate the potential clinical role of 4D-flow cardiac magnetic resonance (CMR)-derived energetics and flow parameters in a cohort of patients’ post-Fontan palliation. In patients with Fontan circulation who underwent 4D-Flow CMR, streamlines distribution was evaluated, as well a 4D-flow CMR-derived energetics parameters as kinetic energy (KE) and energy loss (EL) normalized by volume. EL/KE index as a marker of flow efficiency was also calculated. Cardiopulmonary exercise test (CPET) was also performed in a subgroup of patients. The population study included 55 patients (mean age 22 ± 11 years). The analysis of the streamlines revealed a preferential distribution of the right superior vena cava flow for the right pulmonary artery (62.5 ± 35.4%) and a mild preferential flow for the left pulmonary artery (52.3 ± 40.6%) of the inferior vena cave-pulmonary arteries (IVC-PA) conduit. Patients with heart failure (HF) presented lower IVC/PA-conduit flow (0.75 ± 0.5 vs 1.3 ± 0.5 l/min/m ² , p = 0.004) and a higher mean flow-jet angle of the IVC-PA conduit (39.2 ± 22.8 vs 15.2 ± 8.9, p < 0.001) than the remaining patients. EL/KE index correlates inversely with VO ₂ /kg/min: R: – 0.45, p = 0.01 peak, minute ventilation (VE) R: – 0.466, p < 0.01, maximal voluntary ventilation: R:0.44, p = 0.001 and positively with the physiological dead space to the tidal volume ratio (VD/VT) peak: R: 0.58, p < 0.01. From our data, lower blood flow in IVC/PA conduit and eccentric flow was associated with HF whereas higher EL/KE index was associated with reduced functional capacity and impaired lung function. Larger studies are needed to confirm our results and to further improve the prognostic role of the 4D-Flow CMR in this challenging population.