Tiffany L. Brazile, M.D., Benjamin D. Levine, M.D., and Keri M. Shafer, M.D.

Baracchini, Nikita; Cardiothoracovascular Department,  ASUGI, University of Trieste, Italy.
Capovilla, Teresa Maria; Rossi, Maddalena; Carriere, Cosimo; et al

International journal of cardiology,2025 Apr 20

• Introduction: Maximal effort, defined by a respiratory exchange ratio (RER) ≥ 1.10, is crucial for accurate interpretation of cardiopulmonary exercise testing (CPET). Standard tests rely on non-metabolic thresholds, such as peak predicted heart rate (ppHR) ≥ 85 %, double product (DP) ≥ 20,000 bpm*mmHg and peak metabolic equivalent of task (MET) ≥ 5.0. This study aimed to assess the effectiveness of non-metabolic thresholds in detecting maximal effort, compared with the RER ≥ 1.10 criterion.
• Methods: We retrospectively analyzed stable patients who underwent CPET from 2022 to 2023, regardless of test indication, history of heart failure (HF), or medication use. All patients also performed transthoracic echocardiography.
• Results: Among 239 middle-aged patients (53 ± 14 years, 67 % male), 86 % achieved a RER ≥ 1.10, and 65 % had a diagnosis of HF. Non-metabolic thresholds correctly identified maximal efforts (RER ≥ 1.10) in 75 % of the cases (AUC < 0.600). Misclassified cases were more likely to have a history of atrial fibrillation (AF), paced rhythm, HF, and beta-blockers or RAAS inhibitors use. These patients exhibited lower VO ₂ peak and higher VE/VCO ₂ slope. Multivariable analysis identified HF history (OR 4.8, CI 95 % 1.6-15.6, p: 0.005), low resting DP (≤ 7500 mmHg*bpm), and ramp protocol as independent predictors of discordant tests.
• Conclusion: Non-metabolic thresholds misclassified up to 25 % of tests with RER ≥ 1.10 as non-maximal, potentially leading to inaccurate interpretation. In patients with HF, poor expected functional capacity and low DP, direct referral to CPET-equipped facilities may provide more accurate assessment than relying on non-metabolic thresholds.

Tetlow, Nicholas; Centre for Peri-operative Medicine, Division of Surgery,  University College London, London, UK.;
Whittle, John

Annals of nutrition & metabolism,2025 Mar 21

• Background: Metabolic flexibility, the capacity to switch between energy sources in response to changing physiological demands, emerges as a critical determinant of perioperative resilience. In the context of surgery, where metabolic demands are high and energy homeostasis is disrupted, patients with metabolic inflexibility may experience worse outcomes due to impaired immune responses and heightened insulin resistance, resulting in prolonged recovery times.
• Summary: This article explores the implications of metabolic flexibility in the perioperative period and examines the potential for prehabilitation strategies, such as targeted exercise and nutritional interventions, to improve patient readiness for surgery. Cardiopulmonary exercise testing is discussed as a valuable assessment tool for metabolic flexibility, capable of providing insights into a patient’s fuel adaptability and overall metabolic health preoperatively. Evidence suggests that targeted exercise and nutritional strategies can enhance mitochondrial function, improve nutrient-sensing pathways, and increase substrate oxidation, which may reduce perioperative complications and support immune resilience.
• Key Messages: Future research should prioritise refining methods to identify metabolically inflexible patients and tailoring prehabilitation interventions to optimise metabolic flexibility. Enhancing perioperative metabolic readiness is important for populations vulnerable to metabolic dysfunction, such as those with obesity, diabetes, and cancer. Aligning metabolic optimisation with surgical recovery demands may help establish new standards in perioperative care and improve patient outcomes.

Mazzella, Antonio; Division of Thoracic Surgery, IEO European Institute of Oncology,  Milan, Italy.
Orlandi, Riccardo; Maisonneuve, Patrick; Uslenghi, Clarissa;

Journal of personalized medicine,2025 Mar 31

Aimshis study aims to determine whether maximal oxygen consumption (VO2max) or predicted postoperative (ppo)-VO2max could still reliably predict postoperative complications and deaths in lung cancer patients undergoing pneumonectomy and which values could be more reliably considered as the optimal threshold.
Methods : We retrospectively collected data of consecutive patients undergoing pneumonectomy for primary lung cancer at the European Oncological Institute (April 2019-April 2023). Routine preoperative assessment included cardiopulmonary exercise testing (CPET) and a lung perfusion scan. We evaluated the morbidity and mortality rates; associations between morbidity, mortality, VO2max, and ppoVO2max values were investigated through ANOVA or Fisher’s exact test as appropriate. Receiver operating characteristic (ROC) curves were applied to further explore the relation between VO2max, ppoVO2max values, and 90-day mortality.
Results : The cardiopulmonary morbidity rate was 32.2%; the 30-day and 90-day mortality rates were 2.2% and 6.7%. The PpoVO2max values were significantly lower in patients experiencing cardiopulmonary complications or deaths compared to the whole cohort, whereas VO2max, though showing a trend towards lower values, did not reach statistical significance. A VO2max value threshold of 15 mL/kg/min correlated significantly with 90-day mortality, while a ppoVO2max cut-off of 10 mL/kg/min was significantly associated with cardiopulmonary complications and 30-day and 90-day mortality rates. ROC curve analysis revealed ppoVO2max as a better predictor of 90-day mortality compared to VO2max.
Conclusions : CPET and a lung perfusion scan are two key elements for the preoperative evaluation of patients undergoing pneumonectomy, since it provides a holistic assessment of cardiopulmonary functionality. We recommend the routine calculation of ppoVO2max, particularly when adopting a 10 mL/kg/min threshold.

Baccelli A; Department of Respiratory Medicine, Royal Brompton Hospital, Guy’s and St Thomas’ NHS Foundation Trust, London, UK.
Giudice FL; Haji G; Davies RJ; K.Gin-Sing W; Howard LS;

Clinical medicine (London, England) [Clin Med (Lond)] 2025 Apr 09, pp. 100313.
Date of Electronic Publication: 2025 Apr 09.

Unexplained breathlessness is a challenging symptom encountered across diverse medical conditions. This review will briefly overview the interplay between central neural mechanisms and peripheral receptor activity leading to symptom perception. A holistic and multidisciplinary approach to unexplained breathlessness is crucial to assess and optimize known comorbidities, as well as investigate potential less common conditions associated with dyspnoea. Specific advanced testing modalities will be briefly discussed in the context of breathing pattern disorders, laryngeal hyperreactivity, disorders of the pulmonary vasculature, autonomic dysfunction, and cardiovascular diseases.

Phillips DB; School of Kinesiology and Health Science, York University, Toronto, Ontario, Canada.
Darko CA; James MD; Vincent SG; McCartney AM; Sreibers LK; Domnik NJ;Neder JA; O’Donnell DE;

Respiratory physiology & neurobiology [Respir Physiol Neurobiol] 2025 Apr 18, pp. 104434.
Date of Electronic Publication: 2025 Apr 18.

The neurophysiological mechanisms of exertional dyspnea in advanced pregnancy remain incompletely understood. This short case report describes the neurophysiological and sensory responses during standardized cardiopulmonary exercise testing (CPET) in one healthy adult female at three timepoints: a) 3 months pre-pregnancy, b) 35 weeks pregnant (third trimester [T3]), and, c) 1 year post-partum.
At rest and during exercise, detailed measurements of neurophysiological, gas-exchange and sensory parameters were completed. Compared to both pre-pregnancy and post-partum, ventilatory requirements, electrical activation of the diaphragm (EMGdi, index of inspiratory neural drive) and esophageal pressure swings were higher in T3 throughout exercise. Moreover, at a given work rate, perceived dyspnea was greater in T3 compared with pre-pregnancy and post-partum and increased in close association with heightened EMGdi throughout exercise. At peak exercise in T3, dyspnea/ventilation and EMGdi/ventilation ratios were greater, compared with pre-pregnancy and post-partum. Compared with pre-pregnancy, EMGdi and perceived dyspnea were greater post-partum near the limits of exercise tolerance, secondary to earlier onset of respiratory compensation-mediated increases in ventilation. In the current case, advanced pregnancy was associated with markedly elevated ratings of dyspnea and lower exercise capacity during a standardized clinical CPET. At submaximal intensities, the heightened dyspnea reflected the awareness of pregnancy-induced increases in ventilatory requirements, inspiratory neural drive, and respiratory muscle effort. At the limits of tolerance, heightened dyspnea and inspiratory neural drive reflected a complex combination of increase ventilatory requirements and mechanical constraints on tidal volume expansion. Compared with pre-pregnancy, residual activity-related dyspnea 1-year post-partum appears to reflect physical deconditioning.

Mamillo, Keti; Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, USA
Frantz, Robert P; Anderson, Jason H; Allison, Thomas G;

JACC. Case reports,2025 Apr 02

Reverse Potts shunt (rPS) is a surgical procedure that creates an anastomosis between the left pulmonary artery and descending aorta to decompress the right ventricle in suprasystemic pulmonary arterial hypertension (PAH). In this paper, we introduce a unique procedure combining cardiopulmonary exercise testing with forehead and popliteal oximetry to evaluate the efficacy of the rPS. Our study involved tests on 4 patients with PAH who had the shunt in place. We found that the level of oxygen saturation in the popliteal artery decreased during exercise and correlated with the rPS efficacy and the overall clinical outcome. In conclusion, we demonstrate a simple, noninvasive technique for evaluating patency and function of rPS in patients with suprasystemic PAH.

Baccelli, Andrea; Guy’s and St Thomas’ NHS Foundation Trust, London, UK.
Rinaldo, Rocco F; Haji, Gulammehdi; Davies, Rachel J;

The European respiratory journal,2025 Apr 10

• Background: Current guidelines recommend a four-strata model based on World Health Organization functional class (WHO-FC), 6-min walk distance (6MWD), and serum levels of brain natriuretic peptide (BNP) or N-terminal pro-BNP (NT-proBNP) for risk stratification in patients with pulmonary arterial hypertension (PAH) during follow-up. We explored the relevance of using cardiopulmonary exercise testing (CPET) as the exercise parameter in place of 6MWD at first reassessment after treatment initiation in PAH.
• Methods: Incident treatment-naïve patients with idiopathic, heritable, drug/toxins-induced, and connective tissue disease-associated PAH between 2010 and 2022 were analysed. Correlations between CPET and haemodynamic and right ventricular (RV) function parameters were explored and those which were significant were carried forward to assess association with survival. Independent predictors were used to derive a four-strata CPET score.
• Results: 262 patients were included. CPET parameters showed better correlations with haemodynamics and RV function than 6MWD. The CPET score included peak oxygen uptake (peak VO ₂ ), the slope relating ventilation to carbon dioxide production (VE/VCO ₂ slope), and peak oxygen pulse. The four-strata model based on WHO-FC, BNP, and CPET score predicted survival at the time of the first re-evaluation, with better accuracy than the model including 6MWD (c-index 0.81 versus 0.71). The CPET score on its own also performed well (c-index 0.82) with a greater spread between categories. Treatment-associated changes in peak VO ₂ and oxygen pulse predicted survival, while changes in 6MWD did not.
• Conclusions: A simplified four-strata CPET score either alone or included with BNP and WHO-FC accurately predicts survival at follow-up in PAH.

Knox-Brown, Ben; Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
Harding, Chris; Chowdhury, Shabana; Pritchard, Andrew; et al;

BMJ open respiratory research,2025 Apr 15

• Introduction: The impact of cycling at different cadences on cardiopulmonary exercise test (CPET) measurements is poorly understood. We aimed to investigate whether higher cadences of pedalling led to meaningful changes in physiological endpoints.
• Methods: Study participants were recruited from healthy staff members working within three NHS trusts across England. At baseline, all participants completed a CPET at 60 rpm and then subsequently completed CPETs at cadences of 70, 80 and 90 rpm, allocated in a random order. To evaluate the mean differences in CPET measurements across the cadences, we used a one-way repeated measures analysis of variance. We then performed post hoc pairwise comparisons with Tukey correction to account for multiple testing.
• Results: Data collection took place between the 19 September 2023 and 9 April 2024. 25 participants had complete data at each cadence. 48% (12 of 25) were female, with a median (IQR) age of 30 years (27-41). There was no significant difference in peak V̇O ₂ across the cadences. Maximum achieved work rate was significantly different across the cadences (p=<0.001). The highest wattage was achieved at 60 rpm (221.2 watts±71.4) and lowest at 90 rpm (210.4 watts, ±77.2). End exercise ventilation increased with increasing cadence (p=0.013), with a mean of 97.6 L/min (±28.3) at 60 prm and 107.0 L/min (±33.9) at 90 prm. Breathing reserve decreased with increasing cadence (p=0.009), with a mean of 45.6 L/min (±28.8) at 60 rpm and 35.1 L/min (±23.5) at 90 rpm. There were minimal differences in other CPET parameters.
• Conclusion: In a healthy population, higher cycling cadences increased ventilatory demand and reduced maximum work rate. This could have implications for CPETs in the clinical setting, where physiological responses to higher cadences may be more exaggerated.
• Competing Interests: Competing interests: KPS reports consultation fees from ndd medical technologies outside of the published work. All other authors declare no conflict of interest.

Rodrigues, Sara;
Verardino, Renata Gomes Sanches; Costa-Hong, Valéria; Jordao, Camila Paixao; et al;

Open heart,2025 Apr 02

• Objective: In this randomised two-period crossover trial, the objective was to compare acute changes in arterial distensibility between high-intensity interval physical exercise (HIIPE) and moderate-intensity continuous physical exercise (MICPE) sessions in subjects with elevated blood pressure (BP).
• Methods and Analysis: Participants underwent either MICPE-HIIPE or HIIPE-MICPE sequences with intensity based on cardiopulmonary exercise testing. The main outcome measures included arterial stiffness (by pulse wave velocity (PWV)) at baseline, until 30 min and 24 hours after each physical exercise session. Other measures include office BP, 24-hour ambulatory blood pressure monitoring (ABPM) and applanation tonometry.
• Results: The study involved 29 subjects with elevated BP (76% female, 48±7 years, body mass index=28.3±4.3 kg/m², systolic BP=126±9 mm Hg and diastolic BP=84±4 mm Hg). They presented lower PWV 24 hours after MICPE compared with baseline and to 24-hour HIIPE ((-0.83 (-1.29;-0.37) p=0.001) and (-0.98 (-1.84;-0.12), p=0.021), respectively). Despite no differences in office BP, aortic systolic BP was lower after HIIPE compared with baseline and to 24-hour MICPE (113±19; 118±10 and 117±10 mm Hg; p=0.013).
• Conclusion: In subjects with elevated BP, arterial distensibility is greater 24 hours after MICPE, while aortic systolic BP is lower after HIIPE. The particularities of each method and each exercise intensity can provide specific mechanisms of vascular response to exercise and detect vascular damage early in these subjects.