V. Kittipibul, Division of Cardiology, Duke University Medical Center, Durham, NC
A. Novelli, D. Yaranov, A. Swavely, L. F. Ferreira, J. Molinger, et al.

Am Heart J 2025

BACKGROUND: Blood volume analysis (BVA) allows direct measurement of red blood cell mass (RBCM) and differentiation of true and dilutional anemia in heart failure (HF). This study aimed to characterize the relationships of RBCM profiles and anemia types to HF outcomes and cardiopulmonary exercise test (CPET) parameters.
METHODS: Chronic stable HF patients were prospectively enrolled. All patients underwent BVA; a subset underwent supine invasive CPET within 24 hours of BVA. RBCM profiles were defined using RBCM %deviation (deficit: <-10%, normal: -10 to 10%, excess: >10%). Anemia defined by World Health Organization criteria alone was categorized using RBCM %deviation (< -10% true anemia, >/= -10% dilutional pseudo-anemia). HF hospitalization at 6 months and CPET parameters were compared among RBCM profiles and anemia types.
RESULTS: One-hundred twenty patients (58 years, 40% female, 41% Black, 63% HFrEF) were enrolled. Forty percent had RBCM deficit, 37.5% had normal RBCM, and 22.5% had excess RBCM. Fifty-eight patients (48%) were anemic: 60% true anemia and 40% dilutional pseudo-anemia. Patients with dilutional pseudo-anemia had a higher incidence of HF hospitalization (44.8%) compared to no anemia (22.7%) and true anemia (20.6%) (p=0.040). There was no difference in HF hospitalization among RBCM profiles (p=0.99). There was a non-significant trend toward worse peak VO(2) in RBCM deficit and true anemia, with no differences in other CPET parameters.
CONCLUSIONS: Dilutional pseudo-anemia demonstrated higher HF hospitalizations compared to true anemia, while true anemia had a trend towards worse peak VO(2). The implications of BVA-identified RBCM profiles and anemia types for clinical management warrant further investigation.

S. Kwast, University Leipzig, Rosa-Luxemburg-Str. 30, 04103, Leipzig, Germany
J. Lassing, R. Falz, J. Hoffmann, C. Pokel, A. Schulze, et al.

BMC Sports Sci Med Rehabil 2025 Vol. 17 Issue 1 Pages 100

BACKGROUND: Impaired exercise capacity influences obesity and diabetes disease progression and vice versa. The primary objective of this prospective, observational, real-world study was to characterize exercise capacity in patients with obesity or type II diabetes mellitus and healthy controls by cardiac capacity (cardiac output (CO), cardiac power output (CPO)) and peripheral muscle capacity (peak power output (Pmax) and arterio-venous oxygen difference (avDO2)). The effects of an exercise and lifestyle intervention on these cardiac and peripheral muscular markers in obese and diabetic patient groups were additionally evaluated.
METHODS: At a university sports medicine outpatient clinic, 24 obese (OB) and 38 diabetes mellitus type II (DM) patients and 20 healthy controls (HE) were investigated in a cross-sectional analysis. OB and DM were reexamined after a standard of care exercise intervention. Parameters were assessed at rest and during a cardiopulmonary exercise test (CPET). Blood pressure, impedance cardiography, and respiratory gas analysis were continuously recorded during CPET.
RESULTS: At Pmax, CO and CPO were lower in DM compared to obese (CO 16.26 l/min vs. 18.13 l/min, p < 0.04; CPO 5.67 W vs. 4.81 W, p < 0.01). HE did not differ in CO (18.19 l/min)) or CPO (5.27 W) from OB and DM. Maximum CPO in OB and DM was based on higher stroke volume and blood pressure, while HE had higher heart rates. Pmax was higher (p < 0.01) in HE (268 W) compared to OB (108 W) and DM (89 W), mainly caused by a higher (p < 0.01) avDO(2) (HE 18.22 ml/dl, OB 10.45 ml/dl, DM 9.65 ml/dl). Exercise intervention improved Pmax in both groups of patients (+ 16 W in OB, + 12 W in DM), which was attributed to increased avDO(2), but not to cardiac parameters.
CONCLUSIONS: Obese patients had higher cardiac power outputs and were primarily limited by muscular performance, while diabetic patients showed both muscular and cardiac limitations. Healthy subjects had comparable cardiac power outputs with significantly lower pressure-volume loads. Resistance training improved the alteration of our patient groups in exercise capacity. Future research is needed to interpret our findings regarding clinical endpoints, such as mortality and hospitalization

T. Soumagne, AP-HP Nord-Université Paris Cité, Paris, France,
G. Garcia, J. Frija, C. Chenivesse, T. Perez, L. Plantier, et al.

J Allergy Clin Immunol Pract 2025

BACKGROUND: Dysfunctional breathing (DB) is common in severe asthma and is associated with poor asthma control. Diagnosing DB remains challenging due to the lack of gold standard.
OBJECTIVE: To investigate the characteristics of patients with severe asthma identified with DB using two distinct diagnostic modalities: the Nijmegen questionnaire (NQ) combined with the hyperventilation provocation test (HVPT), and cardiopulmonary exercise testing (CPET).
METHODS: Patients with severe asthma were prospectively recruited from three asthma expert centers. The diagnosis of DB using NQ-HVPT was confirmed by a panel of four chest physicians based on the results of the NQ and HVPT. CPET-based diagnosis was performed independently by two blinded physiologists, with erratic breathing patterns evaluated by visual inspection and objective criteria.
RESULTS: Among 138 patients with severe asthma, 44% were diagnosed with DB using NQ-HVPT. These patients were predominantly female, had poorer asthma control, lower quality of life and more comorbidities such as depression. Similar findings were noted when DB was defined by a NQ>23. The NQ was independently linked to anxiety, depression and quality of life regardless of DB diagnosis. Using CPET, 45% of patients were diagnosed with DB, but agreement between NQ-HVPT and CPET for DB diagnosis was poor (kappa=0.16). Patients diagnosed via CPET showed less impaired lung function and higher PaO2, possibly indicating a DB pattern more consistent with typical DB presentation.
CONCLUSION: The diagnostic agreement between NQ/HVPT and CPET is poor and both modalities may identify different DB patterns. The combination of NQ et HVPT seems to reflect the global burden of asthma rather than DB. CPET may be a more reliable tool for diagnosing DB, but further studies are needed to confirm its role.

R. Willixhofer, Centro Cardiologico Monzino, IRCCS, Milan, Italy.
E. Salvioni, N. Capra, M. Contini, J. Campodonico and P. Agostoni

Physiol Rep 2025 Vol. 13 Issue 9 Pages e70308

In cardiac amyloidosis (CA) cardiopulmonary exercise testing (CPET) is underexplored. This study evaluated exercise limitations in CA using CPET, focusing on the ventilation-to-carbon dioxide production (VE/VCO(2)) slope and peak oxygen uptake (VO(2)). Seventeen studies involving 1505 patients were analyzed and systematically reviewed according to PRISMA reporting guidelines. Subgroup analyses assessed differences by diagnosis (ATTR vs. AL), CPET modality, and age. The cohort included 12% with AL, 80% with ATTR (23% hereditary [ATTRv], 70% wild-type [ATTRwt], 7% unspecified), and 8% unidentified subtypes. VE/VCO(2) slope was elevated across ATTR subgroups: 38.4 (95% CI: 36.9-40.0, I(2) = 57%) in ATTRwt and 37.9 (95% CI: 35.1-40.7, I(2) = 70%) in ATTRv. ATTR patients were older than AL patients by 9.0 years (95% CI: 0.4-17.6, I(2) = 88%) and had a higher VE/VCO(2) slope: 2.5 (95% CI: 0.2-4.8, I(2) = 0%). CPET modality influenced peak VO(2), which was lowest for treadmill exercise (13.7, 95% CI: 12.7-14.8, I(2) = 0%, mL/min/kg) compared to upright cycle ergometry (14.7, 95% CI: 14.3-15.1, I(2) = 33%) and semi-recumbent cycle ergometry (14.5, 95% CI: 14.1-14.9, I(2) = 28%). A high VE/VCO(2) slope characterizes both ATTRwt and ATTRv, while AL patients are younger with lower VE/VCO(2) slope levels. Peak VO(2) in ATTR patients may depend on exercise modality.

F. I. Lunze, Boston Children’s Hospital, Boston, USA.
S. M. Dusenbery, K. Gauvreau, J. M. Lee, T. Geva, S. D. Colan, et al.

Int J Cardiol 2025 Pages 133305

BACKGROUND: We investigated the mid-term systolic ventricular response to transcatheter pulmonary valve replacement (TPVR) in patients with repaired tetralogy of Fallot (TOF) and pulmonary stenosis (PS), pulmonary regurgitation (PR) and a MIXED subgroup that included patients with both PR and PS. METHODS: We included patients with repaired TOF with PS, atresia and absent pulmonary valve underwent TPVR (2007-2011) and followed at BCH until 2021. We compared their serial clinical, echo imaging as well as cardiopulmonary exercise test data among PS, PR and MIXED subgroups.
RESULTS: In 63 patients (20.8 years of age) the median early follow-up (FU) after TPVR was 6.2 months, and mid-term – 2.8 years. At baseline, the PR (n = 23) had lower LV EF, mass z-scores and global longitudinal strain (GLS) and the percent predicted peak O2 pulse than PS (n = 16) and those in the MIXED (n = 24) subgroups. BiV GLS improvement from baseline to early and to midterm FU occurred for all subgroups except for the LV GLS in the MIXED, which showed improvement from baseline to early follow-up. PR subgroup’s LV GLS had gradual improvement, it remained lower than in PS and MIXED. No significant difference in exercise parameters were seen following TPVR. Freedom from reintervention at 10 years of FU was only 13.4 %.
CONCLUSIONS: Patients with PR had lower LV systolic function and exercise capacity than those with PS or MIXED prior TPVR with normalization of systolic function midterm in all thereafter. O

C. McHugh, Massachusetts General Hospital,  Boston, MA 02114, USA.
S. K. Gustus, B. J. Petek, M. W. Schoenike, K. S. Boyd, J. B. Kennett, et al.

Eur J Prev Cardiol 2025

AIMS: Cardiopulmonary exercise testing (CPET) is often used when athletes present with suspected hypertrophic cardiomyopathy (HCM). While low peak oxygen consumption (pV O2) augments concern for HCM, athletes with HCM frequently display supranormal pV O2, which limits this parameter’s diagnostic utility. We aimed to compare other CPET parameters in healthy athletes and equally fit individuals with HCM.
METHODS AND RESULTS: Using cycle ergometer CPETs from a single centre, we compared ventilatory efficiency and recovery kinetics between individuals with HCM [percent predicted pV O2(ppV O2) > 80%, non-obstructive, no nodal agents] and healthy athletes, matched (2:1 ratio) for age, sex, height, weight and ppV O2. Consistent with matching, HCM (n = 30, 43.6 +/- 14.2 years) and athlete (n = 60, 43.8 +/- 14.9 years) groups had similar, supranormal pV O2 (39.5 +/- 9.1 vs. 41.1 +/- 9.1 mL/kg/min, 125 +/- 26 vs. 124 +/- 25% predicted). Recovery kinetics were also similar. However, HCM participants had worse ventilatory efficiency, including higher early V E/V CO2 slope (25.4 +/- 4.7 vs. 23.4 +/- 3.1, P = 0.02), higher V E/V CO2 nadir (27.3 +/- 4.0 vs. 25.2 +/- 2.6, P = 0.004) and lower end-tidal CO2 at the ventilatory threshold (42.9 +/- 6.4 vs. 45.7 +/- 4.8 mmHg, P = 0.02). HCM participants were more likely to have abnormally high V E/V CO2 nadir (>30) than athletes (20 vs. 3%, P = 0.02).
CONCLUSION: Even in the setting of similar and supranormal pV O2, ventilatory efficiency is worse in HCM participants vs. healthy athletes. Our results demonstrate the utility of CPET beyond pV O2 assessment in ‘grey zone’ athlete cases in which the diagnosis of HCM is being debated.
We sought to examine exercise test findings in healthy athletes and equally fit individuals with a form of heart enlargement that commonly gets confused with ‘athlete’s heart’ called hypertrophic cardiomyopathy (HCM) to see if elements of the exercise test could distinguish between these two groups. This is relevant as fit individuals often present for exercise testing as part of the work up to see if they have HCM or not, and getting the answer right is important because HCM is amongst the most common causes of sudden cardiac death in athletes.By design, individuals with HCM in this study were equally fit as the athletes, with both groups having fitness levels (‘VO2 max’ levels) around 25% higher than expected for individuals of similar age and sex.Despite this similar and supranormal fitness, individuals with HCM had worse ventilatory efficiency than athletes. This is a metric that reflects how well the heart and lungs work together to get rid of the waste gas carbon dioxide during exercise. This finding should focus more attention on this parameter when exercise tests are being performed to evaluate for HCM in clinical practice.

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.