Author Archives: Paul Older

Optimizing the Interpretation of Cardiopulmonary Exercise Testing in Endurance Athletes: Precision Approach for Health and Performance.

Kowalski, Tomasz; Institute of Sport, National Research Institute, Warsaw 01-982, Poland.
Kasiak, Przemysław;Chomiuk, Tomasz;Mamcarz, Artur;
et al

Translational sports medicine,2025 Aug 20

The present review summarizes findings from the NOODLE (“predictioN mOdels fOr enDurance athLetEs”) study. The research aimed to refine variables obtained during cardiopulmonary exercise testing (CPET) in a large cohort of highly trained endurance athletes by adjusting general reference values and predictive equations to better reflect the unique physiological profiles of this population. Ventilatory efficiency, oxygen uptake efficiency slope, oxygen uptake efficiency plateau, and peak oxygen pulse were analyzed, as they were recently applied in various models concerning risk stratification and treatment optimization. As more people engage in endurance sports, tailored CPET assessments are crucial for accurate performance evaluation and health monitoring. By characterizing differences between general formulas and those suited for endurance athletes, we offered improved tools for optimizing training and ensuring athlete safety. The findings are in line with the existing trend of precision medicine that tailors diagnostics, treatments, and interventions to individual patients’ characteristics. Moreover, we review the recent advances from widely applied CPET-obtained indices, such as maximum oxygen uptake, maximum heart rate, and breathing reserve. We also gave the recommendation for a comprehensive CPET assessment based on the relationships between all of the variables.

Development and validation of clinical prediction models for cardiorespiratory fitness in atrial fibrillation patients following radiofrequency catheter ablation.

Zhao, Guiling;  Department of Cardiology, Xinhua Hospital , Shanghai, China.
Sun, Jian;Che, Qianji;Xu, Wenqing; et al

Frontiers in cardiovascular medicine,2025 Aug 29

  • Background: Assessment of cardiorespiratory fitness (CRF) is imperative in patients with atrial fibrillation (AF) who have had radiofrequency catheter ablation (RFCA). This study aimed to develop and validate CRF prediction models in this population.
  • Methods: 141 AF patients with RFCA were recruited. The cardiopulmonary exercise test was used to assess CRF with VO 2peak and METs max . Multidimensional predictors (demographics, serum biomarkers, cardiovascular parameters, and motor function parameters) were analyzed through Spearman correlation analysis and stepwise multivariate linear regression analysis. The internal validity of the prediction equation was tested by paired Student’s t -test, Pearson correlation analysis and Bland-Altman analysis.
  • Results: Sex, BMI, ln NT-proBNP, glucose (GLU), 6-minute walking distance (6MWD), and systolic blood pressure (SBP) were found to be significantly associated with CRF in this population. Multivariate linear regression generated the equations: VO 2peak = 35.080 – 0.286 * BMI – 1.927 * Sex – 1.090 * ln NT-proBNP + 0.011 * 6MWD – 0.039 * SBP – 0.512 * GLU, and METs max = 9.646 – 0.447 * Sex – 0.260 * ln NT-proBNP – 0.140 * GLU – 0.078 * BMI – 0.016 * SBP + 0.004 * 6MWD, (VO 2peak : adjusted R 2 = 0.506, and METs max : adjusted R 2 = 0.469, both P < 0.01). Pearson correlations between the predicted values and the measured values showed good validity (VO 2peak : r = 0.616, and METs max : r = 0.581, both P < 0.01). The Bland-Altman analysis showed that the predicted VO 2peak values were slightly lower than the measured values (mean difference = -0.13; 95% limits of agreement: -5.20 to 4.93), while the predicted METs max values were in close agreement with the measured values (mean difference = -0.00; 95% limits of agreement: -1.59 to 1.59).
  • Conclusion: Sex, BMI, NT-proBNP, glucose, 6MWD, and SBP are robust predictors of VO 2peak and METs max in AF population after RFCA. This study generates and internal validates the first multivariable CRF prediction models with easy-to use clinical paraments in AF patients after RFCA, thereby providing safe and effective alternatives to conventional CPX, which may help to optimize personalized patient management.

Recovery from COVID-19: a 12-month follow-up study on cardiorespiratory fitness and pulmonary function.

Goulart, Cássia da Luz; Federal University of Sao Carlos, UFSCar, Sao Carlos, Brazil.
Maldaner, Vinícius;Alves, Carla Cristina de Araújo;Milani, Mauricio;

Frontiers in cardiovascular medicine,2025 Aug 12

  • Introduction and Aim: Long COVID, characterized by persistent symptoms after acute infection, poses a major public health challenge. Understanding its long-term effects is crucial, particularly in relation to cardiorespiratory recovery. This study aimed to assess changes in cardiorespiratory fitness (CRF) and pulmonary function (PF) over 12 months following acute COVID-19, addressing a significant gap in current knowledge about the disease’s lasting impact.
  • Methods: This prospective cohort study included 29 individuals previously diagnosed with post-acute COVID-19. The baseline data were collected during the acute phase of infection . Participants underwent clinical evaluation, cardiopulmonary exercise testing (CPET), spirometry, and maximal inspiratory pressure (MIP) measurement at baseline and again after 12 months.
  • Results: After one-year, significant improvements were observed across several CPET parameters, including VE/MVV ratio (Cohen’s D = 0.66), peak oxygen uptake (VO 2 peak) in both absolute and relative terms (ml/min: d = 0.67; and ml/kg/min: d = 0.45), oxygen uptake efficiency slope (OUES; D = 0.47) and a reduction in VE/VCO 2 slope ( D = 0.80). Pulmonary function improved with increases in % predicted forced expiratory volume in 1 s (FEV 1 ; d = 0.67) and forced vital capacity (FVC; D = 0.67). MIP improved significantly ( D = 0.67), and the prevalence of inspiratory muscle weakness decreased from 20.7% at baseline to 3.5% at follow-up.
  • Conclusion: Despite the severity of their initial illness, patients demonstrated substantial recovery in CRF, PF, and inspiratory muscle strength over 12 months.

The Effects of Anakinra on Cardiorespiratory Fitness in Heart Failure Stratified by Age in Phase II Clinical Trials.

Hogwood AC; Robert M. Berne Cardiovascular Research Center, and Division of Cardiology, University of Virginia, Charlottesville, Virginia, United States.
Golino M; Moroni F; Canada JM; Del Buono MG; Arena R;Van Tassell B; Abbate A;

Journal of cardiovascular pharmacology [J Cardiovasc Pharmacol] 2025 Sep 09.
Date of Electronic Publication: 2025 Sep 09.

Competing Interests: Dr. Abbate has served as consultant to Kiniksa, Monte Rosa Therapeutics, and Novo Nordisk.
Cardiorespiratory fitness (CRF) in heart failure (HF) declines with age. Interleukin-1 (IL-1) is a pro-inflammatory cytokine involved in aging and HF. We aimed to determine the changes in CRF before and after treatment with anakinra, recombinant IL-1 receptor antagonist, in patients with HF stratified according to age below and above 60 years in phase II clinical trials. We analyzed data from 73 patients (37 [51%] female), 49 (67%) patients ˂60 years and 24 (33%) ≥60 years. All patients received anakinra 100 mg subcutaneously daily for a median of 4 (interquartile range from 2 to 12) weeks. We measured peak oxygen consumption (VO2peak) and high-sensitivity C-reactive protein (hsCRP). When compared with older patients, younger patients had higher baseline peak VO2 (15.2 [12.4-17.7] vs. 12.4 [10.3-14.3] mL·kg-1·min-1, p=0.001), yet no significant differences in hsCRP (6.6 [3.6-16.6] vs. 5.2 [2.7-11.2] mg/L, p=0.18). In both groups, anakinra decreased hsCRP (&lt;60 years: -3.6 [-8.1 to -1.9] mg/L; p&lt;0.001; ≥60 years: -2.7 [-9.0 to -1.4] mg/L; p&lt;0.001) and increased peak VO2peak (&lt;60 years: +0.5 [-0.9 – 2.5] mL·kg-1·min-1; p=0.036; ≥60 years: +1.1 [0.2 – 2.3] mL·kg-1·min-1; p&lt;0.001). No significant differences in changes across time were observed between the age groups. Older patients with HF have a greater baseline impairment in CRF compared to younger patients despite similar levels of systemic inflammation, and they appear to have a similar improvement in CRF following treatment with anakinra. The lack of an active control group (placebo) is a significant limitation and additional studies are needed to validate and expand these findings assessing clinical outcomes.

Exploring the limits of exercise capacity in adults with type II diabetes.

Michielsen M; Department of Rehabilitation Sciences, KU Leuven, Leuven, Belgium.
Bekhuis Y; Claes J; Decorte E; De Wilde C; Gojevic T; Costalunga L; Amyay S; Lazarou V; Daraki D; Kounalaki E; Chatzinikolaou P;Goetschalckx K;
Hansen D;Claessen G;Diepenbeek, Belgium.; De Craemer M; Cornelissen V;

PloS one [PLoS One] 2025 Sep 09; Vol. 20 (9), pp. e0331737.
Date of Electronic Publication: 2025 Sep 09 (Print Publication: 2025).

Objective: This study investigates the mechanisms behind exercise capacity in adults with type 2 diabetes mellitus (T2DM), focusing on central and peripheral components, as described by the Fick equation.
Methods: A cross-sectional study of 141 adults with T2DM was conducted, using cardiopulmonary exercise testing, near-infrared spectroscopy (NIRS) and exercise echocardiography. Participants with sufficient-quality NIRS data were stratified into tertiles based on percentage predicted VO₂peak. Group comparisons and stepwise regression were used to examine the contributions of central and peripheral components to VO₂peak.
Results: Sixty-seven participants had insufficient quality NIRS data. Those with lower-quality data were more likely to be female (p &lt; 0.001) and had a lower exercise capacity (p &lt; 0.001). Among participants with good-quality NIRS data, those in the lowest fitness tertile were older (p &lt; 0.01), had a longer diabetes duration (p = 0.04), lower eGFR (p &lt; 0.001) and more frequent use of beta-blockers (p = 0.02) and diuretics (p = 0.04). Significant differences were observed in peak cardiac output (p &lt; 0.001) and NIRS-derived parameters across fitness groups. Multivariate regression identified cardiac output as the strongest predictor of VO₂peak, while peripheral oxygen extraction did not improve model performance.
Conclusion: Cardiac output is the primary determinant of exercise capacity in adults with T2DM. This suggests that muscle perfusion may be the main limiting factor in relatively fit individuals with T2DM. However, cardiac output and local muscle perfusion are not directly equivalent, as mechanical factors, such as intramuscular pressure during high-intensity exercise, may prevent maximal perfusion.

Breathlessness abnormality is best assessed at peak exercise during incremental cardiopulmonary cycle exercise testing.

Ekström M; Lund University, Faculty of Medicine, Lund, Sweden  Quebec canada
Li PZ; Bourbeau J; Tan WC; Jensen D;

Chest [Chest] 2025 Sep 10.
Date of Electronic Publication: 2025 Sep 10.

Background: Breathlessness on exertion is a common, distressing and limiting symptom that can be quantified on incremental cardiopulmonary exercise testing (CPET) using normative reference equations.
Research Question: Is the breathlessness abnormality best uncovered and assessed at symptom limitation (peak exercise) compared with submaximal exercise intensities?
Study Design and Methods: Analysis of people aged ≥40 years undergoing symptom-limited incremental cycle CPET in the Canadian Cohort Obstructive Lung Disease (CanCOLD) study. Each Borg 0-10 scale breathlessness intensity rating during CPET was converted to its probability of being normal (P norm ), in relation to power output (W), rate of oxygen uptake (V’O 2 ) and minute ventilation (V’ E ) using normative reference equations. Abnormally high exertional breathlessness (abnormal breathlessness) was defined as a P norm &lt;0.05.
Results: Of 1,161 participants (42% women), abnormally high breathlessness was present in 22%, 23% and 16% in relation to W, V’O 2 and V’ E at peak exercise. Among those with abnormal breathlessness at peak exercise, 55-60% had normal breathlessness across all submaximal exercise intensities. Among those with normal breathlessness at peak exercise, 93-97% were normal across all serial breathlessness ratings throughout the CPET (interclass correlation coefficients=0.93-0.95). Findings were similar in people with or without chronic airflow limitation, and in people who did or did not reach maximal exertion at the end (symptom limitation) of the CPET.
Interpretation: Abnormal breathlessness is uncovered and should be assessed at peak exercise during symptom-limited incremental CPET. These findings inform symptom assessment in research and clinical practice.

Wave intensity analysis with exercise identifies impairments in pulmonary hypertension.

Lechuga CG;  Department of Biomedical Engineering, University of California, Irvine, Irvine, CA.
Raza F; Colebank MJ; Korcarz CE;Eickhoff JC; Chesler NC;

American journal of physiology. Heart and circulatory physiology [Am J Physiol Heart Circ Physiol] 2025 Sep 12.
Date of Electronic Publication: 2025 Sep 12.

Wave intensity analysis provides a novel approach to understanding the dynamic interactions between the right ventricle and pulmonary vasculature, particularly in pulmonary hypertension, a condition characterized by elevated pulmonary arterial pressures and vascular remodeling. This prospective study used wave intensity analysis to evaluate right ventricular and pulmonary vascular mechanics in 22 participants with pulmonary hypertension (including pre-capillary, isolated post-capillary, and combined pre-/post-capillary pulmonary hypertension), and 3 without pulmonary hypertension. Forward and backward compression and decompression waves were quantified at rest and during incremental exercise (25, 50, 75 watts). Relationships between metrics of wave intensity analysis, hemodynamics, right ventricular function, and oxygen consumption were analyzed using linear mixed-effects modeling. Wave intensity patterns highlighting vessel-specific pulmonary vascular and right ventricular pathobiology were observed in different phenotypes. Pre-capillary pulmonary hypertension exhibited highest forward compression waves, which correlated with right ventricular contractility (p&lt;0.01). Backward compression waves correlated strongly with characteristic impedance (p=0.002) in combined pre-/post-capillary pulmonary hypertension and inversely with pulmonary arterial compliance (p=0.003) in pre-capillary pulmonary hypertension. The ratio of backward to forward compression (systolic) waves decreased in isolated post-capillary pulmonary hypertension during exercise (p&lt;0.001), suggesting right ventricular reserve capacity that improves vascular-ventricular coupling. Wave intensity metrics demonstrated strong correlations with oxygen consumption in participants without pulmonary hypertension, indicating sensitivity to exercise-induced changes in cardiopulmonary status. Wave intensity analysis with exercise suggests vessel-specific pulmonary vascular and right ventricular characteristics unique to pulmonary hypertension phenotypes. These findings highlight wave intensity analysis as a promising tool for advancing understanding of cardiopulmonary pathobiology in pulmonary hypertension.

Central and Peripheral Mechanisms of Low Exercise Capacity in Prematurely Born Adults.

Manferdelli G; Institute for Exercise and Environmental Medicine, Texas Health Presbyterian Hospital Dallas, Dallas, Texas, USA.;
Barton GP; Babb TG;Millet GP;Nelson MD; Levine BD; Goss KN;

Comprehensive Physiology [Compr Physiol] 2025 Oct; Vol. 15 (5), pp. e70049.

Purpose: Premature birth (&lt; 37 weeks gestation) is associated with lower exercise capacity. However, the specific underlying mechanisms remain poorly defined. This study investigated the mechanisms of exercise limitation across the oxygen transport chain in preterm-born adults with normal resting cardiopulmonary function but exertional dyspnea.
Methods: 10 preterm born (6F, age: 30 ± 5 years, body mass index [BMI]: 27.0 ± 6.3 kg/m 2 , gestational age: 30 ± 3 weeks) and 8 term born (3F, age: 29 ± 5 years, BMI: 25.4 ± 4.6 kg/m 2 , gestational age: 40 ± 0 weeks) adults performed resting spirometry and a cardiopulmonary exercise test, consisting of two 5-min submaximal cycling exercises (30 and 60 W), followed by an incremental protocol to exhaustion. We measured breath-by-breath gas exchange (custom designed system), heart rate (HR, 12-lead ECG), cardiac output (Q̇c, acetylene rebreathe), and calculated arterial-venous oxygen difference (a-vO 2 diff, Fick equation).
Results: Oxygen uptake (V̇O 2 ) was similar between groups at rest, 30 and 60 W. At peak, compared to term-born peers, preterm adults showed lower power output (108 ± 18 vs. 208 ± 69 W, p &lt; 0.001), V̇O 2 (1.58 ± 0.29 vs. 2.52 ± 0.85 L/min, p = 0.017), Q̇c index (7.5 ± 1.0 vs. 8.9 ± 1.6 L/min/m 2 , p = 0.057), while a-vO 2 diff (12.6 ± 1.7 vs. 14.1 ± 1.6 mL/dL, p = 0.096) and HR were similar between groups (175 ± 16 vs. 185 ± 8 bpm, p = 0.104). The increase in stroke volume index from rest to peak exercise was blunted in preterm compared to term-born adults (8 ± 7 vs. 15 ± 6 mL/m 2 , p = 0.032).
Conclusion: Preterm born adults present with lower exercise capacity compared to age-matched peers born at term. Central mechanisms, primarily stroke volume, underlie exercise limitation in this population.

Interpretable framework for predicting preoperative cardiorespiratory fitness using wearable data.

Hussain I; Department of Anesthesiology, Weill Cornell Medicine, United States.
Zeepvat J; Reid MC; Czaja S; Pryor KO; Boyer R

Computer Methods & Programs in Biomedicine. 271:108980, 2025 Nov.

OBJECTIVES: Predicting preoperative cardiorespiratory fitness (CRF) is
crucial for assessing the risk of complications and adverse outcomes in
patients undergoing surgery. CRF is formally evaluated through submaximal
exercise testing with cardiopulmonary exercise testing (CPET) or the
6-minute walk test (6MWT). However, formal CRF testing is impractical as a
preoperative screening tool. Wrist-worn devices with actigraphy and heart
rate monitoring have become increasingly capable of predicting
physiological measurements. Our aim was to develop a clinically
interpretable machine learning (ML) model using wearable-derived
physiological data to predict CRF for older adults, and to access whether
this model can accurately estimate the 6MWT distances for preoperative
risk evaluation.

METHODS: We examined heart rate and activity data collected from Fitbit
devices worn by older adults (N = 65) who were scheduled to undergo major
noncardiac surgery. Data collection took place over a 1-week period prior
to surgery while participants engaged in their typical daily activities.
Our primary aim was to leverage this wearable technology to forecast CRF
among this group. We employed a machine-learning ensemble regression model
to predict CRF, using 6MWT outcomes as an index. Further, we applied the
shapley feature attribution approach to gain insights into how specific
features derived from wearable data contribute to CRF prediction within
the model, aiding in personalized fitness prediction.

RESULTS: Adults with higher CRF exhibited elevated levels of
moderate-to-vigorous physical activity (MVPA), maximal activity energy
expenditure (aEEmax), heart rate recovery (HRR), and non-linear heart rate
variability (HRV). These measures increased concurrently with improvements
in 6MWT outcomes. Our regression models, employing random forest and
linear regression techniques, demonstrated strong predictive capabilities,
with coefficient of determination values of 0.91 and 0.81, respectively,
for estimating CRF. The shapley feature attribution approach elucidated
those greater levels of MVPA, aEEmax, HRR, and nonlinear dynamics of HRV
serve as reliable indicators of enhanced CRF test performance.

CONCLUSION: The integration of wearable data-driven activity and heart
rate metrics forms the basis for utilizing wearables to provide
preoperative cardiorespiratory fitness assessments, supporting surgical
risk stratification, personalized prehabilitation, and improved patient
outcomes.

VI 1

VO2 Max in Clinical Cardiology: Clinical Applications, Evidence Gaps, and Future Directions. [Review]

Abdalla HM; Department of Internal Medicine, Mayo Clinic, USA.
Dreher L; VanDolah H; Bacon A; El-Nayir M; Abdelnabi M;
Ibrahim R; Pham HN; Bcharah G; Pathangey G; Wheatley-Guy C; Reddy S;
Farina J; Ayoub C; Arsanjani R

Current Cardiology Reports. 27(1):130, 2025 Sep 06. VI 1

PURPOSE OF REVIEW: VO2 max is a fundamental marker of cardiorespiratory
fitness with substantial prognostic and diagnostic value within the field
of cardiology. This review analyzes current and emerging evidence
regarding its clinical uses, highlights key evidence gaps, and explores
emerging developments poised to broaden its clinical application.

RECENT FINDINGS: Evidence supports VO2 max as a powerful independent
predictor for heart failure, coronary artery disease, hypertrophic
cardiomyopathy, and cardiac amyloidosis, supporting it use in identifying
high-risk patients for advanced interventions. Recent developments
including the integration of machine learning and wearable devices can
facilitate accurate VO2 estimation in routine clinical practice without
the necessity of specialized diagnostic tools. Despite its robust
diagnostic and prognostic value, VO2 max assessment remains underutilized
in routine cardiovascular care, primarily due to the need for specialized
equipment and personnel. Future research should explore emerging
technological innovations for VO2 max estimation and the development of
evidence-based protocols to support i