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 (<60 years: -3.6 [-8.1 to -1.9] mg/L; p<0.001; ≥60 years: -2.7 [-9.0 to -1.4] mg/L; p<0.001) and increased peak VO2peak (<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<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.

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 < 0.001) and had a lower exercise capacity (p < 0.001). Among participants with good-quality NIRS data, those in the lowest fitness tertile were older (p < 0.01), had a longer diabetes duration (p = 0.04), lower eGFR (p < 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 < 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.

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 <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.

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<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<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.

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 (< 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 < 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.

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

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

McHugh C; Cardiology Division, Massachusetts General Hospital, Boston,  USA.
Gustus SK; Petek BJ; Schoenike MW; Boyd KS; Kennett JB; VanAtta
C; Tower-Rader AF; Fifer MA; DiCarli MF; Wasfy MM

European Journal of Preventive Cardiology. 32(12):1112-1119, 2025 Sep 08. VI 1

AIMS: Cardiopulmonary exercise testing (CPET) is often used when athletes
present with suspected hypertrophic cardiomyopathy (HCM). While low peak
oxygen consumption (pVO2) augments concern for HCM, athletes with HCM
frequently display supranormal pVO2, 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 pVO2(ppVO2) > 80%, non-obstructive, no nodal
agents] and healthy athletes, matched (2:1 ratio) for age, sex, height,
weight and ppVO2. Consistent with matching, HCM (n = 30, 43.6 +/- 14.2
years) and athlete (n = 60, 43.8 +/- 14.9 years) groups had similar,
supranormal pVO2 (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
VE/VCO2 slope (25.4 +/- 4.7 vs. 23.4 +/- 3.1, P = 0.02), higher VE/VCO2
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 VE/VCO2
nadir (>30) than athletes (20 vs. 3%, P = 0.02).

CONCLUSION: Even in the setting of similar and supranormal pVO2,
ventilatory efficiency is worse in HCM participants vs. healthy athletes.
Our results demonstrate the utility of CPET beyond pVO2 assessment in
‘grey zone’ athlete cases in which the diagnosis of HCM is being debated.
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Other Abstract
plain-language-summary
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.

Driessens H; University of Groningen, Groningen, the Netherlands.
Hoeijmakers LSM; Zwerver ODJ; Wijma AG; Hildebrand ND;
Queisen RRYC; Kuikhoven M; den Dulk M; Olde Damink SWM; Klaase JM; Bongers BC

BACKGROUND: The widespread implementation of a preoperative assessment of
aerobic capacity requires a practical field test. This study investigated
the validity of the modified steep ramp test (SRT) for evaluating
preoperative aerobic capacity and to evaluate its usefulness for
preoperative risk assessment in patients planned for pancreatic surgery.

METHODS: Patients scheduled for pancreatic surgery who preoperatively
performed cardiopulmonary exercise testing (CPET) and the modified SRT
within 14 days were included. To assess its criterion validity, the
correlation between the achieved work rate at peak exercise (WRpeak) at
the modified SRT and oxygen uptake (VO2) at peak exercise (VO2peak) during
CPET was determined. To evaluate the ability of the modified SRT to
correctly classify patients as fit or unfit, receiver operating
characteristic (ROC) analyses were performed based on the CPET VO2peak
cutoff 18.0 ml.kg-1.min-1 and VO2 at the ventilatory anaerobic threshold
(VAT) cutoff 11.0 ml.kg-1.min-1.

RESULTS: Forty-eight patients (21 females) aged 68.7 +/- 7.6 years were
included. Modified SRT WRpeak (W/kg) demonstrated a very strong
correlation with CPET VO2peak (rho = 0.865, r = 0.926). The modified SRT
WRpeak cutoff to most accurately classify patients as fit or unfit was
2.095 W/kg for the CPET VO2peak cutoff (area under the curve (AUC) of
0.948) and the CPET VO2 at the VAT cutoff (AUC of 0.814).

CONCLUSIONS: The modified SRT is a valid short-term practical exercise
test to preoperatively assess aerobic capacity in patients undergoing
pancreatic surgery. A modified SRT performance below 2.1 W/kg seems
clinically most suitable to select candidates for further preoperative
CPET evaluation and/or prehabilitation, given its positive and negative
predictive value.

El Assaad I; Division of Cardiology & Cardiovascular Medicine, Cleveland, Ohio, USA.
Heilbronner AK; Zahka K; Hammond B; Patel A; Aziz PF

Journal of Cardiovascular Electrophysiology. 36(9):2287-2295, 2025 Sep. VI 1

OBJECTIVE: To describe our institutional experience with utilizing
cardiopulmonary exercise testing (CPET) to assess for chronotropic
suppression and to compare frequency of life-threatening events (LTEs) on
intentional “submaximal” treatment to those on maximal treatment.

METHODS: We queried our Inherited Arrhythmia Registry and identified
patients with LQTS who were on “submaximal” beta blocker doses (nadolol <
0.75-mg/kg/day & propranolol < 2 mg/kg/day) with at least 6 months follow
up. Adequate beta blockade effect was defined as at least 15% decrease
from maximal HR.

RESULTS: The study included 127 LQTS patients: 47% on maximal therapy,
43% on submaximal therapy, and 10% not receiving treatment. Thirty three
percent of patients were on submaximal therapy due to side effects, none
in patients less than 10 years of age. Baseline characteristics were
similar between the groups. There was no significant difference in LTEs
between maximal and submaximal therapy (8% vs. 5.4%, p = 0.72). During
CPET, patients on maximal therapy were more likely to exhibit adequate
chronotropic suppression (60% vs. 40%, p = 0.01). None of the patients on
submaximal therapy with adequate chronotropic effect experienced LTEs
during follow-up.

CONCLUSIONS: Adequate chronotropic suppression was achieved with
“submaximal” beta blocker dose in 40%. Despite similar baseline risk
profiles, LTEs were not significantly different in patients with
submaximal versus maximal therapy. CPET may be a useful modality to devise
an individualized treatment plan, especially in those who cannot tolerate
the recommended guideline directed dose.