James MD; Respiratory Investigation Unit, Queen’s University, Kingston, Canada
McCleary J; Back GD; Alosta KA; et al

Copd: Journal of Chronic Obstructive Pulmonary Disease. 23(1):2650696,
2026 Mar 24.

A sizable fraction of dyspneic patients with only mild to moderate COPD
exhibit a heightened ventilatory response to exercise relative to
metabolic demands, i.e. a high ventilation (V.E)/CO2 output (V.CO2). The
lack of continuous assessment of gas exchange efficiency and estimates of
arterial CO2 partial pressure has hindered our understanding of the
physiological underpinnings of this dynamic phenomenon. We compared key
indices of gas exchange efficiency relative to the intra-breath CO2
profile as a function of expired volume using breath-by-breath volumetric
capnography in 30 patients (FEV1 = 76 +/- 17%) and 30 sex- and age-matched
controls during incremental cycle ergometry. Wasted ventilation in the
physiological dead space (VDphys) was calculated as the sum of airway and
alveolar (alv) dead space divided by tidal volume (VT). Transcutaneous
(tc) readings provided estimates of arterialised PCO2. Patients exhibited
lower exercise tolerance, reporting higher dyspnoea throughout exercise (p
< 0.05). Higher V.E/V.CO2 was associated with higher absolute (L) alveolar
dead space (VDalv), but similar VT; thus, both VDphys/VT and VDalv/VT were
consistently higher in patients (p < 0.05). V.E/V.CO2 was elevated (>=34)
in normocapnic patients (PtcCO2>=35 mmHg) who had a high VDphys/VT
(>=0.3); conversely, high V.E/V.CO2 coexisted with a lower VDphys/VT only
in hypocapnic subjects (p < 0.05). Higher VDalv and lower PtcCO2 were
independently associated with a high V.E/V.CO2 nadir and iso-work rate
dyspnoea (p < 0.001). Based on this innovative, high-density
data-acquisition approach, we conclude that both wasted ventilation and
alveolar hyperventilation, in a highly variable combination, contribute to
excessive ventilation in dyspneic patients with mild-to-moderate COPD

Mapelli M; Centro Cardiologico Monzino, IRCCS, Milan, Ital
Baracchini N; Campana N; Capovilla TM; et al

Scientific Reports. 16(1), 2026 Feb 17.

In hypertrophic cardiomyopathy (HCM), cardiopulmonary exercise testing
(CPET) is considered the gold standard for assessing exercise tolerance,
with O2-pulse commonly used as a surrogate for stroke volume (SV).
However, because SV reduction can be masked by increased oxygen
extraction, direct non-invasive measurement of SV is valuable. This study
involved 102 HCM patients (mean age 53 +/- 16 years, 78% male),
predominantly with a non-obstructive phenotype (74%), who underwent CPET
with SV measurement using Physioflow (PF). Abnormal O2-pulse kinetics were
observed in 12 patients, all confirmed by abnormal SV trends with PF.
Additionally, PF identified another 28 patients with altered SV kinetics.
Abnormal SV trends were associated with higher peak VE/VO2 ratios (42.6
[37.4-47.5] vs. 38.0 [33.6-41.3]) and lower end-tidal CO2 values (31.8 +/-
4.9 vs. 34.3 +/- 5.6 mmHg, p < 0.05). Patients with greater SV growth
during the final 25% of exercise showed improved anaerobic threshold VO2
(49.8 +/- 12.3% vs. 43.9 +/- 15.2% predicted peak VO2), VO2/work slope
(10.2 +/- 2.0 vs. 9.3 +/- 1.3 mL/min/Watt), and peak PetCO2 (34.5 +/- 5.6
vs. 32.3 +/- 5.2 mmHg), alongside a lower VE/VCO2 slope (28.7 [24.9-31.0]
vs. 31.3 [27.3-34.2], p < 0.05). Integrating PF and CPET may enhance the
detection of abnormal SV kinetics, which are associated with reduced
functional capacity in HCM patients.

McDowell R; University of Bath, Bath, UK.
Ogbonnaya C; Shannon H; Douglas H

BMC Pulmonary Medicine. 26(1), 2026 Feb 19.

BACKGROUND: Cystic Fibrosis is an inherited, life-limiting condition
causing a range of symptoms including lowered exercise tolerance.
Approximately 95% of people with cystic fibrosis in the United Kingdom are
now eligible for new genetic modulator therapies. As a result, cystic
fibrosis centres are treating older populations in greater numbers.
Cardiopulmonary exercise testing measures aerobic capacity, however it is
resource intensive. Identifying whether routinely collected clinical
measures are associated with reduced aerobic capacity is needed to aid
prioritisation of cardiopulmonary exercise testing.
METHODS: Maximal
cardiopulmonary exercise testing data were collected from July 2022 to
January 2024, alongside routine clinical data (spirometry, body mass
index, diabetic status, Pseudomonas aeruginosa colonisation status,
modulator status, age and sex). Peak oxygen uptake was analysed as a
percentage predicted value (VO2peakpp).
RESULTS: Overall aerobic capacity
at the centre was low (mean peak oxygen uptake 79.16% predicted). No
relationship was identified between body mass index and aerobic capacity
(beta = 0.23, 95%CI -0.91, 1.37, p = 0.69). When adjusting for other
clinical measures, having cystic fibrosis related diabetes (beta=-17.56,
95%CI -27.17, -7.95, p < 0.001) and younger age (beta = 16.62, 95%CI 4.13,
29.12, p = 0.01) were associated with a reduction in VO2peakpp.
CONCLUSION
: Annual CPET for all pwCF may not be necessary or available. This service
evaluation found associations with younger age and CFRD and reduced
VO2peak who could be targeted

Fujisawa T; Department of Cardiology Ehime University Graduate
School of Medicine, Ehime, Japan
Kawakami H; Kurokawa K; Horie R; Tamaki S; et al

Heart Rhythm. 23(7):e1000-e1011, 2026 Jul.

BACKGROUND: The clinical importance of catheter ablation (CA) in
asymptomatic persistent atrial fibrillation (PeAF) remains uncertain,
given that current indications mainly focus on symptom relief.
Asymptomatic patients may have unrecognized impairments in exercise
capacity or quality of life (QoL), but prospective data are limited.

OBJECTIVE: This study aimed to prospectively evaluate changes in exercise
capacity and QoL after CA in patients with asymptomatic PeAF.

METHODS: This single-center prospective observational study enrolled
consecutive patients with clinically asymptomatic PeAF who underwent CA
between August 2021 and July 2024. Asymptomatic status was defined as
modified European Heart Rhythm Association class I without subjective
symptoms. Cardiopulmonary exercise testing-including anaerobic threshold,
peak oxygen (O2) uptake, metabolic equivalents, and O2 pulse-and QoL
assessments (Atrial Fibrillation Quality of Life Questionnaire and EuroQol
5-Dimension 5-Level) were performed at baseline and 3 and 12 months after
ablation. A symptomatic PeAF cohort assessed under the same protocol was
included for a secondary descriptive comparison.

RESULTS: Among the 68 patients with asymptomatic PeAF, 52 completed the
12-month evaluation. All cardiopulmonary exercise testing parameters
improved significantly after ablation (anaerobic threshold 12.8 -> 14.0
mL/kg/min; peak O2 uptake 18.0 -> 19.4 mL/kg/min; metabolic equivalents
5.3 -> 5.8; O2 pulse 9.4 -> 12.4 mL/beat; all P < .05). The Atrial
Fibrillation Quality of Life Questionnaire scores improved early and
remained stable, whereas the EuroQol 5-Dimension 5-Level score
significantly improved only at 12 months. Secondary comparison with
symptomatic patients showed higher exercise capacity in asymptomatic
patients at baseline and 12 months, whereas the QoL scores became
comparable after ablation.

CONCLUSION: CA in asymptomatic PeAF was associated with sustained
improvements in exercise capacity and QoL, suggesting that rhythm-control
therapy may provide functional benefit even without overt symptoms.

Kler A; Countess of Chester Hospital NHS Foundation Trust, UK
Tay J; Slawinski C; Welch C; Moug S; et al

Annals of the Royal College of Surgeons of England. 108(6):430-437, 2026 Jul.

INTRODUCTION: Surgical resection is the main treatment for non-metastatic
colorectal cancer (CRC). However, 6% of patients do not undergo surgery
owing to frailty, according to the National Bowel Cancer Audit (NBOCA).
The impact of preoperative evaluation and decision making on outcomes in
frail patients is underexplored. This study examines variation in decision
making for frail, older patients and the availability/use of resources by
colorectal multidisciplinary teams (MDTs) across United Kingdom (UK)
hospitals.

METHODS: A UK-wide questionnaire was distributed to colorectal MDTs via
the NBOCA newsletter and social media (18 May to 30 June 2021). Part A
assessed MDT structure and resource use; Part B explored MDT decisions for
two simulated 75-year-old patients with colonic and rectal cancer.

RESULTS: Twenty MDTs responded. Decisions were MDT-driven in 55% (n = 11)
and surgeon-driven in 45% (n = 9). Clinical examination (85%) and
performance status (90%) were most used. Resource utilisation during MDT
meetings varied across sites; for example, echocardiogram results were
available and considered in MDT decision making in only 15% of centres.
Cardiopulmonary exercise testing was used in 75%, anaesthetic assessment
in 80%, frailty scoring in 25%, and preoperative geriatric assessment in
5%. Management of right-sided cancer was more consistent; rectal cancer
decisions were more variable.

CONCLUSIONS: Variation exists across MDTs in the availability and use of
resources when managing frail CRC patients. There is less consensus for
rectal than caecal cancer. These findings highlight the need for
standardised MDT

Agostoni P; Centro Cardiologico Monzino Istituto di Ricovero e
Cura a Carattere Scientifico, Milan, Italy.
Willixhofer R; Galotta A; Rubbo FM; et al

Open Heart. 13(1), 2026 Jun 3

AIMS: Cardiopulmonary exercise testing (CPET) parameters are used for
heart failure (HF) prognostication. While the ventilation to carbon
dioxide production (VE/VCO2) slope >=34 identifies high risk, patients
with intermediate values remain heterogeneous. The VE/VCO2 Y-intercept,
reflecting dead space ventilation at rest and its changes during effort,
may refine prognostication.

METHODS: We retrospectively analysed 2642 HF. Follow-up was 26 (9-63)
months. The study endpoint was the composite of all-cause death, urgent
transplant or left ventricular assist device implantation.

RESULTS: Median age was 62 (53-70) years and left ventricular ejection
fraction (LVEF) 33% (27%-39%). 27% of patients were New York Heart
Association class III-IV. During follow-up, 534 events occurred. Both
VE/VCO2 slope and peakVO2 were associated with outcome in univariable and
multivariable models (HR 1.04, 95% CI 1.03 to 1.06; HR 0.90, 95% CI 0.88
to 0.93, p<0.001, respectively). Y-intercept was not prognostic
univariately but added independent value in multivariable models (HR 1.08,
95% CI 1.04 to 1.13, p<0.001). Prognosis and clinical profiles improved
from group A (VE/VCO2 slope >=34, n=858) to B (28-34, n=943) to C (<28,
n=841). Group A versus C patients had lower LVEF (30% (25%-36%) vs 35%
(30%-40%), ptrend<0.001), peakVO2 (12.7 (10.06-15.3) vs 17.7 (14.6-21.6)
mL/kg/min, ptrend<0.001) and higher N-terminal pro-B-type natriuretic
peptide (1400 (572-3122) vs 454 (174-1081) pg/mL, ptrend<0.001). Only
within group B, a high median Y-intercept (B1>=3.9 L/m) clearly identified
patients with higher HF severity and worse survival than B2 (<3.9 L/m,
log-rank p<0.001).

CONCLUSION: An increase in the VE/VCO2 slope is associated with a
progressive lower survival. Y-intercept enhances risk assessment in HF
with intermediate VE/VCO2 slope values.

F. P. Rischard, PVDOMICS Study Group
M. Mendoza, M. Insel, G. J. Beck, S. C. Erzurum, R. P. Frantz, et al

medRxiv 2026

Background: World Symposium on Pulmonary Hypertension (WSPH) Group 2 pulmonary hypertension (PH) is a clinically integrated phenotype attributed to left heart disease, whereas pre- versus post-capillary classification is operationalized primarily by pulmonary capillary wedge pressure (PCWP). Although current recommendations emphasize contextual interpretation and provocative testing for intermediate PCWP values, the relationship between PCWP-based classification and underlying phenotype has not been systematically evaluated. We aim to quantify phenotype-hemodynamic discordance across the PCWP spectrum and evaluate a staged physiology-guided framework incorporating inhaled nitric oxide (iNO), ventricular geometry, and provocative testing.

Methods: We studied 1,032 participants from the NHLBI-sponsored PVDOMICS cohort with multidisciplinary adjudicated phenotypes integrating clinical, imaging, physiologic, and hemodynamic data. Stage-specific PCWP thresholds classified pre- versus post-capillary physiology at rest, during iNO, and during provocation (fluid challenge or invasive cardiopulmonary exercise testing [iCPET]). Echocardiographic right ventricular-to-left ventricular (RV/LV) ratio was evaluated as a marker of ventricular interdependence. Restricted cubic spline and staged concordance analyses defined certainty-based PCWP ranges and incremental diagnostic yield.

Results: Adjudicated Group 2 PH was present in 37.0% of participants. Resting PCWP demonstrated good discrimination (AUC 0.86), but substantial bidirectional phenotype-hemodynamic discordance persisted across intermediate PCWP ranges. At a resting PCWP of 12 mmHg, 25% of participants classified as pre-capillary had adjudicated Group 2 PH, whereas at 18 mmHg, 35% classified as post-capillary remained discordant non-Group 2. Concordance did not approach 90% until PCWP values were <9 mmHg or >24 mmHg. Dynamic testing incrementally improved concordance within these overlap zones. Nearly half of adjudicated Group 2 PH participants (46.5%) were not identified by resting PCWP alone; incorporation of iNO and provocative testing increased cumulative Group 2 identification by 63.4% and improved sensitivity from 79.9% to 83.7%. Model discrimination improved from an AUC of 0.863 to 0.908 (likelihood-ratio P<0.001). iNO increased PCWP in discordant Pre/G2 participants, unmasking latent left-sided limitation, while lowering PCWP in discordant Post/NonG2 participants, consistent with ventricular interdependence. RV/LV ratio ≥0.94 reduced discordant Post/NonG2 classification by 70.5%, and incorporation of PCWP/cardiac output slope improved physiologic specificity during exercise.

Conclusions: Group 2 PH is a dynamic, load-dependent phenotype inadequately characterized by resting PCWP alone. Intermediate PCWP values represent continuous probabilities of bidirectional discordance rather than discrete diagnostic states. A staged physiology-guided approach integrating iNO, ventricular geometry, and provocative testing improves concordance between hemodynamic classification and clinically integrated phenotype assignment.

Y. Tatsuoka, Department of Anesthesiology, TidalHealth Peninsula Regional,Maryland, USA.
M. Longley, D. MacCarter and Z. J. Carr

Clin Physiol Funct Imaging 2026 Vol. 46 Issue 4 Pages e70076

Background: Gas-exchange derived pulmonary capacitance (GXCAP) is a non-invasive index of pulmonary arterial capacitance obtainable from submaximal cardiopulmonary exercise testing (CPET), but reference intervals in older adults, a key target population, are lacking.

Methods: A secondary analysis of an open-label clinical device trial, including 207 adults ≥ 60 years undergoing elective non-cardiac surgery was performed. Submaximal CPET with the Shape II system provided peak GXCAP, GXCAP-time slope, and GXCAP-VO₂ slope. Sex-specific empirical 95% reference intervals (2.5th-97.5th percentiles) and indirect reference intervals were calculated using the refineR algorithm, which models the latent healthy subpopulation within routine data. Associations with age and sex were examined using correlation and group comparisons.

Results: The analytic cohort comprised 207 nonsmoking participants (119 males, 88 females). Males demonstrated higher peak GXCAP and steeper GXCAP-time and GXCAP-VO₂ slopes than females. Age was modestly and inversely associated with peak GXCAP and GXCAP-time slope. Empirical reference intervals were wide and right-skewed, whereas refineR produced narrower, physiologically plausible intervals, for example, peak GXCAP 144.9-810.0 mL.mmHg (overall), with higher upper limits in males.

Conclusions: In older adults undergoing preoperative evaluation, GXCAP metrics show clear sex differences. Indirect, refineR-based, reference intervals provide stable, clinically interpretable ranges that may enhance the use of GXCAP for noninvasively assessing pulmonary arterial capacitance in submaximal CPET. GXCAP derivatives (GXCAP-time slope and GXCAP-VO₂ slope were introduced and may offer distinct advantages in submaximal cardiopulmonary exercise testing.

J. Lee,  Biomedical Research Institute, Pusan National University Hospital, South Korea
H. S. Cho, J. S. Cho, Y. D. Kim, H. Y. Ahn and S. H. Kim

Interdiscip Cardiovasc Thorac Surg 2026

Objectives: We examined whether cardiopulmonary exercise testing (CPET) variables predict 30‑day postoperative complications in patients undergoing anatomical resection for non‑small cell lung cancer (NSCLC).

Methods: Consecutive patients who underwent segmentectomy or greater between January 2023 and March 2025 at a single tertiary center were reviewed. All patients underwent CPET within 30 days preoperatively. Data on demographics, comorbidities, pulmonary function, operative factors, and outcomes were collected. Associations were assessed using univariable and multivariable logistic regression; discrimination was evaluated with receiver operating characteristic curve (ROC). Results with two‑sided α = 0.05 were considered significant. Statistical analyses were conducted with R 4.4.2 (stats).

Results: Among 353 patients (mean age 68.4 ± 8.4 years; 58.1% male individuals), 33 (9.4%) experienced complications. Patients were older (71.8 vs 68.0 years) and more often male individuals (81.8% vs 55.6%) than controls; they had lower BMI (23.1 vs 24.4 kg/m2) and lower FEV1/FVC (69.5% vs 72.7%). In the univariable analysis, age (OR 1.07), female sex (OR 0.28 vs male), BMI (OR 0.88 per kg/m2), FEV1/FVC (OR 0.96 per %), VE/VCO2 slope (OR 1.06 per unit), attained stage (OR 0.66 per stage), and operation time (OR 1.58 per hour) were associated with complications. In the multivariable analysis, BMI (OR 0.86, 95% CI 0.75-1.00), FEV1/FVC (OR 0.94, 95% CI 0.90-0.99), and VE/VCO2 slope (OR 1.06, 95% CI 1.00-1.11) remained independent predictors. ROC curves showed poor discrimination: VO2peak AUC, 0.52; AT, 0.59; VE/VCO2 slope, 0.40; and AT time 0.43. Dichotomized cut‑offs were generally non‑informative.

Conclusions: Individual CPET variables had limited discriminative accuracy (AUC < 0.6). CPET should complement clinical and spirometric predictors rather than serve as a stand‑alone gatekeeper.

X. Zheng, The Second Affiliated Hospital of Harbin Medical University, Harbin, China,
P. Wang, S. Wang, H. Cui, H. Tan, L. Guan, et al.

Cardiol Res Pract 2026 Vol. 2026 Pages 4446755

Background: Peak heart rate (HR peak) and first ventilatory threshold heart rate (HR VT1) guide exercise prescription formulation, but existing formulas lack accuracy in coronary heart disease (CHD) patients due to unaccounted pathophysiological differences. This study aimed to construct prediction equation for HR peak and HR VT1 in CHD patients.

Methods: This was a multicenter retrospective study that included 14,465 cases of cardiopulmonary exercise test (CPET) data from CHD patients in 20 hospitals in China. Seventy percent of the cohort was divided into a development group (n = 10,125), and the remaining 30% served as a validation group (n = 4340). Stepwise multiple backward regression established HR peak and HR VT1 equations, with accuracy compared to traditional formulas.

Results: Age, weight, resting heart rate (HR rest), CHD diagnostic category, and β-blockers were included in the equation. The mean absolute percentage error (MAPE) of China-CPET-HR peak is 9.04%, with an adjusted coefficient of determination (R ²) of 0.399. For the China-CPET-HR VT1 formula, the MAPE is 7.32% and the adjusted R ² is 0.509. The %HR peaks of the FOX, TANAKA, KETEYIAN, and China-CPET-HR peak formulas are 82 ± 11%, 79 ± 11%, 105 ± 13%, and 100 ± 11%, respectively.

Conclusion: Based on CPET data from CHD patients, we developed prediction equations for HR peak and HR VT1. The prediction accuracy of these equations is significantly higher than others, which helps to formulate accurate individualized exercise prescriptions and rehabilitation training guidance for CHD patients.