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.

G. Mitsiou, 1st Critical Care Medicine Department, Evangelismos Hospital,  Athens, Greece.
S. P. Tokmakidis, I. Patsaki, K. Psarra, C. Kourek, E. Karatzanos, et al.

J Cardiovasc Dev Dis 2026 Vol. 13 Issue 6

Endothelial progenitor cells (EPCs) constitute a cell population that enters the circulation during aerobic exercise and facilitates vascular function. In a similar action, hematopoietic progenitor cells (HPCs) are also released into circulation in response to exercise. Peripheral vascular dysfunction is frequently present in patients with heart failure. Whether acute interval exercise performed with high intensity induces EPC and HPC mobilization and affects microcirculation remains under investigation. The study population consisted of nineteen male patients with chronic heart failure (CHF) and eleven age-matched healthy individuals who underwent a high-intensity interval exercise session. Blood was drawn before, immediately after exercise, and 40 min after exercise to identify the numbers of circulating EPCs and HPCs by flow cytometry. Microcirculatory assessment was performed using near-infrared spectroscopy before and after exercise. Vascular endothelial growth factor (VEGF) change was also assessed before and after exercise in patients with CHF using flow cytometry. The interval exercise protocol revealed significant effects (p < 0.05) on EPC and HPC mobilization and systemic microcirculation (p < 0.05) in patients with CHF and healthy individuals. No significant differences were observed between patients with CHF and healthy individuals during interval exercise. VEGF did not reveal any changes immediately after interval exercise in CHF patients. Acute high-intensity interval training was associated with increased EPC and HPC mobilization and changes in microcirculation in patients with CHF and healthy individuals.

A. S. Dumitrescu, West University of Timișoara,  Timisoara, Romania.
A. Alexandru and S. O. Brindescu

Sports (Basel) 2026 Vol. 14 Issue 6

G. Halasz, Azienda Ospedaliera San Camillo Forlanini, Cir.ne Gianicolense 87, 00152 Rome, Italy.
R. Mistrulli, M. Di Francesco, G. Giacalone, G. Ferri, S. Beato, et al.

Healthcare (Basel) 2026 Vol. 14 Issue 11

Cardiopulmonary exercise testing (CPET) is the reference method for the objective assessment of exercise capacity because it provides an integrated appraisal of cardiovascular, respiratory and metabolic responses to exertion. However, CPET alone quantifies the magnitude of functional impairment without fully resolving the central and peripheral mechanisms that determine exercise intolerance. The integration of CPET with exercise stress echocardiography and near-infrared spectroscopy (NIRS) has therefore emerged as a clinically relevant multimodal strategy. Stress echocardiography provides real-time information on ventricular reserve, filling pressures, pulmonary pressure response, valvular function, pulmonary congestion and dynamic outflow obstruction, whereas NIRS provides continuous insight into skeletal muscle oxygen delivery, extraction and utilization. This narrative review summarizes the physiological rationale, practical workflow, methodological limitations and clinical applications of combined CPET, stress echocardiography and NIRS across heart failure, pulmonary hypertension, peripheral artery disease, cardiomyopathies and sports cardiology. By linking systemic gas exchange, central hemodynamics and peripheral oxygen handling, this approach may move exercise evaluation from a descriptive measure of performance toward a mechanism-based framework for phenotyping, risk stratification and individualized therapeutic decision-making. Further studies are needed to harmonize protocols, validate reproducible multimodal indices and demonstrate incremental prognostic value over conventional testing.

S. Kadosh, School of Public Health, Gray Faculty of Medicine, Tel Aviv University, Tel-Aviv, Israel.
Y. Baidats, A. M. Jones, D. Wilkerson, A. Velner, R. Reuveny, et al.

Compr Physiol 2026 Vol. 16 Issue 3 Pages e70194

Aim: We studied the effect of O₂ supplementation on physiological responses to exercise in patients with pulmonary vascular disease.

Methods: Six patients with pulmonary arterial hypertension (PAH), four patients with chronic thromboembolic pulmonary hypertension (CTEPH) (age 54 ± 17 years; 8 females) and 13 healthy individuals (age 50 ± 17 years; 5 females) were tested. PAH/CTEPH was defined hemodynamically by mPAP > 20 mmHg and PVR > 3 WU. Patients performed symptom-limited cardiopulmonary exercise tests, and constant work-rate tests (CWRTs) at 80% of the work-rate (WR) at the gas exchange threshold (GET). Tests breathing room air (RA, 21% O₂) were compared to tests performed breathing 30% O₂. Oxygen-uptake (V̇O₂) kinetics were calculated from the CWRT results.

Results: In the PAH/CTEPH group, peak WR, peak V̇O₂ and V̇O₂ at the GET improved significantly when breathing 30% O₂ compared to RA (mean ± SD 85 ± 26 vs. 77 ± 25 W, 18.3 ± 5.8 vs. 15.6 ± 5.7 mL/kg/min and 764 ± 181 vs. 685 ± 154 mL/min; p = 0.011, p = 0.015 and p = 0.012, respectively). Peak V̇O_2/HR was higher with 30% O₂ compared with RA (8.8 ± 2.2 vs. 7.7 ± 1.8 mL/beat, p = 0.021). The time constant (tau) of V̇O₂ kinetics was faster in PAH/CTEPH patients while breathing 30% O₂ compared to RA (36 ± 4 vs. 43 ± 6 s, p = 0.009). In healthy individuals there was no improvement in V̇O₂ kinetics while breathing 30% O₂ compared to RA (tau 35 ± 6 vs. 35 ± 6 s, p = 0.916).

Conclusion: A clinically applicable level of O₂ supplementation (30%) improved maximal and aerobic exercise capacity and V̇O₂ kinetics in PAH/CTEPH patients. O₂ supplementation may be considered to support exercise training in PAH/CTEPH patients.

K. Z. Abbas, Department of Thoracic Medicine and Surgery, Temple University Hospital, Philadelphia, USA
T. Caton and P. Rali

direcct link
https://www.ncbi.nlm.nih.gov/pubmed/42309631

Heart Fail Clin 2026 Vol. 22 Issue 3 Pages 387-397

Pulmonary embolism (PE) is associated with substantial long-term morbidity that extends past initial diagnosis. Patients diagnosed with PE face risks of chronic thromboembolic pulmonary hypertension, post-PE syndrome, recurrent venous thromboembolism, psychological distress, and impaired quality of life. Optimal follow-up is critical for early recognition and intervention. This article synthesizes contemporary evidence, including guideline recommendations, registry data, and recent clinical studies. The aim of this article is to outline a structured approach to PE follow-up, addressing who should be monitored, when, and with which modalities.