Kamigaichi A; Department of Surgical Oncology, Hiroshima University, Hiroshima, Japan.
Tsutani Y; Tsuchiya A; Utsunomiya H;Miyata Y; DMimae T; DeTsubokawa N; Nakano Y;Okada M;

JTO clinical and research reports [JTO Clin Res Rep] 2025 Sep 12; Vol. 6 (11), pp. 100903.
Date of Electronic Publication: 2025 Sep 12 (Print Publication: 2025).

Introduction: The rationale underlying the benefits of the parenchyma-preserving nature of sublobar resection (SR) compared with lobectomy remains unclear. This study aimed to assess postoperative changes in cardiopulmonary function after lobectomy and SR using exercise stress testing.
Methods: This prospective, observational study enrolled patients scheduled for lobectomy or SR. Changes in cardiopulmonary function at 6 months postoperatively were evaluated using exercise stress echocardiography and cardiopulmonary exercise tests.
Results: Initially, 41 patients were enrolled, with 20 patients in the lobectomy group and 18 patients in the SR group (16 segmentectomies, two wedge resections) after excluding three ineligible patients. Preoperatively, all patients demonstrated well-preserved cardiopulmonary function. The systolic pulmonary artery pressure (SPAP) change at peak exercise was significantly higher for lobectomy (median 26.5%; interquartile range [IQR] 0.6-60.1) than for SR (median -8.2%; IQR -38.7-11.7; p = 0.001), despite nonsignificant differences at rest ( p = 0.599). Postoperative exercise-induced pulmonary hypertension (exPH) occurred in nine patients (45%) in the lobectomy group but none in the SR group (0%, p = 0.010). Postoperative peak oxygen consumption during exercise decreased significantly in the lobectomy group (median -14.3%; IQR -24.0 to -4.2) compared with that in the SR group (median -7.8%; IQR -13.5-8.7; p = 0.024). The postoperative increase in SPAP at peak exercise (r = 0.402, p = 0.012), prevalence of postoperative exPH (r = 0.978, p = 0.004), and postoperative decrease in peak oxygen consumption (r = -0.330; p = 0.041) were correlated with the number of resected segments.
Conclusions: Lobectomy induces increased SPAP during exercise, exPH, and effort intolerance, compared with SR. This highlights the importance of preserving lung parenchyma in lung surgery.
Clinical Trial Registration: This trial is registered in the UMIN Clinical Trials Registry under the code UMIN000053694.

Gentili F; Clinical Area of Fetal, Neonatal and Cardiological Sciences, Bambino Gesù Children’s Hospital, IRCCS, 00165 Rome, Italy.
Cafiero G; Tranchita E; Kowalczyk J; Badolato F; Pagliari P; Leonardi B; Calcagni G; Rinelli G; Montanaro C; Drago F; Giordano U;

Journal of cardiovascular development and disease [J Cardiovasc Dev Dis] 2025 Sep 25; Vol. 12 (10).
Date of Electronic Publication: 2025 Sep 25.

Cardiopulmonary exercise testing (CPET) is recommended as part of routine care in people with congenital heart disease. A significant difference has been observed in many CPET parameters, depending on the ergometer and exercise protocol used. The aim of this study is to investigate such differences in Fontan patients. All Fontan patients (<40 years old, NYHA class I/I-II) underwent two consecutive CPETs on different ergometers (treadmill with ramped Bruce protocol versus cycle ergometer with ramp protocol) within less than 12 months. The exclusion criterion was the presence of significant clinical/anthropometric changes between the two tests. Anthropometric, surgical, clinical, electrocardiogram (ECG) and CPET data were collected. 47 subjects were enrolled (25 males, mean age 16.4 at first test). Peak heart rate (HR) tended to be higher on the treadmill ( p = 0.05 as % of predicted, p = 0.062 in absolute value). Peak oxygen consumption (VO ₂ ) (mL/min, mL/kg/min, and % of predicted) was significantly higher on the treadmill ( p < 0.01), as well the VO ₂ at the ventilatory anaerobic threshold (VAT) and the peak oxygen pulse. A different kinetics of the oxygen pulse wave was observed in the same patient comparing the two testing modalities. Maximal respiratory-exchange-ratio values (>1.1) were reached more frequently on the cycle ergometer ( p < 0.001). The minute ventilation-carbon dioxide output slope (VE/VCO ₂ slope) was not different between the two tests ( p = 0.400). Many parameters of CPET may differ depending on the ergometer used. These should be considered in clinical evaluation of Fontan patients and when exercise is to be prescribed.

Zhang ZF; Department of Rehabilitation Medicine, The Affiliated Rehabilitation Hospital of Chongqing Medical University, Chongqing, China.;
Sun XG; Chen JH;Xu F;Xiang MJ;Huang J; Xie B;Shi C;Zhang YF; Liu F;Li L; Xie YH;

Journal of thoracic disease [J Thorac Dis] 2025 Sep 30; Vol. 17 (9), pp. 7124-7140.
Date of Electronic Publication: 2025 Sep 26.

Background: Cycle ergometer is commonly used for cardiopulmonary exercise testing (CPET), which is the objective and quantitative golden standard for functional evaluation and training, while arm CPET is less commonly used to clinically assess a patient’s overall functioning. To determine optimal CPET protocols, we studied the effect of different work rate increasing rates of arm ergometer on CPET key variables.
Methods: We recruited fourteen non-symptomatic participants without any clinical diagnosis, and first performed maximal leg CPET for functional evaluation, followed by four maximal arm ergometer CPETs using different work rate increasing rates (5, 20, 35, and 50 W/min) in random order on various days in one week (7 days). The key variables are oxygen uptake ( INLINEMATH ), heart rate (HR), minute ventilation ( INLINEMATH ), tidal volume (VT), breathing frequency (Bf), anaerobic threshold (AT), work rate, incremental exercise time (Tlim), respiratory exchange ratio (RER). One-way analysis of variance (ANOVA) with Tukey’s post-hoc test compared outcomes across the four increasing rate protocols, and a paired t-test assessed arm vs. leg differences.
Results: All participants safely finished maximal CPET using leg and arm ergometers, and they had normal leg CPET peak INLINEMATH [92.89±18.37 (73.34-143.63) %predicted]. Each arm ergometer protocol elicited similar INLINEMATH (1.37±0.31, 1.35±0.32, 1.34±0.31 and 1.33±0.30 L/min, P=0.99), HR (P=0.96), INLINEMATH (P=0.98), VT (P=0.98) and Bf (P=0.81) at peak and AT (P=0.96). However, there were significantly different peak work rate (58±11, 80±18, 95±22 and 110±22 W, P<0.001), peak RER (1.08±0.07, 1.17±0.12, 1.20±0.12 and 1.21±0.14, P=0.03) and maximal RER during recovery (1.36±0.13, 1.45±0.18, 1.49±0.13 and 1.53±0.20, P=0.04), which were positively correlated with work rate increasing rate (R2=0.985, 0.823, 0.939, respectively). There were significantly different Tlim with negative relationship (11.61±2.29, 4.02±0.91, 2.71±0.64 and 2.19±0.44 min, P<0.001, R ² =0.383).
Conclusions: The study indicates that same as leg ergometer CPET, the arm ergometer CPET also needs optimized increasing rate of incremental exercise for each subject. We preliminarily recommend a work rate increasing rate of about 10-20 W/min in arm ergometer CPET for healthy individuals, which needs further investigation for functional evaluation and training.

Xie B; Department of Rehabilitation, The Affiliated Rehabilitation Hospital of Chongqing Medical University, Chongqing, China.;
Sun XG;Huang J; Chen JH; Xu F; Zhang ZF; Zhou QQ; Shi C; Zhang YF;Wang JN; Liu F; Xie YH;

Journal of thoracic disease [J Thorac Dis] 2025 Sep 30; Vol. 17 (9), pp. 7098-7111.
Date of Electronic Publication: 2025 Sep 26.

Background: Type II diabetes mellitus (T2DM) is characterized by glucose metabolic dysregulation, which may be addressed through integrative physiological interventions. Guided by Holistic Integrative Physiology and Medicine (HIPM) theory, this study investigates dynamic blood glucose changes in 11 T2DM patients with chronic comorbidities before and after cardiopulmonary exercise testing (CPET)-prescribed exercise to identify optimal multifactorial glycemic control strategies.
Methods: Eleven patients with T2DM who underwent 11 T2DM patients (2020-2022, Fuwai Hospital) underwent CPET for exercise intensity prescription. Continuous ambulatory blood glucose monitoring was conducted for each participant. Various parameters, including their fasting and postprandial peak glucose levels, exercise start and end times, post-exercise relative lows, rebound peak, low before eating fruits and vegetables at lunch, blood glucose levels, and the corresponding times at which carbohydrates were eaten, were observed and recorded. The time before exercise started was considered the zero point, and the difference in blood glucose between each point and the start of exercise, as well as the percentage difference, were calculated. Analysis of variance (ANOVA) was used to compare time points and blood glucose data for the entire group. Paired samples t -tests were used to compare adjacent time points and blood glucose data.
Results: All patients exhibited post-breakfast peak fasting plasma glucose. Exercise initiation induced significant declines in blood glucose, continuing to nadir post-exercise. Levels subsequently rose slightly to a secondary peak before gradually declining to a second nadir prior to fruit/veg intake. Pre-lunch carbohydrate intake was associated with stable euglycemia (all P<0.001).
Conclusions: HIPM-based lifestyle management (exercise, nutrition, rest) rapidly modulates hyperglycemia in T2DM patients. Exercise-induced metabolic improvements enhance respiratory-circulatory homeostasis, providing a mechanistic basis for integrated chronic disease management strategies.

Chen JH; Department of Internal Medicine,  Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Sun XG; Huang J; Xie B; Xu F; Xiang MJ; Zhang ZF; Zhou QQ; Shi C; Zhang YF; Wang JN;Liu F;Xie YH;

Journal of thoracic disease [J Thorac Dis] 2025 Sep 30; Vol. 17 (9), pp. 6516-6529.
Date of Electronic Publication: 2025 Sep 25.

Background: The theory of Holistic Integrative Physiology and Medicine (HIPM) emphasizes the perspective of integrated regulation, which includes interconnected systems of respiration, circulation, and metabolism. Based on this perspective, we aim to comprehend the relationship between respiration and circulatory parameters such as heart rate variability (HRV) and blood pressure variability (BPV), thereby clarifying the interrelation of two essential physiological systems.
Methods: This study conducted a retrospective analysis of data obtained during polysomnography (PSG) and cardiopulmonary exercise testing (CPET). These parameters included the mean amplitude of HRV, HRV percentage (HRV%), mean amplitude of systolic blood pressure variability (SBPV-M), mean amplitude of diastolic blood pressure variability (DBPV-M), along with the percentages of SBPV-M (SBPV-M%) and DBPV-M (DBPV-M%). Furthermore, we analyzed the relationship between nasal airflow respiratory cycles and circulatory cycles. We analyzed two groups: seven individuals without known diseases and eight patients with chronic diseases, all without sleep apnea syndrome on PSG.
Results: Our study demonstrated significant differences between individuals without known diseases and patients with chronic diseases. In control group, the peak oxygen uptake (peak INLINEMATH ) was 97.82±18.51 %Pred, the anaerobic threshold (AT) was 83.61±10.46 %Pred, the peak work rate was 111.09±31.01 %Pred, the HRV was 6.15±1.52 bpm and HRV% was 11.15%±3.71%, respectively. These values were significantly higher than those observed in patients with chronic diseases (P values were 0.009, 0.05, 0.005, <0.001 and 0.001). In the context of SBPV-M, DBPV-M, SBPV-M% and DBPV-M%, the values for individuals without known diseases were 2.27±0.83 mmHg, 2.12±0.40 mmHg, 2.07%±0.71%, and 3.10%±0.66%, respectively. No significant changes were seen when compared to those in patients with chronic diseases (P values were 0.36, 0.20, 0.66, and 0.08). The ratio of respiratory cycles to circulatory cycles was nearly 1:1 in both groups.
Conclusions: This study demonstrates two principal observations: (I) precise synchronization between respiratory cycles and cardiovascular variability cycles during stable sleep phases; (II) lower HRV magnitudes observed in participants with chronic diseases compared to controls.

Mavromoustakou K; First Department of Cardiology, University of Athens, Hippokration General Hospital, 115 27 Athens, Greece.
Botis M; Iliakis P; Leontsinis I; Xydis P; Dimitriadis K; Chrysohoou C; Tsioufis K;

Biomedicines [Biomedicines] 2025 Oct 02; Vol. 13 (10).
Date of Electronic Publication: 2025 Oct 02.

Background/Objectives : Patients with non-valvular heart failure frequently develop valvular disease. However, the prevalence of valvular disease across patients with different heart failure etiologies remains underexplored. This study aimed to investigate the burden of VHD among patients with non-valvular heart failure, and secondly evaluate its association with cardiopulmonary test.
Methods : We analyzed data from patients with non-valvular heart failure (HF) who were evaluated as outpatients at the HF clinic between February 2020 and November 2024. Patients were categorized into three groups: coronary artery disease-related HF (CAD-HF), dilated cardiomyopathy (DCM), and other causes (e.g., hypertension, diabetes, and various cardiomyopathies). Demographic and clinical characteristics, as well as echocardiographic and cardiopulmonary exercise testing (CPET) results, were evaluated.
Results : Among all groups mild mitral regurgitation (MR) was the most common valvular disease, followed by mild tricuspid regurgitation (TR). Patients with CAD-HF frequently had mild aortic regurgitation (AR) compared to DCM (23.6% vs. 14.9%, p = 0.05). In the CPET subgroup, which included 41 patients who consented to participate, in patients with moderate-to-severe VHD had significantly lower VO ₂ /HR (oxygen pulse), VO ₂ max, and OUES, indicating worsened functional capacity despite similar left ventricular ejection fraction. Hypertension and atrial fibrillation were independently associated with greater valvular disease severity on multivariable analysis.
Conclusions : No significant differences in valvular disease between patients with DCM and CAD-HF were documented, apart from a higher prevalence of mild AR in the CAD-HF group. Patients with moderate-to-severe valvular regurgitation demonstrated worse cardiopulmonary performance, regardless of ejection fraction, highlighting the important role of CPET in evaluating the functional impact of valvular heart disease in this population.

Halasz G; Division of Cardiology, Cardio-Thoracic and Vascular Department, Azienda Ospedaliera San Camillo Forlanini, 00152 Rome, Italy.
Ciacci P; Mistrulli R; Giacalone G;Ferro A; Romiti GF; Albi F; Gabrielli D; Re F;

Journal of clinical medicine [J Clin Med] 2025 Oct 14; Vol. 14 (20).
Date of Electronic Publication: 2025 Oct 14.

Background: Hypertrophic cardiomyopathy (HCM) is a heterogeneous myocardial disease in which conventional prognostic models, primarily focused on sudden cardiac death, often fail to identify patients at risk of clinically relevant events such as heart failure progression or rehospitalization. Cardiopulmonary exercise testing (CPET) quantifies functional capacity, while stress echocardiography (SE) provides mechanistic insights into exercise-induced hemodynamic changes. Their combined application (CPET-SE) may enhance risk stratification in patients with HCM.
Methods: In this retrospective study, 388 patients with obstructive and non-obstructive HCM (mean age 48 ± 15 years, 63.1% male) underwent baseline CPET-SE between 2010 and 2022 and were followed for a median of 7.4 years [IQR 4.3-10.2]. Echocardiographic parameters were assessed at rest and peak exercise, and CPET indices included peak oxygen consumption (pVO ₂ ), ventilatory efficiency, and anaerobic threshold. The primary outcome was a composite of heart failure hospitalization or progression to end-stage HCM.
Results: Over a median follow-up of 7.4 years, 63 patients (16.2%) experienced an event of the primary outcome. Patients who developed a primary outcome had greater left atrial diameter (45.0 vs. 41.0 mm, p < 0.001) and indexed volume at rest (36.4 vs. 29.0 mL/m ² , p < 0.001), with further dilation during stress ( p = 0.046); increased LV wall thickness ( p = 0.001); higher average E/e’ at rest and during stress ( p ≤ 0.004); and higher pulmonary artery systolic pressure at rest ( p = 0.027) and during stress ( p = 0.044). CPET findings included lower pVO ₂ (16.0 vs. 19.5 mL/kg/min, p = 0.001), reduced % predicted pVO ₂ ( p = 0.006), earlier anaerobic threshold ( p = 0.032), impaired ventilatory efficiency ( p = 0.048), and chronotropic incompetence ( p < 0.001) in patients who experienced a primary outcome. Multivariable analysis identified dyslipidemia (OR 2.58), higher E/e’ (OR 1.06), and lower pVO ₂ (OR 0.92) as independently associated with the primary outcome.
Conclusions: CPET-SE provided a comprehensive evaluation of patients with HCM, associating aerobic capacity to its hemodynamic determinants. Reduced pVO ₂ showed the strongest association with adverse outcomes, while exercise-induced diastolic dysfunction and elevated pulmonary pressures identified a high-risk phenotype. Incorporating CPET-SE into longitudinal management of patients with HCM may enable earlier detection of physiological decompensation and guide personalized therapeutic strategies.

Poparcea D; 1Division of Pneumology and Allergology, MD-2004, Chisinau, Republic of Moldova.
Corlateanu A; Ceasovschih A; Varga JT;

Physiology international [Physiol Int] 2025 Oct 27.
Date of Electronic Publication: 2025 Oct 27.

Background: Chronic obstructive pulmonary disease (COPD) is a common lung disease causing airflow obstruction and breathing problems. Despite the current advances in the treatment of COPD, exercise intolerance remains a challenge, impacting quality of life and increased morbidity. Cardiopulmonary exercise testing (CPET) is a non-invasive test with concomitant gas exchange analysis that provides a thorough assessment of exercise physiology, involving the integrative respiratory, cardiovascular, muscle and metabolic responses to exercise, and, thus providing insights into exercise limitation mechanisms. This review hypothesizes that CPET offers prognostic value in COPD and can be used to evaluate the response to several therapeutic interventions.
Aim: To investigate the clinical usefulness of CPET in assessing exercise tolerance, disease progression and therapeutic outcomes in COPD patients.
Methods: This this systematic literature review was conducted to analyse studies published between 2020 and 2024 on the role of CPET in COPD management. Studies were reviewed focusing on CPET’s prognostic value, its correlation with disease severity, and its impact on therapeutic strategies. The quality of the selected studies was assessed by using PRISMA guidelines.
Results: As a result, CPET-integrated monitoring supports as a valuable tool for evaluating exercise intolerance in COPD, with parameters such as peak oxygen uptake (V̇O2 peak), ventilatory efficiency (V̇E/V̇CO2 slope), and dynamic hyperinflation correlating with disease severity and prognosis. According to studies a V̇O2 peak value below 15 mL kg-1 min-1 is associated with increased mortality risk and hospitalizations. Undoubtedly, CPET-derived thresholds for ventilatory and cardiovascular limitations remain an invaluable tool for COPD diagnosis and management, and contribute to optimizing rehabilitation strategies and pharmacological interventions.
Conclusion: CPET provides important information about the pathophysiology of exercise intolerance in COPD, helping with personalized treatment planning and risk stratification. CPET should be integrated into COPD management guidelines.

Thorup CV; Department of Cardiology, Aarhus University Hospital, Palle Juul-Jensens, Boulevard 69, 8200, Aarhus N, Denmark.
Jeppesen CNA; Jensen TH; Tinggaard AB; Rudd CL;Hvas CL; Skou MK; Mortensen JK;Reggiori F; Dengjel J; Wang J; Farup J; Jessen N; Kim WY; Wiggers H;

Trials [Trials] 2025 Oct 30; Vol. 26 (1), pp. 452.
Date of Electronic Publication: 2025 Oct 30.

Background: Coronary artery disease (CAD) remains a major cause of morbidity and mortality. Caloric restriction promotes cardiovascular health but is difficult to sustain. Spermidine, a naturally occurring polyamine and caloric-restriction mimetic, has been linked to improved longevity in epidemiological studies and shown to enhance autophagy, mitochondrial function, and cardiovascular ageing in preclinical models. This trial will investigate whether high-dose spermidine improves cardiac remodelling, exercise capacity, muscle mass, and systemic inflammation in elderly patients with CAD.
Methods: This is a single-centre, randomised, double-blind, placebo-controlled, superiority trial at Aarhus University Hospital, Denmark. We have randomised 187 patients aged ≥ 65 years with CAD (prior coronary artery revascularisation or myocardial infarction ≥ 3 months prior to screening) and preserved left ventricular ejection fraction (> 40%) in a 1:1 ratio to receive either 24 mg/day spermidine or placebo for 48 weeks. Participants, investigators, outcome assessors, and data analysts will remain blinded until completion of the analysis of all primary endpoints. Analyses will follow the intention-to-treat principle. The trial is powered to detect between-group differences in four co-primary endpoints: (1) left ventricular mass (g) by cardiac magnetic resonance imaging, (2) peak oxygen consumption (mL·kg⁻ ¹ ·min⁻ ¹ ) by cardiopulmonary exercise testing, (3) appendicular lean mass (g) by dual-energy X-ray absorptiometry, and (4) high-sensitivity C-reactive protein (mg/L). Secondary outcomes include 24-h ambulatory blood pressure, arterial stiffness, physical performance, muscle strength, daily physical activity, quality of life, cognitive function, dietary spermidine intake, and spermidine levels in plasma and skeletal muscle. Safety monitoring includes laboratory testing, telephone interviews and adverse event recording.
Discussion: This is the first trial to investigate the cardiovascular and metabolic benefit from a high-dose spermidine treatment in patients with CAD. The findings will provide important insights into the therapeutic potential of spermidine.
Trial Registration: ClinicalTrials.gov identifier NCT06186102 (first posted 12 June 2023). Participant enrolment began on 4 January 2024, and trial completion is anticipated in August 2026.
Competing Interests: Declarations. Ethics approval and consent to participate {24}: The study will follow the tenets of the Declaration of Helsinki, and the protocol was approved by the Danish ethics committees. Informed consent will be obtained from all the participants. Consent for publication {32}: Not applicable: this protocol does not include any individual person’s data (images, videos, or personal details). Competing interests {28}: The authors declare that there are no conflicts of interest that could be perceived as prejudicing the impartiality of this work. Henrik Wiggers reports receiving research grants from Sygesikring Danmark and the Eva and Frænkels Mindefond. Christian Velling Thorup reports receiving research grants from the Danish Diabetes and Endocrine Academy and the Danish Cardiovascular Academy (grant numbers NNF22SA0079901 and NNF20SA0067242), as well as funding from the Steno Diabetes Center Aarhus (SDCA). The spermidine intervention and placebo capsules were donated by DoNotAge (4 Melbourne Business Ct, Derby, Derbyshire, DE24 8LZ, UK). The investigators have no financial or advisory relationship with the company, and the donor had no role in the design, conduct, analysis, or reporting of the trial.