Afoke, Jonathan; Department of Cardiovascular Surgery, Mayo Clinic, Rochester, USA.
Stephens, Elizabeth H; Allison, Thomas G; Chopko, Trevor C; et al;

The Annals of thoracic surgery,2025 Oct 07

• Background: Optimum timing for surgery in asymptomatic/mildly symptomatic adult patients with Ebstein anomaly remains uncertain. This study assessed the association between pre-operative cardiopulmonary exercise testing (CPET) and mortality; and longitudinal changes in CPET.
• Methods: Retrospective review of consecutive adult patients with Ebstein anomaly who had tricuspid surgery between 2007 and 2018 with pre-operative CPET. Primary outcome was all-cause mortality and secondary outcome were changes in CPET.
• Results: The cohort included 116 patients. Ninety-four (81.1%) were NYHA Class I/II. Median age was 39.6 years and 75 (64.7%) were female. Forty-four (37.9%) had one or more prior sternotomies, 58 (50%) underwent Cone repair and 55 (47.5%) had tricuspid replacement. Median percentage predicted peak VO ₂ was 62% and ventilatory efficiency was 30 l/min/min. Fifteen (12.9%) had severe right ventricle dysfunction and median left ventricular ejection fraction was 58%. At median follow up of 9.8 years, there were 8 deaths. Ventilatory efficiency trended to be associated with mortality (p=0.075) on univariate analysis and was the largest contributor to prediction of mortality in machine learning Random Forest models. 33 patients had CPET at a median of 2.9 years after surgery. There was significant improvement in ventilatory efficiency (30 pre-operatively vs 27 l/min/l/min post-operatively, p=0.015).
• Conclusions: In those with minimal or no symptoms, ventilatory efficiency is one of the most important variables in predicting mortality after surgery. Patients may have improved ventilatory efficiency after tricuspid surgery for Ebstein anomaly. These findings highlight the role of CPET in optimizing timing of surgery.

Wilhite, Daniel P.; VA Airborne Hazards and Burn Pits Center of Excellence, East Orange, NJ.
Alexander, Thomas; Klein-Adams, Jacquelyn C.; Falvo, Michael J.

Medicine & Science in Sports & Exercise; (Baltimore, Maryland) 2025Supplement; v.57, 116-116. (1p)

he article focuses on a study comparing cardiorespiratory fitness and dyspnea on exertion (DOE) between deployed Veterans from post-9/11 conflicts and non-deployed controls. The study involved 25 deployed Veterans and 11 non-deployed controls who underwent cardiopulmonary exercise testing (CPET) using the Bruce treadmill protocol. Results indicated that deployed Veterans experienced significantly higher perceived breathlessness at peak exercise compared to controls, despite no significant differences in peak oxygen consumption (V̇O2peak). The findings suggest that DOE in deployed Veterans may not be solely due to deconditioning, highlighting the need for further research to explore underlying factors contributing to respiratory issues.

Beaven, Michael ;Curtin University, BENTLEY, Australia.
Brown, Henry; Wilson, Andrew; Gibbons, James; et al; 

Medicine & Science in Sports & Exercise; (Baltimore, Maryland) 2025Supplement; v.57, 114-115. (2p)

The article focuses on a study comparing cardiopulmonary exercise test (CPET) outcomes between preterm-born adults and term-born adults, specifically examining how different exercise modes (treadmill vs. cycle ergometry) affect physiological responses. The study involved 22 preterm-born adults (mean gestation: 27 weeks) and 5 term-born adults, who completed maximal CPETs on both exercise modes. Results indicated that preterm-born individuals had higher peak oxygen consumption (peak VO2) during treadmill tests compared to cycle ergometry, but the differences in exercise responses were similar for both groups. The findings suggest that cycle ergometry may underestimate peak VO2 in preterm-born individuals, which is important for interpreting exercise capacity assessments.

Tseng, Watson Hua-Sheng; Department of Medical Education, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan.
Chiu, Chien-Hung; Chang, Sing-Ya; Yang, Lan-Yan ;et al;

Annals of surgical oncology,2025 Oct 10

• Background: Cardiopulmonary exercise testing (CPET) parameters, such as ventilatory equivalent for carbon dioxide (V̇ _E /V̇CO ₂ ), peak oxygen consumption (V̇O _2peak ), and anaerobic threshold (AT), have been proposed as potential predictors of postoperative complications. Yet, few systematic analyses have examined the association between CPET variables and major complications after esophagectomy, as defined by the Clavien-Dindo classification. Associations with cardiopulmonary complications and mortality also require updating on the basis of trial sequential analysis (TSA).
• Materials and Methods: Systematic searches were conducted to identify relevant studies reporting preoperative CPET values and major complications, cardiopulmonary complications, and 1-year mortality. Standardized mean differences (SMD, random-effects model) were calculated and TSA was conducted to evaluate the robustness of evidence in the previous and current meta-analyses.
• Results: A total of 12 studies met inclusion criteria. V̇O _2peak was correlated with major complications (SMD = – 0.42; 95% CI – 0.70 to – 0.14, p = 0.0032) and cardiopulmonary complications (SMD = – 0.39; 95% CI – 0.65 to – 0.13, p = 0.0032). AT showed similar but weaker associations with both outcomes (SMD = – 0.33 and – 0.22; 95% CI – 0.63 to – 0.03 and CI – 0.40 to – 0.04, p = 0.033 and 0.018, respectively). V̇ _E /V̇CO ₂ demonstrated no meaningful relationship with major complications. In addition, the present study found neither V̇O _2peak nor AT was associated with 1-year mortality after esophagectomy.
• Conclusions: V̇O _2peak and AT were inversely associated with morbidity after esophagectomy, while V̇ _E /V̇CO ₂ offered limited prognostic value and none predict 1-year survival. V̇O _2peak is a key predictor of major and cardiopulmonary complications after esophagectomy and warrants further investigation, either alone or as part of a composite model.

Constantine A; Adult Congenital Heart Disease Unit, Queen Elizabeth Hospital Birmingham, Birmingham, UK.
Dimopoulos K; McCabe C;

The European respiratory journal [Eur Respir J] 2025 Aug 22; Vol. 66 (2).
Date of Electronic Publication: 2025 Aug 22 (Print Publication: 2025).

Editorial comment.
No abstract available

Stefanetti RJ; Faculty of Medical Sciences & clinical research institute, Newcastle University, Newcastle upon Tyne,  UK.;
Charman SJ; TNewman J; Hallsworth K; Blain AP; Gorman GS;

Brain communications [Brain Commun] 2025 Sep 09; Vol. 7 (5), pp. fcaf342.
Date of Electronic Publication: 2025 Sep 09 (Print Publication: 2025).

The m.3243A>G variant in the MT-TL1 gene is the most prevalent pathogenic variant in mitochondrial DNA in adults, associated with a wide clinical spectrum from asymptomatic individuals to mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes syndrome. Although pharmacological trials in mitochondrial disorders are increasing, the lack of validated endpoints remains a significant barrier to therapeutic development. This cross-sectional observational study aimed to evaluate patients with and without mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes syndrome to identify factors associated with disease burden. Seventeen individuals genetically confirmed to harbour the heteroplasmic m.3243A>G pathogenic variant were enrolled: six who met the consensus-based diagnostic criteria for mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes syndrome (median age: 30.0 (inter-quartile range: 29.3-45.0) years). Ten patients who did not have a previous history of stroke-like episodes were assigned as ‘non-mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes’ (age: 37.5 (32.8-48.3) years). Of these patients in the non-mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes group, seven exhibited variable features of mitochondrial disease, including hearing loss, diabetes mellitus, migraine and gastrointestinal involvement, while the remaining three were asymptomatic. One patient was excluded from analysis due to a confirmed ischaemic stroke unrelated to mitochondrial disease. Assessments included disease severity (Newcastle mitochondrial disease adult scale) and patient-reported outcomes of fatigue (fatigue impact scale), health-related quality of life (Newcastle Mitochondrial-QoL), mental well-being (Warwick-Edinburgh mental wellbeing scale), autonomic symptoms (the composite autonomic symptom) and physical activity (The International Physical Activity Questionnaire). Performance outcomes included timed-up and go, handgrip strength, cardiopulmonary exercise testing and accelerometry. Age- and sex-matched healthy controls were included for comparison of accelerometry data (age: 35.5 (28.8-50.5) years). Despite comparable age and mitochondrial DNA heteroplasmy, patients with mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes syndrome had significantly higher disease burden, reduced exercise capacity and lower levels of objectively measured physical activity compared to non-mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes and controls ( P < 0.05-0.001). Patient-reported outcomes did not significantly differ between mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes syndrome/non-mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes. While non-mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes patients showed expected alignment between perceived and objective measures, mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes syndrome patients demonstrated weak, absent, or paradoxical associations. This mismatch may reflect altered symptom perception, cognitive impairment, or disease-related adaptation. These findings underscore the complexity of disease expression in mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes syndrome. Regulatory agencies encourage the inclusion of patient-centred endpoints; however, this study highlights the potential limitations of relying solely on patient-reported outcomes. The divergence between subjective and objective assessments supports the need for multi-dimensional outcomes that integrate both patient perspectives and objective measures to enhance the reliability and interpretability of clinical trials in primary mitochondrial disease.

Wijma AG; Division of Hepato-Pancreato-Biliary Surgery and Liver Transplantation, University Medical Center Groningen, the Netherlands.
Bongers BC; Kuikhoven M; Hoogwater FJH;Nijkamp MW; Klaase JM;

Pancreatology : official journal of the International Association of Pancreatology (IAP) … [et al.] [Pancreatology] 2025 Sep 20.
Date of Electronic Publication: 2025 Sep 20.

Background: In various surgical cancer populations, a clear association has been reported between low preoperative aerobic fitness and poor postoperative outcomes. Yet, in pancreatic surgery, postoperative complications are mainly linked to pancreatic texture and duct diameter, and the role of aerobic fitness remains unclear.
Methods: Patients referred for pancreatoduodenectomy at the University Medical Center Groningen were screened for low aerobic fitness using a questionnaire and referred for cardiopulmonary exercise testing (CPET) for aerobic fitness assessment accordingly. Based on CPET results, patients were classified as unfit when they had an oxygen uptake (VO ₂ ) at the ventilatory anaerobic threshold ≤13 ml/kg/min and/or a VO ₂ at peak exercise ≤18 ml/kg/min. All patients received an advice to be physically active preoperatively and postoperative outcomes were compared to fit patients.
Results: Of 175 screened patients, 120 (68.6 %) were considered at risk for low aerobic fitness and underwent preoperative CPET. After excluding patients who participated in a supervised prehabilitation program, 106 CPET reports were used in the analysis. Forty-four (41.5 %) patients were classified as unfit. Postoperatively, unfit patients had a higher rate of gastroparesis grade ≥ B complications (40.9 % versus 22.6 % in fit patients, p = 0.043), and a prolonged length of stay (13 days versus 11 days in fit patients, p = 0.014).
Conclusions: Low preoperative aerobic fitness is prevalent in patients undergoing pancreatoduodenectomy and a predictor of impaired postoperative outcomes. Aerobic fitness should therefore be included in the preoperative work-up and optimized accordingly in unfit patients scheduled to undergo pancreatoduodenectomy.

Liou IH; Department of Physical Medicine and Rehabilitation, Kaohsiung Veterans General Hospital, Taiwan (R.O.C.).
Chen GB; Sun SF; Ding RS; Huang WY;Tuan SH;

ernational journal of medical sciences [Int J Med Sci] 2025 Sep 29; Vol. 22 (15), pp. 4152-4160.
Date of Electronic Publication: 2025 Sep 29 (Print Publication: 2025).

Background: Ventricular septal defect (VSD) is the most common congenital heart defect in children. While previously considered benign, recent studies suggest long-term impacts on cardiopulmonary fitness (CPF). Overweight and obesity, increasingly prevalent among children, may further impair CPF in this population. This study aimed to evaluate the relationship between adiposity and CPF in children with VSD using cardiopulmonary exercise testing (CPET).
Methods: This retrospective study included 349 children and adolescents with VSD and 349 age-, sex-, and body mass index (BMI)-matched healthy controls. Participants underwent symptom-limited treadmill CPET. Children with VSD were stratified into BMI categories (underweight, normal, overweight, obesity) based on national standards. Multiple CPET parameters were analyzed, including anaerobic threshold metabolic equivalents (AT MET) and peak metabolic equivalents (peak MET).
Results: Children with VSD had significantly higher rates of both underweight (15.5% vs. 4.3%) and obesity (14.6% vs. 9.7%) compared to controls (p < 0.001). Within the VSD group, AT MET and peak MET declined progressively with increasing BMI. [AT MET: 7.41 ± 1.57 (underweight), 6.86 ± 1.38 (normal), 6.01 ± 1.23 (overweight), 5.62 ± 1.23 (obese), p < 0.001; Peak MET: 10.37 ± 2.22 (underweight), 9.58 ± 1.94 (normal), 8.56 ± 1.70 (overweight), 7.81 ± 1.60 (obese), p < 0.001]. Compared to controls, children with VSD showed lower AT MET (6.56 ± 1.51 vs. 6.97 ± 1.47, p < 0.001) and peak MET (9.32 ± 2.03 vs. 10.17 ± 1.95, p < 0.001), along with reduced peak heart rate and heart rate at AT.
Conclusion: Children with VSD, regardless of surgical status, exhibit diminished CPF compared to healthy peers. Moreover, both undernutrition and excessive adiposity are more prevalent in the VSD group. Obesity was associated with significantly impaired cardiopulmonary fitness, highlighting the need for early identification and lifestyle interventions. Routine CPET and weight management strategies should be incorporated into long-term care for pediatric VSD patients.

Nasser R; Department of Cardiology, Antwerp University Hospital (UZA), Edegem, Belgium & other centres
Verelst FR; Mueller S; Winzer EB; Beckers PJ;Van De Heyning CM; Wisløff U; Pieske B; r site Berlin, Berlin, Germany.Adams V; Halle M;
Van Craenenbroeck EM; Gevaert AB;

European journal of preventive cardiology [Eur J Prev Cardiol] 2025 Sep 30.
Date of Electronic Publication: 2025 Sep 30.

Background and Aims: Chronotropic incompetence (CI) is common in heart failure with preserved ejection fraction (HFpEF) and contributes to reduced exercise tolerance. However, the effects of exercise training on CI in HFpEF remain unknown. We aimed to assess the effect of different exercise training intensities on chronotropic reserve in HFpEF.
Methods: This is a subanalysis of the OptimEx-Clin trial. Patients with HFpEF were randomized to high-intensity interval training (HIIT), moderate continuous training (MCT) or guideline control (GC). CI was assessed during cardiopulmonary exercise testing at baseline and 3 months. CI was defined as a chronotropic index ≤0.62 in patients on negative chronotropic medications and ≤0.80 in others.
Results: Among 175 patients with HFpEF (66% female, mean age 70±8 years), 144 completed follow-up. CI was present in 51% and was associated with lower peak oxygen uptake (16.5±4.2 vs. 21.1±5.2 mL/kg/min, p<.001), lower peak workload (89±28 vs. 116±39 W, p<.001), and poorer ventilatory efficiency (35.2±7.1 vs. 32.6±6.8, p=.014) at baseline. HIIT and MCT did not improve chronotropic index, %predicted peak heart rate, nor CI prevalence after 3 months (all p>.500), and adjusting for negative chronotropic drug use did not change results. Nevertheless, HIIT and MCT improved V̇O2peak and workload (p<.001) versus GC, regardless of the presence of CI.
Conclusion: In elderly patients with HFpEF, neither HIIT nor MCT during 3 months significantly improved chronotropic reserve or reduced CI prevalence, but exercise capacity was improved.

Filakovszky Á; Department of Anesthesiology and Critical Care Medicine,  Kepler University Hospital, Linz, Austria & Czech Republic
Brat K; Tschoellitsch T; Bartos S;Mazur A;Meier J; Olson L; Cundrle I;

Thorax [Thorax] 2025 Oct 02.
Date of Electronic Publication: 2025 Oct 02.

Rationale: Despite significant advances in patient care and outcomes, criteria for cardiopulmonary exercise testing (CPET) in risk stratification guidelines for lung resection have not been updated in over a decade. We hypothesised that CPET no longer holds additional predictive value for postoperative complications.
Methods: In this secondary analysis, we included lung resection candidates from two prospective, multicentre studies eligible for CPET and assessed with preoperative pulmonary function tests (PFTs) and arterial blood gas analysis. Postoperative pulmonary (PPCs) and cardiovascular complications (PCCs) were documented during hospitalisation. We trained five types of machine learning models applying nested cross-validation to predict complications and compared predictive performance based on four metrics, including area under the receiver operating characteristic curve (AUC-ROC).
Results: A total of 497 patients were included. PPCs developed in 71 (14%) patients. Adding CPET parameters to PFTs and baseline clinical data did not improve the ability of models to predict PPCs in unselected patients (AUC-ROC=0.72-0.78; p=0.47), nor in those meeting American College of Chest Physicians (ACCPs) (n=236; AUC-ROC=0.64-0.78; p=0.70) or European Respiratory Society/European Society of Thoracic Surgery (ERS/ESTS) criteria (n=168; AUC-ROC=0.59-0.76; p=0.92). PCCs developed in 90 (18%) patients. CPET parameters likewise did not improve model performance for the prediction of PCCs in unselected patients (AUC-ROC=0.65-0.73; p=0.96), nor in the ACCP (AUC-ROC=0.61-0.73; p=0.82) or ERS/ESTS subgroups (AUC-ROC=0.62-0.69; p=0.87).
Conclusions: In contemporary surgical practice, CPET did not improve the predictive performance of machine learning models for PPCs or PCCs in patients with an indication based on established guidelines or in those without. The role of CPET in preoperative risk stratification for lung resection should be re-evaluated.