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.
Schellenberg J; Sports and Rehabilitation Medicine, University Hospital Ulm, Germany.
Matits L; Bizjak DA; Deibert P; et al;
Infection. 53(5):1685-1697, 2025 Oct. VI 1
SARS-CoV-2 infection has been predominantly reported in hospitalized
patients, but long-term cardiac sequelae in large, well-characterized
cohorts remain inconclusive. This study evaluated cardiac structure and
function in individuals with post-Coronavirus disease (COVID) syndrome
(PCS) compared to recovered controls (CON), focusing on associations with
cardiopulmonary symptoms and rapid physical exhaustion (RPE).
METHODS: This multicenter, population-based study included 1154
participants (679 PCS, 475 age- and sex matched CON; mean age 49 +/- 12
years; 760 women) 1.5 years post-infection. Transthoracic echocardiography
assessed LV global longitudinal strain (GLS), RV GLS and RV free wall
strain (FWS), and other measures. Cardiopulmonary exercise testing (CPET)
measured maximum respiratory oxygen uptake (VO2max) as a marker of
cardiopulmonary fitness.
RESULTS: PCS participants exhibited significantly lower LV GLS (-20.25%
[-21.28 – -19.22] vs. -20.73% [-21.74 – -19.72], p = 0.003), reduced
diastolic function (E/A 1.16 [1.04-1.27] vs. 1.21 [1.1-1.32], p = 0.022)
and decreased TAPSE (24.45 mm [22.14-26.77] vs. 25.05 mm [22.78-27.32], p
= 0.022) compared to CON, even after adjusting for confounders. RV strain
values were similar between groups. LV GLS correlated inversely with
VO2max (p = 0.004) and positively with RPE (p = 0.050), though no
associations were observed with other cardiopulmonary symptoms.
CONCLUSIONS: This study demonstrates subtle yet consistent reductions in
LV function, specifically LV GLS and diastolic function, and exercise
capacity in PCS compared to CON. While these changes are within reference
ranges, their potential impact on clinical outcomes warrants further
investigation. These findings highlight the need for cardiac assessments
and long-term follow-up in symptomatic PCS patients.
Bruce, Richard M; Faculty of Life Science and Medicine, King’s College London, London, UK
Rafferty, Gerrard F;Finnegan, Sarah L; et al;
The Journal of physiology,2025 Sep
In this study we have used a highly immersive virtual reality (VR) cycling environment where incongruence between virtual hill gradient (created by visual gradient and bike tilt angle) and actual workload (pedalling resistance) can experimentally manipulate perception of exercise effort. This therefore may provide a method to examine the role of effort perception in cardiorespiratory control during exercise. Twelve healthy untrained participants (7 men, age 26 ± 5 years) were studied during five visits. On visit 1 participants underwent cardiopulmonary exercise testing, and during subsequent visits (2-4) participants performed repeated hill climbs at different gradients (of 3%, 6% and 9% in counterbalanced order) with the actual workload ‘congruent’ with virtual hill gradient. On visit 5 participants completed three incongruent trials with virtual hill gradients of 3%, 6% and 9% but a fixed workload equal to that for the 6% climb (iVR3%, iVR6% and iVR9% trials). Despite no difference in power output, there was a significantly elevated rating of perceived exertion (RPE) and mean arterial blood pressure in iVR9% compared to iVR3% and iVR6%, although this effect decayed over time. There was no effect on any respiratory variable, and no significant reduction in RPE or cardiovascular responses was observed during the iVR3% trial. These data suggest that perception of effort and cardiovascular responses to exercise can be manipulated experimentally via virtual hill gradient (using visual and/or vestibular cues) in a VR environment. This work supports those previously showing the existence of a control mechanism which integrates perception of effort and the cardiovascular response to exercise in humans.
KEY POINTS: We aimed to assess whether using a highly immersive virtual reality (VR) cycling environment to create incongruence between perceived effort (virtual hill gradient) and actual effort (pedal resistance) can manipulate cardiorespiratory responses to exercise. At an equivalent power output cycling up a steeper virtual hill produced greater ratings of perceived exertion (RPEs) and blood pressure responses compared to a virtual hill congruent to power output. This work suggests the existence of a control mechanism which integrates perception of exercise effort and the cardiovascular response to exercise, which can be experimentally manipulated by VR.
Gutiérrez-Ballesteros, Guillermo; Maimonides Institute for Research in Biomedicine of Córdoba (IMIBIC), Córdoba, Spain.
Mazuelos-Bellido, Francisco;López-Aguilera, José;Crespín-Crespín, Manuel; et al
Frontiers in cardiovascular medicine,2025 Sep 02
Christopher Gregory; Cardiovascular Innovation and Research Center (CIRC) University of California, Irvine, Irvine, CA.
Raza, Farhan;Colebank, Mitchel J;Korcarz, Claudia E; et al
American journal of physiology. Heart and circulatory physiology,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.