Holden A; Royal Hospital for Children, Glasgow, UK.
Burns P; Devenny A; Thomson L; et al

Journal of Cystic Fibrosis. 25(5):819-826, 2026 Sep.

BACKGROUND: Improved survival in cystic fibrosis (CF) has shifted clinical
focus toward late complications, including altered body composition, bone
health and cardiopulmonary fitness. The effects of
Elexacaftor/Tezacaftor/Ivacaftor (ETI) on these outcomes in paediatric
patients remain unclear.

METHODS: This retrospective cohort study included paediatric CF patients
undergoing dual-energy X-ray absorptiometry (DXA) at annual review before
and 2 years after ETI initiation. Lean mass index (LMI), fat mass index
(FMI), lumbar spine bone mineral apparent density (LS-BMAD) and total body
less head bone mineral content (TBLH-BMC) were converted to age and
sex-adjusted standard deviation scores (SDS). Spirometry and
cardiopulmonary exercise testing (CPET) assessed lung function and
cardiopulmonary fitness. A matched CF control group not receiving
modulators was included.

RESULTS: 47 children were included (ETI n = 23, controls n = 24). LMI
declined significantly following ETI (mean change -0.64, p = 0.02) but
remained stable in controls (p = 0.36). LS-BMAD declined in the ETI group
(mean change -0.45, p = 0.009) with no change in controls (p = 0.31).
VO2peak % predicted decreased in the ETI group (median change -12%, p =
0.0018) alongside reductions in anaerobic threshold (-14%, p < 0.01) and
increased breathing reserve (+15%, p < 0.01), controls showed no
significant changes. FEV1 % predicted remained stable in both groups.

CONCLUSIONS: Despite preserved lung function, ETI treated children
exhibited declines in lean mass, trabecular bone density and
cardiopulmonary fitness, consistent with deconditioning. DXA and CPET
provide important complementary information beyond BMI and spirometry,
supporting targeted physical activity and nutritional interventions in ETI
treated paediatric CF patients.

Fadel, B., Department of Sport Medicine Clermont-Ferrand, France.
Gaucherot, A., Pereira, B., Egron, C., et al

Pediatr Res 2026 Sep 26 Online ahead of print.

BACKGROUND: Respiratory function (RF), body composition (BC), and cardiorespiratory fitness (CRF) links remain underexplored during multidisciplinary weight loss interventions (MWLI) in adolescents with obesity.
OBJECTIVES: To investigate the impact of a 16-week MWLI on resting and exercise RFs and their associations with BC and CRF.
METHODS: RFs were measured in 92 adolescents (13.1 +/- 1.19 years, 58%female, BMI 34.31 +/- 4.93 kg/m(2)) by spirometry and at several intensities during cardiopulmonary exercise tests (CPET) before MWLI (T0) and after (T1). BC and CRF were measured by dual X-ray absorptiometry and peak oxygen consumption (VO(2peak)).
RESULTS: Between T0 and T1, forced vital capacity (FVC), expiratory volume in one second (FEV1) and median expiratory flow (MEF25-75) increased (p < 0.001). Ventilatory efficiency increased (p < 0.01), while VO(2) and minute ventilation (VE) at similar calibrated exercise power outputs during exercise decreased. Body mass, total, trunk and visceral fat mass (FM) decreased while lean mass (LM) and CRF increased (p < 0.001). DeltaFVC, DeltaFEV1 and DeltaMEF25-75 were associated positively with DeltaLM% and DeltaCRF (FVC, FEV1: p < 0.001; MEF25-75: p < 0.05) and negatively with Deltatotal, Deltatrunk and Deltavisceral FM% (FVC, FEV1: p < 0.001; MEF25-75: p < 0.05). DeltaVO(2) and DeltaVE were associated negatively with DeltaLM% and DeltaCRF and positively with Deltatotal, Deltatrunk and Deltavisceral FM% (p < 0.001).
CONCLUSION: MWLI improves respiratory health and exercise tolerance in association with BC and CRF. IMPACT: This study is among the first to examine the effects of a multidisciplinary weight-loss intervention on both resting and exercise respiratory function in adolescents with obesity. The intervention improved respiratory function, body composition, and cardiorespiratory fitness. Respiratory improvements were associated with decreases in total, trunk, and visceral fat mass percentages and increases in lean mass percentage and cardiorespiratory fitness. The observed improvements in ventilatory efficiency and breathing reserve suggest a lower work of breathing and fewer ventilatory limitations during exercise, supporting multidisciplinary lifestyle interventions to improve respiratory health and exercise tolerance.

Wilson, W.M., University of Melbourne Australia
Burchill, L., Finch, S., Grigg, L. et al

ACC Adv 2026 Issue 10 Pt 2 Pages 103276

BACKGROUND: There are few proven therapies for improving exercise capacity in patients with transposition of the great arteries who have undergone an atrial switch repair.
OBJECTIVES: The objective of the study was to evaluate the effect of heart rate lowering using ivabradine on exercise capacity and quality of life in this cohort.
METHODS: In this single-center, randomized, double-blind, crossover study, patients were randomized to ivabradine or placebo for 4 weeks then crossover treatment for 4 weeks. A cardiopulmonary stress test and quality of life assessment were performed at baseline then at weeks 4 and 8. Estimates of difference were described using a mixed effects model.
RESULTS: A total of 19 patients were eligible and 10 patients completed the study. Compared to placebo, ivabradine treatment was associated with lower heart rate at baseline (65 +/- 3 beats/min on ivabradine vs 79 +/- 5 beats/min on placebo, difference -14.6 [-24, -5]; P = 0.008) and at peak exercise (131 +/- 7 beats/min vs 146 +/- 7 beats/min, difference -15.3 [-24, -6]; P = 0.003). Peak oxygen consumption was 20.4 +/- 1.2 mL/kg/min on ivabradine vs 19.2 +/- 1.2 mL/kg/min on placebo (difference +1.2 [-0.09, 2.6]; P = 0.06). Peak oxygen pulse was higher on ivabradine compared to placebo (12.5 +/- 1.2 vs 10.7 +/- 1.2 mL/beat, difference +1.7 [0.9, 2.6]; P = 0.002). Visual analog score was 73.5 +/- 5.6 on ivabradine vs 62.5 +/- 5.6 on placebo (mean difference 11.0 [-1.6, 23.6]; P = 0.08). One patient developed symptomatic bradycardia and one patient experienced phosphenes.
CONCLUSIONS: Ivabradine use in patients with transposition of the great arteries and atrial switch repair lowered peak heart rate with exercise and was associated with a higher oxygen pulse.

K. Batten, Australia
N. Van Doorn, J. H. Moon, D. Simar,et al

JIMD Rep 2026 Vol. 67 Issue 5 Pages e70123
https://www.ncbi.nlm.nih.gov/pubmed/42781531

Glycogen storage disease VII (GSD VII), also known as Tarui disease, is caused by a deficiency of the skeletal muscle enzyme, phosphofructokinase (PFK). Classical GSD VII is characterised by reduced exercise capacity and exercise-induced myopathic symptoms, exacerbated with carbohydrate intake. No recommended medical or dietary therapy currently exists to improve exercise symptomology in GSD VII. An 11-year-old female was recommended four trial dietary therapies for 8 weeks each: (1) usual diet, (2) 150 mg/kg exogenous ketones pre-exercise, (3) modified Atkins diet (MAD), (4) MAD and pre-exercise ketones. Clinical assessments comprised cardiopulmonary exercise test, anthropometry, biochemical tests including creatine kinase (CK), quality of life (QoL), heart rate (HR) monitoring and subjective symptom reports. Exogenous ketones improved exercise capacity demonstrated by reduced HR for equivalent exercise workload, and participation in higher intensity exercise for longer duration. MAD improved QoL physical domain score by 29%, normalised CK and halved the number of symptoms reported per ‘physically active day’. Dissatisfaction with MAD resulted in unintentional weight loss, and a 20% reduction in QoL emotional domain score, leading to the patient declining the fourth study phase. This study is the first to demonstrate a beneficial effect of exogenous ketones, and separately, MAD, in a child with GSD VII. Exogenous ketones or MAD could be recommended under medical and dietetic supervision in GSD VII. However, consideration must be given to the potential negative impact of MAD on weight and emotional health. Further interventional studies are warranted in this condition.

O. K. Nordfonn,  Department of Heart Disease,Bergen,  Norway,
K. Johnsen Ramstad, T. Roed Pettersen,et al

JMIR Cardio 2026 Vol. 10 Pages e93398

BACKGROUND: Cardiac rehabilitation (CR) is a class IA-recommended treatment and secondary preventive strategy for people with coronary artery disease. eHealth solutions show promise in providing accessible CR. However, few provide a comprehensive and multimodal CR program, and most programs are developed without input from end users.
OBJECTIVE: The aim of this study was to provide a detailed description of the multidisciplinary co-creation process used to develop a person-centered, multimodal digital CR program that integrated the perspectives of stakeholders and end users throughout, with the rationale to optimize the acceptance and feasibility of the CR program.
METHODS: We incorporated a user-centered design with a 3-phase, iterative, multidisciplinary stakeholder co-creation process. This included defining needs (phase 1), development and refinement (phase 2), and testing and optimization (phase 3). Overall, 26 internal stakeholders from the project team participated, including clinicians, researchers, software developers, and user representatives. In addition, 35 external stakeholders (20 clinicians and 15 people with cardiac-related problems) participated in a user-centered development process that included workshops, intervention content development, and usability testing. Data were collected through contextual inquiry, 4 workshops with stakeholders, 12 co-creation sessions with user representatives, 2 usability testing sessions using a think-aloud methodology, standardized usability surveys, and individual and focus group interviews. Intervention content was developed and finalized based on existing evidence, stakeholder input, and user testing. A smoke test and a minimum viable product test were conducted. Data were analyzed using rapid qualitative content analysis and descriptive statistics.
RESULTS: Analyses of data gathered across the 3 phases identified 5 themes important to stakeholders and end users: a program with (1) personalized and tailored solutions with reliable, trustworthy, and evidence-based content (ie, a face-to-face introduction session at the start of the program and a tailored registration page to individually register personal risk factors, goals, and medications); (2) options for feedback (ie, an asynchronous messaging service and tailored face-to-face video consultations with clinicians); (3) peer support (ie, exercise sessions in groups); (4) digital reminders (ie, notifications on a smartphone or tablet); and (5) motivational features (ie, interactive cardiac-specific learning modules on coronary artery disease and secondary prevention). Evidence-based content development resulted in 9 cardiac-specific interactive learning modules, a module for personal health data entry, live exercise sessions, tailored digital follow-up, and an asynchronous messaging service. Readability was assessed using the Gunning Fog Index, with levels ranging from 4 to 13. The overall System Usability Scale score was 86.2 (SD 12.2), indicating excellent usability.
CONCLUSIONS: A multidisciplinary stakeholder co-creation process combining well-known evidence-based concepts with stakeholder input identified several areas for improvement and facilitated the development of the digital CR program. Contextually tailored, co-designed interventions may improve relevance and responsiveness to user needs. The feasibility and effectiveness of the program will be further evaluated in the eCardiacRehab trial.

Byandova A; Plovdiv, Bulgaria.
Marinov B

Folia Medica (Plovdiv). 68(4), 2026 Aug 20.

No abstract available

Mima H; Osaka Graduate School of Medicine Osaka Japan.
Sera F; Ohtani T; Akazawa Y; et al

Journal of the American Heart Association. 15(17):e050214, 2026 Sep.

BACKGROUND: In nonischemic cardiomyopathy, the clinical relevance of
decreased resting myocardial technetium-99m sestamibi (99mTc-MIBI) uptake
regarding exercise capacity and clinical outcomes remains incompletely
understood. We investigated whether decreased 99mTc-MIBI uptake is
associated with impaired exercise capacity and adverse clinical outcomes
in nonischemic cardiomyopathy.

METHODS: We retrospectively analyzed 182 patients (mean age 51.4+/-14.0
years; 27% female) with nonischemic cardiomyopathy and left ventricular
ejection fraction <50% who underwent 99mTc-MIBI scintigraphy and
cardiopulmonary exercise testing from 2016 to 2023. Myocardial uptake of
99mTc-MIBI was evaluated using the summed rest score (SRS). Exercise
capacity was assessed by percentage of predicted peak oxygen consumption
(PPVO2), with <=60% defining impairment.

RESULTS: Seventy-four patients (41%) had PPVO2 <=60% and higher SRS
(median: 12 versus 8; P < 0.001). Higher SRS remained significantly
associated with PPVO2 <=60% after adjustment for relevant clinical
covariates, including brain natriuretic peptide level, left ventricular
ejection fraction, and heart failure duration. Over a median follow-up of
807 days, 23 patients (13%) experienced the composite outcome of all-cause
death, ventricular assist device implantation, or heart transplantation.
Higher SRS was associated with composite outcomes after adjusting for
PPVO2 <=60%. Among the 4 groups stratified by median SRS of 9 and PPVO2 of
60%, patients with high SRS and low PPVO2 had the highest incidence of
adverse events.

CONCLUSIONS: Decreased myocardial 99mTc-MIBI uptake was associated with
impaired exercise capacity and adverse outcomes in patients with
nonischemic cardiomyopathy. Our findings suggest that myocardial injury
assessment using 99mTc-MIBI scintigraphy may provide prognostic
information complementary to exercise capacity.

Zubac D; Center for Integrated Oncology Aachen, Germany
Sonntag T; Kranjc D; Baumann FT

Physiological Reports. 14(17):e71090, 2026 Sep.

This study examined whether cardiopulmonary exercise test (CPET)
performance parameters are associated with chronic cancer-related fatigue
in patients receiving immunotherapy checkpoint inhibitors (ICI) and
healthy controls. Also, the differences in energy expenditure of
steady-state cycling and gross efficiency were assessed during submaximal
cycling efforts. This study involved patients (n = 19, 48 +/- 13 years)
receiving PD-1, PD-L1 checkpoint inhibitors and controls of similar age (n
= 21, 49 +/- 17 years). During the first visit, data on medical history,
previous physical activity records, and CPET to voluntary exhaustion were
collected. The second visit involved body composition assessment, the
MFI-20 fatigue questionnaire, and 30-min steady-state cycling at 90% gas
exchange threshold. There were no significant differences observed between
the groups in age, stature, BMI, or resting blood pressure. Peak VO2 was
33% lower, and the group under ICI treatment had lower cycling efficiency
(22.49% vs. 20.07%, p = 0.031), compared to controls. All self-reported
fatigue items derived from MFI-20 were significantly higher in the ICI
group compared to controls (p = 0.001). The regression analysis found no
association between the self-reported general fatigue and data collected
during CPET. Patients under ICI treatment reported higher levels of
chronic fatigue, lower peak VO2, and reduced cycling efficiency.
Interestingly, variables collected during CPET did not explain
self-reported chronic fatigue, underlying the complexity of this
phenomenon.

Wu X; Harbin Medical University, Heilongjiang, China.
Cui H; Wang S; Zheng X; et al

Clinical & Experimental Medicine. 26(1), 2026 Jun 22.

Heart failure after acute myocardial infarction (post-MI HF) has become a
major global health problem. Accurate risk prediction is essential for
optimising management and preventing post-MI HF. However, existing models
rely mainly on resting-state clinical examinations and inadequately
reflect the complex pathophysiology of post-MI HF. We aimed to develop and
validate a multimodal machine learning (ML) model incorporating
cardiopulmonary exercise testing (CPET) data to predict post-MI HF risk
and to quantify CPET’s incremental value. This study included 3172 acute
myocardial infarction (AMI) patients who underwent CPET at three hospitals
from 2018 to 2023. The primary outcome was post-MI HF within 1 year.
Thirteen ML algorithms were used to select clinical and CPET variables and
to construct multimodal prediction models. The incremental predictive
value of CPET was evaluated by the area under the curve (AUC), integrated
discrimination improvement index (IDI), and net reclassification
improvement index (NRI). After screening, 2221 patients were included, of
whom 221 (10.0%) developed post-MI HF. The optimal multimodal ML model
achieved an AUC of 0.987 (95% CI: 0.982-0.992) in training set and 0.929
(95% CI: 0.903-0.955) in external validation set. Ablation analyses showed
that CPET significantly improved discrimination (AUC: 0.890 vs. 0.929,
P=0.003), calibration (IDI=0.135 [95% CI: 0.082-0.189], P<0.001), and
reclassification (NRI=0.154 [95% CI: 0.073-0.234], P<0.001). The model
effectively stratified low- and high-risk patients (3.1% vs. 54.7%,
P<0.001). The multimodal ML model accurately predicted post-MI HF and
highlighted the additive value of CPET in risk stratification. The
web-based risk calculator derived from this model may support early
identification of high-risk patients and facilitate personalised
management.

de Almeida IS; Centro Infant, Rio Grande do Sul, Brazil
Vendrusculo FM; da Costa MS; Donadio MVF

Pediatric Pulmonology. 61(9):e71826, 2026 Sep.

INTRODUCTION: Cystic fibrosis transmembrane conductance regulator (CFTR)
modulator therapy has led to relevant clinical advances in people with
cystic fibrosis (pwCF). However, its effects on aerobic fitness are
unclear.

OBJECTIVE: To evaluate the effects of CFTR modulator therapy on aerobic
fitness in pwCF through a systematic review and meta-analysis.

METHODS: This systematic review (CRD420251066602) was conducted by
searching major databases without date or language restrictions.
Analytical studies evaluating cardiopulmonary exercise testing outcomes
before and after CFTR modulator therapy were included. The primary outcome
was peak oxygen uptake (peak VO2). Secondary outcomes included peak VO2 (%
predicted), VO2 at the first ventilatory threshold (VT1), breathing
reserve, workload, forced expiratory volume in one second (FEV1), and body
mass index. Meta-analyses were performed using a random-effects model with
heterogeneity assessed by the I2 statistic, and sensitivity analyses
conducted.

RESULTS: Thirteen studies (n = 578 participants) were included, of which
11 were eligible for meta-analysis. The meta-analysis did not identify a
significant improvement in peak VO2 (mL.kg-1.min-1) after CFTR modulator
use (MD = -0.22; 95% CI: -2.10 to 1.65; p = 0.82). For submaximal
outcomes, after sensitivity analysis, VO2 at VT1 was significantly lower
in the post-intervention period (MD = -1.85; 95% CI: -2.61 to -1.10; p <
0.00001). Breathing reserve increased significantly (MD = 7.94; 95% CI:
2.15 to 13.73; p = 0.007), and workload also increased significantly (MD =
15.39; 95% CI: 2.20 to 28.58; p = 0.02).

CONCLUSION: CFTR modulator therapy is not consistently associated with
improvements in aerobic fitness, as assessed by peak VO2, although it
appears to variably influence outcomes related to ventilatory response and
exercise performance.