Salisbury, Dereck L; University of Minnesota, Minneapolis, MN, USA.
Lin, Feng Vankee;Yu, Fang

Alzheimer’s & dementia : the journal of the Alzheimer’s Association,2025 Dec

• Background: Cardiorespiratory fitness (CRF) has been positively associated with brain volumes and health in older adults and negatively associated with dementia onset or risk and mortality. Cardiopulmonary exercise testing (CPET) is a gold standard test for evaluating CRF for exercise prescription, but requires specialized equipment and is time- and resource-intensive, highlighting the need for more feasible and valid options for evaluating CRF. Therefore, the purpose of this study was to evaluate the validity and relationship of the shuttle walk test (SWT) distance with peak oxygen consumption (VO _2Peak ) from cycle ergometer-based CPET in persons with amnestic mild cognitive impairment (aMCI) or mild-to-moderate AD dementia.
• Method: This study used baseline data from two Phase II, single-blinded clinical trials (The ACT Trial and The FIT-AD Trial). The sample included 80 participants with aMCI and 90 with mild-to-moderate AD. Across the two studies, CRF was measured with VO _2Peak obtained from the symptom-limited peak cycle-ergometer test and the SWT. Data were analyzed with simple and multiple linear regression. Adjusted models included age, sex, cognition (Montreal Cognitive Assessment [MoCA] or Mini Mental State Examination [MMSE], and body mass index (BMI) that were significantly associated with VO _2peak .
• Result: The participants included 80 from the ACT Trial (55% male, 74.1 [5.7] years, and MoCA 23.2 [2.0]) and 90 from the FIT-AD Trial (56% males, age 77.1 [6.6] years, and MMSE 21.8 [3.4]). In persons with aMCI, SWT was positively correlated with VO _2Peak (r = .57 p < 0.01). When controlling for age, sex, MoCA, and BMI, SWT distance remained significantly and positively associated with VO _2Peak and collectively represented 54% of the variance in VO _2Peak (F (5,69) =18.37, p <0.001). In persons with AD dementia, SWT was positively correlated with VO _2Peak (r = .44 p <0.01). When controlling for age, sex, MMSE, and BMI, SWT distance remained significantly and positively associated with VO _2Peak and collectively represented 43% of the variance in VO _2Peak (F (5,77) =11.46, p <0.001).
• Conclusion: SWT distance is a significant predictor of VO _2Peak in persons with cognitive impairment and remains a significant predictor in the presence of related, clinically measured covariates including age, sex, cognition, and BMI.

Mouraux, Stéphane; Lausanne University Hospital (CHUV), Lausanne, Switzerland.
Lechartier, Benoît;Imler, Théo;von Garnier, Christophe; et al

Chest,2025 Dec 22

• Background: Dyspnea increases mortality and remains unexplained in 15% of patients. Although obstructive sleep apnea (OSA) is linked to reduced exercise capacity during cardiopulmonary exercise testing, the association between dyspnea and OSA remains uncertain.
• Research Question: Is there an association between exertional dyspnea and OSA in the general population? What are the polysomnographic OSA-related measures associated to exertional dyspnea?
• Study Design and Methods: We used data from a prospective cohort study of general population conducted in an urban area. Participants underwent polysomnography and completed a respiratory questionnaire. Logistic regression models were used to determine the association between self-reported dyspnea (mMRC score ≥1) and OSA categories or apnea-hypopnea index (AHI) cut-offs. We performed an adjusted model for sex, BMI, age, FEV1, psychiatric disorders, cardiac and respiratory disorders and smoking history.
• Results: We included 1’200 participants (mean age 62.1 years; 54% female) of whom 515 (42.9%) reported exertional dyspnea. The adjusted model revealed a positive association between exertional dyspnea and AHI ≥ 15/h (OR 1.57, CI95 [1.13-2.19]), AHI ≥ 30/h (OR 1.72, CI95 [1.06-2.78]), moderate OSA (OR 1.60, CI95 [1.04-2.46]) and severe OSA (OR 2.25, CI95 [1.28-3.96]). Moreover, in adjusted model, dyspnea was associated with AHI, respiratory disturbance index, respiratory pulse wave drop index, sleep apnea-specific pulse-rate response, respiratory arousal index and oxygen desaturation index 3%.
• Interpretation: Exertional dyspnea is associated with moderate and severe OSA, potentially due to heightened autonomic and cortical responses to increased respiratory efforts. Further research is needed to assess the effectiveness of OSA treatment on dyspnea in OSA patients.

Galán-Rioja, Miguel Ángel; Faculty of Sport Sciences, University of Castilla la Mancha, Toledo, Spain.
González-Mohíno, Fernando;Turner, Anthony P;González Ravé, José María

International journal of sports medicine,2025 Dec 23

AIMS This study aimed to assess the level of agreement between internal (i.e., oxygen uptake, heart rate, or ratings of perceived exertion) and external load markers (power output) at critical power intensity, compared to the first ventilatory threshold, respiratory compensation point, and maximum oxygen uptake derived from the cardiopulmonary exercise test, and estimate critical power from values derived from the cardiopulmonary exercise test in trained cyclists.
METHODS Fourteen (13 males and 1 female) road master cyclists completed a cardiopulmonary exercise test to determine the first ventilatory threshold, respiratory compensation point, and maximum oxygen uptake. On a subsequent day, they completed three maximal time-trial tests to estimate critical power and W’. Associated physiological and perceptual values at critical power were estimated from linear regressions applied to the cardiopulmonary exercise test results. Internal and external markers significantly ( p <0.05) increased from the first ventilatory threshold to the respiratory compensation point and then maximum oxygen uptake.
RESULTS There were no significant differences between internal and external markers at the respiratory compensation point vs. critical power with strong correlations between responses. However, there was a mean bias for responses at respiratory compensation point markers to overestimate some responses at critical power (power output and oxygen uptake by ~8%).
CONCLUSION This study shows that critical power can be estimated from a single cardiopulmonary exercise test. While the respiratory compensation point is not a reliable critical power substitute, predictive equations improve its estimation for more precise prescriptions in trained cyclists.

Maier, Rebecca; Academic Cardiovascular Unit, South Tees Hospitals NHS Foundation Trust, Middlesbrough, UK
Dunning, Joel;Wason, James;Chadwick, Thomas;

BMJ open,2025 Dec 24

• Introduction: Severe pectus excavatum (PE) may impair cardiopulmonary and physical function. The effectiveness of surgical treatment to correct PE and restore physical function is widely debated due to a lack of high-quality comparative evidence. The RESTORE trial aims to determine the clinical and cost-effectiveness of corrective surgery for severe PE compared with conservative management for the first time in a randomised controlled trial (RCT).
• Methods and Analysis: RESTORE is a pragmatic, multicentre, RCT with an embedded observational cohort. 200 participants aged ≥12 years with severe PE will be recruited at around 12 National Health Service cardiothoracic surgical centres in England. Participants will be randomised 1:1 to receive either surgery within 3 months of randomisation (intervention arm) or no surgery until after the primary outcome measurement at 1 year (comparator arm). The primary outcome is change in physical functioning from baseline to 1 year as measured by the Short Form Health Survey (SF-36v2) physical function score. The primary economic outcome is cost-effectiveness. The key secondary outcome is change in % predicted VO _2peak at 1 year measured by cardiopulmonary exercise test (CPET). Outcomes will be assessed at 1 year post-randomisation in the comparator arm and 1 year post-surgery in the intervention arm. The primary analyses will be undertaken on an intention-to-treat population using a linear mixed-effects model, adjusted for stratification variables via a binary covariate. Other secondary outcomes will include change from baseline of cardiopulmonary function (CPET and spirometry), health-related quality of life using the EuroQol 5 Dimension 5 Level (EQ-5D-5L) and SF-36v2 questionnaires, Hospital Anxiety and Depression Scale and disease specific symptoms (Phoenix Comprehensive Assessment for Pectus Excavatum Symptoms and Pectus Excavatum Evaluation Questionnaire). Adverse events, complications from surgery and operative technical success (Haller and Compression Indices from preoperative and postoperative CT scans) will also be assessed. Health economic analysis will estimate the incremental cost per quality adjusted life year at 1 year.
• Ethics and Dissemination: The trial was approved by East of Scotland Research and Ethics Service (24/ES/0034). Participants who are ≥16 years of age will be required to provide written informed consent. For participants <16 years of age who are not judged to be Gillick competent, written assent and written informed consent from a parent/guardian will be required. Results will be submitted for publication in peer-reviewed journals and shared with participants, clinicians and commissioners.

Jiang, Yumei; School of Medicine, Tongji University, Shanghai, 200065, China.
Shen, Ting;Shi, Cheng;Li, Dejie; et al

BMC cardiovascular disorders,2025 Dec 27

• Background: Acute coronary syndrome (ACS) is a major global health burden with a high risk of adverse outcomes. Existing predictive models (e.g., GRACE) primarily rely on static indicators and focus on short-term prognosis, limiting their ability to comprehensively assess patient status and predict long-term mortality. To address the need for improved long-term risk prediction in this specific patient subgroup, this study developed and validated a long-term mortality prediction model for ACS patients incorporating cardiopulmonary exercise testing (CPET) and other clinical indicators.
• Methods: This retrospective cohort study included ACS patients treated at Tongji Hospital from January 1, 2007, to December 31, 2018. Demographic data, medical histories, CPET indicators, laboratory indicators, and other baseline data were collected, and all-cause mortality was followed up until June 30, 2023. All data sets were randomly divided into derivation and validation cohorts in a ratio of 7/3. Least absolute shrinkage and selection operator regression and Cox multivariate analysis were used to identify independent risk factors and a risk prediction model was established using nomograms.
• Results: A total of 299 patients were included in this cohort (211 in the derivation cohort and 88 in the validation cohort), with an average age of 57.00 years, including 280 males (93.6%). The median follow-up time was 3821 days, and 46 cases (15.4%) reached the study endpoint. The derivation cohort identified four independent predictive factors: age, blood urea nitrogen (BUN), ejection fraction (EF), and heart rate reserve (HRR), and a Nomogram scoring model was constructed based on these factors. The model demonstrated good discrimination in the derivation cohort (C-index: 0.83) but this decreased in the validation cohort (C-index: 0.72), suggesting potential overfitting. Time-dependent calibration analysis showed poor agreement at 5 years in the validation cohort (R ² = 0.1819), but improved at 10 years (Slope = 0.8006, R ² = 0.5575) and 15 years (R ² = 0.5638). The model’s applicability is strictly limited to the studied population: a predominantly male, lower-risk subset of ACS survivors capable of completing CPET.
• Conclusions: A model based on four readily available variables-age, BUN, EF, and the key CPET parameter, HRR-may have utility for predicting long-term all-cause mortality. This model provides a preliminary tool for the long-term management of a specific subpopulation of acute coronary syndrome (ACS) survivors, namely a predominantly male, lower-risk cohort with the capacity to complete CPET. Further external validation in similar populations is required before prospective clinical application.

Lim, Kenneth; Division of Nephrology & Hypertension, Indiana University School of Medicine, Indianapolis, IN, USA.
Campos, Monique;Moe, Sharon

Kidney360,2025 Dec 15

Cardiovascular outcome trials are challenging to conduct in patients with CKD. Despite this, well-designed randomized controlled trials are critical to inform optimal management strategies and improve clinical care. Unfortunately, many cardiovascular outcome trials in nephrology have not demonstrated a treatment benefit. Contributing to this are the difficulties associated with endpoint selection and the limitations of many traditional endpoints such as resting left ventricular geometric measures and circulating biomarkers in patients with CKD, which are well known to be a major impediment to the conduct of cardiovascular trials in this population. The emergence of state-of-the-art Cardiopulmonary Exercise Testing (CPET) technology in nephrology has taken center stage in this field due to the possibilities and solutions afforded by CPET-derived functional endpoints. CPET is a powerful tool that incorporates ventilatory gas exchange measurements during graded exercise and robustly quantifies VO2Peak, the gold standard index for cardiovascular functional capacity. The use of functional endpoints such as VO2Peak is a critical mechanism to promote patient-centered clinical trials in patients with CKD. Furthermore, the Food and Drug Administration (FDA) has now approved both drugs and devices that have utilized VO2Peak as an endpoint outside of nephrology. With accumulating scientific evidence base supporting the rationale for CPET-derived endpoints in patients with CKD, the potential use of VO2Peak in clinical trials as a basis for regulatory approval creates an exciting opportunity in nephrology.

Moncion, Kevin; Montreal Center for Interdisciplinary Research in Rehabilitation (CRIR), Laval, Quebec, CANADA.
Rodrigues, Lynden ;De Las Heras, Bernat; Wiley, Elise; et al

Medicine and science in sports and exercise,2025 Dec 16

• Background: Accurate assessment of cardiorespiratory fitness is a critical component of cardiopulmonary exercise testing (CPET) and prescription for people with stroke. However, post-stroke disability and neuromuscular impairments are common and may disproportionately affect females throughout the continuum of recovery. There is a need to evaluate alternative whole-body CPET protocols and to characterize the sex-specific CPET responses throughout the continuum of stroke recovery.
• Purpose: To characterize the sex-specific CPET responses on a whole-body recumbent stepper CPET using American College of Sports Medicine (ACSM) criteria in people with subacute (7-90 days) and chronic (≥6-60 months) stroke.
• Methods: Participants underwent a whole-body recumbent stepper symptom-limited CPET. Each CPET was assessed for ventilatory threshold (VT), peak oxygen uptake (V̇O2peak) and ACSM maximal oxygen uptake V̇O2max criteria including respiratory exchange ratio [RER] ≥1.10; V̇O2 plateau, heart rate [HR] within 10 beats of HRmax, and ratings of perceived exertion [RPE] ≥17/20 or ≥7/10. Sex differences by stroke chronicity were evaluated via ttests, ranksum tests, Chi-squared, or Fisher’s exact tests.
• Results: In total, 145 participants underwent a symptom limited CPET. In subacute stroke (n=69), no sex differences were found for VT or V̇O2peak (p>0.05), but females were more likely to achieve a V̇O2 plateau (p=0.002). In chronic stroke (n=76), no sex differences were observed for VT or V̇O2max criteria (p>0.05), but females had lower V̇O2peak (p=0.002). Irrespective of sex, achieving the RPE (n=41 subacute [61%], n=38 chronic [54%]) or RER criteria (n=28 subacute [41%], n=39 [51%]) were the most commonly met ACSM criteria.
• Conclusions: This whole-body CPET protocol is appropriate for eliciting peak and maximal efforts in people post-stroke, however, clinicians should consider biological sex and stroke chronicity.

Carlén, Anna; Faculty of Sport Sciences, University of Granada, Granada, Spain.
Sánchez-Aranda, Lucía; Solis-Urra, Patricio; Coca-Pulido, Andrea; et al

European journal of preventive cardiology,2025 Dec 16

• Aim: Patients with coronary artery disease (CAD) are at risk of accelerated cognitive decline. We aimed to explore how different cardiorespiratory fitness (CRF) indicators associate with brain structure and cognitive function in these patients.
• Methods: We studied 105 stable CAD patients (62.1±6.6 years, 21% female), using baseline data from the randomized controlled Heart-Brain trial. Time-to-exhaustion (TTE), peak oxygen uptake (VO2peak), ventilatory anaerobic threshold (VAT), oxygen uptake efficiency slope (OUES), peak O2-pulse and 60-s heart rate recovery (HRrec) were determined from cardiopulmonary exercise tests. From magnetic resonance imaging, we extracted brain volumes (total-, grey-, and white matter volumes [TBV, GMV and WMV]) and hippocampal volume (HV), and calculated the difference between estimated and chronological brain age (brainPAD). Episodic memory, processing speed, working memory, executive function/attentional control and general cognition were evaluated.
• Results: TTE, VO2peak and OUES were positively associated with TBV (βstd 0.15 to 0.19, p<0.05) and HV (βstd 0.23 to 0.36, p<0.05). Higher OUES, HRrec and O2-pulse were associated with lower brainPAD (βstd -0.23 to -0.32, p<0.05). Higher VAT was associated with better working memory (βstd=0.26, p=0.023), and higher OUES with better executive function/attentional control (βstd=0.20, p=0.021). Hippocampal atrophy was more prevalent in lower vs middle/upper VO2peak tertile (p=0.001).
• Conclusion: In CAD patients, both maximal and submaximal CRF-indicators were associated with larger brain volumes, with stronger region-specific association with HV, and younger physiological appearance of the brain, while associations with cognitive functions were fewer and weaker. Our findings support CRF as a biomarker of structural brain health in CAD patients.

Beke, Nóra; Centre for Translational Medicine, Semmelweis University, Budapest, Hungary.
Jockers, Xenia; Hernádfői, Márk; Kói, Tamás; et al

Pediatric research,2025 Dec 17

• Background: Anthracycline-induced cardiotoxicity is a major concern in childhood cancer survivors. Detecting subclinical cardiac dysfunction early is critical, but the accuracy of current diagnostic tools is uncertain.
• Methods: We performed a systematic review and meta-analysis of studies evaluating the prognostic accuracy of echocardiography, serum biomarkers, microRNAs (miRNAs), and artificial intelligence (AI) models in predicting chemotherapy-induced cardiotoxicity in pediatric patients. Seventy-three studies were included in the qualitative synthesis, and ten in the meta-analysis. Quality was assessed using the QUAPAS tool (CRD42023485629).
• Results: AI-based models showed the highest pooled predictive performance area under the curve (AUC)~0.80, despite significant heterogeneity (I² = 93%). Global longitudinal strain (GLS) had moderate accuracy (AUC~0.72). Cardiac biomarkers like troponin and N-terminal pro-B-type natriuretic peptide (NT-proBNP) showed variable sensitivity and specificity, largely influenced by timing and thresholds. Preliminary evidence on miRNAs was promising but lacked standardization. Additional methods (e.g., cardiac MRI, cardiopulmonary exercise testing (CPET)) were excluded from meta-analysis due to methodological variability.
• Conclusion: No single modality reliably detects early cardiotoxicity. Promising tools like AI models and miRNAs need further validation. A multimodal diagnostic strategy combining imaging, biomarkers, and clinical data may be the most effective approach. Standardized definitions and protocols are urgently needed.
• Impact: Early detection of chemotherapy-induced cardiotoxicity in children remains unresolved. Multimodal assessment is most effective because no single test is sufficiently reliable. There are critical methodological gaps and heterogeneity that impede standardization in pediatric cardio-oncology. AI and microRNAs are promising but still unvalidated tools. The findings guide future clinical monitoring strategies and support standardized multimodal diagnostic algorithms.

D’Ambrosio, Paolo; Department of Medicine, The University of Melbourne, Parkville, VIC, Australia and many other centres
De Paepe, Jarne; Spencer, Luke W;Ohanian, Monique; et al

Circulation,2025 Dec 18

• Background: Sinus bradycardia is a well-recognized physiological adaptation in endurance athletes, primarily attributed to sinus node remodeling or increased vagal modulation. Although genetic influences on resting heart rate (HR) have been observed, the genetic contribution to athletic bradycardia has not been elucidated.
• Methods: We phenotyped current and former elite endurance athletes in the Pro@Heart cohort study using multimodal cardiac imaging, cardiopulmonary exercise testing, and Holter monitoring. Genetic susceptibility to bradycardia was assessed using a validated HR-associated polygenic risk score (HR-PRS), in which lower scores are associated with a lower HR, and compared with healthy nonathletic controls. Clinical and genetic features of bradycardic endurance athletes with minimum HR ≤40 bpm on a Holter monitor (bradycardic athletes [BAs]) were compared with non-BAs). A healthy cohort of nonathletes from the ASPREE study (Aspirin in Reducing Events in the Elderly) were used for genetic comparisons.
• Results: Among 465 endurance athletes (median age, 23 [18-49] years, 75% men), 175 (38%) had a minimum HR on a Holter monitor ≤40 bpm, of whom 7 (2% of total) had a HR ≤30bpm. Pauses ≥2 s were observed in 115 (25%) athletes, of whom 12 (3% of total) had pauses ≥3 s. Mobitz I second-degree atrioventricular block was observed in 15 (3% of total) athletes. BAs were younger and fitter and exhibited greater athletic cardiac remodeling than non-BAs. Mean HR-PRS was significantly lower in all athletes compared with ASPREE nonathletes ( P <0.001) and in BAs compared with non-BAs ( P =0.006). When the distribution of HR-PRS within our athletic cohort was considered, athletes with scores in the bottom quartile had a lower minimum HR (median HR, 41 [35-45] bpm versus 45 [40-49] bpm, P <0.001) and higher bradycardia burden (14 [2-37]% versus 2 [0%-25]%, P <0.001) than those with scores in the top quartile. After adjusting for age, sex, fitness, and indexed right atrial volume, HR-PRS was independently associated with lower minimum HR and increased the odds of resting bradycardia by 2-fold (odds ratio [OR], 2.2 [95% CI, 1.3-3.9]; P= 0.004). Neither bradycardia nor pauses were associated with increased risk of adverse outcomes over 5.5 years.
• Conclusions: Resting bradycardia (HR ≤40 bpm) and pauses of 2 to 3 s are present in a significant proportion of endurance athletes and are well tolerated. Our data suggest that both fitness and genetic variation contribute to sinus node function in endurance athletes. Intriguingly, HR-PRS differed between athletes and nonathletes, raising the possibility that genetics may be a determinant of athleticism.