Author Archives: Paul Older

Moderate intermittent hypoxic conditioning to enhance vascular function and cardiorespiratory fitness in the elderly: A randomized controlled trial.

Randy H; Université Grenoble Alpes, Inserm, CHU Grenoble Alpes, HP2, Grenoble, France.
Perrin TP; Ghaith A; Kohlbrenner D; Flore P; Champigneulle B; Guinot M; Doutreleau S;
Brugniaux J;Verges S;Marillier

Physiological reports [Physiol Rep] 2025 Oct; Vol. 13 (19), pp. e70432.

Vascular aging involves reduced endothelial function, a key factor in cardiovascular diseases. Intermittent hypoxia may improve endothelial function and cardiorespiratory fitness (CRF), but its effects in elderly individuals, especially in the mid-term, have not yet been studied. This randomized, single-blind controlled trial aimed to investigate whether an 8-week intermittent hypoxic conditioning (IHC) program may enhance flow-mediated dilation (FMD) and CRF in elderly individuals. Twenty-six participants (60-80 year-old) were assigned to either the IHC (n = 12) or the control group (CTL: n = 14). The IHC group underwent 24 passive intermittent hypoxia sessions (3/week). Brachial artery FMD, cardiopulmonary exercise testing (CPET), and ambulatory 24-h blood pressure were assessed at baseline (Pre), immediately post-intervention (Post 1), and 2 months later (Post 2). FMD showed a trend toward improvement in the IHC group, being significant when normalized for baseline artery diameter (p = 0.023; η p2  = 0.150) between Pre and Post 2. Peak ventilation during CPET increased from Pre to Post 1 (p = 0.021), with no other significant CRF changes. Daytime systolic blood pressure decreased by 6 mmHg (p = 0.070, η p2  = 0.105). No significant alterations in these outcomes were observed in the CTL group (p > 0.05). Moderate IHC enhanced mid-term endothelial function, suggesting potential to mitigate age-related vascular decline.

Heart failure and chronic obstructive pulmonary disease. A combination not to be underestimated.

 Magrì, Damiano; Department of Clinical and Molecular Medicine, Sapienza University of Rome, Rome, Italy.
Fiori, Emiliano; Agostoni, Piergiuseppe; Correale, Michele ;et al;

Heart failure reviews [Heart Fail Rev] 2025 Oct 07.
Date of Electronic Publication: 2025 Oct 07.

Chronic obstructive pulmonary disease (COPD) and heart failure (HF) frequently coexist and interact through complex and bidirectional hemodynamic mechanisms that amplify symptoms’ burden and complicate clinical management. The present review explores the impact of COPD across the HF spectrum, particularly in HF with preserved ejection fraction (HFpEF), where comorbidities, such as COPD, exert a dominant role in disease expression. COPD-induced hyperinflation reduces cardiac preload and increases right ventricular afterload, while HF-related congestion impairs pulmonary function and gas exchange, illustrating a tight cardiorespiratory coupling. Diagnostic challenges stem from overlapping symptoms and the limited specificity of biomarkers, such as natriuretic peptides, especially in HFpEF. Cardiopulmonary exercise testing (CPET) emerges as a valuable tool for distinguishing between cardiac and pulmonary limitations and guiding individualized treatment strategies. From a therapeutic standpoint, β1-selective blockers are not only safe in COPD patients but are pivotal in those with HF with reduced ejection fraction (HFrEF), where they have been demonstrated to improve survival and reduce both HF and COPD exacerbations. Concerns regarding bronchodilator safety in HF remain largely theoretical, with current evidence supporting their continued use when clinically indicated. Ultimately, optimal care for patients with coexisting COPD and HF requires a phenotype-specific approach, incorporating insights from pathophysiology, diagnostic innovation, and evidence-based pharmacotherapy to improve outcomes in this challenging patient population.

 

Cardiac Reserve And Cardiorespiratory Fitness After Reperfused ST-elevation Myocardial Infarction: 1677…American College of Sports Medicine (ACSM) Annual Meeting, May 27-30, 2025, Atlanta, Georgia.

Hogwood, Austin C.; University of Virginia, Charlottesville, VA. USA
Golino, Michele; Canada, Justin M.; West, Joshua; et al;

Medicine & Science in Sports & Exercise; (Baltimore, Maryland) 2025Supplement; v.57, 511-512. (2p)

The article focuses on the relationship between cardiac reserve and cardiorespiratory fitness (CRF) in patients who have experienced reperfused ST-elevation myocardial infarction (STEMI). A study involving fifty-six patients assessed cardiac reserve through Doppler echocardiography and CRF via a symptom-limited cardiopulmonary exercise test conducted approximately six weeks post-STEMI. Results indicated significant correlations between cardiac reserve metrics, such as stroke volume and cardiac output, and CRF measures, including peak oxygen uptake and ventilatory efficiency. The findings suggest that enhancing cardiac reserve may also improve CRF in this patient population.

 

Shifting Paradigms: Exercise Testing as a Metric of Long-Term Success in Surgery for Ebstein Anomaly.

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.

 

Dyspnea On Exertion In Deployed Veterans: Deconditioning Or Underlying Dysfunction?: 363…American College of Sports Medicine (ACSM) Annual Meeting, May 27-30, 2025, Atlanta, Georgia.

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.

Comparing The Physiological Responses To Cycle And Treadmill Exercise Between Preterm-born And Term-born Adults: 359…American College of Sports Medicine (ACSM) Annual Meeting, May 27-30, 2025, Atlanta, Georgia.

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.

Predictive Value of Preoperative Cardiopulmonary Exercise Testing for Complications and Mortality After Esophagectomy: A Meta-analysis.

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.

Cardiopulmonary exercise testing unmasks right ventricular failure in pulmonary arterial hypertension risk stratification: time to reframe the role of the 6-minute walk test?

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

Outcomes misaligned in mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS): implications for trial design.

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.

Preoperative aerobic fitness is a predictor of postoperative outcomes in patients undergoing pancreatoduodenectomy.

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.