Author Archives: Paul Older

Doi S; Department of Cardiovascular Disease, Mayo Clinic, Rochester, MN, USA.
Tada A; Harada T; Naser JA; Ibe T; Smith JR; Reddy YNV;

European journal of heart failure [Eur J Heart Fail] 2025 Jun 18.
Date of Electronic Publication: 2025 Jun 18.

Aims: Oxygen consumption at peak exercise is widely used to assess functional impairment in heart failure with preserved ejection fraction (HFpEF), but few patients exercise to this intensity in daily living. Alternative metrics that quantify submaximal fitness may provide more patient-centred evaluations, but the pathophysiology of submaximal exercise intolerance in HFpEF is unexplored.
Methods and Results: Patients with HFpEF underwent invasive haemodynamic cardiopulmonary exercise testing with blood lactate measurement during exercise to volitional fatigue. Lactate threshold (LT) was defined as the exercise workload at which arterial lactate exceeded >2.0 mmol/L, taken as a measure of submaximal fitness. Of patients with HFpEF (n = 286), 194 (68%) reached LT at a workload of 40 W or less (LT ≤40 W), while 92 (32%) reached a workload exceeding 40 W at LT (LT >40 W). As compared to LT >40 W, patients with LT ≤40 W were more likely to be female, anaemic, and had greater pulmonary vascular disease (all p < 0.01). During 20 W exercise, participants with LT ≤40 W had higher pulmonary artery pressure, biventricular filling pressures, minute ventilation and respiratory drive, higher perceived dyspnoea and fatigue ratings, greater arterial-venous oxygen content difference, despite similar cardiac output and oxygen delivery. At peak exercise, most of these differences were no longer apparent. Findings were replicated using non-invasively-measured workload at ventilatory threshold.
Conclusions: Two-thirds of patients with HFpEF reach LT at workloads typical of activities of daily living. Patients with HFpEF and impaired submaximal fitness are more likely to be female, have greater pulmonary vascular disease and anaemia severity, and display greater haemodynamic, symptomatic, and ventilatory control abnormalities during low-level exercise, which are not apparent at maximal exertion. These findings have therapeutic implications and suggest a potentially important role for wider evaluation of submaximal fitness in addition to peak aerobic capacity.

Physiological responses to exercise in survivors of preterm birth: a meta-analysis.

Beaven ML; Curtin University, Perth, Australia.; The Kids Research Institute Australia, Perth, Australia & University Hospital of Wales, Cardiff, UK.
Gibbons JTD; Course CW; Kotecha SJ; Hixson T; Maiorana A; Zuidersma M; Kotecha S; Smith EF; Simpson SJ;

European respiratory review : an official journal of the European Respiratory Society [Eur Respir Rev] 2025 Jun 18; Vol. 34 (176).
Date of Electronic Publication: 2025 Jun 18 (Print Publication: 2025).

Rationale: Survivors of preterm birth (<37 weeks’ gestation) have low peak oxygen uptake, a global measure of aerobic fitness and an established predictor of increased morbidity and mortality. However, little is known about other cardiopulmonary outcome measures in this population. We addressed the hypothesis that preterm birth is associated with abnormal respiratory, cardiovascular and metabolic responses to exercise, as assessed by cardiopulmonary exercise testing, via a systematic review and meta-analysis.
Methods: Six databases were systematically searched up to 29 November 2024 (PROSPERO: CRD42022320775). Studies reporting cardiopulmonary outcome measures obtained during a standardised exercise test were included if they had preterm-born participants and matched term-born controls. The standardised mean difference (SMD) between pooled preterm-born and term-born cohorts was calculated using random-effects models for the meta-analysis.
Results: Of the 12 143 records identified, 47 cohorts were included in the final meta-analysis. At peak exercise, the preterm-born cohort (n=2149) demonstrated lower oxygen uptake (SMD -0.39, 95% CI -0.52 to -0.26), work rate (SMD -0.53, 95% CI -0.70 to -0.35), minute ventilation (SMD -0.43, 95% CI -0.60 to -0.26), tidal volume (SMD -0.38, 95% CI -0.62 to -0.15), oxygen pulse (SMD -0.47, 95% CI -0.75 to -0.19), heart rate (SMD -0.18, 95% CI -0.28 to -0.07), anaerobic threshold (SMD -0.29, 95% CI -0.49 to -0.08) and gas exchange efficiency (SMD 0.22, 95% CI 0.04 to 0.41), compared to the term-born cohort (n=1650).
Conclusions: In addition to a reduced peak oxygen uptake, survivors of preterm birth have impairments in the respiratory, cardiovascular and metabolic domains during cardiopulmonary exercise testing. Given that reduced aerobic capacity is associated with increased morbidity and mortality, exercise interventions that target cardiorespiratory fitness should be prioritised across the lifespan in those born preterm.

Physiological differences in cardiopulmonary exercise testing between children and adults.

Papic V; Department of Sport, Exercise and Health, University of Basel, Basel, Switzerland.
Ledergerber R; Roth R; Knaier R;

Pediatric research [Pediatr Res] 2025 Jun 19.
Date of Electronic Publication: 2025 Jun 19.

Background: Physiological responses to exercise differ between children and adults, but achieving maximal exertion in children complicates the interpretation of VO ₂_max . This study, therefore, examines age- and sex-related physiological differences in submaximal parameters during incremental exercise.
Methods: In this cross-sectional study, 24 children (7-11 years), 20 moderately trained adults (MTA), and 20 well-trained adults (WTA; 20-30 years) completed a maximal incremental exercise test on a cycle ergometer with continuous respiratory measurement. Linear regression models analysed age and sex differences in ventilatory thresholds (VT1, VT2) and oxygen uptake efficiency slope and plateau (OUES), with Cohen’s d effect sizes reported.
Results: Children showed higher body mass-adjusted VO ₂ at VT1 and VT2 (d = 0.58-0.66) compared to MTA, and slightly lower VT2 values than WTA (d = 0.35). Adults had higher absolute OUES (d = 0.37-1.45) and OUEP (d = 0.60-0.81), while children exhibited higher body mass-adjusted OUES (d = 0.87 - 1.80). Males had higher VO ₂ at VT2, OUES, and OUEP (d = 0.41-0.81), while females showed higher relative VO ₂ at VT1 and VT2 (d = 0.44-0.59) compared to males.
Conclusions: Children rely more on oxidative metabolism than adults. Maturation influences exercise efficiency more than body mass, underscoring physiological differences. These age- and sex-specific patterns call for longitudinal studies to further explore the roles of growth and training.
Impact: This study identifies clear physiological differences in submaximal CPET parameters between children and adults. It adds novel insight by including both ventilatory thresholds and oxygen uptake efficiency, adjusted for body mass and training status. The findings suggest children rely more on oxidative metabolism, emphasizing the importance of maturation on exercise efficiency and informing age- and sex-specific assessment protocols in pediatric exercise physiology.

Skeletal Muscle Quantity Versus Quality in Heart Failure: Exercise Intolerance and Outcomes in Older Patients With HFpEF Are Related to Abnormal Skeletal Muscle Metabolism Rather Than Age-Related Skeletal Muscle Loss.

Lewsey SC; Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore,
Samuel TJ; Schär M; Sourdon J; Goldenberg JR; Yanek LR; Lai S; Steinberg AM; Bottomley PA; Gerstenblith G; Weiss RG;

Circulation. Heart failure [Circ Heart Fail] 2025 Jun 19, pp. e012512.
Date of Electronic Publication: 2025 Jun 19.

Background: Heart failure with preserved ejection fraction (HFpEF) is a systemic process with contributions from peripheral factors, including skeletal muscle (SM). Age-associated SM loss and impaired energy metabolism occur without heart failure, but the relative importance of changes in SM quantity versus metabolic quality in patients with HFpEF for exercise intolerance (EI) or outcomes has not been studied. We hypothesized that EI and subsequent clinical outcomes across the adult lifespan in patients with HFpEF are related to impaired SM energy metabolism rather than age-associated SM loss.
Methods: Patients with HFpEF (n=64; aged 34-86 years) with left ventricular ejection fraction ≥50% were stratified by age in a prospective study. They underwent 3T magnetic resonance imaging to measure calf muscle quantity and ³¹ P magnetic resonance spectroscopy to measure muscle high-energy phosphate metabolism during plantar flexion exercise.
Results: Older patients with HFpEF exhibited more severe EI, less calf muscle, faster exercise-induced high-energy phosphate decline, and worse SM energetics at fatigue than younger patients. EI correlated closely with muscle metabolic quality, not quantity. Neither magnetic resonance imaging exercise time, 6-minute walk distance, nor peak oxygen uptake at cardiopulmonary exercise testing on cardiopulmonary bicycle exercise testing correlated with calf SM area. In contrast, the 6-minute walk distance and peak oxygen uptake at cardiopulmonary exercise testing were inversely related to rapid exercise-induced high-energy phosphate decline and worse SM energetic profile at fatigue. Rapid exercise-induced high-energy phosphate decline and lower ATP at fatigue were associated with increased cardiovascular death and heart failure hospitalizations in univariate analysis over a median of 39.3 months.
Conclusions: EI in older patients with HFpEF is closely linked to age-associated abnormalities in SM energy metabolism, namely, rapid exercise-induced energetic decline and worse energetic profile at fatigue, and not SM quantity. Abnormal SM energy metabolism is associated with worse outcomes in patients with HFpEF in unadjusted analysis. These findings support SM energy metabolism as a barometer of systemic HFpEF severity and the pursuit of new SM metabolic modulators to reduce disabling EI and possibly adverse outcomes in patients with HFpEF.

Cardiorespiratory fitness and muscle strength in offspring conceived through assisted reproductive technologies: results from the Munich heARTerY-study.

Kramer M; Division of Pediatric Cardiology and Intensive Care, University Hospital, LMU Munich, 81377, Munich, Germany.
Li P; Langer M; Vilsmaier T; Sciuk F; Kolbinger B; Jakob A; Rogenhofer N; Dalla-Pozza R;Thaler C; Haas NA; Oberhoffer FS;

European journal of pediatrics [Eur J Pediatr] 2025 Jun 21; Vol. 184 (7), pp. 431.
Date of Electronic Publication: 2025 Jun 21.

Children conceived through assisted reproductive technologies (ART) potentially display an increased cardiovascular morbidity. Despite cardiorespiratory fitness (CRF) and muscle strength being key indicators of cardiovascular outcomes, they have not been investigated in ART offspring yet. This observational pilot cohort study aimed to evaluate CRF and muscle strength in ART participants and spontaneously conceived controls.
Anthropometric variables, diet quality, level of physical activity, and sedentary behavior were evaluated. Participants performed a 6-min walking test (6MWT) and a 20-m shuttle run test (20mSRT). 6MWT distance and the number of archived laps were assessed, the maximal oxygen uptake (V̇O2 _max ) was estimated, and pulse rate recovery was calculated. Maximal hand grip strength (HGS) was determined as a marker of muscle strength. Generalized linear models were used to adjust data for age, birthweight, and gestational age. Sixty-seven ART participants and 86 spontaneously conceived peers were included. Both groups did not differ significantly in age (11.3 (IQR 8.1-18.2) vs. 11.9 (IQR 8.7-18.3) years), gender ratio, anthropometric variables, diet quality, level of physical activity and sedentary behavior. The amount of 20mSRT laps (P _adj =0.02), estimated VO2 _max (45.0 (IQR 37.9-47.1) vs. 45.8 (IQR 43.1-48.0) ml·kg⁻ ¹ ·min⁻ ¹ , P _adj =0.04), and pulse rate recovery (P _adj =0.03) were significantly lower in ART participants after adjustment. HGS did not differ between groups.
Conclusion: This study indicates a significantly lower CRF in ART participants. Significant differences in muscle strength were not demonstrated between groups. Future studies should validate these results by using cardiopulmonary exercise testing for VO2 _max assessment.

Stable Longitudinal Quality of Life in the SERVE Trial Among Adults With Transposition of the Great Arteries and a Systemic Right Ventricle.

Castiglione A; Department of Cardiology, Center for Congenital Heart Diseases, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
& many other centres in Switzerland
Schwerzmann M; Bouchardy J; Buechel RR; Engel R; Freese M; Gabriel H; Greutmann M; Heg D; Possner M; Ruperti-Repilado FJ; Rutz T; Schwitter J; Thomet C; Tobler D; Wilhelm M; Wustmann K; Schwitz F;

CJC pediatric and congenital heart disease [CJC Pediatr Congenit Heart Dis] 2024 Dec 12; Vol. 4 (2), pp. 81-91.
Date of Electronic Publication: 2024 Dec 12 (Print Publication: 2025).

Background: Adults with a transposition anatomy and a systemic right ventricle (RV) face long-term complications that may impact their quality of life (QoL). Few data are available regarding the QoL in this patient group and its evolution over time.
Methods: This study was performed in the SERVE trial’s (identifier: NCT03049540) prospective cohort of patients (n = 100) with congenitally corrected transposition of the great arteries (TGA) or dextro-TGA after the atrial switch procedure and a longitudinal follow-up of 3 years. We aimed to describe the longitudinal QoL levels and their predictors. QoL was assessed using the Linear Analog Scale. QoL parameters were collected at baseline, after 12 months, and after 36 months, together with clinical parameters and a questionnaire assessing general self-efficacy (GSE).
Results: The mean QoL on the Linear Analog Scale was 79.1 ± 13.6 at baseline, 75.5 ± 14.8 at 1 year, and 79.2 ± 13.6 at 3-year follow-up ( P = 0.900). No significant differences in QoL were observed between congenitally corrected TGA or dextro-TGA patients. Cardiopulmonary exercise testing maximum work rate and maximum oxygen uptake, New York Heart Association class, end-diastolic RV volumes, N-terminal pro-B-type natriuretic peptide concentration, and GSE showed significant correlations with QoL levels. Multivariable regression analysis identified GSE value and New York Heart Association class ( r² = 0.283, P < 0.001) as independent predictors of QoL at baseline.
Conclusions: Patients with a systemic RV reported a stable good QoL during 3 years of follow-up. Exercise capacity and self-efficacy were the only independent predictors of QoL.

Chronotropic incompetence and the importance of cardiopulmonary exercise testing following myocardial infarction.

Griffith GJ; Northwestern University Feinberg School of Medicine, Department of Physical Therapy and Human Movement Sciences, USA

International journal of cardiology [Int J Cardiol] 2025 May 31; Vol. 437, pp. 133445.
Date of Electronic Publication: 2025 May 31.

Chronotropic incompetence (CI) is characterized by an inadequate or blunted heart rate (HR) response to exercise, [1] and the clinical and prognostic importance of CI is being increasingly recognized. Associations between CI and mortality [2,3] and exercise capacity [4] have been demonstrated in a variety of cardiovascular disease patient populations. In this issue of the International Journal of Cardiology, the original research article by Smarz and colleagues further established the importance of CI to a population of post-myocardial infarction (MI) patients with preserved or mildly reduced ejection fraction. [5] This compelling research article provides important insight into the prognostic benefit of identification of CI and importantly highlights that methodological considerations relating to the assessment of CI are of the utmost importance. Firstly, there exists a general lack of universal agreement regarding the mathematical and functional definition of CI. Secondly, implementation of cardiopulmonary exercise testing (CPET) is oftentimes underutilized, and the multitude of variables obtained from it are rarely optimized in the characterization of patient prognosis following maximal exercise testing. The aims of this article are to 1) provide insight into best methodological practices surrounding CI as identified via CPET, 2) contextualize the importance of CI in MI patients, and 3) provide recommendations for future avenues of research to continue to build the body of evidence surrounding the importance of CPET and CI.

Characterization of dysfunctional breathing using cardiopulmonary exercise testing.

Möbus SF; School of Clinical Medicine, University of Cambridge, Cambridge, UK.
Harding CJ; Taylor CL; Sylvester KP; Fuld JP;

Physiological reports [Physiol Rep] 2025 Jun; Vol. 13 (11), pp. e70388.

Cardiopulmonary exercise testing (CPET) is emerging as a useful tool in the identification of dysfunctional breathing (DB). We aimed to evaluate the prevalence and functional impact of different patterns of DB in 628 adult patients referred for CPET due to unexplained dyspnoea (August 2019-December 2023). Patients were assigned to four groups following CPET interpretation: normal, breathing pattern disorder (BPD), hyperventilation (HV), and combined BPD with HV (BPDHV). Demographic and CPET performance data were analyzed using non-parametric tests as appropriate. 94 (15.0%) patients had normal CPETs and 267 (42.5%) were identified as having DB. The remaining 267 were excluded as having alternative diagnoses. Of those with DB, 145 (54.3%) had BPD, 41 (15.4%) had HV, and 81 (30.3%) had BPDHV. VE/VCO ₂ was significantly increased in HV or BPDHV only (p < 0.001). Patients in all three DB groups exhibited significantly impaired peak VO ₂ compared to those with normal CPETs (p < 0.001). These CPET findings highlight DB as a common driver of symptoms in unexplained dyspnoea. Over half of patients with DB had isolated BPD, which requires visual inspection of relevant CPET plots to diagnose. Those identified with DB had significantly reduced peak VO ₂ , which may be a useful classifier of functional severity in DB.

Blood Pressure Responses During Exercise Were Associated With Average Home Blood Pressure and Home Blood Pressure Variability: The Electronic Framingham Heart Study.