Author Archives: Paul Older

Oxygen Supplementation Improves Oxygen Uptake Kinetics and Exercise Performance in PAH and CTEPH Patients

S. Kadosh, School of Public Health, Gray Faculty of Medicine, Tel Aviv University, Tel-Aviv, Israel.
Y. Baidats, A. M. Jones, D. Wilkerson, A. Velner, R. Reuveny, et al.

Compr Physiol 2026 Vol. 16 Issue 3 Pages e70194

Aim: We studied the effect of O2 supplementation on physiological responses to exercise in patients with pulmonary vascular disease.

Methods: Six patients with pulmonary arterial hypertension (PAH), four patients with chronic thromboembolic pulmonary hypertension (CTEPH) (age 54 ± 17 years; 8 females) and 13 healthy individuals (age 50 ± 17 years; 5 females) were tested. PAH/CTEPH was defined hemodynamically by mPAP > 20 mmHg and PVR > 3 WU. Patients performed symptom-limited cardiopulmonary exercise tests, and constant work-rate tests (CWRTs) at 80% of the work-rate (WR) at the gas exchange threshold (GET). Tests breathing room air (RA, 21% O2) were compared to tests performed breathing 30% O2. Oxygen-uptake (V̇O2) kinetics were calculated from the CWRT results.

Results: In the PAH/CTEPH group, peak WR, peak V̇O2 and V̇O2 at the GET improved significantly when breathing 30% O2 compared to RA (mean ± SD 85 ± 26 vs. 77 ± 25 W, 18.3 ± 5.8 vs. 15.6 ± 5.7 mL/kg/min and 764 ± 181 vs. 685 ± 154 mL/min; p = 0.011, p = 0.015 and p = 0.012, respectively). Peak V̇O2/HR was higher with 30% O2 compared with RA (8.8 ± 2.2 vs. 7.7 ± 1.8 mL/beat, p = 0.021). The time constant (tau) of V̇O2 kinetics was faster in PAH/CTEPH patients while breathing 30% O2 compared to RA (36 ± 4 vs. 43 ± 6 s, p = 0.009). In healthy individuals there was no improvement in V̇O2 kinetics while breathing 30% O2 compared to RA (tau 35 ± 6 vs. 35 ± 6 s, p = 0.916).

Conclusion: A clinically applicable level of O2 supplementation (30%) improved maximal and aerobic exercise capacity and V̇O2 kinetics in PAH/CTEPH patients. O2 supplementation may be considered to support exercise training in PAH/CTEPH patients.

Long-term Complications of Pulmonary Embolism: Which Is the Optimal Follow-Up?

K. Z. Abbas, Department of Thoracic Medicine and Surgery, Temple University Hospital, Philadelphia, USA
T. Caton and P. Rali

direcct link
https://www.ncbi.nlm.nih.gov/pubmed/42309631

Heart Fail Clin 2026 Vol. 22 Issue 3 Pages 387-397

Pulmonary embolism (PE) is associated with substantial long-term morbidity that extends past initial diagnosis. Patients diagnosed with PE face risks of chronic thromboembolic pulmonary hypertension, post-PE syndrome, recurrent venous thromboembolism, psychological distress, and impaired quality of life. Optimal follow-up is critical for early recognition and intervention. This article synthesizes contemporary evidence, including guideline recommendations, registry data, and recent clinical studies. The aim of this article is to outline a structured approach to PE follow-up, addressing who should be monitored, when, and with which modalities.

Safety and Efficacy of Exercise-based Cardiac Rehabilitation in Patients with Refractory Angina

L. O. C. Dourado, Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP – Brasil.
C. P. Jordao, M. L. C. Vieira, L. H. W. Gowdak, C. E. Negrao, L. A. M. Cesar, et al.

Arq Bras Cardiol 2025 Vol. 122 Issue 12 Pages e20250331

Background: Evidence on the safety and anti-ischemic effects of exercise-based cardiac rehabilitation (ECR) in patients with refractory angina (RA) remains limited.

Objective: To evaluate the safety and efficacy of a 12-week ECR program in patients with RA, focusing on improvements in symptoms, functional capacity, and ischemic burden assessed by exercise stress echocardiography (ESE).

Methods: This was a prospective, single-center, randomized controlled trial evaluating a 12-week ECR program in patients with RA. Forty-five patients were randomized to either the rehabilitation group (RG), receiving ECR, or the control group (CG), receiving medical treatment (MT) alone. Outcomes included mortality, cardiovascular events, anginal symptoms, and parameters from ESE and cardiopulmonary exercise testing (CPET). Statistical significance was set at p < 0.05.

Results: In ESE, exercise duration was significantly greater in RGpost (after ECR) compared to RGpre (before ECR) (∆ = 63.24 ± 19.87 s; p < 0.01). Angina quantification was lower in RGpost than in RGpre, CGpost (after MT alone), and CGpre (before MT alone) (∆ = -1.64 ± 0.48 n, p < 0.01; -3.10 ± 0.97 n, p < 0.01; and -2.73 ± 0.92 n, p = 0.01, respectively). The angina threshold was higher in RGpost than in RGpre and CGpost (∆ = 89.66 ± 33.16 s, p = 0.04; and 111.76 ± 42.25 s, p = 0.04, respectively). Improvement in ischemic burden on ESE was demonstrated by increased time to ischemic threshold in RGpost compared to RGpre, CGpost, and CGpre (∆ = 83.23 ± 21.84 s, p < 0.01; 98.44 ± 35.11 s, p = 0.03; and 109.34 ± 34.00 s, p < 0.01, respectively). In CPET, RGpost showed increased exercise duration (∆ = 104.54 ± 28.09 s, p < 0.01) and distance covered (∆ = 131.23 ± 30.48 m, p < 0.01) compared to RGpre. No significant differences in VO2 were observed between groups. Two patients in the CG group died. One patient in the RG group experienced prolonged angina during training. No significant differences in major cardiovascular events were observed between groups.

Conclusion: The 12-week ECR-program was safe and effective in improving exercise duration, distance covered and ischemic burden on ESE in patients with RA.

Exercise Capacity and the Force Frequency Relationship in Multi-Point Versus Single-Point Pacing: A Randomized Trial

N. Z. Safdar, The Leeds Teaching Hospitals NHS Trust, Leeds, UK.
R. M. Gadani, C. A. Cole, J. E. Lowry, S. Kamalathasan, S. Datla, et al.

Pacing Clin Electrophysiol 2026 Vol. 49 Issue 6 Pages 685-697

Background: Quadripolar left ventricular (LV) epicardial leads capable of multipoint pacing (MPP) may have an advantage over conventional bipolar leads for delivering cardiac resynchronization therapy (CRT) by stimulating the lateral LV wall from two distinct locations simultaneously.

Aim: We aimed to determine the acute and longer-term effects of MPP compared with single-point pacing (SPP) on LV contractility and exercise capacity in individuals with heart failure with reduced ejection fraction receiving CRT.

Methods: Participants were enrolled into a randomized crossover study with echocardiographic assessment of the comparative effects of acute MPP and SPP on LV contractility and cardiopulmonary exercise testing at 6-weeks and 6-months following device implantation. Participants were then randomized in a parallel-group study to either MPP or SPP for further 6-months.

Results: Twenty-three participants (mean age 73 years [95% confidence interval: 69, 78], 91% male, 91% New York Heart Association [NYHA] class II, LV ejection fraction 31.3% [27.4, 35.1]) were included. At resting heart rates, LV contractility was significantly higher with MPP compared to SPP (2.29 mmHg/mL/m2 [1.74, 2.84] vs. 2.03 [1.58, 2.47]; p = 0.019). However, it was not different between MPP and SPP at higher heart rates or at 6-months, and there were no differences in exercise performance between MPP and SPP at any point including following 6 months of chronic treatment.

Conclusion: Although CRT with MPP resulted in improved LV contractility at resting heart rates acutely post implantation, it did not translate into consistent mechanistic or patient-orientated benefits in the short or longer-term.

Assessing lactate stability at the minimum lactate steady state velocity in male trained middle-distance runners

S. H. Shahidi Department of Sports Coaching, Istanbul Gedik University, Istanbul, Turkey.

PLoS One 2026 Vol. 21 Issue 3 Pages e0344573

Objectives: This study investigated the physiological behavior of the running velocity associated with the Minimum Lactate Steady State (vMLaSS), derived from a 6 × 800-m interval protocol, and examined whether this intensity produced stable metabolic and lactate responses during a 30-minute constant-load validation run in trained endurance runners.

Methods: Fifteen trained male middle- and long-distance runners completed a graded treadmill test to determine maximal oxygen uptake. Following a supramaximal sprint to induce hyperlactatemia, each athlete performed a 30-minute constant-load run at a velocity derived from the lactate-minimum approach. Following a supramaximal sprint to induce hyperlactatemia, each athlete performed a 30-minute constant-speed run at their individually determined MLaSS velocity. Blood lactate samples were collected at 10-minute intervals, and breath-by-breath cardiopulmonary variables were continuously recorded. Lactate kinetics were analyzed using a Friedman test with Wilcoxon signed-rank post-hoc comparisons (p < 0.05).

Results: Blood lactate exhibited significant time-dependent fluctuations during the 30-minute trial (Friedman χ² (3) = 28.72, p < 0.001). Lactate increased sharply by minute 10, declined at minute 20, and rose again at minute 30, exceeding the classical MLSS criterion of ≤1 mmol·L ⁻ ¹ change during the final 20 minutes. In contrast, cardiopulmonary variables remained stable throughout V̇O₂ (3.43 ± 0.11 L·min ⁻ ¹; p = 0.86) and V̇CO₂ (3.21 ± 0.14 L·min ⁻ ¹; p = 0.91). Carbohydrate oxidation predominated (214.5 ± 19.3 g·h ⁻ ¹), whereas fat oxidation remained minimal (-0.9 ± 2.7 g·h ⁻ ¹).

Conclusion: Despite stable cardiorespiratory and substrate-utilization profiles, the significant variability in blood lactate concentration during the 30-minute constant-load run indicates that the running velocity derived from the lactate-minimum approach did not elicit a lactate steady state in this trained cohort. These findings suggest that physiological responses at the MLaSS-derived intensity may differ from classical steady-state expectations in highly trained endurance runners and highlight the need for direct MLSS verification in future studies.

Obesity and Ventilatory Responses During Exercise in the Fitness Registry and the Importance of Exercise National Database (FRIEND)

T. G. Bissen, Cardiovascular and Applied Physiology Laboratory, Florida State University,FL, USA.
R. Arena, M. P. Harber, L. A. Kaminsky, J. Myers and J. C. Watson

Scand J Med Sci Sports 2026 Vol. 36 Issue 3 Pages e70264

A high minute ventilation/rate of carbon dioxide production (V̇E/V̇CO2) slope during exercise is prognostic for cardiovascular mortality among clinical populations. Obesity represents a major modifiable risk factor for cardiovascular disease. However, it is unclear whether body mass index (BMI) is associated with V̇E/V̇CO2 slope among apparently healthy adults. Therefore, we used the Fitness Registry and the Importance of Exercise National Database (FRIEND) to determine whether BMI is positively associated with V̇E/V̇CO2 slope in the context of apparently healthy adults. All participants completed a cardiopulmonary exercise test on a cycle ergometer. Linear regressions adjusted for age, sex, and race/ethnicity were used to compare the V̇E/V̇CO2 slope between adults with and without obesity (BMI </≥ 30 kg/m2). Partial correlation adjusted for age, sex, race/ethnicity, and cardiorespiratory fitness was used to determine the relation between the V̇E/V̇CO2 slope and BMI. All data are presented as median [IQR]. We set α a priori to < 0.05. The sample (n = 3534) characteristics were as follows: (1) age = 40 (17) years; (2) 20% female; (3) cardiorespiratory fitness = 27.8[10.8] mL O2●kg-1●min-1 & 2.3[0.9] L O2●min-1; and (4) BMI = 26.1[5.0] kg/m2. V̇E/V̇CO2 slope was higher in adults with obesity 25.0[3.5] compared to those without obesity 24.7[3.6] with a negligible effect size (R2 = 0.132, adjusted R2 = 0.131, F4,3529 = 134, p < 0.001). V̇E/V̇CO2 slope was weakly associated with BMI across the cohort (ρ = 0.079, p < 0.001). Obesity was positively, but negligibly, associated with a higher V̇E/V̇CO2 slope in the FRIEND Registry.

Effects of reducing sedentary behaviour on cardiovascular health, skeletal muscle oxidative capacity and functional exercise capacity in sedentary adults: a randomised controlled trial

W. M. A. Franssen, Hasselt University, Hasselt, Belgium.& other centres
I. Nieste, K. Koppo, P. Joris, F. Vandereyt, H. Savelberg, et al.

BMJ Open Sport Exerc Med 2026 Vol. 12 Issue 1 Pages e002759

Purpose: This study aimed to investigate the effectiveness of a 12-week intervention using self-monitoring alone and in combination with motivational interviewing to reduce sedentary behaviour (SB) and improve cardiovascular health, as reflected by cardiac autonomic function, endothelial function, skeletal muscle oxidative capacity and functional exercise capacity in sedentary adults.

Methods: In a three-armed randomised controlled trial, 59 (36% male; age: 53.3±8.7 years) sedentary adults were randomly allocated to a control group, a self-monitoring (consumer wearable activity tracker, CWAT) group or the self-monitoring+motivational (CWAT+) group for 12 weeks. SB and physical activity were assessed using activPAL3 accelerometer. Endothelial function was assessed using non-invasive peripheral arterial tonometry with the EndoPAT2000 device and fasting blood samples. Muscle oxidative capacity was evaluated using a submaximal cardiopulmonary exercise test, functional exercise capacity via a 6 min walk test, and cardiac autonomic function through heart-rate variability analysis.

Results: The CWAT+group significantly reduced time spent in SB, which resulted in improvements in muscle oxidative capacity (time constant τ: -4.9 s±10.9 s; p=0.010), functional exercise capacity (6 min walking distance: +53 m±36 m; p=0.014) and measurements of heart rate variability (HRV) reflected by the root mean square of successive differences between normal adjacent R-R intervals (112 23 ms; p=0.014), low-frequency component (1178 (11, 2344) ms2; p=0.039) and high-frequency component (471 (18, 960) ms2; p=0.035), compared with controls.

Conclusion: A reduction in SB results in improvements of HRV, skeletal muscle oxidative capacity and functional exercise capacity in sedentary adults, mainly driven by an increase in moderate-to-vigorous physical activity.

Complexity of Cardiovascular Regulation and Its Association with Physical and Cardiorespiratory Fitness in Men with Type 2 Diabetes Mellitus

E. F. Signini, Universidade Federal de São Carlos, São Carlos 13565-905, Brazil.
R. M. de Abreu, A. Castro, A. M. Santos, G. A. M. Galdino, S. C. G. Moura, et al.

Background/Objectives: Cardiovascular regulation complexity (CRC) is an underexplored health marker in the context of type 2 diabetes mellitus (T2DM). Additionally, associating CRC with physical and cardiorespiratory fitness variables could provide greater insight into how physical conditioning impacts cardiovascular health in the context of T2DM. This study aims to investigate whether the relationship between physical and cardiorespiratory fitness and CRC differs according to the presence or absence of T2DM.
Methods: Sixty-eight men were equally divided into the T2DM group (T2DMG; 57 ± 6 years old and 28.4 ± 3.1 kg/m2) and the control group (CG; 52 ± 5 years old and 25.1 ± 2.8 kg/m2). Participants underwent a resting cardiovascular data collection and a cardiopulmonary exercise test on a cycle ergometer. For each group, the relative peak power (W/kgPEAK) and peak oxygen consumption (VO2PEAK) were correlated with the CRC indices, namely, Shannon entropy, the complexity index, the normalized complexity index, and the sample entropy from heart period (HP) and systolic arterial pressure (SAP) series. A partial correlation was performed for each group, controlling for age, physical activity level, and metabolic cart.
Results: Only the CG showed positive and significant correlations between relative VO2PEAK and W/kgPEAK and CRC indices derived from the HP series (0.354 ≤ r ≤ 0.548 and 0.001 ≤ p ≤ 0.047). Correlations with the SAP series were not significant, regardless of the groups.
Conclusions: In this sample, there was no positive relationship between physical and cardiorespiratory fitness variables and CRC indices among individuals with T2DM. Further large sample studies are needed to elucidate the factors involved in T2DM that impact CRC.