Khilzi, Pulmonology Department-Hospital del Mar Pulmonary Hypertension Unit Barcelona Spain.
Karys; Piccari, Lucilla; Franco, Gerard, et al.

Pulmonary circulation,2025 Feb 05Although current guidelines recommend standard cardiopulmonary exercise testing (CPET) to evaluate symptomatic patients after pulmonary embolism (PE), CPET with simultaneous echocardiography could provide relevant information to evaluate right ventricular-pulmonary arterial coupling.
AIMS
The aim of this study was to investigate exercise-induced changes in echocardiographic variables of RV function or RV- arterial coupling in patients with residual thrombotic defects at 3 months after PE.
METHODS
This retrospective study investigated patients with residual thromboembolic disease on V/Q scintigraphy with persistent symptoms despite adequate anticoagulation after 3 months of acute PE, and resting echocardiography with a low probability of PH. At rest and during exercise, CPET and doppler echocardiography were performed following a standard protocol. Forty-five patients were included, completing a follow-up period of at least 24 months. The mean (standard deviation) age was 63 (15) years, and 24 (53%) patients were male.
RESULTS
Four patients developed CTEPH after 2 years follow up. Correlation analyses showed that the peak TAPSE was significantly associated with peak workload ( r = 0.454, p = 0.003), peak VO ₂ ( r = 0.558, p < 0.001), VE/VECO ₂ (AT) ( r = -0.531, p < 0.001), and oxygen pulse ( r = 0.375, p = 0.02). TAPSE/PASP was only slightly associated with peak workload ( r = 0.300, p = 0.045). By contrast, the change on TAPSE (from rest to peak) was significantly correlate with peak oxygen uptake ( r = 0.491, p = 0.01). Also, reduced VO ₂ at AT and TAPSE/PASP was seen in patients with CTEPH. CPET with synchronic echocardiography could be a useful tool in early assessment of symptomatic patients with perfusion defects on imaging after 3 months of correctly treated PE.

T. Atanasovska, Melbourne Australia
T. Farr, R. Smith, A. C. Petersen, A. Garnham, M. J. Andersen, et al.

J Physiol 2024 Vol. 602 Issue 24 Pages 6849-6869

We investigated acute effects of the Na(+),K(+)-ATPase (NKA) inhibitor, digoxin, on muscle NKA content and isoforms, arterial plasma [K(+)] ([K(+)](a)) and fatigue with intense exercise.
In a randomised, crossover, double-blind design, 10 healthy adults ingested 0.50 mg digoxin (DIG) or placebo (CON) 60 min before cycling for 1 min at 60% V̇O2peak then at 95% V̇O2peak until fatigue. Pre- and post-exercise muscle biopsies were analysed for [(3)H]-ouabain binding site content without (OB-F(ab)) and after incubation in digoxin antibody (OB+F(ab)) and NKA alpha(1-2) and beta(1-2) isoform proteins. In DIG, pre-exercise serum [digoxin] reached 3.36 (0.80) nM [mean (SD)] and muscle NKA-digoxin occupancy was 8.2%. Muscle OB-F(ab) did not differ between trials, whereas OB+F(ab) was higher in DIG than CON (8.1%, treatment main effect, P = 0.001), whilst muscle NKA alpha(1-2) and beta(1-2) abundances were unchanged by digoxin. Fatigue occurred earlier in DIG than CON [-7.7%, 2.90 (0.77) vs. 3.14 (0.86) min, respectively; P = 0.037]. [K(+)](a) increased during exercise until 1 min post-exercise (P = 0.001), and fell below baseline at 3-10 (P = 0.001) and 20 min post-exercise (P = 0.022, time main effect). In DIG, [K(+)](a) (P = 0.035, treatment effect) and [K(+)](a) rise pre-fatigue were greater [1.64 (0.73) vs. 1.55 (0.73), P = 0.016], with lesser post-exercise [K(+)](a) decline than CON [-2.55 (0.71) vs. -2.74 (0.62) mM, respectively, P = 0.003]. Preserved muscle OB-F(ab) with digoxin, yet increased OB+F(ab) with unchanged NKA isoforms, suggests a rapid regulatory assembly of existing NKA alpha and beta subunits exists to preserve muscle NKA capacity. Nonetheless, functional protection against digoxin was incomplete, with earlier fatigue and perturbed [K(+)](a) with exercise.
KEY POINTS: Intense exercise causes marked potassium (K(+)) shifts out of contracting muscle cells, which may contribute to muscle fatigue. Muscle and systemic K(+) perturbations with exercise are largely regulated by increased activity of Na(+),K(+)-ATPase in muscle, which can be specifically inhibited by the cardiac glycoside, digoxin. We found that acute oral digoxin in healthy adults reduced time to fatigue during intense exercise, elevated the rise in arterial plasma K(+) concentration during exercise and slowed K(+) concentration decline post-exercise. Muscle functional Na(+),K(+)-ATPase content was not reduced by acute digoxin, despite an 8.2% digoxin occupancy, and was unchanged at fatigue. Muscle Na(+),K(+)-ATPase isoform protein abundances were unchanged by digoxin or fatigue. These suggest possible rapid assembly of existing subunits into functional pumps. Thus, acute digoxin impaired performance and exacerbated plasma K(+) disturbances with intense, fatiguing exercise in healthy participants. These occurred despite the preservation of functional Na(+),K(+)-ATPase in muscle.

Daza JF; University of Toronto, Toronto, Ontario, Canada
Chesney TR; Morales JF; Xue Y; Lee S; Amado LA; Pivetta B;
Mbadjeu Hondjeu AR; Jolley R; Diep C; Alibhai SMH; Smith PM; Kennedy ED;
Racz E; Wilmshurst L; Wijeysundera DN

Annals of Internal Medicine. 178(1):75-87, 2025 Jan.

BACKGROUND: Functional capacity is critical to preoperative risk
assessment, yet guidance on its measurement in clinical practice remains
lacking.
PURPOSE: To identify functional capacity assessment tools studied before
surgery and characterize the extent of evidence regarding performance,
including in populations where assessment is confounded by
noncardiopulmonary reasons.
DATA SOURCES: MEDLINE, EMBASE, and EBM Reviews (until July 2024).
STUDY SELECTION: Studies evaluating performance of functional capacity
assessment tools administered before elective noncardiac surgery to
stratify risk for postoperative outcomes.
DATA EXTRACTION: Study details, measurement properties, pragmatic
qualities, and/or clinical utility metrics.
DATA SYNTHESIS: 6 categories of performance-based tests and 5 approaches
using patient-reported exercise tolerance were identified. Cardiopulmonary
exercise testing (CPET) was the most studied tool (132 studies, 32 662
patients) followed by field walking tests (58 studies, 9393 patients)
among performance-based tests. Among patient-reported assessments, the
Duke Activity Status Index (14 studies, 3303 patients) and unstructured
assessments (19 studies, 28 520 patients) were most researched. Most
evidence focused on predictive validity (92% of studies), specifically
accuracy in predicting cardiorespiratory complications. Several tools
lacked evidence on reliability (test consistency across similar
measurements), pragmatic qualities (feasibility of implementation), or
concurrent criterion validity (correlation to gold standard). Only CPET
had evidence on clinical utility (whether administration improved
postoperative outcomes). Older adults (>=65 years) were well represented
across studies, whereas there were minimal data in patients with obesity,
lower-limb arthritis, and disability.
LIMITATION: Synthesis focused on reported data without requesting missing
information.
CONCLUSION: Though several tools for preoperative functional capacity
assessment have been studied, research has overwhelmingly focused on CPET
and only 1 aspect of validity (predictive validity). Important evidence
gaps remain among vulnerable populations with obesity, arthritis, and
physical disability.

Fakhri S; Boston University Medical Center, Boston, Massachusetts, USA.
Campedelli L; Risbano MG

European Journal of Clinical Investigation. 55(2):e14343, 2025 Feb.

BACKGROUND: Preload insufficiency is an underrecognized cause of exercise
intolerance identified during invasive cardiopulmonary exercise testing,
and defined hemodynamically by decreased biatrial filling pressures,
cardiac output, and oxygen consumption (VO2) at peak effort. Patients with
preload insufficiency, however, typically present with symptoms of dyspnea
on exertion, and/or exercise intolerance at submaximal efforts,
particularly when performing activities of daily living. The
cardiopulmonary hemodynamics and physiology at submaximal work levels of
preload insufficiency have not been previously investigated. We
hypothesized that preload insufficiency hemodynamics exist along a
continuum, with submaximal exercise values reflecting peak exercise
cardiopulmonary hemodynamics.
METHODS: We compared submaximal cardiopulmonary hemodynamics, measured at
anaerobic threshold, between preload insufficiency patients and
age-matched controls referred for dyspnea but with normal exercise
responses.
RESULTS: Our study included 66 patients: 41 with preload insufficiency
and 25 controls. Preload insufficiency patients exhibit significantly
reduced VO2, watts, and METS at submaximal levels compared to controls,
alongside earlier anaerobic threshold achievement and similar heart rates
at anaerobic threshold.
CONCLUSIONS: These findings underscore the profound impact of preload
insufficiency on submaximal exercise capacity, emphasizing the importance
of its recognition and management. This insight sets the stage for further
investigations into interventions targeting preload insufficiency at
submaximal exercise levels to enhance both exercise performance and
quality of life.

Nilsson H; Linkoping University, Linkoping,Sweden
Bellander C; Carlen A; Nylander E; Hedman K; Tamas E

Open Heart. 12(1), 2025 Jan 21.
VI 1

AIMS: Exercise testing remains underused in patients with aortic stenosis
(AS), partly due to concerns about an exercise-induced drop in systolic
blood pressure (SBP). We aimed to study the SBP response to exercise in
patients with severe symptomatic AS prior to surgery and 1 year
postoperatively.

METHODS: Patients scheduled for aortic valve replacement due to severe
symptomatic AS were enrolled at a single centre in a prospective
observational cohort study. Maximal cardiopulmonary exercise testing
(CPET) was performed on a cycle ergometer at baseline and 1 year
postoperatively, using standard termination criteria. The SBP response was
categorised according to the last measurements of SBP during exercise, in
relation to workload (the SBP/watt-slope) as ‘normal’ (>0.25 mm Hg/watt),
‘flat’ (0-0.25 mm Hg/watt) or ‘drop’ (<0 mm Hg/watt).

RESULTS: 45 patients (28 male, 66+/-9 years, left ventricular ejection
fraction 59%+/-5%, aortic jet velocity 4.6+/-0.5 m/s) were included, with
pairwise comparison available in 31 cases. There were no adverse events.
Preoperatively, 4/45 patients were categorised as ‘drop’, 23 as ‘flat’ and
18 as ‘normal’. There was a change in the distribution of categories from
preoperative to postoperative measurements (43% ‘normal’ vs 74% ‘normal’,
p=0.0046). Maximal SBP and workload-indexed SBP were higher
postoperatively than preoperatively (203+/-26 vs 182+/-28 mm Hg, p<0.001
and 0.43+/-0.14 vs 0.29+/-0.15 mm Hg/watt, p<0.001).

CONCLUSION: As a drop in SBP was infrequent (<10%) in patients with
severe symptomatic AS and no adverse events occurred, our results indicate
that CPET may be performed under careful monitoring in AS patients.
Postoperatively, the SBP reaction improved, with no patient having a drop
in SBP.

• Kaikkonen, Piia; UKK Institute, Kaupinpuistonkatu 1, 33500, Tampere, Finland
  Pasanen, Kati; Parkkari, Jari;Mustakoski, Iida; Vasankari, Tommi; Leppänen, Mari

  European Journal of Applied Physiology (EUR J APPL PHYSIOL), Jan2025; 125(1): 71-79. (9p)

  No abstract available

• Engel, Luisa; Witten/Herdecke University, Faculty of Health/School of Medicine, Witten, Germany
  Strassmann, Stephan; Merten, Michaela; Schaefer, Simone; Färber, Johanna;Windisch, Wolfram; Karagiannidis, Christian

  Respiration (RESPIRATION), Jan2025; 104(1): 15-25. (11p)

  Introduction: Survivors of severe COVID-19 face complex challenges and a high degree of pulmonary sequelae. Therefore, we aim to describe their ongoing health burden.
  Methods: In this single-center prospective cohort study, COVID-19 ICU survivors were invited 3 and 6 months after ICU discharge. We examined pulmonary function with pulmonary function tests (PFT) and cardiopulmonary exercise testing (CPET), and we established health-related quality of life (HRQL) and health status (HS) with the EuroQol five-dimension five-level (EQ-5D-5L), the short-form health survey 12 (SF-12), and the modified British Medical Research Council dyspnea scale (mMRC) questionnaires.
  Results: Out of the 53 individuals screened, 23 participated in this study. Throughout both assessment points, participants maintained PFT results within range, apart from a decline in the transfer factor of the lung for carbon monoxide (TLCO). CPET showed improved fitness but persistent ventilatory deficiencies, indicated by altered dead space ventilation (VD/VT) and elevated arterial-alveoli gradient for oxygen (AaDO2). HRQL and HS remained compromised, with both physical (PCS) and mental component summary (MCS) scores significantly lower than the standardized norm population scores. Also, there was a rise in the prevalence of issues related to mobility, pain/discomfort, and anxiety/depression, and an increase in reported dyspnea.
  Conclusion: These results enhance our comprehension of the complex difficulties faced by COVID-19 ICU survivors. Six months post-discharge, CPET revealed the presence of ventilatory insufficiencies. Additionally, there was a decline in HRQL and HS, notably affected by mental health concerns and an increase in the level of dyspnea.

Peled K; Pediatric Cardiology unit, Padeh Medical Center, Poriya, Israel.; Pediatric Department, E. Wolfson Medical Center, Holon, Israel.
Kodesh E; Zucker-Toledano M; Bar-Yoseph R; Borik-Chiger S; Mainzer G;

Pediatric obesity [Pediatr Obes] 2025 Jan 06, pp. e13201.
Date of Electronic Publication: 2025 Jan 06.

Background: Peak oxygen uptake (VO ₂ ) is considered the most important indicator of aerobic exercise capacity during cardiopulmonary exercise testing (CPET). However, its accuracy is compromised when maximal effort is not achieved. In such cases, submaximal parameters can serve as surrogates for assessing exercise performance.
Objectives: To compare the differences in maximal and submaximal exercise parameters between children with obesity and normal weight.
Methods: A prospective study evaluating CPET using a treadmill completed by children with and without obesity.
Results: A total of 153 children (50.9% females) were divided into two groups: obese (n = 87) and non-obese (n = 66). Children with obesity achieved lower exercise capacity (peakVO ₂ of 68% ± 16% vs. 89% ± 15%; p < 0.0001) with fewer achieving maximal effort (26.4% vs. 78.7%, respectively). VO ₂ -derived submaximal parameters showed a significantly lower oxygen uptake efficiency slope per body weight (OUES/kg) (30.5 ± 6.1 vs. 39.0 ± 9.5; p < 0.0001) and lower VO ₂ at ventilatory threshold (VO ₂ @AT) (21.2 ± 4.6 vs. 26.4 ± 5.3, p = 0.0001) in the obese group, with no significant differences in the CO ₂ -derived parameters.
Conclusions: Maximal exercise data in children with obesity is frequently unavailable due to failure to achieve maximal effort. Submaximal parameters, such as OUES and VO ₂ @AT, may be useful substitute options for assessing the health and functional level of this population.

Hansen K; Department of Cardiology, Boston Children’s Hospital, Boston, MA, USA.;
Curran T; Reynolds L; Cameron C; Pymm J; O’Neill JA; Losi R; Sherman C;Ackermans E; Yin S; Singh T; Alexander ME; Gauvreau K; Gauthier N;

International journal of cardiology. Congenital heart disease [Int J Cardiol Congenit Heart Dis] 2024 Aug 27; Vol. 18, pp. 100540.
Date of Electronic Publication: 2024 Aug 27 (Print Publication: 2024).

Background: Change in the oxygen consumption (VO ₂ ) at the ventilatory anaerobic threshold (VAT) is an important outcome in research studies of children with congenital heart disease (CHD). The range of values reported by different raters for any given VAT is needed to contextualize a change in VAT in intervention studies.
Methods: Sixty maximal cardiopulmonary exercise tests (CPET) for CHD patients 8-21 years old were independently reviewed by six exercise physiologists and four pediatric cardiologists. For each of the unique rater pairs for the 60 CPETs, the absolute difference in VAT was calculated and displayed on a histogram to demonstrate the distribution of inter-rater variability. This method was repeated for subgroups of test modality (cycle/treadmill), patient factors (diagnoses, exercise capacity), and rater factors (cardiologist/physiologist, years of experience).
Results: Rater agreement was good with an intraclass correlation coefficient of 0.79-0.91 but the distribution of differences was broad. The median difference was 2.7 % predicted peak VO ₂ (60 mL/min, 1.0 mL/kg/min), the 75th percentile was 6.4 % (140 mL/min, 2.5 mL/kg/min), and the 95th percentile was 16.3 % (421 mL/min, 6.5 mL/kg/min). Distributions were similar for CPET modality and years of rater experience, but differed for other factors.
Conclusions: The baseline distribution of reported VAT is relatively broad, varied by units, and was not explained by differences in rater experience or test modality, but varies by patient factors. When evaluating clinical relevance, a change in the VO ₂ at VAT in response to an intervention of <6.5 % predicted falls within the majority (75th percentile) of expected variability and should be interpreted with caution.