Vanreusel, Inne; Department of Cardiology, Antwerp University Hospital, Edegem, Belgium.;
Hens, W; Van Craenenbroeck, E; Paelinck, B; et al;

Cardiology in the young,2025 Mar 11

• Introduction: Vitamin D is crucial for normal organ function, vascular health and exercise performance, yet its deficiency is widespread. Patients with CHD often exhibit reduced exercise capacity. Limited research exists on vitamin D in CHD.
• Methods: This study investigates serum 25-hydroxy vitamin D levels in 55 adult CHD patients (median age 31 years) compared to 55 age- and gender-matched controls without cardiac disease and examines associations with exercise capacity, peripheral microvascular function, muscle strength and biventricular function in CHD. Therefore, patients underwent fingertip arterial tonometry, transthoracic echocardiography, muscle strength measurements and cardiopulmonary exercise testing.
• Results: Results indicated that 93% of CHD patients and 91% of controls had 25-hydroxy vitamin D levels <30 ng/ml, with both groups showing varying values depending on the season in which the studies were conducted. No significant difference in 25-hydroxy vitamin D levels was found between patients and controls. While vitamin D levels in CHD patients did not significantly correlate with age, body mass index, blood pressure, peripheral microvascular function, high-sensitivity C-reactive protein, cholesterol levels, N-terminal-pro hormone B-type natriuretic peptide, ventricular function or muscle strength, a significant correlation was found with percent-predicted peak oxygen consumption ( ρ =0.41, p = 0.005 and  ρ =0.34, p = 0.02 for reference values following Wasserman and the LowLands registry, respectively), even after adjusting for season ( p = 0.03 and 0.05, respectively).
• Conclusions: In conclusion, vitamin D levels were similar between CHD patients and controls, but vitamin D insufficiency is common and linked to reduced exercise capacity in CHD. Further research is needed to determine whether vitamin D supplementation combined with exercise could be beneficial in CHD with vitamin D insufficiency.

Forbes, Lindsay; Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado, Aurora, CO, USA.
Bull, Todd; Lahm,Tim; Sisson,Tyler; et al;

Background Acute hypoxia increases pulmonary arterial (PA) pressures, though its effect on right ventricular (RV) function is controversial. The objective of this study was to characterize exertional RV performance during acute hypoxia.
Methods Ten healthy participants (34 ± 10 years, 7 males) completed three visits: visits 1 and 2 included non-invasive normoxic (fraction of inspired oxygen ( INLINEMATH ) = 0.21) and isobaric hypoxic ( INLINEMATH  = 0.12) cardiopulmonary exercise testing (CPET) to determine normoxic/hypoxic maximal oxygen uptake ( INLINEMATH ). Visit 3 involved invasive haemodynamic assessments where participants were randomized 1:1 to either Swan-Ganz or conductance catheterization to quantify RV performance via pressure-volume analysis. Arterial oxygen saturation was determined by blood gas analysis from radial arterial catheterization. During visit 3, participants completed invasive submaximal CPET testing at 50% normoxic INLINEMATH and again at 50% hypoxic INLINEMATH ( INLINEMATH  = 0.12).
Results Median (interquartile range) values for non-invasive INLINEMATH values during normoxic and hypoxic testing were 2.98 (2.43, 3.66) l/min and 1.84 (1.62, 2.25) l/min, respectively (P < 0.0001). Mean PA pressure increased significantly when transitioning from rest to submaximal exercise during normoxic and hypoxic conditions (P = 0.0014). Metrics of RV contractility including preload recruitable stroke work, dP/dt _max , and end-systolic pressure increased significantly during the transition from rest to exercise under normoxic and hypoxic conditions. Ventricular-arterial coupling was maintained during normoxic exercise at 50% INLINEMATH . During submaximal exercise at 50% of hypoxic INLINEMATH , ventricular-arterial coupling declined but remained within normal limits. In conclusion, resting and exertional RV functions are preserved in response to acute exposure to hypoxia at an INLINEMATH  = 0.12 and the associated increase in PA pressures.
KEY POINTS: The healthy right ventricle augments contractility, lusitropy and energetics during periods of increased metabolic demand (e.g. exercise) in acute hypoxic conditions. During submaximal exercise, ventricular-arterial coupling decreases but remains within normal limits, ensuring that cardiac output and systemic perfusion are maintained. These data describe right ventricular physiological responses during submaximal exercise under conditions of acute hypoxia, such as occurs during exposure to high altitude and/or acute hypoxic respiratory failure.

Schellenberg, Jana; Sports and Rehabilitation Medicine, University Hospital Ulm, Leimgrubenweg, Ulm, Germany.
Matits, Lynn; Bizjak, Daniel A; Deibert, Peter; et al;

Infection,2025 Feb 24

• Purpose: Impaired left and right ventricular (LV/RV) function during acute SARS-CoV-2 infection has been predominantly reported in hospitalized patients, but long-term cardiac sequelae in large, well-characterized cohorts remain inconclusive. This study evaluated cardiac structure and function in individuals with post-Coronavirus disease (COVID) syndrome (PCS) compared to recovered controls (CON), focusing on associations with cardiopulmonary symptoms and rapid physical exhaustion (RPE).
• Methods: This multicenter, population-based study included 1154 participants (679 PCS, 475 age- and sex matched CON; mean age 49 ± 12 years; 760 women) 1.5 years post-infection. Transthoracic echocardiography assessed LV global longitudinal strain (GLS), RV GLS and RV free wall strain (FWS), and other measures. Cardiopulmonary exercise testing (CPET) measured maximum respiratory oxygen uptake (VO ₂ max) as a marker of cardiopulmonary fitness.
• Results: PCS participants exhibited significantly lower LV GLS (-20.25% [-21.28 – -19.22] vs. -20.73% [-21.74 – -19.72], p = 0.003), reduced diastolic function (E/A 1.16 [1.04-1.27] vs. 1.21 [1.1-1.32], p = 0.022) and decreased TAPSE (24.45 mm [22.14-26.77] vs. 25.05 mm [22.78-27.32], p = 0.022) compared to CON, even after adjusting for confounders. RV strain values were similar between groups. LV GLS correlated inversely with VO ₂ max (p = 0.004) and positively with RPE (p = 0.050), though no associations were observed with other cardiopulmonary symptoms.
• Conclusions: This study demonstrates subtle yet consistent reductions in LV function, specifically LV GLS and diastolic function, and exercise capacity in PCS compared to CON. While these changes are within reference ranges, their potential impact on clinical outcomes warrants further investigation. These findings highlight the need for cardiac assessments and long-term follow-up in symptomatic PCS patients.

Fan, Yuxuan; Department of Cardiology Rehabilitation, Daqing Oilfield General Hospital, Daqing, Heilongjiang, China.
Sun, Xiaopeng;Li, Guihua;Wang, Xiaojing; et al;

Frontiers in cardiovascular medicine,2025 Feb 25

• Objective: This study aimed to evaluate the correlation between aerobic exercise intensity based on the 6 min walk test (6MWT) and the anaerobic threshold (AT)-based equivalent in patients with acute myocardial infarction (AMI). The feasibility of using the 6MWT for exercise prescription in primary care settings was also investigated.
• Methods: A retrospective analysis was conducted on data from AMI patients, including statistics on all values of the cardiopulmonary exercise test and 6MWT parameters.
• Results: Regression analysis showed that the regression equation based on 6MWD exercise intensity (EI _6MWD ) could predict AT-based exercise intensity (EI _AT ). Moreover, EI _6MWD correlated with EI _AT in 91.9%-93.0% of patients’ EI _6MWD , with AMI equivalent to the EI _AT model.
• Conclusions: The findings suggest that the anaerobic threshold in AMI patients corresponds to 91.9%-93.0% of the distance covered during the 6MWT. Thus, the 6MWT is a feasible tool for developing exercise prescriptions in primary care hospitals.

• Bork J;German Centre for Cardiovascular Research (DZHK), Partner Site Greifswald, Greifswald, Germany.
• Markus MRP; Ewert R; Nauck M; Templin C; Völzke H; Kastenmüller G;Artati A; Adamski J; Dörr M; Friedrich N; Bahls M;

Scandinavian journal of medicine & science in sports [Scand J Med Sci Sports] 2025 Mar; Vol. 35 (3), pp. e70034.

High cardiorespiratory fitness (CRF) is associated with better overall health. This study aimed to find a metabolic signature associated with CRF to identify health-promoting effects. CRF based on cardiopulmonary exercise testing, targeted and untargeted metabolomics approaches based on mass spectrometry, and clinical data from two independent cohorts of the Study of Health in Pomerania (SHIP) were used. Sex-stratified linear regression models were adjusted for age, smoking, and height to relate CRF with individual metabolites. A total of 132 (SHIP-START-2: 483 men with a median age of 58 years and 450 women with a median age of 56 years) and 118 (SHIP-TREND-0: 341 men and 371 women both with a median age of 51 years) metabolites were associated with CRF. Lipids showed bidirectional relations to CRF independent of sex. Specific subsets of sphingomyelins were positively related to CRF in men (SM (OH) C14:1, SM(OH)C22:2 SM C16:0, SM C20:2 SM(OH)C24:1) and inversely in women (SM C16:1, SM C18:0, SM C18:1). Metabolites involved in energy production (citrate and succinylcarnitine) were only associated with CRF in men. In women, xenobiotics (hippurate, stachydrine) were related to CRF. The sex-specific metabolic signature of CRF is influenced by sphingomyelins, energy substrates, and xenobiotics. The greater effect estimates seen in women may emphasize the important role of CRF in maintaining metabolic health. Future research should explore how this profile changes with different types of exercise interventions or diseases in diverse populations and how these metabolites could be implemented in primary prevention settings.

Sumitani, Hitoshi; Department of Respiratory Medicine, NHO Osaka Toneyama Medical Center, Toyonaka, Japan.
Miki, Keisuke;Yamamoto, Yukio;Mihashi, Yasuhiro et al;

Respiratory care,2025 Mar 11

Background: Improving the anaerobic threshold (AT) provides benefits by avoiding overload, especially for patients with advanced COPD. However, the variables related to improving AT are poorly known. The aim of this study was to investigate which variables are related to improved AT after pulmonary rehabilitation (PR) using cardiopulmonary exercise testing (CPET).
Methods: Stable patients with severe and very severe COPD who performed 4-week PR and whose ATs were identified both before and after PR were selected; they were divided into two groups based on whether the AT increased after PR, and their responses were compared.
Results: In the 26 eligible subjects, there was no correlation between the mean change from baseline after PR in the inspired minus expired mean O ₂ concentrations (ΔFO ₂ ) and minute ventilation (V˙ _E ) at peak exercise. Compared with the AT no-increase group, the AT increase group, at peak exercise, showed significant increases in peak oxygen uptake (V˙ _{O 2} ) and ΔFO ₂ but not in V˙ _E , after PR. The increase in V˙ _{O 2} at the AT after PR was well correlated with the mean change after PR in ΔFO ₂ at peak exercise (r = 0.66, P < .001), rather than V˙ _E . Of all the peaks and throughout exercise variables, ΔFO ₂ at peak exercise was identified as one of the variables more closely correlated with improved AT after PR.
Conclusions: Improvement of ΔFO ₂ at peak exercise, rather than V˙ _E , correlated with an increased AT in subjects with advanced COPD, which suggests that improving ΔFO ₂ independent of V˙ _E may be a useful strategy to individualize PR.

• Girardi M; Institute of Respiratory Medicine and Exercise Physiology, The  Harbor-UCLA Medical Center, Torrance, California, USA.
• Capelli C; Ferguson C; Ward SA; Rossiter HB;

Experimental physiology [Exp Physiol] 2025 Feb 21.
Date of Electronic Publication: 2025 Feb

Tidal breathing in awake humans is variable. This variability causes changes in lung gas stores that affect gas exchange measurements. To overcome this, several algorithms provide solutions for breath-by-breath alveolar gas exchange measurement; however, there is no consensus on a physiologically robust method suitable for widespread application. A recent approach, the ‘independent-breath’ (IND) algorithm, avoids the complexity of measuring breath-by-breath changes in lung volume by redefining what is meant by a ‘breath’. Specifically, it defines a single breathing cycle as the time between equal values of the INLINEMATH / INLINEMATH (or INLINEMATH / INLINEMATH ) ratio, that is, the ratio of fractional concentrations of lung-expired O ₂ (or CO ₂ ) and nitrogen (N ₂ ). These developments imply that the end of one breath is not, by necessity, aligned with the start of the next. Here we demonstrate how the use of the IND algorithm fails to conserve breath-by-breath mass balance of O ₂ and CO ₂ exchanged between the atmosphere and tissues (and vice versa). We propose a new term, within the IND algorithm, designed to overcome this limitation. We also present the far-reaching implications of using algorithms based on alternative definitions of the breathing cycle, including challenges in measuring and interpreting the respiratory exchange ratio, pulmonary gas exchange efficiency, dead space fraction of the breath, control of breathing, and a broad spectrum of clinically relevant cardiopulmonary exercise testing variables. Therefore, we do not support the widespread adoption of currently available alternative definitions of the breathing cycle as a legitimate solution for breath-by-breath alveolar gas exchange measurement in research or clinical settings.

Hesse, A; Department of Kinesiology University of Minnesota Twin Cities, USA
White, M; Lundstrum, C;

International Journal of Sports Medicine (INT J SPORTS MED), Apr2025; 46(4): 227-236. (10p)

Cardiopulmonary exercise testing involves collecting variable breath-by-breath data and sometimes requiring data processing of outlier removal, interpolation, and averaging before later analysis. These data processing choices, such as averaging duration, affect calculated values such as ˙VO₂ max. However, assessing the implications of data processing without knowing popular methods worth comparing is difficult. In addition, such details aid study reproduction. We conducted a semi-automated scoping review of articles with exercise testing that collected data breath-by-breath from three databases. Of the 8,344 articles, 376 (mean: 4.5% and 95% confidence interval: 4.1–5.0%) and 581 (mean: 7.0% and 95% confidence interval: 6.4–7.5%) described outlier removal and interpolation, respectively. A random subset of 1,078 articles revealed (mean: 60.9% and 95% confidence interval: 57.9–63.7%) the reported averaging methods. The commonly documented outlier cutoffs were±3 or 4 SD (39.1 and 51.6%, respectively). The dominating interpolation duration and procedure were 1 s (93.9%) and linear interpolation (92.5%). Averaging methods commonly described were 30 (30.9%), 60 (12.4%), 15 (11.6%), 10 (11.0%), and 20 (8.1%) second bin averages. This shows that studies collecting breath-by-breath data often lack detailed descriptions of data processing methods, particularly for outlier removal and interpolation. While averaging methods are more commonly reported, improved documentation across all processing steps will enhance reproducibility and facilitate future research comparing data processing choices.

Watson WD; Transplant Department, Royal Papworth Hospital, Cambridge, UK.; University of Cambridge, Cambridge, UK.
Burrage MK; Ong LP; Bhagra S; Garbi M; Pettit S; T

JHLT open [JHLT Open] 2024 Mar 13; Vol. 4, pp. 100080.
Date of Electronic Publication: 2024 Mar 13 (Print Publication: 2024).

Background: Secondary mitral regurgitation (MR) is common in heart failure with reduced ejection fraction (HFrEF) and is associated with poor outcomes. However, there is little evidence regarding secondary MR in advanced HFrEF. Poor outcomes for MR intervention suggest a need for further risk stratification.
Methods: Patients were assessed with echocardiography, right heart catheterization (RHC), and cardiopulmonary exercise testing. Ventricular-secondary MR was identified by echocardiography and categorized as mild, moderate, or severe according to guidelines. RV ability to compensate for pulmonary pressure rise was assessed by RV-pulmonary artery (PA) coupling, calculated as ratio of tricuspid annular plane systolic excursion (TAPSE), and systolic pulmonary artery pressure (SPAP) (echocardiography for TAPSE and RHC for SPAP). Primary end-point was a composite of all-cause mortality, urgent heart transplantation, or mechanical circulatory support.
Results: Four hundred and fifty-six patients with ventricular-secondary MR were followed up for a median of 2.39 years, with 237 reaching a primary end-point. Severe MR conferred a worse prognosis than mild or moderate ((hazard ratio) HR 2.6, p  < 0.001). Right atrial pressure was predictive of survival. RV-PA uncoupling, defined as TAPSE/SPAP below median value of 0.37, was associated with reduced survival across all severities of MR ( p  < 0.001).
Conclusions: Ventricular-secondary MR is common and severity correlates with adverse prognosis in advanced heart failure. RV-PA uncoupling can improve risk stratification in all grades of MR severity, particularly with PA pressure determined invasively.

Shen T; Department of Cardiology, Peking University Third Hospital, Beijing 100191, China.
Wang Y; Li J;Xu S; Wang P; Zhao W;

Journal of cardiovascular development and disease [J Cardiovasc Dev Dis] 2025 Feb 24; Vol. 12 (3).
Date of Electronic Publication: 2025 Feb 24.

Objective: To investigate the cut-off value of the breathing reserve for predicting a decline in cardiorespiratory fitness (CRF) among healthy middle-aged Chinese individuals.
Methods: Healthy middle-aged individuals who underwent cardiopulmonary exercise testing (CPET) at the Peking University Third Hospital from May to October 2021 were selected. The study included 321 participants, with an average age of 48.8 ± 5.7 years. They were divided into two groups based on the peak oxygen uptake (VO ₂ peak): the adequate CRF group and the CRF decline group. Multivariate logistic regression analysis was used to explore the factors influencing CRF.
Results: In the male CRF decline group, heart rate, alanine aminotransferase, end-tidal partial pressure of carbon dioxide (PETCO ₂ ), and breathing reserve (BR%) were significantly higher, while the oxygen uptake at the anaerobic threshold (VO ₂ @AT) was lower. An elevated BR% was independently associated with CRF decline (OR = 1.111, 95% CI: 1.068-1.156). The female CRF decline group had significantly higher FEV1/FVC and BR% and significantly lower age, fasting glucose, hemoglobin, and VO ₂ @AT compared to the adequate CRF group. Elevated BR% was independently associated with CRF decline (OR = 1.086, 95% CI: 1.038-1.137). The receiver operating characteristic (ROC) curve for the males showed an area under the curve (AUC) of 0.769 (95% CI: 0.703-0.827) with an appropriate BR% cut-off value of 49.9%, sensitivity of 59.9%, and specificity of 77.8%. For the females, the ROC curve displayed an AUC of 0.694 (95% CI: 0.607-0.773) with an appropriate BR% cut-off value of 57.0%, sensitivity of 58.7%, and specificity of 86.0%.
Conclusions: The breathing reserve was independently associated with CRF. The appropriate cut-off values for BR% to predict CRF decline were 49.9% for the males and 57.0% for the females