Lv H; Institute of Cardiovascular Diseases of PLA,  (Third Military Medical University), Chongqing, P.R. China.
Liu Z; Sun M; Yu S; Hu M; Bian S; Ye X;Wang K; Dong H; Yang B; Zhou C; Huang L; Yang J;

IScience [iScience] 2025 Feb 27; Vol. 28 (3), pp. 112112.
Date of Electronic Publication: 2025 Feb 27 (Print Publication: 2025).

The dynamic characteristics of cardiorespiratory fitness during high-altitude acclimatization and deacclimatization are not well elucidated, and whether ubiquinol exerts beneficial effects on cardiorespiratory fitness remains debated. In this trial, 41 volunteers were randomized to receive oral ubiquinol or placebo administration, 14 days before departure to highlands. All individuals were carried to 3900 m by air and then returned to 300 m after 7 days. Cardiopulmonary exercise testing was performed at baseline, on the third day after arrival in the highlands, and on the seventh day after return. This trial revealed the dynamic characteristics of cardiorespiratory fitness during the entire high-altitude acclimatization and deacclimatization process. The short-term journey to the highlands did not significantly affect cardiorespiratory fitness or physical performance capacity after the return. Cardiovascular and respiratory recoveries were desynchronized after returning from the highlands. Ubiquinol supplementation maintained the physical performance capacity in the highlands and facilitated acclimatization to hypoxia

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.

Mapelli M; Centro Cardiologico Monzino, Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy.
Mattavelli I; Salvioni E; Capra N; Mantegazza V; Garlaschè A; Campodonico J; Rubbo FM; Paganin C; Capovilla TM; Nepitella AA; Caputo R; Gugliandolo P; Vignati C; Pezzuto B; De Martino F; Grilli G; Scatigna M;Bonomi A; Sinagra G; Muratori M; Agostoni P;

Frontiers in cardiovascular medicine [Front Cardiovasc Med] 2025 Mar 17; Vol. 12, pp. 1542870.
Date of Electronic Publication: 2025 Mar 17 (Print Publication: 2025).

Background: Sodium-glucose cotransporter-2 inhibitors (SGLT2-i) are standard therapy for heart failure (HF). We performed a holistic evaluation of dapagliflozin, including its effects on exercise performance, left ventricle (LV) reverse remodeling, cardiac biomarkers, fluid retention, and renal and pulmonary function.
Methods: We enrolled HF reduced ejection fraction (LVEF) outpatients (EF <40%) eligible for SGLT2-i and performed cardiopulmonary exercise tests (CPET), pulmonary function tests, bioelectrical impedance vector analysis, and laboratory and echocardiographic assessments at baseline ( T  = 0), after 2-4 weeks (T1), and after 6 months of treatment (T2).
Results: None of the patients interrupted SGLT2-i for adverse events albeit follow-up was completed by 67 of 75 enrolled patients. At T2, mean LVEF increased (from 34.6 ± 7.8 to 37.5 ± 9.2%; p  < 0.001) while end-diastolic (EDV) and end-systolic (ESV) volumes decreased [EDV: 186 (145-232) vs. 177 (129-225) mL, ESV: 113 (87-163) vs. 110 (76-145) mL; p  < 0.001]. Peak oxygen intake was unchanged [peakVO ₂ : 16.2 (13.4-18.7) vs. 16.0 (13.3-18.9) mL/kg/min; p  = 0.297], while exercise ventilatory efficiency (VE/VCO ₂ slope) improved [from 34.2 (31.1-39.2) to 33.7 (30.2-37.6); p  = 0.006]. Mean hemoglobin increased (from 13.8 ± 1.5 to 14.6 ± 1.7 g/dL; p  < 0.001), while renal function did not change after a transient worsening at T1. NT-proBNP, ST-2, and hs-TNI did not change as overall body fluids and quality of life assessed by KCCQ. NYHA class improved ( p =0.002), paralleled by a decrease of MECKI (Metabolic Exercise test data combined with Cardiac and Kidney Indexes) score, from 3.3% (1.9-8.0) to 2.8% (1.2-5.7), suggestive of a positive impact on 2 years prognosis ( p  < 0.001).
Conclusions: Dapagliflozin induced positive LV remodeling, improvement of exercise ventilatory efficiency, and NYHA class but without peakVO ₂ fluid status and cardiac biomarkers changes.

James MD; Respiratory Investigation Unit, Division of Respirology, Department of Medicine, Queen’s University, Kingston, ON, Canada.
Phillips DB;Domnik NJ; Neder JA;

Respiratory physiology & neurobiology [Respir Physiol Neurobiol] 2025 Mar 29, pp. 104423.
Date of Electronic Publication: 2025 Mar 29.

Physical activity is a leading trigger of dyspnea in chronic cardiopulmonary diseases. Recently, there has been a renewed interest in uncovering the mechanisms underlying this distressing symptom. We start by articulating a conceptual framework linking cardiorespiratory abnormalities with the central perception of undesirable respiratory sensations during exercise. We specifically emphasize that exertional dyspnea ultimately reflects an imbalance between (high) demand and (low) capacity. As such, the symptom arises in the presence of a heightened inspiratory neural drive – the will to breathe – secondary to a) increased ventilatory output relative to the instantaneous ventilatory capacity (excessive breathing) and/or b) its impeded translation into the act of breathing due to constraints on tidal volume expansion (constrained breathing). In patients with chronic obstructive pulmonary disease (COPD), asthma, cystic fibrosis, and interstitial lung disease (ILD), constrained breathing assumes a more dominant role as the disease progresses. Excessive breathing due to heightened wasted ventilation in the physiological dead space is particularly important in the initial stages of COPD, while alveolar hyperventilation has a major contributory role in hypoxemic patients with ILD. Hyperventilation is also a leading driver of dyspnea in heart failure (HF) with reduced ejection fraction (EF), while high physiological dead space is the main underlying mechanism in HF with preserved EF. Similarly, wasted ventilation in poorly perfused lung tissue dominates the scene in pulmonary vascular disease. New artificial intelligence-based approaches to expose the contribution of excessive and constrained breathing may enhance the yield of cardiopulmonary exercise testing in investigating exertional dyspnea in these patients.

Squeo, R;
Ferrera, A; Di Gioia, G; Mango, F; et al;

High blood pressure & cardiovascular prevention :
the official journal of the Italian Society of Hypertension,2025 Mar 14

• Competing Interests: Declarations. Ethical Approval: information: the study design of the present investigation was evaluated and approved by the Ethical Committee (CET – Comitato Etico Territoriale Lazio Area 1, date of approval 06\03\2024 IRB number 0208/2024). All athletes included in this study were fully informed of the types and nature of the evaluation and signed the consent form, according to Italian Law and Institute policy. All clinical data assembled from the study population are maintained in an institutional database. Data Availability: De-identified participant data are available upon reasonable request from the corresponding author. Conflict of interest: None.
• Introduction: Olympic athletes represent a special subset of the athletic population and deserve a specialized medical approach. In view of the 2024 Paris Olympic Games, we developed and implemented a comprehensive medical protocol including (other than the standard screening with ECG, physical and history) cardiopulmonary exercise test, echocardiography and full blood and urine tests.
• Aim: Our aim was to assess the prevalence and type of cardiovascular abnormalities in athletes candidate to Paris 2024 Olympic Games, after implementation of this Olympic medical program.
• Methods: We enrolled 772 elite athletes, who underwent a comprehensive, multidisciplinary evaluation, including full panel of blood and urine tests, electrocardiography, trans-thoracic echocardiography (TTE) and a cardiopulmonary exercise test (CPET).
• Results: Of the 772 elite athletes, 363 (47%) were female. A substantial subset of 145 athletes (18.8%) showed one or more abnormalities. Specifically, either abnormal basal ECG findings (n = 26, 17.9%), abnormal TTE results (n = 45, 31%), high blood pressure (n = 2, 1.4%) or exercise induced arrhythmias (n = 49, 33.8%) were detected. 10 athletes (6.9%) showed both abnormal ECGs and exercise induced arrhythmias, and 13 athletes (9%) showed both ECG and echocardiographic abnormal findings. After further and more detailed investigations, of the 145 athletes showing cardiovascular abnormalities at the initial screening, in 4 of them were cardiac conditions implying potential risk of sudden cardiac death were identified and therefore they were withdrawn from competitive sport. Full blood test analysis identified metabolic abnormalities in 200 subjects. Of these, 165 (21%) showed hypercholesterolemia.
• Conclusions: Olympic athletes, despite the highest level of physical performance, are not exempt from cardiovascular and metabolic diseases, including a small proportion of cardiac conditions at risk of SCD. More advanced diagnostic tools, including CPET, echocardiography and full blood tests, implemented in our protocol, were required to identify hidden cardiovascular abnormalities that could have jeopardized athlete’s health and performance.

Meziab, O; Department of Pediatrics (Cardiology), University of Arizona, Tucson, USA.
Dereszkiewicz, E; Guerrero, E; Hoyer, A;

Pediatric cardiology,2025 Apr

Patients with Fontan physiology have reduced exercise performance compared to their peers as well as a higher incidence of bundle branch block (BBB). This study aims to investigate the association between BBB and exercise performance in the Fontan population through a retrospective review of the Pediatric Heart Network Fontan study public use dataset. “Low Performers” were defined as ≤ 25th percentile (for Fontan patients) for each exercise parameter at anaerobic threshold (AT) for gender and age and “Normal Performers” were all other patients. A total of 303 patients with Fontan physiology who underwent exercise testing reached AT and had complete data for BBB. BBB occurred more frequently in Low Performers for VO ₂ [OR (95% CI): 2.6 (1.4, 4.8)] and Work [OR (95% CI): 2.7 (1.4, 5.1)], suggesting that BBB in the Fontan population is associated with reduced exercise performance. This data adds to the existing clinical evidence of the adverse effects of conduction abnormalities on single ventricle cardiac output and adds support for consideration of cardiac resynchronization and multi-site ventricular pacing in this patient population.

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.