Nesti, Lorenzo; Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
Santoni, Lorenza;Frascerra, Silvia;Chiriacò, Martina; et al

International journal of sport nutrition and exercise metabolism,2025 May 30

Background; Fat oxidation rates are key determinants of exercise capacity and metabolic health, evaluated by indirect calorimetry during step graded exercise test. We sought to verify whether indirect calorimetry applied to ramp graded exercise test provides comparable results to the reference test and to identify the physiological bases of possible dissimilarities.
Methods; To this aim, 14 healthy volunteers performed two cardiopulmonary exercise tests with concomitant stress echocardiography according to standard protocols until limit of tolerance on separate days, in randomized order.
Results; Compared at matched exercise intensities, expressed as percentage of estimated maximal rate of oxygen uptake (%V˙O2max), indirect calorimetry applied to ramp provided identical kinetics of macronutrient oxidation, with a negligible (7%, p > .05) constant overestimation of fat and underestimation of carbohydrate oxidation rates. Despite identical hemodynamic and ventilatory parameters throughout the tests, we observed a minute downward shift of the Δ V˙CO2/Δ V˙O2 intercept with ramp in comparison to step (-0.05 ± 0.09 L/min; p = .077) due to delayed alignment of gas exchange to work rate, which explains the differences in substrate oxidation values between the two tests. Ramp macronutrient oxidation rates were fully normalized by correcting the stoichiometric equations for the Δ V˙CO2/Δ V˙O2 intercept difference.
Conclusions;  In conclusion, cardiopulmonary and metabolic responses are dependent on exercise intensity and not on the protocol used. Indirect calorimetry applied to ramp protocols correctly identifies the kinetics of macronutrient oxidation while introducing minimal differences in the absolute values due to different gas-exchange response that can be mathematically corrected by applying the Δ V˙CO2/Δ V˙O2 correction factor.

Z. J. Carr, Yale University, School of Medicine, New Haven, CT, USA.
J. Charchaflieh, A. Brenes-Bastos, H. He, H. M. Lin, A. Jankelovits, et al.

BJA Open 2025 Vol. 14 Pages 100407

BACKGROUND: Early postoperative complication risk prediction would enhance perioperative surveillance and resource allocation. Reports have described brief submaximal cardiopulmonary exercise testing (CPET) for the routine assessment of cardiopulmonary disease. Compared with conventional CPET, it can be performed in 6 min and is used to predict peak CPET measurements. We aimed to determine whether submaximal CPET-derived measures outperform structured surveys in early postoperative complication detection.
METHODS: An institutional review board-approved, single-centre, open-label, clinical device trial was conducted. A total of 101 participants undergoing noncardiac surgery, aged >60 yr, with revised cardiac risk index </=2, self-reported metabolic equivalents >4 (METs in ml O(2) kg(-1) min(-1); self-endorsed reliably climbing two flights of stairs), were enrolled. Participants completed a subjective METs assessment, Duke Activity Status Index, and submaximal CPET that derived peak oxygen uptake (VO(2), ml O(2)kg(-1) min(-1)), METs, and gas exchange-derived pulmonary capacitance (GXCAP, in ml O(2) beat(-1) kPa(-1)). Elastic net regularisation machine learning identified feature importance among study measures for the primary endpoint (Postoperative Morbidity Survey [POMS] >/=1), secondary endpoints (cardiac, pulmonary and renal domains of the POMS [POMS-CPR >/=1]), and length of stay. Adjusted multivariable regression models were used to identify significance.
RESULTS: Of 101 participants, 53 (52.4%) had POMS >/=1. GXCAP to peak VO(2) slope (GXCAP-VO(2)) was associated with POMS >/=1 (OR(adj) 0.94; 95% CI 0.89-0.99; P=0.011) and increasing length of stay (OR(adj) 0.98; 95% CI 0.96-0.99; P=0.01). GXCAP-VO(2) slope (OR(adj) 0.93; 95% CI 0.88-0.99; P=0.015) was associated with POMS-CPR >/=1.
CONCLUSIONS: Compared with structured surveys (subjective METs or Duke Activity Status Index) or conventional peak CPET values (VO(2) or METs), a novel measure, GXCAP-VO(2) slope, offered superior early postoperative complication discrimination in low-morbidity subjects. These preliminary findings support GXCAP-VO(2) slope as a compelling investigational target for early postoperative complication risk, supporting the use of CPET to enhance early postoperative complication prediction. CLINICAL TRIAL REGISTRATION: NCT05743673.

Blumer V; Inova Schar Heart and Vascular, Falls Church, Virginia, USA, & many other institutions worldwide
Januzzi JL Jr; Liu Y; Butler J; Ezekowitz JA;Rosenstock J; Del Prato S; Tang WHW; Urbinati A; Zannad F; Lewis GD; Solomon SD; Hedge S; Ibrahim NE;
Lam CSP;

JACC. Heart failure [JACC Heart Fail] 2025 Apr 23. The ARISE-HF trial
Date of Electronic Publication: 2025 Apr 23.

Background: Diabetic cardiomyopathy (DbCM) is a significant cause of heart failure (HF) in individuals with type 2 diabetes mellitus. Although sex differences are noted in HF patients, it is unclear if such differences exist in those with DbCM and whether sex-based differences affect treatment responses.
Objectives: This analysis focuses on sex differences in baseline characteristics of study participants with DbCM at high risk for progression to overt HF and sex-based treatment responses to high-dose AT-001, a novel aldose reductase inhibitor.
Methods: The ARISE-HF trial was a Phase 3, randomized, international, placebo-controlled study designed to evaluate the efficacy and safety of AT-001 in study participants with DbCM.
Results: Of 691 participants, 348 (50.4%) were women. At baseline, women had higher N-terminal pro-B-type natriuretic peptide concentrations (92 vs 60 ng/L; P &lt; 0.001), lower peak oxygen uptake (13.87 vs 17.59 mL/kg/min; P &lt; 0.001), shorter cardiopulmonary exercise testing durations (8.47 vs 11.05 minutes; P &lt; 0.001), and worse quality of life and health status (Kansas City Cardiomyopathy Questionnaire overall summary score 87.79 vs 92.55; P &lt; 0.001; Physical Activity Scale for the Elderly score 137.87 vs 171.09; P &lt; 0.001) compared with men. Despite these differences, there were no significant sex differences in the efficacy or tolerability of high-dose AT-001 compared with placebo. The placebo-corrected oxygen uptake change was 0.26 for women and 0.27 for men (P = 0.58), and changes from baseline to month 15 in Kansas City Cardiomyopathy Questionnaire and Physical Activity Scale for the Elderly scores showed no significant sex differences (all P &gt; 0.05).
Conclusions: Despite baseline differences between women and men with DbCM, the efficacy and safety of high-dose AT-001 are comparable across sexes. These findings highlight the presence of sex-specific characteristics in DbCM and underscore the importance of further research to understand potential sex-specific mechanisms. (Aldose Reductase Inhibition for Stabilization of Exercise Capacity in Heart Failure Trial [ARISE-HF]; NCT04083339).

Romanowicz J;  Section of Cardiology, Children’s Hospital Colorado and University of Colorado Anschutz,  USA.
Park S; Bunn J; Jacobsen RM; Fonseca B; Zablah JE; Englund EK; Barker AJ; A.Davidson JA;

Journal of cardiovascular magnetic resonance : official journal of the Society for Cardiovascular Magnetic Resonance [J Cardiovasc Magn Reson] 2025 May 04, pp. 101907.
Date of Electronic Publication: 2025 May 04.

Background: Accumulation of progressive extracardiac disease is nearly universal for patients with single ventricle heart disease palliated to a Fontan circulation; however, etiologies are poorly understood. Limited flow reserve in the Fontan circulation may underlie extracardiac disease found in Fontan physiology through reduced oxygen and nutrient delivery to the tissues. This study aimed to determine regional flow volumes and oxygen delivery to key organ systems in children and adolescents with a Fontan circulation.
Methods: In 17 Fontan subjects and 14 biventricular controls, regional arterial flow volumes to the carotid, celiac, superior mesenteric, renal, and iliac arteries were quantified with MRI. Arterial oxygen content was calculated using subject hemoglobin level and pulse oximetry, and regional oxygen delivery was calculated using regional flow volume and oxygen content for the above listed arteries. Cardiac output was measured from ascending aorta flow, systemic blood flow from the caval veins, and aorto-pulmonary collateral flow was calculated as the difference between the two. Flows were compared between groups (t-test) and associations were analyzed between flows and with maximal exercise performance on clinical cardiopulmonary exercise testing (Pearson correlation).
Results: On average, renal and iliac arterial flows were lower in the Fontan group, compared to controls. Carotid, celiac, and superior mesenteric arterial flows were preserved in the Fontan group. Arterial oxygen content was equivalent between groups, and thus, regional oxygen delivery followed the same pattern as regional flows. Cardiac output was no different between groups, but systemic blood flow was lower in Fontans due to loss of flow to aorto-pulmonary collaterals. Systemic blood flow correlated with iliac flow such that those with the lowest systemic flow had the least amount of iliac flow. Celiac arterial flow correlated with percent-predicted peak oxygen consumption (VO2) on exercise testing.
Conclusions: Our results are consistent with a limited flow reserve in the Fontan circulation with sacrifice of iliac arterial flow as global systemic blood flow decreases. Importantly, these data were measured with subjects supine and at rest. Future work requires the addition of exercise to determine how flow to specific organs is affected by increasing metabolic demand from the extremities.

Dandamudi K; Department of Internal Medicine, Virginia Commonwealth University, Richmond, VA.
Mallepally A; Zavar T; Canada JM;Arena R; Trankle C;Tchoukina I;

The American journal of cardiology [Am J Cardiol] 2025 May 05.
Date of Electronic Publication: 2025 May 05.

Background: An objective of the Duke Activity Status Index (DASI) is to standardize assessments of exertional intolerance. However, patient factors associated with inaccurate assessments of exercise capacity with this tool are not well described.
Methods: Patients who completed the DASI in preparation for a treadmill cardiopulmonary exercise test (CPET) at our institution from 2022-2023 were analyzed. Metabolic equivalents of task (METs) were calculated from the DASI score and measured from CPET. Clinical characteristics were compared using Chi square or Mann-Whitney U tests between those who overestimated versus underestimated exercise capacity via the DASI. Correlations were assessed with a Spearman test, and a binary logistic regression model was fit to the clinical characteristics to identify patient characteristics associated with overestimating METs with the DASI.
Results: 512 patients were included in the current study, and the majority (419 [82%]) overestimated exercise capacity via the DASI. DASI-predicted METs had moderate correlation with CPET-achieved METs (Spearman’s rho=+0.620, p&lt;0.001). Patients who overestimated exercise capacity by DASI were more likely to be older, female sex, Black race, on beta blockers, of higher body mass index, and with cardiac comorbidities. The regression model (Χ ² =87.6, p&lt;0.001, Nagelkerke R ² =0.259) found older age, female sex, diagnosis of heart failure, and congenital heart disease most strongly associated with overestimating exercise capacity (all p≤0.002).
Conclusions: A majority of patients referred for CPET overestimate exercise capacity by DASI score, particularly those with older age, female sex, heart failure, and congenital heart disease.

Gallo G; Department of Clinical and Molecular Medicine, Sapienza University of Rome,  Italy.;
Autore C; Volterrani M; Barbato E; Volpe M;

High blood pressure & cardiovascular prevention:the official journal of the Italian Society of Hypertension [High Blood Press Cardiovasc Prev]2025May 06.
Date of Electronic Publication: 2025 May 06.

Heart failure (HF) is characterized by poor exercise tolerance and reduced ability to perform routine daily activities. Cardiac rehabilitation (CR), which includes exercise training, has shown a role in improving cardiac remodeling, functional capacity and HF outcomes as a consequence of its beneficial effects on neurohormonal dysfunction, endothelial function, vascular tone and peripheral oxygen extraction. Although a multiparametric evaluation, including physical examination, blood sampling, echocardiographic and cardiopulmonary exercise testing parameters, is routinely performed during CR programs, the use of cardiac biomarkers, in particular natriuretic peptides (NPs), is still poorly adopted and characterized. In this article we analyze the potential role of biomarkers in monitoring the success of rehabilitation programs and the potential implications of their use in clinical practice. Indeed, NPs measurements might represent an important tool to modulate the rehabilitative interventions with a favorable cost-effectiveness profile.

Pamart N; Inter-University Laboratory of Human Movement Science, University of Lyon,  Saint-Etienne, France.
Drigny J; Azambourg H; Remilly M; Lahjaily K; Rocamora A; Tournoux F; Saloux E; Reboursière E; Gauthier A; Hodzic A;

BMC sports science, medicine & rehabilitation [BMC Sports Sci Med Rehabil] 2025 May 07; Vol. 17 (1), pp. 116.
Date of Electronic Publication: 2025 May 07.

Background: High-intensity resistance training induces structural and functional adaptations in skeletal muscle, yet its impact on cardiac remodeling remains debated. This study aimed to investigate the longitudinal biventricular cardiac response to a 20-week high-intensity resistance training program in previously untrained, healthy males and examine the association between muscle strength gains and cardiac remodeling.
Methods: Twenty-seven male volunteers (aged 18-40 years) participated in a high-intensity resistance training program for 20 weeks. Assessments at baseline, 12 weeks, and 20 weeks included resting blood pressure, electrocardiogram (ECG), three-dimensional transthoracic echocardiography (3DTTE), cardiopulmonary exercise testing ([Formula: see text]O _2peak ), isokinetic dynamometry for muscle strength, and actimetry recordings. Time effects were analyzed using one-way repeated measures ANOVA (P &lt; 0.05).
Results: Twenty-two participants completed the study. Resistance training led to significant reductions in arterial systolic and diastolic blood pressure and heart rate. After 20 weeks of training, 3DTTE showed a significant increase in left ventricular (LV) mass (120.1 ± 15.4 g vs. 133.7 ± 16.3 g, p &lt; 0.001), without inducing LV hypertrophy. Balanced increases were observed in LV end-diastolic volume (146.4 ± 18.9 ml vs. 157.9 ± 19.6 ml, p &lt; 0.001) and right ventricular (RV) end-diastolic volume (119 ± 19.4 ml vs. 129.2 ± 21.6 ml, p &lt; 0.001). LV and RV systolic and diastolic function remained unchanged. There were no changes in [Formula: see text]O _2peak or daily activity levels. Maximal muscle strength in the quadriceps, hamstrings, triceps, and biceps was significantly correlated with LV and RV end-diastolic volumes and LV mass (p ≤ 0.001).
Conclusion: The resistance training program resulted in significant and rapid muscle strength gains and reduced blood pressure. Cardiac adaptations, including moderate biventricular dilatation, were observed without changes in cardiac function or [Formula: see text]O _2peak and were associated with muscle strength gains. Our study highlights that intensive resistance training in novice male resistance trainers induces an adaptive cardiac response, reflecting a physiological adaptation linked to enhanced muscle performance.

Racodon M; Clinique La Mitterie, Service de Rééducation Réadaptation Cardiovasculaire, 59160, Lille, France.
Fabre C; Vanhove P; Vale JD; Bolpaire R; Moutailler E; Malanda F; Secq A;

Journal of cardiovascular translational research [J Cardiovasc Transl Res] 2025 May 08.
Date of Electronic Publication: 2025 May 08.

The Six-Minute Walk Test (6MWT) traditionally assesses exercise capacity in cardiac patients but requires a large space. The Six-Minute Stepper Test (6MST) has been validated as an alternative in various populations. This study evaluates the reproducibility, sensitivity, and validity of the 6MST in 60 cardiac patients (15 women, 45 men, 58 ± 11.2 years). Participants underwent cardiopulmonary exercise tests (CPET), two 6MSTs, and one 6MWT at the start and end of cardiac rehabilitation (CR). Performance in the 6MST improved significantly after CR (343 ± 89.0 vs. 451 ± 105.6 steps, p &lt; 0.0001). The 6MST showed moderate correlation with the 6MWT and CPET (r = 0.54, p &lt; 0.0001). Dyspnoea and leg fatigue were higher in the 6MST than in the 6MWT (p &lt; 0.0001).
Conclusion: The 6MST is a safe, valid, sensitive, and reproducible tool for evaluating exercise capacity in cardiac patients, comparable to the 6MWT.

Chaliki K, Department of Cardiovascular Diseases, Mayo Clinic, USA.
Sharma A, Sharma A, Yee C, Chaliki H, Reddy S

J Clin Med. 2025 Apr 27;14(9):3013.

Background/Objectives: The peak oxygen consumption (VO2) during cardiopulmonary exercise testing (CPET) is a strong predictor of all-cause mortality. The cardiac output, a key determinant of VO2, can be assessed using resting echocardiographic parameters. The heart rate recovery and ventilatory efficiency (VE/VCO2 slope) from CPET offer additional insights into cardiovascular fitness.
Methods: This study aimed to identify resting echocardiographic parameters that predict the percentage of predicted peak VO2, heart rate recovery, and VE/VCO2 slope in a general cardiology population. This retrospective analysis included 1909 patients who underwent echocardiography within 3 months of CPET from 2017 to 2022. Patients with potentially confounding co-morbid conditions were removed. Spearman correlations were used to compare 19 echocardiographic parameters to peak VO2, heart rate recovery, and the VE/VCO2 slope, followed by multiple linear regression of peak VO2.
Results: Eleven echocardiographic parameters correlated with peak VO2, with the strongest correlations seen with the left ventricular stroke volume index (R = 0.284, p < 0.001), mitral valve medial annular a’ wave velocity (R = 0.142, p < 0.0001), and mitral E-to-e’ ratio (R = -0.117, p < 0.0001). The left ventricular diastolic parameters and mitral E/A ratio correlated strongly with the heart rate recovery and VE/VCO2 slope. The multiple linear regression analysis identified the left ventricular mass index, stroke volume index, mitral valve E wave velocity, tricuspid valve regurgitation peak systolic velocity, tricuspid lateral annular systolic velocity S’, and left atrial volume index as independent predictors of peak VO2 (R2 = 0.191).
Conclusions: The left ventricular stroke volume, diastolic function, and RV systolic function markers are significant predictors of cardiopulmonary fitness, aiding clinical decision-making in patients without CPET data.