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 < 0.001), lower peak oxygen uptake (13.87 vs 17.59 mL/kg/min; P < 0.001), shorter cardiopulmonary exercise testing durations (8.47 vs 11.05 minutes; P < 0.001), and worse quality of life and health status (Kansas City Cardiomyopathy Questionnaire overall summary score 87.79 vs 92.55; P < 0.001; Physical Activity Scale for the Elderly score 137.87 vs 171.09; P < 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 > 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<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<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 < 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 < 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 < 0.001) and right ventricular (RV) end-diastolic volume (119 ± 19.4 ml vs. 129.2 ± 21.6 ml, p < 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 < 0.0001). The 6MST showed moderate correlation with the 6MWT and CPET (r = 0.54, p < 0.0001). Dyspnoea and leg fatigue were higher in the 6MST than in the 6MWT (p < 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.

D. Qin, Tianjin Medical University, Tianjin, 300070, People’s Republic of China.
G. Liu, J. Zhang, S. Lin, X. Liu, J. Zhao, et al.

Diabetes Metab Syndr Obes 2025 Vol. 18 Pages 1239-1254

PURPOSE: This study aimed to evaluate the effects of Adaptive Postural Balance Cardiac Rehabilitation Exercise (APBCRE) on glycolipid metabolism and exercise endurance in patients with coronary artery disease (CAD) and type 2 diabetes mellitus (T2DM). Specifically, we compared the efficacy of APBCRE with aerobic exercise (AE) alone and irregular exercise (IE).
PATIENTS AND METHODS: This randomized controlled trial included 348 patients with CAD, comprising 261 patients with T2DM and 87 non-diabetic CAD patients as a control group. Participants were randomly assigned to one of four groups: the APBCRE group, the AE group, the IE group, or the non-diabetic AE control group. The intervention lasted 8 weeks, including a structured 6-week training phase. Metabolic markers and exercise endurance were assessed at baseline (week 1) and post-intervention (week 8). Cardiopulmonary exercise testing (CPET) was utilized to individualize exercise prescriptions and optimize intervention intensity.
RESULTS: The APBCRE group demonstrated significant improvements in fasting blood glucose (FBG) (-11.34%, from 7.89 to 6.99 mmol/L, p < 0.05), HbA1c (-8.87%, from 7.20% to 6.56%, p < 0.05), and LDL-C levels (-12.21%, from 2.44 to 2.14 mmol/L, p < 0.05) compared to the AE and IE groups. While both APBCRE and AE improved lipid profiles, APBCRE demonstrated superior enhancements in exercise endurance, with VO (2) max increasing by 18.71% (from 14.19 to 16.86 mL/min/kg, p < 0.05) and AT VO (2) increasing by 16.00% (from 11.62 to 13.48 mL/min/kg, p < 0.05).
CONCLUSION: These findings support the efficacy of APBCRE in improving glycolipid metabolism, exercise endurance, and neuromuscular coordination in patients with CAD and T2DM compared to AE alone.

T. J. Siddiqi, Department of Medicine, Baylor University Medical Center, Dallas, TX, USA.
Y. Liu, F. Zannad, W. H. W. Tang, S. Solomon, J. Rosenstock, et al.

J Diabetes Complications 2025 Vol. 39 Issue 7 Pages 109059

AIMS: Assess the determinants of health status and its correlation with key parameters in individuals with diabetic cardiomyopathy (DbCM).
METHODS: In the ARISE-HF trial, the Kansas City Cardiomyopathy Questionnaire (KCCQ), cardiopulmonary exercise testing (CPET), Physical Activity Scale for the Elderly (PASE) score, echocardiographic, and laboratory assessments were performed at baseline in 691 persons with DbCM.
RESULTS: Study participants with lower KCCQ-Clinical Summary Score (CSS) were predominantly women, had poorer kidney function, higher body-mass index and natriuretic peptides, and lower hemoglobin levels. Lower KCCQ-CSS scores were associated with shorter CPET duration, lower peak exercise oxygen consumption (VO(2)) and lower PASE scores, but the correlations were weak (CPET duration: r = 0.14, 95 % CI: 0.07-0.22; peak VO(2): r = 0.21, 95 % CI: 0.14-0.28; PASE score: r = 0.19, 95 % CI: 0.11-0.26), indicating that although worse health status was linked to poorer function and activity, the strength of these relationships was limited. No meaningful associations were observed between KCCQ-CSS and echocardiographic measurements, cardiac biomarkers, or kidney function.
CONCLUSION: Health status in Stage B heart failure due to DbCM is frequently impaired. Among those with DbCM the KCCQ is only weakly correlated with the CPET parameters and PASE score implying these assessments provide unique information.

S. D. Haas, Department of Pediatric Cardiology, Emma Children’s Hospital, Amsterdam, The Netherlands.
A. E. van der Hulst, C. Adel, A. Malekzadeh, N. A. Blom, M. Konigs, et al.

Trends Cardiovasc Med 2025

Congenital heart disease (CHD) is the most common birth defect, and despite advancements in medical care, children with surgically corrected CHD often experience reduced cardiorespiratory fitness, which is associated with negative long-term health outcomes. This meta-analysis aimed to quantify peak oxygen consumption (V̇O2peak) impairments in children with surgically corrected CHD, examine isolated diagnosis-specific impairments, and explore the relationship between clinical variables and cardiorespiratory fitness. A total of 45 studies encompassing 2,536 children with CHD and 3,108 healthy controls were included in the meta-analysis, revealing that children with CHD had significantly lower V̇O2peak (standardized mean difference = 1.13, 95%CI 0.98-1.28), with those having univentricular hearts being most affected (standardized mean difference = 1.61, 95%CI 1.34-1.87). Reduced saturation during exercise, chronotropic impairment and early onset of anaerobic threshold are likely to play a role in this impairment.