Sarullo FM; U.O.S.D. di Riabilitazione Cardiovascolare Ospedale Buccheri La Ferla Fatebenefratelli, Palermo, Italy.
Nugara C; Sarullo S; Iacoviello M; Di Gesaro G; Miani D; Driussi M; Correale M; Bilato C; Passantino A; Carluccio E; Villani A; Degli Esposti L; D’Agostino C; Peruzzi E; Poli S; Di Lenarda A;

Frontiers in cardiovascular medicine [Front Cardiovasc Med] 2024 May 10; Vol. 11, pp. 1347908.
Date of Electronic Publication: 2024 May 10 (Print Publication: 2024).

Background: Heart failure (HF) significantly affects the morbidity, mortality, and quality of life of patients. New therapeutic strategies aim to improve the functional capacity and quality of life of patients while controlling HF-related risks. Real-world data on both the functional and cardiopulmonary exercise capacities of patients with HF with reduced ejection fraction upon sacubitril/valsartan use are lacking.
Methods: A multicenter, retrospective, cohort study, called REAL.IT, was performed based on the data collected from the electronic medical records of nine specialized HF centers in Italy. Cardiopulmonary exercise testing was performed at baseline and after 12 months of sacubitril/valsartan therapy, monitoring carbon dioxide production (VCO ₂ ) and oxygen consumption (VO ₂ ).
Results: The functional capacities of 170 patients were evaluated. The most common comorbidities were hypertension and diabetes (i.e., 53.5 and 32.4%, respectively). At follow-up, both the VO ₂ peak (from 15.1 ± 3.7 ml/kg/min at baseline to 17.6 ± 4.7 ml/kg/min at follow-up, p  < 0.0001) and the predicted % VO ₂ peak (from 55.5 ± 14.1 to 65.5 ± 16.9, p  < 0.0001) significantly increased from baseline. The VO ₂ at the anaerobic threshold (AT-VO ₂ ) increased from 11.5 ± 2.6 to 12.5 ± 3.3 ml/kg/min ( p  = 0.021), and the rate ratio between the oxygen uptake and the change in work (ΔVO ₂ /Δwork slope) improved from 9.1 ± 1.5 to 9.9 ± 1.6 ml/min/W ( p  < 0.0001).
Conclusions: Sacubitril/valsartan improves the cardiopulmonary capacity of patients with HFrEF in daily clinical practice in Italy.
Competing Interests: MI: Lectures or consultant for Novartis, Vifor Pharma, Boehringer, Lilly, Bayer, AstraZeneca, Roche Diagnostics, Neopharmed Gentili. ADL: Lectures for Novartis, Vifor Pharma, Boheringer, Daiichi, Bayer, Pfizer, AstraZeneca, Research Funds from Novartis, Amgen, AstraZeneca, Vifor Pharma, Bayer. CDA, EP, and SP are employees of Novartis. LDE was employed by company CliCon S.r.l. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The authors declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision. The authors declare that this study received funding from Novartis Farma. The funder had the following involvement in the study: study design, data collection and analysis, supporting manuscript preparation.

Durstenfeld MS; Division of Cardiology at ZSFG and Department of Medicine, University of California, San Francisco (UCSF), USA.
Wilson MP; Jankowski CM; Ditzenberger GL; Longenecker CT; Erlandson K

The Journal of infectious diseases [J Infect Dis] 2024 May 28.
Date of Electronic Publication: 2024 May 28.

Background: People with HIV (PWH) have lower exercise capacity compared to peers without HIV, which may be explained by chronotropic incompetence (CI), the inability to increase heart rate during exercise.
Methods: The Exercise for Healthy Aging Study included adults ages 50-75 with and without HIV. Participants completed 12 weeks of moderate intensity exercise, before randomization to moderate or high intensity for 12 additional weeks. We compared adjusted heart rate reserve (AHRR; CI <80%) on cardiopulmonary exercise testing by HIV serostatus and change from baseline to 12 and 24 weeks using mixed effects models.
Results: Among 32 PWH and 37 controls (median age 56, 7% female, mean BMI 28 kg/m2), 28% of PWH compared to 11% of controls had CI at baseline (p = 0.067). AHRR was lower among PWH (91 vs 101%; difference 10%, 95% CI 1.9-18.9; p = 0.02). At week 12, AHRR normalized among PWH (+8%, 95% CI 4-11; p < 0.001) and was sustained at week 24 (+5, 95%CI 1-9; p = 0.008) compared to no change among controls (95%CI -4 to 4; p = 0.95; pinteraction = 0.004). After 24 weeks of exercise, only 15% PWH and 10% of controls had CI (p = 0.70).
Conclusions: Chronotropic incompetence contributes to reduced exercise capacity among PWH and improves with exercise training.

Stastna N; Department of Pulmonology, Second Faculty of Medicine, Charles University and Motol University Hospital, Prague, Czech Republic.
Hrabovska L;Homolka P; Homola L; Svoboda M; Brat K;Fila L;

BMC pulmonary medicine [BMC Pulm Med] 2024 May 28; Vol. 24 (1), pp. 260.
Date of Electronic Publication: 2024 May 28.

Background: Physical activity is a crucial demand on cystic fibrosis treatment management. The highest value of oxygen uptake (VO _2peak ) is an appropriate tool to evaluate the physical activity in these patients. However, there are several other valuable CPET parameters describing exercise tolerance (W _peak , VO _2VT1 , VO _2VT2, VO ₂ /HR _peak , etc.), and helping to better understand the effect of specific treatment (V _E , V _T , V _D /V _T etc.). Limited data showed ambiguous results of this improvement after CFTR modulator treatment. Elexacaftor/tezacaftor/ivacaftor medication improves pulmonary function and quality of life, whereas its effect on CPET has yet to be sufficiently demonstrated.
Methods: We performed a single group prospective observational study of 10 adolescent patients with cystic fibrosis who completed two CPET measurements between January 2019 and February 2023. During this period, elexacaftor/tezacaftor/ivacaftor treatment was initiated in all of them. The first CPET at the baseline was followed by controlled CPET at least one year after medication commencement. We focused on interpreting the data on their influence by the novel therapy. We hypothesized improvements in cardiorespiratory fitness following treatment. We applied the Wilcoxon signed-rank test. The data were adjusted for age at the time of CPET to eliminate bias of aging in adolescent patients.
Results: We observed significant improvement in peak workload, VO _{2 peak} , VO _2VT1 , VO _2VT2 , V _E /VCO ₂ slope, V _E , V _T , RQ, VO ₂ /HR peak and RR peak. The mean change in VO ₂  peak was 5.7 mL/kg/min, or 15.9% of the reference value (SD ± 16.6; p= 0.014). VO _2VT1 improved by 15% of the reference value (SD ± 0.1; p= 0.014), VO _2VT2  improved by 0.5 (SD ± 0.4; p= 0.01). There were no differences in other parameters.
Conclusion: Exercise tolerance improved after elexacaftor/tezacaftor/ivacaftor treatment initiation. We suggest that the CFTR modulator alone is not enough for recovering physical decondition, but should be supplemented with physical activity and respiratory physiotherapy. Further studies are needed to examine the effect of CFTR modulators and physical therapy on cardiopulmonary exercise tolerance.

Martens P; Department of Cardiovascular Medicine, Heart, Vascular and Thoracic Institute, Cleveland Clinic, OH. USA
Van Iterson EH; Tang WHW; Finet JE;

Circulation. Heart failure [Circ Heart Fail] 2024 May 31, pp. e010807.
Date of Electronic Publication: 2024 May 31.

No abstract available

Bhammar DM; Center for Tobacco Research, Division of Medical Oncology, Ohio State University, Columbus
Nusekabel CW; Wilhite DP;Daulat S;Liu Y; Glover RIS; Babb TG;

Medicine and science in sports and exercise [Med Sci Sports Exerc] 2024 May 15.
Date of Electronic Publication: 2024 May 15.

Purpose: Ventilatory constraints are common during exercise in children, but the effects of obesity and sex are unclear. The purpose of this study was to investigate the effects of obesity and sex on ventilatory constraints (i.e., expiratory flow limitation (EFL) and dynamic hyperinflation) during a maximal exercise test in children.
Methods: Thirty-four 8-12-year-old children without obesity (18 females) and 54 with obesity (23 females) completed pulmonary function testing and maximal cardiopulmonary exercise tests. EFL was calculated as the overlap between tidal flow-volume loops during exercise and maximal expiratory flow-volume loops. Dynamic hyperinflation was calculated as the change in inspiratory capacity from rest to exercise.
Results: Maximal minute ventilation was not different between children with and without obesity. Average end-inspiratory lung volumes (EILV) and end-expiratory lung volumes (EELV) were significantly lower during exercise in children with obesity (EILV: 68.8 ± 0.7%TLC; EELV: 41.2 ± 0.5%TLC) compared with children without obesity (EILV: 73.7 ± 0.8%TLC; EELV: 44.8 ± 0.6%TLC; P < 0.001). Throughout exercise, children with obesity experienced more EFL and dynamic hyperinflation compared with those without obesity (P < 0.001). Also, males experienced more EFL and dynamic hyperinflation throughout exercise compared with females (P < 0.001). At maximal exercise, the prevalence of EFL was similar in males with and without obesity, however the prevalence of EFL in females was significantly different with 57% of females with obesity experiencing EFL compared with 17% of females without obesity (P < 0.05). At maximal exercise, 44% of children with obesity experienced dynamic hyperinflation compared with 12% of children without obesity (P = 0.002).
Conclusions: Obesity in children increases the risk of developing mechanical ventilatory constraints such as dynamic hyperinflation and EFL. Sex differences were apparent with males experiencing more ventilatory constraints compared with females.
Competing Interests: Conflict of Interest and Funding Source: This research was supported by NIH R01 HL136643, Texas Health Presbyterian Hospital Dallas, King Charitable Foundation Trust, and unrestricted funds from Dr. Pepper Snapple. The authors have no relevant conflicts of interest to disclose.

Nemoto S; Showa University School of Nursing and Rehabilitation Sciences,  Yokohama, Kanagawa,  Japan.
Nakabo T; Tashiro N; Kishino A; Yoshikawa A; Nakamura D; Geshi E;

Scientific reports [Sci Rep] 2024 May 22; Vol. 14 (1), pp. 11676.
Date of Electronic Publication: 2024 May 22.

Peak oxygen uptake (VO ₂ ), evaluated as exercise tolerance, is a strong predictor of life prognosis regardless of health condition. Several previous studies have reported that peak VO ₂ is higher in those with a greater decrease in muscle oxygen saturation (SmO ₂ ) in the active muscles during incremental exercise. However, the skeletal muscle characteristics of individuals exhibiting a greater decrease in SmO ₂ during active muscle engagement in incremental exercise remain unclear. This study aimed to clarify the relationship among muscle strength, muscle endurance, and skeletal muscle oxygenation dynamics in active leg muscles during incremental exercise. Twenty-four healthy young men were included and categorized into the non-moderate-to-high muscular strength and endurance group (those with low leg muscle strength, endurance, or both; n = 11) and the moderate-to-high muscular strength and endurance group (those with both moderate-to-high leg muscle strength and endurance; n = 13). All participants underwent cardiopulmonary exercise testing combined with near-infrared spectroscopy to assess whole-body peak VO ₂ and the change in SmO ₂ at the lateral vastus lateralis from rest to each exercise stage as skeletal muscle oxygenation dynamics. A linear mixed-effects model, with the change in SmO ₂ from rest to each stage as the dependent variable, individual participants as random effects, and group and exercise load as fixed effects, revealed significant main effects for both group (P = 0.001) and exercise load (P < 0.001) as well as a significant interaction between the two factors (P < 0.001). Furthermore, multiple-comparison test results showed that the change in SmO ₂ from rest to 40%-100% peak VO ₂ was significantly higher in the moderate-to-high muscular strength and endurance group than in the non-moderate-to-high muscular strength and endurance group. Maintaining both muscle strength and endurance at moderate or higher levels contributes to high skeletal muscle oxygenation dynamics (i.e., greater decrease in SmO ₂ ) during moderate- or high-intensity exercise.

Thron M; Institute of Sports and Sports Science, Karlsruhe Institute of Technology, Karlsruhe, Germany.
Woll A; Doller L; InQuittmann OJ; Härtel S; Ruf L; Altmann S;

Journal of strength and conditioning research [J Strength Cond Res] 2024 May 24.
Date of Electronic Publication: 2024 May 24.

Physiological and locomotor profiling enables to differentiate between sprinters, 400-m runners, and middle-distance runners. [J Strength Cond Res XX(X): 000-000, 2024]-Different approaches exist for characterizing athletes, e.g., physiological and locomotor profiling. The aims of this study were to generate and compare physiological and locomotor profiles of male and female runners and to evaluate relationships between the different approaches. Thirty-four highly trained adolescent and young adult female and male athletes (n = 11 sprinters; n = 11,400-m runners; n = 12 middle-distance runners) performed two 100-m sprints on a running track to determine maximal sprinting speed (MSS) and maximal lactate accumulation rate (ċLamax).
A cardiopulmonary exercise test was performed on a treadmill to determine maximal aerobic speed (MAS) and maximal oxygen uptake (V̇o2max). Anaerobic speed reserve (ASR) was calculated as the difference between MSS and MAS. Group comparisons were conducted with a 2-way ANOVA (discipline × sex; p < 0.05) and Bonferroni post hoc tests and Cohen’s d as effect size. Parameters were correlated by Pearson’s correlation coefficients. Maximal aerobic speed and V̇o2max were higher in 400-m and middle-distance runners compared with sprinters (p ≤ 0.02; -2.24 ≤ d ≤ -1.29). Maximal sprinting speed and ċLamax were higher in sprinters and 400-m runners compared with middle-distance runners (0.03 ≤ p ≤ 0.28; 0.73 ≤ d ≤ 1.23). Anaerobic speed reserve was highest in sprinters and lowest in middle-distance runners (p ≤ 0.03; 1.24 ≤ d ≤ 2.79). High correlations were found between ASR and MAS, MSS, and ċLamax (p < 0.01; -0.55 ≤ r ≤ 0.91) and between ċLamax and MSS (p < 0.01; r = 0.74).
Our results indicate that athletes of different sprinting and running disciplines show differing physiological and locomotor profiles, and that the parameters of these approaches are related to each other. This can be of interest for assessing strengths and weaknesses (e.g., for talent identification) or training prescription in these disciplines.

de Souza IPMA; Author Affiliations: D’Or Institute for Research and Education, Cardio Pulmonar Hospital, Salvador, Bahia, Brazil (Mss de Souza and de Oliveira, Drs Darzé and Ritt); Bahiana School of Medicine and Public Health, Salvador, Bahia, Brazil (Ms de Souza, Drs Ramos, Ribeiro, Pazelli, Darzé, and Ritt); and Clinicas Hospital, Federal University of Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil (Drs da Silveira and Stein).
Ramos JVSP; da Silveira AD; Stein R; Ribeiro RS; Pazelli AM; de Oliveira QB; Darzé ES; Ritt LEF;

Journal of cardiopulmonary rehabilitation and prevention [J Cardiopulm Rehabil Prev] 2024 May 07.
Date of Electronic Publication: 2024 May 07.

Purpose: The objective of this study was to evaluate the independent and added value of a cardiopulmonary exercise test (CPX) to New York Heart Association (NYHA) functional analysis in patients with heart failure (HF) and ejection fraction (EF) <50%.
Methods: Patients (n = 613) with HF and EF < 50% underwent CPX and were followed for 28 ± 17 mo with respect to primary outcomes (death or heart transplantation).
Results: Mean patient age was 57 ± 12 yr and 64% were male. Most patients were classified as NYHA class II (41%). The composite rate of primary outcomes was 12%; death occurred in 9% and heart transplant in 4%. Independent predictors of primary outcomes were: EF (HR = 0.95: 95% CI, 0.92-0.98; P = .001) and NYHA (HR = 2.06: 95% CI, 1.54-2.75; P < .0001). When added to the model, peak oxygen uptake (peak) was an independent predictor (HR = 0.90: 95% CI, 0.84-0.96; P = .001), as was the percentage of predicted peak (HR = 0.03: 95% CI, 0.007-0.147; P < .001), minute ventilation/carbon dioxide production slope (HR = 1.02: 95% CI, 1.01-1.04; P = .012), and CPX score (HR = 1.16: 95% CI, 1.06-1.27; P = .001).
Conclusions: CPX variables were independent predictors of HJ prognosis, even when controlled by NYHA functional class. Despite being independent predictors, the value added to NYHA classification was modest and lacked statistical significance.

Meziab O; Department of Pediatrics (Cardiology), University of Arizona,  Tucson, AZ, 85724, USA.
Dereszkiewicz E; Guerrero CE; Hoyer AW; Barber BJ; Klewer SE; Seckeler M;

Pediatric cardiology [Pediatr Cardiol] 2024 May 09.
Date of Electronic Publication: 2024 May 09.

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.

(© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Wang AP; Division of Pediatric Cardiology, Ann & Robert H. Lurie Children’s Hospital of Chicago, Chicago, IL, USA.
Ward K; Griffith G; Gambetta K;

Pediatric transplantation [Pediatr Transplant] 2024 Jun; Vol. 28 (4), pp. e14772.

Background: Obesity and impaired exercise tolerance following heart transplantation increase the risk of post-transplant morbidity and mortality. The aim of this study was to evaluate the effect of body mass index on markers of exercise capacity in pediatric heart transplant recipients and compare this effect with a healthy pediatric cohort.
Methods: A retrospective analysis of cardiopulmonary exercise test data between 2004 and 2022 was performed. All patients exercised on a treadmill using the Bruce protocol. Inclusion criteria included patients aged 6-21 years, history of heart transplantation (transplant cohort) or no cardiac diagnosis (control cohort) at the time of testing, and a maximal effort test. Patients were further stratified within these two cohorts as underweight, normal, overweight, and obese based on body mass index groups. Two-way analyses of variance were performed with diagnosis and body mass index category as the independent variables.
Results: A total of 250 exercise tests following heart transplant and 1963 exercise tests of healthy patients were included. Heart transplant patients across all body mass index groups had higher resting heart rate and lower maximal heart rate, heart rate recovery at 1 min, exercise duration, and peak aerobic capacity (VO _2peak ). Heart transplant patients in the normal and overweight body mass index categories had higher VO _2peak and exercise duration when compared to underweight and obese patients.
Conclusion: Underweight status and obesity are strongly associated with lower VO _2peak and exercise duration in heart transplant patients. Normal and overweight heart transplant patients had the best markers of exercise capacity.