Joosen, Renée S; Department of Pediatric Cardiology, University Medical Center Utrecht,  the Netherlands.
Voskuil, Michiel;de Pater, Wieke G;Wijk, Sebastiaan W H van;

International journal of cardiology. Congenital heart disease,2025 Feb 15

• Background: Patients with transposition of the great arteries (TGA) experience reduced exercise capacity after the arterial switch operation (ASO), possibly due to limited stroke volume. This study evaluates the role of stroke volume in reduced exercise capacity in these patients.
• Methods: A retrospective analysis was conducted on TGA patients who underwent a transthoracic echocardiogram (TTE), cardiac magnetic resonance (CMR) and cardiopulmonary exercise test (CPET) within one year between September 2009 and February 2024 at the University Medical Center Utrecht. Excluding those with submaximal CPET results, the remaining patients were divided into <18 and ≥ 18 years old groups. Reduced exercise capacity was defined as a peak oxygen uptake (VO ² peak) with a Z-score < -2. Left and right ventricular (LV and RV) data including volumes, function, strain and RV outflow tract obstructions were collected from TTE and CMR.
• Results: A total of 126 patients (72 % male, mean age 19 ± 8 years) were included. Left ventricular function, RV volumes, function and strain were relatively preserved on CMR. Reduced VO ² peak was seen in 55 % of patients ≥18 years, significantly more than those <18 years (23 %, p < 0.001). Reduced VO ² peak was independently associated with time since ASO, body mass index, peak heat rate (HRpeak), and O ² pulse. VO ² peak showed weak to moderate correlations with time after ASO (R = -0.295,p < 0.001), body mass index (R = -0.468,p < 0.001) and HRpeak (R = 0.270,p = 0.002) and a strong correlation with O ² pulse (R = 0.621,p < 0.001).
• Conclusion: Exercise capacity in TGA patients after ASO might be limited by an impaired ability to increase stroke volume.
• Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: J.M.P.J. Breur reports financial support was provided by Netherlands Heart Foundation. J.M.P.J. Breur reports financial support was provided by Stichting Hartekind. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Bomma, Meghana; Department of Physiology and Aging, University of Florida, Gainesville, FL, USA.
Lott, Donovan;Forbes, Sean;Shih, Renata; et al

Journal of neuromuscular diseases,2025 Mar 04

• Background: Cardiopulmonary exercise testing (CPET) is the gold-standard for quantification of peak oxygen uptake (VO ₂ ) and cardiorespiratory and muscle responses to exercise. Its application to Duchenne muscular dystrophy (DMD) has been scarce due to the notion that muscle weakness inherent to disease restricts the cardiorespiratory system from reaching maximal capacity.
• Objective: To investigate the utility of CPET in DMD by 1) establishing whether patients can perform maximal-effort exercise for valid VO ₂ peak assessment; 2) quantifying VO ₂ peak repeatability; 3) characterizing muscle and cardiorespiratory responses; 4) comparing VO ₂ peak to 6-min walk distance (6MWD).
• Methods: Twenty-seven DMD and eight healthy boys (6 years and older) underwent CPET using an incremental work-rate protocol for leg (ambulatory) or arm (non-ambulatory) cycling with measurement of heart rate (HR) and gas-exchange variables from rest to maximal-effort. The oxygen cost of work (ΔVO ₂ /Δwork-rate) was calculated, and peak exercise parameters (VO ₂ , HR, O ₂ pulse, ventilation (VE) and ventilatory threshold (VT)) were considered valid if the respiratory exchange ratio ≥1.01.
• Results: VO ₂ peak was valid (81.5% of patients), repeatable (intraclass correlation coefficient = 0.998) and low in ambulatory and non-ambulatory DMD compared to controls (19.0 ± 6.0; 10.7 ± 2; 35.2 ± 4.5 mL/kg/min respectively). VT was low (30.8 ± 10.7; 19.4 ± 3.0; 61.2 ± 6.9% VO ₂ peak) reflecting significant muscle metabolic impairment. Peak HR in ambulatory-DMD (172 ± 14 bpm) was similar to controls (183 ± 8.3 bpm), but O ₂ pulse was low (3.4 ± 1.0; 6.5 ± 1.1 mL/beat). Peak VE/VO ₂ (ambulatory = 42.1 ± 6.8; non-ambulatory = 42.2 ± 7.8; controls = 34.3 ± 4.6) and ΔVO ₂ /Δwork-rate were elevated (ambulatory = 12.4 ± 4.9; non-ambulatory = 19.0 ± 9.7; controls = 10.1 ± 0.8) revealing ventilatory and mechanical inefficiency. Despite strong correlation between VO ₂ peak and 6MWD, severity of impairment was discordant.
• Conclusion: Valid CPET is feasible in DMD, revealing low VO ₂ peak due to abnormal muscle metabolic and cardiorespiratory responses during dynamic exercise. CPET reveals cardiorespiratory limitations in DMD boys with unremarkable 6MWD, and should be considered an integrative approach in clinical care and assessment of emerging therapeutics.

Marra, Alberto Maria; Department of Internal Medicine, Naples, Italy
D’Assante, Roberta; De Luca, Mariarosaria, et al.

JACC. Heart failure [JACC Heart Fail] 2025 Feb 18.
Date of Electronic Publication: 2025 Feb 18.

• Background: Growing evidence suggests that reduced activity of the growth hormone (GH)/insulin-like growth factor (IGF)-1 axis is common and associated with poor clinical status and outcome in heart failure (HF). In addition, preliminary results of growth hormone deficiency (GHD) correction in HF showed an improvement in quality of life, cardiac structure and function, and cardiovascular performance.
• Objectives: The aim of the present double-blind, randomized, placebo-controlled trial was to evaluate the cardiovascular effects of 1 year of GH replacement therapy in a cohort of patients with heart failure and reduced ejection fraction (HFrEF).
• Methods: Consecutive patients with HFrEF in NYHA functional class I/II/III and concomitant GHD were recruited. GHD patients were randomized to receive GH (0.012 mg/kg every second day ∼2.5 IU), or placebo, on top of background therapy. The primary endpoint was peak oxygen consumption (VO ₂ ). Secondary endpoints included hospitalizations, end-systolic left ventricular volumes, N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels, health-related quality of life score, and muscle strength (handgrip).
• Results: A total of 318 consecutive patients were screened, with 86 (27%) fulfilling the criteria for GHD. Of these, 22 subjects refused to participate in the study. The final study groups consisted of 64 patients, 30 randomized in the active treatment group and 34 in the control group. After 1 year, 45 patients completed the study (21 in the control group and 24 in the active group). A statistically significant improvement of peak VO ₂ was reached in the active group (from 12.8 ± 3.4 mL/kg/min to 15.5 ± 3.15 mL/kg/min; P < 0.01; delta peak VO ₂ between groups: +3.1 vs -1.8; P < 0.01). Other cardiopulmonary exercise test parameters (ie, peak workload, VO ₂ at the aerobic threshold, O ₂ pulse and VE/VCO ₂ slope; P < 0.05) also improved, paralleled by an increase in 6-minute walking test distance (P < 0.05) and handgrip strength (P < 0.01). GH improved right ventricular function (ie, TAPSE and TAPSE/pulmonary artery systolic pressure ratio; P < 0.01), leading to an amelioration of clinical status (NYHA functional class; P < 0.05) and health-related quality of life (Minnesota Living With Heart Failure Questionnaire; P < 0.05). A significant decrease of NT-proBNP was also found (P < 0.05).
• Conclusions: This randomized, double-blind, placebo-controlled trial demonstrates that GH replacement therapy in HFrEF patients with GHD improves exercise performance, and left ventricular and right ventricular structure and function, leading to an amelioration of clinical status and health-related quality of life. (Treatment of GHD Associated With CHF; NCT03775993).
• Competing Interests: Funding Support and Author Disclosures This study was supported by Merck’s Grant for Growth Innovation 2016. Drs Crisci and Giardino have received a research grant from the CardioPath program from Federico II University of Naples, Italy. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

E. Kleinhendler, Division of Pulmonary Medicine, Tel-Aviv Sourasky Medical Center, Tel Aviv, Israel.
A. Pinkhasov, S. Hayek, A. Man, O. Freund, T. M. Perluk, et al.

Expert Rev Respir Med 2025 Pages 1-8

BACKGROUND: Cardiopulmonary exercise testing (CPET) is used in the evaluation of unexplained dyspnea. However, its interpretation requires expertise that is often not available. We aim to evaluate the utility of ChatGPT (GPT) in interpreting CPET results.
RESEARCH DESIGN AND METHODS: This cross-sectional study included 150 patients who underwent CPET. Two expert pulmonologists categorized the results as normal or abnormal (cardiovascular, pulmonary, or other exercise limitations), being the gold standard. GPT versions 3.5 (GPT-3.5) and 4 (GPT-4) analyzed the same data using pre-defined structured inputs.
RESULTS: GPT-3.5 correctly interpreted 67% of the cases. It achieved a sensitivity of 75% and specificity of 98% in identifying normal CPET results. GPT-3.5 had varying results for abnormal CPET tests, depending on the limiting etiology. In contrast, GPT-4 demonstrated improvements in interpreting abnormal tests, with sensitivities of 83% and 92% for respiratory and cardiovascular limitations, respectively. Combining the normal CPET interpretations by both AI models resulted in 91% sensitivity and 98% specificity. Low work rate and peak oxygen consumption were independent predictors for inaccurate interpretations.
CONCLUSIONS: Both GPT-3.5 and GPT-4 succeeded in ruling out abnormal CPET results. This tool could be utilized to differentiate between normal and abnormal results.

Zamodics M, Heart and Vascular Center, Faculty of Medicine, Semmelweis University, Budapest, Hungary
Babity M, Schay G, Leel-Ossy T, Bucsko-Varga A, Kulcsar P, Benko R, Boroncsok D, Fabian A, Ujvari , Ladanyi Z, Balla D, Vago H, Kovacs A, Hosszu E, Meszaros S, Horvath C, Merkely B, Kiss O:

Sports (Basel). 2025 Feb 10;13(2):51

AIMS
Body composition and cardiopulmonary exercise testing (CPET) are vital for optimizing sports performance, but the correlations between them are still underexplored. Our study aimed to investigate the relationships between body composition and specific CPET variables describing physical fitness in young athletes, also adjusting for age and height, in a less-studied, female population.
METHODS
Seventy players participated in our study (age: 16.10 ± 1.63 y). After determining body composition using dual-energy X-ray absorptiometry, we conducted treadmill-based maximal-intensity CPET. Data were analyzed in R using multivariate linear regression, accounting for age and height as confounders.
FINDINGS
Lean body mass (LBM), body fat mass (BFM), and bone mineral content (BMC) showed no effect on resting, maximum, or recovery heart rates and no correlation with resting or maximal lactate values. LBM positively correlated with maximum ventilation (VE-max) (Est: 1.3 × 10-3; SE: 6.1 × 10-4; p < 0.05) and maximum absolute oxygen consumption (VO2abs-max) (Est: 7.710-5; SE: 6.9 × 10-6; p < 0.001)-with age as an influencing factor for VE-max and height as an influencing factor for VO2abs-max. Conversely, BFM showed a negative correlation with maximum relative oxygen consumption (VO2rel-max) (Est: -4.8 × 10-4; SE: 1.2 × 10-4; p < 0.001). Moreover, BFM and BMC were also negatively correlated with maximal exercise duration (Est: -2.2 × 10-4; SE: 8.0 × 10-5; p < 0.01; Est: -3.2 × 10-3; SE: 1.4 × 10-3; p < 0.05) with height as an influencing factor.
CONCLUSION
Our findings indicate complex correlations between body composition and CPET parameters, providing important information for the analysis of individual ergospirometric data. Our results draw attention to the fact that body composition is more precise than weight and height in the evaluation of athletes’ physical fitness.

Tarras, Elizabeth S; Yale University School of Medicine, New Haven, CT 06511, USA.
Singh, Inderjit;Kreiger, Joan;Joseph, Phillip

Journal of clinical medicine,2025 Jan 26

ABSTRACT Pulmonary arterial hypertension (PAH) is a rare, progressive disease of the pulmonary vasculature that is associated with pulmonary vascular remodeling and right heart failure. While there have been recent advances both in understanding pathobiology and in diagnosis and therapeutic options, PAH remains a disease with significant delays in diagnosis and high morbidity and mortality. Information from invasive cardiopulmonary exercise testing (iCPET) presents an important opportunity to evaluate the dynamic interactions within and between the right heart circulatory system and the skeletal muscle during different loading conditions to enhance early diagnosis, phenotype disease subtypes, and personalize treatment in PAH given the shortcomings of contemporary diagnostic and therapeutic approaches. The purpose of this review is to present the current applications of iCPET in PAH and to discuss future applications of the testing methodology.

Markus, MRP; German Centre for Cardiovascular Research  University Medicine Greifswald,
Weiss, Frank-Ulrich;Hertel, Johannes;Weiss, Stefan;+14 more

Scientific reports,2025 Feb 12

ABSTRACT Sedentarism is characterized by low levels of physical activity, a risk factor for obesity and cardio-metabolic diseases. It can also adversely affect the composition and diversity of the gut microbiome which may result in harmful consequences for human health. While cardiorespiratory fitness (CRF) is inversely and independently associated with cardiovascular risk factors and diseases and all-cause mortality, the relationship between low CRF and the gut microbiome is not well known. A total of 3,616 individuals from two independent population-based cohorts of the Study of Health in Pomerania (SHIP-START and SHIP-TREND) performed standardized, symptom-limited cardiopulmonary exercise testing (CPET) and had faecal samples collected to determine gut microbiota profiles (16S rRNA gene sequencing). We analysed cross-sectional associations of CRF with the gut microbiome composition controlling for confounding factors. Lower CRF was associated with reduced microbial diversity, loss of beneficial short-chain fatty acid producing bacteria (i.e. Butyricoccus, Coprococcus, unclassified Ruminococcaceae or Lachnospiraceae) and an increase in opportunistic pathogens such as Escherichia/Shigella, or Citrobacter. Decreased cardiorespiratory performance was associated with a gut microbiota pattern that has been previously related to a proinflammatory state. These associations were independent of body weight or glycemic control.

Cifra B; Cordina RL; Gauthier N; Murphy LC; Pham TD; Veldtman GR; Ward K; White DA; Paridon SM; Powell AW 

Journal of the American Heart Association [J Am Heart Assoc] 2025 Feb 18; Vol. 14 (4), pp. e038200.
Date of Electronic Publication: 2025 Jan 09.

• Survivorship from congenital heart disease has improved rapidly secondary to advances in surgical and medical management. Because these patients are living longer, treatment and disease surveillance targets have shifted toward enhancing quality of life and functional status. Cardiopulmonary exercise testing is a valuable tool for assessing functional capacity, evaluating cardiac and pulmonary pathology, and providing guidance on prognosis and interventional recommendations. Despite the extensive evidence supporting the ability of cardiopulmonary exercise testing to quantitatively evaluate cardiovascular function, there remains confusion on how to properly interpret cardiopulmonary exercise testing in patients with congenital heart disease. The purpose of this statement is to provide a lifespan approach to the interpretation of cardiopulmonary exercise testing in patients with congenital heart disease. This is an updated report of the American Heart Association’s previous publications on exercise in children. This evidence-based update on the significance of cardiopulmonary exercise testing findings in pediatric, adolescent, and adult patients with various congenital cardiac pathologies and surgically modified physiology is formatted in a way to guide cardiopulmonary exercise testing interpretation practically for the clinicians and exercise physiologists who care for patients with congenital heart disease. Focus is placed on the indications for exercise testing, expected findings, and how exercise testing should guide the management of patients with various congenital heart disease subtypes. Areas for future intervention that could lead to improved care and outcomes for those with congenital heart disease are noted.

Comments

• Erratum in: J Am Heart Assoc. 2025 Feb 14:e10680. doi: 10.1161/JAHA.124.034848.. (PMID: 39950537)

Willixhofer, Robin;Ermolaev, Nikita;Kronberger, Christina;Eslami, Mahshid; et al

Circulation reports,2025 Jan 21

• Background: This study assessed the prognostic value of submaximal cardiopulmonary exercise testing (CPET) in cardiac amyloidosis and explored CPET as an alternative to the 6-min walk test (6MWT).
• Methods and Results: In this single-center prospective observational study, 160 patients with cardiac amyloidosis (87% male; mean age 78±7 years) were evaluated. A total of 145 performed maximum symptom limited CPET. The V̇E/V̇CO ₂ slope was 39±8, submaximal power output (SPO) was 24.75±11.50 W, and V̇O ₂ at anaerobic threshold (AT) was 8.13±2.29 mL/min/kg. During follow up, 34 (21.25%) patients died, and another 34 (21.25%) experienced heart failure (HF)-related hospitalization, with 15 (9.38%) patients experiencing both events. Univariate analysis showed that V̇E/V̇CO ₂ slope (hazard ratio [HR] 0.89; 95% confidence interval [CI] 0.86-0.93; P<0.001) and SPO (HR 0.91; 95% CI 0.87-0.96; P<0.001) were predictors of mortality. In multivariate analysis, V̇E/V̇CO ₂ slope remained a significant predictor (HR 0.92; 95% CI 0.88-0.97; P<0.001) for both all-cause mortality and HF-related hospitalization independently. A SPO cut-off of <28 W predicted a worse outcome for both measures independently. Moderate correlations for V̇E/V̇CO ₂ slope (-0.56 [CI -0.67, -0.42]) and SPO (0.55 [CI 0.42, 0.67]) with 6MWT distance have been found.
• Conclusions: These findings highlight CPET parameters, particularly V̇E/V̇CO ₂ slope and SPO with a cut-off <28 W, as predictors of survival and HF-related hospitalization in cardiac amyloidosis.
• Competing Interests: R.B.E. received a research grant from AstraZeneca Austria. R.W. and N.E. have been reimbursed by Pfizer Austria for attending several conferences.

Santana,  J; Stanford Cardiovascular Institute, Stanford University, Stanford, CA, USA.;
Kim, D; Christle, J, et al

European journal of preventive cardiology,2025 Feb 07

• Aims: Cardiorespiratory fitness (CRF), measured by peak oxygen uptake (VO2peak), is a strong predictor of mortality. Despite its widespread clinical use, current reference equations for VO2peak show distorted calibration in obese individuals. Using data from the Fitness Registry and the Importance of Exercise National Database (FRIEND), we sought to develop novel reference equations for VO2peak better calibrated for overweight/obese individuals – in both males and females, by considering body composition metrics.
• Methods: Graded treadmill tests from 6,836 apparently healthy individuals were considered in data analysis. We used the National Health and Nutrition Examination Survey equations to estimate lean body mass (eLBM) and body fat percentage (eBF). Multivariable regression was used to determine sex-specific equations for predicting VO2peak considering age terms, eLBM and eBF.
• Results: The resultant equations were expressed as VO2peak (male) = 2633.4 + 48.7✕eLBM (kg) – 63.6✕eBF (%) – 0.23✕Age2 (R2=0.44) and VO2peak (female) = 1174.9 + 49.4✕eLBM (kg) – 21.7✕eBF (%) – 0.158✕Age2 (R2=0.53). These equations were well-calibrated in subgroups based on sex, age and body mass index (BMI), in contrast to the Wasserman equation. In addition, residuals for the percent-predicted VO2peak (ppVO2) were stable over the predicted VO2peak range, with low CRF defined as < 70% ppVO2 and average CRF defined between 85-115%.
• Conclusions: The derived VO2peak reference equations provided physiologically explainable and were well-calibrated across the spectrum of age, sex and BMI. These equations will yield more accurate VO2peak evaluation, particularly in obese individuals.