Souza FR; Instituto do Coração do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP – Brasil.
Lopes RD; Fonseca GWPD; Barretto RBM; Val RMD; Kalil-Filho R; Alves MNN;

Arquivos brasileiros de cardiologia [Arq Bras Cardiol] 2025 Apr; Vol. 122 (5), pp. e20240838.

Background: A Brazilian athlete has proposed setting a new world record for consecutive marathons by running 366 marathons in 366 consecutive days. The impact of such a feat on the cardiovascular system is unknown.
Objective: To monitor the cardiovascular system to assess the athlete’s cardiovascular adaptations or maladaptations over the period.
Methods: During the pre-study evaluation, we conducted the pre-participation clinical evaluation (PPE) composed of anamnesis, electrocardiogram, blood test, and functional capacity by maximum cardiopulmonary exercise test (CPET). At follow-up, serial CPET, body composition assessment, blood sample, and echocardiogram were periodically performed for 12 months.
Results: At PPE, male, 43-year-old, height: 1.83 m, weight: 76.9 kg, maximum oxygen consumption (VO2max): 52 ml/kg/min, body fat: 12.6%, systolic and diastolic blood pressure: 120/80 mmHg, blood glucose: 92 mg/dL, total cholesterol (TC): 185 mg/dL, high-sensitivity C-reactive protein (hs-CRP): 0.08 mg/dL, creatine phosphokinase (CPK): 183 U/L, and high-sensitivity troponin T (hs-TnT): 7.1 ng/L. At follow-up, the average of VO2max remained at 48.7 ± 1.2 ml/kg/min, left ventricular ejection fraction (LVEF) at 62 ± 2%, LV strain global longitudinal at 19 ± 1%, LV mass index at 83 ± 7 g/m2, hs-CRP at 0.07 ± 0.01 mg/L, CPK at 169 ± 36 U/L, hs-TnT at 8.2 ± 1.4 ng/L, and no malignant arrhythmias were observed.
Conclusion: The athlete’s cardiovascular system had adapted to an extremely high volume of consecutive marathons at moderate intensity for one year and remained functioning at normal range. In addition, the athlete set a new world record for most consecutive days to run a marathon, recognized by Guinness World Records.

Choi HJ; Department of Pediatrics, Keimyung University Dongsan Hospital, Daegu, Korea.
Kim SJ; Lee DW; Gwon SH; Son NH; Cho MJ;Oh KJ;Lee JS;Na JY; Seol JH

Korean circulation journal [Korean Circ J] 2025 Apr 30.
Date of Electronic Publication: 2025 Apr 30.

Background and Objectives: As long-term survival after the Fontan operation has improved, exercise capacity has become a crucial determinant of prognosis. Various exercise rehabilitation programs involving different populations and protocols have been developed to improve these outcomes. This systematic review and meta-analysis compared the effects of exercise rehabilitation in patients with Fontan circulation according to age group and exercise method.
Methods: We searched the PubMed, Embase, and Cochrane Library databases for articles on exercise rehabilitation programs for patients who had undergone the Fontan procedure up to November 2023. After selection and eligibility assessment, 20 studies (5 randomized controlled trials [RCTs], 2 randomized trials, and 13 cohort studies) were included in the meta-analysis of peak oxygen consumption (VO₂) and minute ventilation equivalents for carbon dioxide production (VE/VCO₂ slope).
Results: Peak VO₂ was significantly better in groups with exercise training than in the control groups in 5 RCTs (standardized mean difference [SMD], 0.48; p=0.0017); it showed a notable increase in 20 studies before and after exercise training (SMD, 0.44; p=0.001). VE/VCO₂ showed no significant changes in the RCTs (SMD, 0.22; p=0.68) or before and after exercise training (SMD, -0.11; p=0.25). Subgroup analyses revealed significant improvements in peak VO₂ for aerobic exercise (SMD, 0.32; p=0.0136) and in groups that included children (SMD, 0.49; p=0.0013 in “children and adults” and SMD, 0.49; p 0.047 in “children” group).
Conclusions: Exercise training is effective for improving exercise capacity in patients after the Fontan procedure, particularly when initiated at a young age and implemented as an aerobic exercise.

Kleinhaus N; Joyce and Irving Goldman Medical School, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva 8410501, Israel.
Raviv Y;Ben Shitrit I;Wiesen J; Boehm Cohen L; Kassirer M; Bilenko N;

Journal of clinical medicine [J Clin Med] 2025 May 23; Vol. 14 (11).
Date of Electronic Publication: 2025 May 23.

Background: Cardiopulmonary exercise testing (CPET) is a valuable diagnostic and prognostic tool for assessing the integrated function of the cardiopulmonary and muscular systems during exercise. The initiation of a CPET program is complex, and data on early implementation in academic centers remain relatively limited.
Objective: to evaluate the initial integration of CPET within a pulmonary department, focusing on patient demographics, referral indications, test performance, and factors associated with anaerobic threshold achievement.
Methods: A retrospective cohort study was conducted at a single tertiary care center, including all patients who underwent their first CPET between February 2016 and December 2022. Demographic, clinical, and functional parameters were extracted. Multivariable logistic regression was used to identify variables associated with anaerobic threshold achievement, defined as a respiratory exchange ratio (RER) ≥ 1.1.
Results: The cohort included 434 patients (mean age 60.3 ± 14.1 years; 54% male; mean BMI 29.2 ± 5.6 kg/m ² ). The most common indication for testing was dyspnea (50%). Tests were most frequently terminated due to leg discomfort (39%) and dyspnea (38.8%). Achievement of RER ≥ 1.1 was independently associated with lower BMI (aOR = 0.91; 95% CI: 0.88-0.95; p < 0.001), higher FVC % predicted (aOR = 1.02; 95% CI: 1.00-1.03; p = 0.028), and greater minute ventilation volume (aOR = 1.02; 95% CI: 1.01-1.03; p < 0.001), and it was less likely in patients referred for cardiovascular disease (aOR = 0.37; 95% CI: 0.21-0.64; p < 0.001). No consistent temporal trend in RER achievement was observed across the study period.
Conclusions: CPET was most commonly utilized in response to patient-reported dyspnea, with test termination frequently driven by subjective symptoms rather than objective clinical criteria. Anaerobic threshold achievement was more strongly associated with individual physiological characteristics than with institutional experience. These findings underscore the importance of patient preparation and pulmonary functional capacity in optimizing CPET performance.

Santek N; Department of Rheumatology, Physical Medicine and Rehabilitation, University of Zagreb, 10000 Zagreb, Croatia.
Langer S; Kirac I; Velemir Vrdoljak D; Tometic G; Musteric G; Mayer L; Cigrovski Berkovic M;

Cancers [Cancers (Basel)] 2025 May 26; Vol. 17 (11).
Date of Electronic Publication: 2025 May 26.

Background/Objectives: Colorectal cancer is a significant health problem worldwide. Surgery is the primary curative treatment for most colorectal cancers. Cardiopulmonary exercise testing is now performed widely before surgery, and it is the most objective and precise means of evaluating pre-surgical physical fitness. Also, we can use the 6 min walk test to measure cardiorespiratory fitness before surgery.
Methods: We included colorectal patients who were awaiting open abdominal or laparoscopic surgery. After admission to the hospital, patients who signed informed consent forms fulfilled a short questionnaire about health and physical status, preoperative physical activities, and quality of life questionnaire (EORTC QLQ-C30). Patients performed a 6 min walk test (6MWT) 2 days before surgery and 7 days after surgery. 6MWT is a tool for measuring the functional status of fitness. Also, they fulfilled the quality of recovery questionnaire (QoR 15) 7 days after surgery.
Results: In a final analysis, we included 72 patients with a mean age of 62.48. We compared the number of steps, walk distance, average and maximal walk speed, and average and maximal heart rate before and after surgery, overall, and by group. Our findings show a statistically significant difference between men and women in the walk distance ( F = 4.99, p = 0.02) The number of steps showed a statistically significant difference according to patients’ ages ( F = 2.90, p = 0.02). Also, we detected differences in the average and maximum heart rate during walking when comparing body mass index (average heart rate F = 5.72, p = 0.00, maximum heart rate F = 2.52, p = 0.04).
Conclusions: Our study provides evidence that average and maximal heart rate during the 6 min walk test was higher in the postoperative period, especially in overweight and obese participants.

Lee S; Cardiology Division, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA;
Houstis NE; Cunningham TF; Brooks LC; Chen K; Slocum CL; Ostrom K; Birchenough C; Moore E;  Tattersfield H; Sigurslid H; Guo Y; Landsteiner I;
Rouvina JN; Lewis GD; Malhotra R;

JACC. Heart failure [JACC Heart Fail] 2025 Jun 10; Vol. 13 (8), pp. 102478.
Date of Electronic Publication: 2025 Jun 10.

Background: Iron is a critical factor in cardiac function, oxygen carrying capacity in the blood, and mitochondrial function in skeletal muscle, all of which are key elements of oxygen uptake and utilization during exercise. However, the impact of iron status on hemodynamic responses to exercise and component variables of peak oxygen consumption in patients with heart failure with preserved ejection fraction (HFpEF) is unknown.
Objectives: The authors sought to determine the relationship between markers of iron status and comprehensive exercise response patterns and clinical outcomes in patients with HFpEF.
Methods: Cardiopulmonary exercise testing using cycle ergometry with invasive hemodynamic assessment was performed in 372 patients with HFpEF. Serum iron, transferrin saturation (Tsat), hepcidin, and ferritin were measured at the time of cardiopulmonary exercise testing, and additionally the Tsat/hepcidin ratio was used as a measure of iron homeostasis and hepcidin dysregulation, with low values reflecting inappropriate elevation in hepcidin level relative to iron bioavailability.
Results: In this cohort, 66% had iron deficiency defined as ferritin <100 μg/L or ferritin 100-300 μg/L with Tsat <20%. Higher peak oxygen consumption was associated with higher Tsat% (ρ = 0.33; P < 0.0001), Tsat/hepcidin ratio (ρ = 0.23; P < 0.0001), and serum iron (ρ = 0.30; P < 0.0001) but was not associated with ferritin level. After adjustment for age, hypertension, diuretic use, hemoglobin level, and cardiac index at rest, the association between higher peak oxygen consumption with higher Tsat, Tsat/hepcidin, and iron remained significant (P ≤ 0.006 for all). Tsat, Tsat/hepcidin, and iron were also associated with lower pulmonary artery pressure/cardiac output slope and pulmonary capillary wedge pressure/cardiac output slope, whereas ferritin did not correlate with these exercise hemodynamic measures. Finally, Tsat independently predicted heart failure-free survival, with every higher tertile of Tsat corresponding to an HR of 0.60 (P = 0.002), whereas ferritin was not associated with outcomes.
Conclusions: In patients with HFpEF, Tsat%, but not ferritin levels, relates to more favorable overall metabolic and hemodynamic responses to exercise and better outcomes.
Competing Interests: Funding Support and Author Disclosures Support for this work was provided by the National Heart, Lung, and Blood Institute, including R01HL159514 (to Drs Lewis and Malhotra), R01HL131029 (to Dr Lewis), and R01HL151841 (to Dr Lewis). Drs Lewis and Malhotra have served as consultants for Pharmacosmos. Dr Lewis has served on the scientific advisory board for American Regent.

Weigelt A; Department of Pediatric Cardiology, University Hospital Erlangen,  Germany.
Akhundova G; Raming R; Tratzky JP; Regensburger AP; Kraus C; Waellisch W; Trollmann R; Woelfle J;Dittrich S; Heiss R; Knieling F; Schoeffl I;

European journal of pediatrics [Eur J Pediatr] 2025 Jun 10; Vol. 184 (7), pp. 413.
Date of Electronic Publication: 2025 Jun 10.

Few studies have examined post-COVID-19 sequelae in children, particularly regarding cardiopulmonary capacity. Longitudinal data are especially scarce. This study aimed to retest pediatric patients previously assessed in a cross-sectional design. In this longitudinal study, children meeting post-COVID-19 criteria and an age- and sex-matched control group underwent cardiopulmonary exercise testing at baseline and after 6 months. Thirteen of 20 post-COVID-19 children (mean age: 13.6 ± 2.6 years, 48% female) and 23 of 28 controls (mean age: 11.9 ± 3.1 years, 62% female) completed follow-up testing. All participants completed a maximal treadmill test. No significant differences were found in peak oxygen uptake ( INLINEMATH 39.5 ± 11.0 ml/kg/min vs. 45.5 ± 8.4 ml/kg/min; p = 0.101). Over 6 months, cardiopulmonary performance improved significantly across all subjects. Subgroup analysis showed improvements in both groups, although changes were not statistically significant. Oxygen pulse also proved to be significantly higher and the half-time recovery of INLINEMATH proved to be significantly longer after 6 months which was true for the overall group but not for the subgroups.
Conclusion: This is the first longitudinal study to reassess cardiopulmonary capacity in children with post-COVID-19. The initially reduced INLINEMATH normalized, and all children showed improved cardiopulmonary capacity after 6 months. The primary improvement was observed in the O ₂ pulse, a surrogate marker of stroke volume and, by extension, cardiac output. This finding suggests an enhancement in cardiovascular performance, reflecting improved central hemodynamic in all children 6 months after the pandemic. Deconditioning thus remains a plausible cause for the post-COVID-19 symptoms.
Trail Registration: ClinicalTrials.gov Identifier: NCT05445531.
What Is Known: • Children with post-COVID-19 (PASC) may exhibit reduced cardiopulmonary function (V̇O2 peak). Fatigue and exercise intolerance are common but poorly understood and objectified. • Previous studies have provided valuable cross-sectional insights but have yet to include longitudinal follow-up data.
What Is New: • First longitudinal CPET-based study reassessing children with PASC after 6 months. • Cardiopulmonary performance, including V̇O2 peak and O2 pulse, improved significantly over time, probably due to reversible deconditioning rather than organ damage.

Ferguson ON; Centre for Heart Lung Innovation, The University of British Columbia (UBC) and St. Paul’s Hospital (SPH), Vancouver, British Columbia, Canada; Jensen D; Guenette JA; Lewthwaite H;

Respiratory physiology & neurobiology [Respir Physiol Neurobiol] 2025 Jun 11; Vol. 336, pp. 104456.
Date of Electronic Publication: 2025 Jun 11.

Dyspnea, or breathlessness, is a complex, multidimensional symptom of breathing discomfort, which significantly impacts quality of life and clinical prognosis. While traditional assessments have primarily focused on breathlessness sensory intensity, this approach does not consider affective and/or qualitative dimensions. Growing evidence highlights the need for multidimensional assessment approaches that provide a more comprehensive understanding of breathlessness, particularly in the context of exercise. Cardiopulmonary exercise testing (CPET) provides a standardized physiological stimulus to assess breathlessness responses in real-time, offering valuable insights into its underlying mechanisms and response to therapeutic intervention. Normative reference equations can help identify abnormally high breathlessness intensity during CPET. This review examines current methodologies for multidimensional breathlessness assessment during exercise, including single-item rating scales, multidimensional tools, descriptor lists, and locus of symptom limitation. We also discuss best practices for linking breathlessness with physiological responses during CPET to enhance mechanistic understanding, inform targeted interventions, and evaluate interventional efficacy. Standardizing assessment approaches and ensuring transparent reporting are critical steps toward improving the clinical and research utility of exertional breathlessness assessments.

Kennouche D; Université Jean Monnet Saint-Etienne, Lyon 1, Saint-Etienne, FRANCE.
Foschia C; Brownstein CG; Gondin J; Lapole T; Rimaud D; Royer N; Thiery G;  Gauthier V; Giraux P; Oujamaa L; Sorg M; Vergès S; Doutreleau S; Marillier M; Prudent M; Bitker L; SFéasson L; Gergelé L; Stauffer E; Guichon C;

Medicine and science in sports and exercise [Med Sci Sports Exerc] 2025 Jun 13.
Date of Electronic Publication: 2025 Jun 13.

Purpose: Although most patients recover well from Covid-19 infection, this may not be the case of those who experienced severe dysfunction after being admitted to intensive care unit (ICU). This study aimed to assess the recovery of patients who experienced severe multiple dysfunctions after being admitted to intensive care unit (ICU) for Covid-19 infection.
Methods: Forty-seven patients hospitalized and mechanically ventilated in ICU for SARS-CoV-2 infection underwent evaluations at 4-8 weeks (T1) and 6 months (T2) post ICU discharge. Evaluations included questionnaires, lung function tests, incremental cardiopulmonary exercise testing, and neuromuscular function tests.
Results: From T1 to T2, the percentage of patients classified as fatigued decreased from 56% to 21% whereas forced vital capacity and the forced expiratory volume in one second increased by 13% and 8% (p < 0.05) to reach 93% and 95% of predicted values at T2, respectively. Peak work rate also increased from 97 to 135 W (+35 ± 32%, p < 0.001). Likewise, V̇O2peak increased from 18.3 to 21.6 ml/min/kg (+18 ± 27%, p < 0.001) to reach 72% of predicted values. Maximal strength and the number of contractions during the fatigability test increased between T1 and T2 by 41% and 39%, respectively (both p < 0.001).
Conclusions: Six months of recovery improved patients’ physical function and reduced fatigue.

Doi S; Department of Cardiovascular Disease, Mayo Clinic, Rochester, MN, USA.
Tada A; Harada T; Naser JA; Ibe T; Smith JR; Reddy YNV;

European journal of heart failure [Eur J Heart Fail] 2025 Jun 18.
Date of Electronic Publication: 2025 Jun 18.

Aims: Oxygen consumption at peak exercise is widely used to assess functional impairment in heart failure with preserved ejection fraction (HFpEF), but few patients exercise to this intensity in daily living. Alternative metrics that quantify submaximal fitness may provide more patient-centred evaluations, but the pathophysiology of submaximal exercise intolerance in HFpEF is unexplored.
Methods and Results: Patients with HFpEF underwent invasive haemodynamic cardiopulmonary exercise testing with blood lactate measurement during exercise to volitional fatigue. Lactate threshold (LT) was defined as the exercise workload at which arterial lactate exceeded >2.0 mmol/L, taken as a measure of submaximal fitness. Of patients with HFpEF (n = 286), 194 (68%) reached LT at a workload of 40 W or less (LT ≤40 W), while 92 (32%) reached a workload exceeding 40 W at LT (LT >40 W). As compared to LT >40 W, patients with LT ≤40 W were more likely to be female, anaemic, and had greater pulmonary vascular disease (all p < 0.01). During 20 W exercise, participants with LT ≤40 W had higher pulmonary artery pressure, biventricular filling pressures, minute ventilation and respiratory drive, higher perceived dyspnoea and fatigue ratings, greater arterial-venous oxygen content difference, despite similar cardiac output and oxygen delivery. At peak exercise, most of these differences were no longer apparent. Findings were replicated using non-invasively-measured workload at ventilatory threshold.
Conclusions: Two-thirds of patients with HFpEF reach LT at workloads typical of activities of daily living. Patients with HFpEF and impaired submaximal fitness are more likely to be female, have greater pulmonary vascular disease and anaemia severity, and display greater haemodynamic, symptomatic, and ventilatory control abnormalities during low-level exercise, which are not apparent at maximal exertion. These findings have therapeutic implications and suggest a potentially important role for wider evaluation of submaximal fitness in addition to peak aerobic capacity.