Wogksch MD; Department of Epidemiology and Cancer Control, St. Jude Children’s Research Hospital, Memphis, TN.
Ware ME; O’Neil ST; Nolan VG;Smeltzer MP; Mzayek F; Mulrooney DA; Ehrhardt MJ; Dixon SB; Rhea IB; Srivastava DK; Armstrong GT; Hudson MM;
Ness KK;

Medicine and science in sports and exercise [Med Sci Sports Exerc] 2025 Jul 01.
Date of Electronic Publication: 2025 Jul 01.

Purpose: Childhood cancer survivors are at increased risk of premature cardiovascular events compared to peers. Increased cardiopulmonary fitness reduces the risk of cardiovascular morbidity/mortality within the general population but are poorly described in cancer survivors. We examined the associations between fitness and cardiovascular events in childhood cancer survivors.
Methods: Participants (n = 2,433) completed a baseline, cardiopulmonary exercise test (CPET) to assess peak maximal oxygen consumption (VO2peak). Metabolic equivalents (METs) were calculated by dividing VO2peak by 3.5 ml·kg1·min and peak METs achieved on CPET was used to document cardiopulmonary fitness. Additionally, we categorized participants (based on age- and sex-matched controls) as low (<50th percentile ofachieved METs) and normal ( ≥50th percentile). Subsequent cardiovascular disease was graded with the Common Terminology Criteria for Adverse Events v. 4.03. Associations between peak METs and subsequent cardiovascular disease in survivors were evaluated with multivariable Cox-proportional hazard regression, adjusted for cancer treatment, lifestyle, baseline cardiovascular disease, and cardiovascular risk factors. Additionally, a univariate analysis was conducted to examine the peak METs achieved on the CPET in survivors who died from a cardiovascular event and those who did not.
Results: Each 1 MET increase on the survivor’s CPET performance decreased the risk of incident cardiovascular disease (Hazard Ratio [HR] 0.80, 95% Confidence interval [CI] 0.72, 0.90). Among survivors with low baseline cardiopulmonary fitness, those who achieved 1 MET higher value on their CPET had lower risk of incident cardiovascular disease (HR:0.78, 95% CI 0.65, 0.96). The average peak METs achieved was lower (5.9 ± 2.17) among survivors who died from cardiovascular disease compared to those who did not (7.6 ± 2.5).
Conclusions: Higher cardiopulmonary fitness was associated with lower risk for incident cardiovascular disease. Early identification of survivors with low cardiopulmonary fitness provides opportunities for risk mitigation through promotion of regular physical activity.
Competing Interests: Conflict of Interest and Funding Source: Support to St. Jude Children’s Research Hospital provided by the National Cancer Institute (U01 CA195547, K. Ness and M. Hudson, Principal Investigators; R01 CA157838, G. Armstrong, Principal Investigator), the Cancer Center Support (CORE) grant (P30 CA21765, C. Roberts, Principal Investigator), and the American Lebanese-Syrian Associated Charities (ALSAC).

Mali RMA; Department of Medicine – Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, the Netherlands.
Ninaber MK; van Mens TE; Konstantinides SV; Klok FA;

European heart journal. Quality of care & clinical outcomes [Eur Heart J Qual Care Clin Outcomes] 2025 Jul 01.
Date of Electronic Publication: 2025 Jul 01.

Background: A considerable proportion of patients develop long-term sequelae after an acute pulmonary embolism (PE). Beyond chronic thrombo-embolic pulmonary hypertension (CTEPH), current guidelines provide limited guidance regarding a structured approach for assessment and management of these patients.
Objectives: To establish a framework of multidisciplinary follow-up care of PE-survivors.
Methods: A Delphi study was conducted among a multidisciplinary panel of PE specialists from across Europe to gather expert opinions, and where possible reach consensus, on key aspects of PE follow-up care.
Results: Two rounds of surveys were distributed among 45 venous thromboembolism (VTE) experts, with 39 completing both rounds. Consensus was reached that follow-up of PE survivors should address the entire spectrum of post-PE sequelae, i.e., CTEPH, chronic thromboembolic pulmonary disease, but also all other presentations of the post-PE syndrome. Routine assessment at three months should involve patient-reported outcome measures, including quality of life. A single, uniform protocol was preferred over locally adapted approaches. Earlier follow-up, prior to the three-month mark, to detect post-PE sequelae was not considered necessary for most patient subgroups. Right heart catheterization to confirm CTEPH should be reserved for specialized pulmonary hypertension centers, while other diagnostic modalities such as computed tomography, V/Q scan, cardiopulmonary exercise testing and transthoracic echocardiography can be performed in non-referral centers.
Conclusion: This Delphi study among a panel of VTE experts across Europe describes a consensus-based framework for structured follow-up care for PE-survivors, emphasizing the need for a standardized, multidisciplinary approach to detecting long-term sequelae of PE.

Driessens H;Division of Hepato-Pancreato-Biliary Surgery and Liver Transplantation,  University of Groningen, Groningen, the Netherlands.
Hoeijmakers LSM; Zwerver ODJ; Wijma AG; Hildebrand ND; Queisen RRYC; Kuikhoven M; den Dulk M; Olde Damink SWM;Klaase JM; Bongers BC;

Journal of clinical anesthesia [J Clin Anesth] 2025 Jul 04; Vol. 106, pp. 111916.
Date of Electronic Publication: 2025 Jul 04.

Background: The widespread implementation of a preoperative assessment of aerobic capacity requires a practical field test. This study investigated the validity of the modified steep ramp test (SRT) for evaluating preoperative aerobic capacity and to evaluate its usefulness for preoperative risk assessment in patients planned for pancreatic surgery.
Methods: Patients scheduled for pancreatic surgery who preoperatively performed cardiopulmonary exercise testing (CPET) and the modified SRT within 14 days were included. To assess its criterion validity, the correlation between the achieved work rate at peak exercise (WR _peak ) at the modified SRT and oxygen uptake (VO ₂ ) at peak exercise (VO _2peak ) during CPET was determined. To evaluate the ability of the modified SRT to correctly classify patients as fit or unfit, receiver operating characteristic (ROC) analyses were performed based on the CPET VO _2peak cutoff 18.0 ml.kg ^-1 .min ^-1 and VO ₂ at the ventilatory anaerobic threshold (VAT) cutoff 11.0 ml.kg ^-1 .min ^-1 .
Results: Forty-eight patients (21 females) aged 68.7 ± 7.6 years were included. Modified SRT WR _peak (W/kg) demonstrated a very strong correlation with CPET VO _2peak (ρ = 0.865, r = 0.926). The modified SRT WR _peak cutoff to most accurately classify patients as fit or unfit was 2.095 W/kg for the CPET VO _2peak cutoff (area under the curve (AUC) of 0.948) and the CPET VO ₂ at the VAT cutoff (AUC of 0.814).
Conclusions: The modified SRT is a valid short-term practical exercise test to preoperatively assess aerobic capacity in patients undergoing pancreatic surgery. A modified SRT performance below 2.1 W/kg seems clinically most suitable to select candidates for further preoperative CPET evaluation and/or prehabilitation, given its positive and negative predictive value.

Anderson-Bell DM; Department of Internal Medicine, University of Utah, Salt Lake City, UT, USA.
Hardison EH; Rashid M; Hammond BH; Hegewald M;Rapp TE; Ploutz M; Williams RV;Ziebell D; Chaiyakunapruk N;

Pediatric cardiology [Pediatr Cardiol] 2025 Jul 05.
Date of Electronic Publication: 2025 Jul 05.

Cardiopulmonary exercise testing (CPET) is a useful metric to track the functional capacity and prognosis in patients with Fontan circulation. Systemic ventricular morphology may influence CPET interpretation. This systematic review and meta-analysis assessed the impact of systemic ventricular morphology on CPET outcomes. PubMed, Embase, and Cochrane were searched from inception through December 2024. Inclusion criteria were (1) Fontan circulation, (2) CPET via treadmill or cycle ergometer, and (3) outcomes stratified by systemic ventricle. Extracted outcomes included peak VO ₂ , O ₂ -pulse, VE/VCO ₂ slope, and VO ₂ at anaerobic threshold (VAT). A random-effects model was used with pooled estimates reported as a mean difference (MD) or standardized mean difference (SMD). Risk of Bias (RoB) was assessed using the Newcastle-Ottawa Scale. Of 1372 screened studies, 27 met inclusion criteria (59% retrospective cohort, 30% cross-sectional, 7% randomized control trials, and 4% quasi-experimental design) encompassing 2972 participants. All studies but one had low RoB with the remainder having some RoB. Patients with a systemic left ventricle (SLV) outperformed those with a systemic right ventricle (SRV) in all metrics including a higher peak VO ₂ (MD 6.73% predicted; p < 0.01, 95% CI 4.52, 8.95), greater O ₂ -pulse (0.19 SMD; p = 0.04, 95% CI 0.01, 0.38), greater VAT (0.16 SMD; p = 0.01, 95% CI 0.03, 0.28), and lower VE/VCO ₂ slope (MD – 2.44; p = 0.01, 95% CI – 4.41, – 0.48). These findings suggest superior exercise performance in Fontan patients with a SLV and should inform CPET interpretation. Further prospective studies are warranted to assess their impact on outcomes such as transplant timing or mortality.

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.