Turquetto ALR; Instituto do Coração do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP, Brazil.
Amato LP; Thorup L; Kelly B; Hjortdal VE; de Souza FR;Canêo LF; Machado DS; Filho ACB; Ligeiro MG; Mohanakumar S; Rondon E; Binotto MA; Jatene MB; Jatene FB;

International journal of cardiology [Int J Cardiol] 2025 Jun 05, pp. 133480.
Date of Electronic Publication: 2025 Jun 05.

Introduction: Survival rates for post-Fontan patients have improved, allowing many to reach adulthood with better quality of life (QOL). However, they remain at risk for reduced functional capacity (FC), skeletal muscle loss, and lymphatic dysfunction, which negatively affect clinical outcomes. This study evaluated the feasibility of an online rehabilitation program for adult Fontan patients in the late postoperative period and its effects on FC, peripheral lymphatic function (PLF), and QOL.
Methods: This prospective, non-randomized, controlled clinical trial evaluated the impact of a fitness center’s 36-session online aerobic and resistance training program. Participants were divided into a control group (CG), continuing usual activities, and an exercise group (EG). Outcomes included QOL (Short Form-36 questionnaire: SF-36), FC via cardiopulmonary exercise testing (CPET), and PLF assessed using near-infrared fluorescence imaging and venous occlusion plethysmography.
Results: A total of 26 participants (13 EG,13 CG), with a median age of 30 (25-35) years, and follow-up time after Fontan of 19 (15-21) years, were enrolled. The EG showed significant improvements in peak VO2 (ml/kg/min), predicted peak VO2 (%), peak ventilation (L/min), and oxygen pulse (mL/beat), indicating enhanced cardiovascular efficiency. Additionally, 62 % of SF-36 domains improved in the EG, while no changes were observed in the CG. However, the program did not produce significant modifications in PLF.
Conclusions: The proposed online rehabilitation program proved to be feasible and effectively improved FC and quality of life in adults after Fontan surgery; however, this training model did not significantly influence peripheral lymphatic function.

Dudek M; 1 st Department of Cardiology, Poznan University of Medical Sciences, Poznan, Poland.
Górecki M; Marszałek S; Kufel-Grabowska J; Litwiniuk M; et al

European journal of applied physiology [Eur J Appl Physiol] 2025 Jun 05.
Date of Electronic Publication: 2025 Jun 05.

Purpose: Younger women are diagnosed more often with aggressive breast cancer (BC) subtypes, the treatment of which usually incorporates chemotherapy. Physical training plays a significant role in mitigating the adverse effects of systemic cancer therapy, improving quality of life, and potentially enhancing treatment efficacy. High-intensity interval training (HIIT) emerged as a promising intervention to counteract the fatigue induced by chemotherapy, which in younger women often causes depression and disruption of employment. This study aimed to investigate whether supervised HIIT employed concurrently with chemotherapy impacts the cardiorespiratory fitness of young BC patients.
Methods: Twenty-six young (18-40 years old) BC patients scheduled for chemotherapy were randomised to intervention comprising supervised HIIT employed concurrently with chemotherapy or no supervised training (control) for 6 months. Outcomes measured using cardiopulmonary exercise testing (CPET) and non-invasive cardiac output testing were cardiorespiratory fitness and cardiac output.
Results: Compared to control, employment of HIIT mitigated the decrease in relative peakVO ₂ from 33.630 to 29.540 ml/kg/min for HIIT group and from 29.679 to 22.571 ml/kg/min for control group (ANCOVA p = 0.018, ES = 0.469), and also a mitigated the decrease in exercise time from 685.600 to 666.500 s for HIIT group and from 703.357 to 555.500 s for control group (ANCOVA p = 0.008, ES = 0.815) measured during CPET.
Conclusions: Supervised HIIT implemented alongside chemotherapy can mitigate the decline in cardiorespiratory fitness caused by BC chemotherapy in young patients.

Carr ZJ; Yale University, School of Medicine, New Haven, CT, USA.; Department of Anesthesiology, Yale New Haven Hospital, New Haven, CT, USA.
Charchaflieh J; Brenes-Bastos A; He H;  Lin HM; Jankelovits A; Gu E; Zafar J; Ghali F; Tan WS; Heerdt P;

BJA open [BJA Open] 2025 Apr 24; Vol. 14, pp. 100407.
Date of Electronic Publication: 2025 Apr 24 (Print Publication: 2025).

Background: Early postoperative complication risk prediction would enhance perioperative surveillance and resource allocation. Reports have described brief submaximal cardiopulmonary exercise testing (CPET) for the routine assessment of cardiopulmonary disease. Compared with conventional CPET, it can be performed in 6 min and is used to predict peak CPET measurements. We aimed to determine whether submaximal CPET-derived measures outperform structured surveys in early postoperative complication detection.
Methods: An institutional review board-approved, single-centre, open-label, clinical device trial was conducted. A total of 101 participants undergoing noncardiac surgery, aged >60 yr, with revised cardiac risk index ≤2, self-reported metabolic equivalents >4 (METs in ml O ₂ kg ^-1 min ^-1 ; self-endorsed reliably climbing two flights of stairs), were enrolled. Participants completed a subjective METs assessment, Duke Activity Status Index, and submaximal CPET that derived peak oxygen uptake (VO ₂ , ml O ₂ kg ^-1 min ^-1 ), METs, and gas exchange-derived pulmonary capacitance (GXCAP, in ml O ₂ beat ^-1 kPa ^-1 ). Elastic net regularisation machine learning identified feature importance among study measures for the primary endpoint (Postoperative Morbidity Survey [POMS] ≥1), secondary endpoints (cardiac, pulmonary and renal domains of the POMS [POMS-CPR ≥1]), and length of stay. Adjusted multivariable regression models were used to identify significance.
Results: Of 101 participants, 53 (52.4%) had POMS ≥1. GXCAP to peak VO ₂ slope (GXCAP-VO ₂ ) was associated with POMS ≥1 (OR _adj 0.94; 95% CI 0.89-0.99; P =0.011) and increasing length of stay (OR _adj 0.98; 95% CI 0.96-0.99; P =0.01). GXCAP-VO ₂ slope (OR _adj 0.93; 95% CI 0.88-0.99; P =0.015) was associated with POMS-CPR ≥1.
Conclusions: Compared with structured surveys (subjective METs or Duke Activity Status Index) or conventional peak CPET values (VO ₂ or METs), a novel measure, GXCAP-VO ₂ slope, offered superior early postoperative complication discrimination in low-morbidity subjects. These preliminary findings support GXCAP-VO ₂ slope as a compelling investigational target for early postoperative complication risk, supporting the use of CPET to enhance early postoperative complication prediction.
Competing Interests: ZJC declares partial research funding from Shape Medical Systems, Inc (MN, USA). PMH declares consulting for Cardiage LLC and Baudax Bio, consulting and sponsored research for Edwards Lifesciences, and equity interest in emka Medical.

Pagliaro A; Division of Cardiology, Department of Medical Biotechnologies, University of Siena, 53100 Siena, Italy.
Cavigli L; Molle R; Iardino E; Anselmi F; Righini F; Martini L; Zacà V; Mandoli GE; Pastore MC; Focardi M; Cameli MBernazzali S; Maccherini M; Chiostri M; D’Ascenzi F; Valente S;

Journal of cardiovascular development and disease [J Cardiovasc Dev Dis] 2025 May 02; Vol. 12 (5).
Date of Electronic Publication: 2025 May 02.

Background Accurate prognostic stratification in patients with chronic heart failure and reduced ejection fraction (HFrEF) remains a significant clinical challenge. Many different parameters, including left ventricular (LV) and right ventricular (RV) function and cardiopulmonary exercise testing (CPET) parameters, are available in the literature. LV ejection fraction (LVEF) is the most used parameter in clinical practice.
Aims This study aimed to analyze CPET and echocardiographic data in patients under evaluation for heart transplantation (HTx) to identify the parameter that best correlates with cardiac events.
Methods and Results. Echocardiography and CPET were performed in patients with HFrEF under evaluation for HTx. The population comprised 170 patients (mean age: 55 ± 9 years; 88% male; non-ischemic etiology: 63%). LVEF was 30.4 ± 7.6%, peak oxygen uptake (Vo _2peak ) was 17.08 ± 4.6 mL/Kg/min; minute ventilation (VE)/carbon dioxide production (Vco ₂ ) slope was 34.8 ± 8.7. During a follow-up of 4 ± 1 years, 37 hospitalizations, 4 deaths, 14 HTx, and 5 LV assist device implantation occurred. Patients who experienced major events had a lower Vo _2peak ( p < 0.005), higher VE/Vco ₂ slope ( p < 0.005), greater LV end-systolic diameter ( p < 0.005), and RV end-diastolic diameter ( p < 0.005) than patients without events. Conversely, LVEF did not differ between these two groups. VE/Vco ₂ slope and RV dimensions significantly correlated with hard cardiac events ( p = 0.019 and p = 0.008, respectively).
Conclusions. In patients with HFrEF, parameters quantifying the system reserve (i.e., Vo _2peak and VE/Vco ₂ slope) and those demonstrating advanced biventricular remodeling may help stratify the risk of cardiac events. Conversely, LVEF showed a limited prognostic value in this setting.

Wernhart S; Department for Preventive Sports Medicine and Sports Cardiology, Munich, Germany.
Fiorentini C; Glowka S; Madl B;Grill S; Kiechle M;Mueller S; Schmid V; Foulkes S; Haykowsky MJ; Halle M;

International journal of cardiology [Int J Cardiol] 2025 May 25; Vol. 436, pp. 133421.
Date of Electronic Publication: 2025 May 25.

Background: Breast cancer survivors (BCS) have an increased risk of developing cardiovascular disease risk factors (CVDRF). However, the role of cardiopulmonary fitness, echocardiography and treatment regimen e.g. anthracycline, HER2-targeted therapy (AC/H) or endocrine therapy (ET) are uncertain.
Methods: This single-center, retrospective study included BCS without visceral metastases, who had been treated with either AC/H or ET and assessed by echocardiography, cardio-pulmonary exercise testing (CPET) and the H ₂ FPEF score at baseline. We included BCS with a left ventricular ejection fraction ≥50 % and absence of CVDRF at baseline. The primary outcome was the incidence of CVDRF.
Results: A total of 112 BCS were included (mean age of 54.6 ± 9.9 years, BC stage I-III). After a median follow-up of 21 months new-onset arterial hypertension was the most common CVDRF observed (n = 17). New onset hypertension was related to higher baseline resting systolic blood pressure (127.4 ± 9.2 mmHg vs. 117.3 ± 13.1 mmHg, p = 0.002) and H ₂ FPEF scores (1.2 ± 0.8 vs. 0.8 ± 1.1, p = 0.043). Echocardiographic and CPET findings associated with new-onset arterial hypertension included greater left ventricular mass index (77.3 ± 24.2 g/m ² vs. 65.6 ± 15.5 g/m ² , p = 0.007), higher peak systolic blood pressure (193.1 ± 19.5 mmHg vs. 173.3 ± 21.2 mmHg, p = 0.017) and ventilatory power (6.4 ± 1.3 mmHg vs. 5.7 ± 1.2 mmHg, p = 0.022). Treatment regimen had no influence on the development of CVDRF.
Conclusions: The most common CVDRF among BCS is hypertension, underscoring the importance of monitoring this outcome irrespective of breast cancer treatment regimens. The H ₂ FPEF score, CPET and echocardiography may help identify BCS at risk of developing hypertension. Strain and biomarkers were not available, impeding detection of cardiotoxicity.
Competing Interests: Declaration of competing interest Simon Wernhart has received honoraria for lectures from Bristol-Myers Squibb. Stephan Mueller has received personal fees from Bristol-Myers Squibb (consulting services). Mark Haykowsky is funded, in part, by a Research Chair in Aging in the Faculty of Nursing, College of Healthy Sciences at UofA. Martin Halle reports honoraria for lectures beyond this cancer topic from Abbott, Amgen, Astra-Zeneca, Boehringer-Ingelheim, BMW, Bristol-Myers Squibb, Daiichi-Sankyo, Lilly, Medi, MSD Sharp & Dohme GmbH, Norsan, Novartis, Pfizer and Roche, consulting fees from Medical Park. Sabine Grill has received honoraria for lectures from AstraZeneca, Roche, Pfizer and Daiichi Sankyo. No other potential conflicts of interest are reported.

Afoke J; Imperial College Healthcare, Hammersmith Hospital, London, UK.; Imperial College, London, UK.
Gibbs S; Kanaganayagam S; Bruno D; Howard L; Punjabi P;

Perfusion [Perfusion] 2025 May 27, pp. 2676591251346035.
Date of Electronic Publication: 2025 May 27.

Aims Describe differences in changes in cardiopulmonary exercise testing after surgery for severe primary mitral regurgitation between class I and class II indications for surgery.
Methods Prospective observational study of patients who underwent transthoracic echocardiogram and cardiopulmonary exercise testing pre-operatively and six months after surgery.
Results Forty three of the fifty patients recruited between February 2017 and October 2018 were included in per protocol analysis. Seven patients were excluded-two patients did not meet inclusion criteria after further investigation, two patients were unable to perform pre-operative cardiopulmonary exercise testing, two patients had post-operative mortality, one patient declined post-operative cardiopulmonary exercise testing. Median age was 64 years and 15 patients (34.9%) were female. Thirty five patients had impaired post-operative functional capacity defined as post-operative left ventricular ejection fraction on echocardiogram <50% and/or post-operative percentage predicted peak VO2 ≤ 84%). In patients with class I indication for surgery (n = 30), there was no significant change post-operatively in ppVO2 (81 (69-88) % vs. 79 (60-87) %, p = 0.09). In patients with class II indication for surgery (n = 13), there was a significant fall post-operatively in ppVO2 (82 (79-92) % vs. (74 (68-86) %, p < 0.01). In the univariate analysis, pre-operative ppVO2 ≤ 84% (p < 0.01) was a predictor for impaired post-operative functional capacity.
Conclusions Patients with class I indication have persistently abnormal exercise performance six months after surgery. Patients with class II indication for surgery have worse exercise performance parameters six months after surgery. Pre-operative ppVO2 ≤84% is an independent predictor of impaired post-operative functional capacity at six months.

Sivasubramaniam G; National Pulmonary Hypertension Service, Hammersmith Hospital, London, UK.;
Baccelli A; Haji G; Lo Giudice F; Weaver C; Howard L;Davies R;

ERJ open research [ERJ Open Res] 2025 May 27; Vol. 11 (3).
Date of Electronic Publication: 2025 May 27 (Print Publication: 2025).

Baseline PVR and P_{ETCO 2} are independently associated with a positive acute vasoreactive response. Lower mean PAP and mean RAP, and higher RVEF, are seen when responders and non-responders are compared, independent of the degree of pulmonary vasculopathy.

Nesti, Lorenzo; Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
Santoni, Lorenza;Frascerra, Silvia;Chiriacò, Martina; et al

International journal of sport nutrition and exercise metabolism,2025 May 30

Background; Fat oxidation rates are key determinants of exercise capacity and metabolic health, evaluated by indirect calorimetry during step graded exercise test. We sought to verify whether indirect calorimetry applied to ramp graded exercise test provides comparable results to the reference test and to identify the physiological bases of possible dissimilarities.
Methods; To this aim, 14 healthy volunteers performed two cardiopulmonary exercise tests with concomitant stress echocardiography according to standard protocols until limit of tolerance on separate days, in randomized order.
Results; Compared at matched exercise intensities, expressed as percentage of estimated maximal rate of oxygen uptake (%V˙O2max), indirect calorimetry applied to ramp provided identical kinetics of macronutrient oxidation, with a negligible (7%, p > .05) constant overestimation of fat and underestimation of carbohydrate oxidation rates. Despite identical hemodynamic and ventilatory parameters throughout the tests, we observed a minute downward shift of the Δ V˙CO2/Δ V˙O2 intercept with ramp in comparison to step (-0.05 ± 0.09 L/min; p = .077) due to delayed alignment of gas exchange to work rate, which explains the differences in substrate oxidation values between the two tests. Ramp macronutrient oxidation rates were fully normalized by correcting the stoichiometric equations for the Δ V˙CO2/Δ V˙O2 intercept difference.
Conclusions;  In conclusion, cardiopulmonary and metabolic responses are dependent on exercise intensity and not on the protocol used. Indirect calorimetry applied to ramp protocols correctly identifies the kinetics of macronutrient oxidation while introducing minimal differences in the absolute values due to different gas-exchange response that can be mathematically corrected by applying the Δ V˙CO2/Δ V˙O2 correction factor.

Z. J. Carr, Yale University, School of Medicine, New Haven, CT, USA.
J. Charchaflieh, A. Brenes-Bastos, H. He, H. M. Lin, A. Jankelovits, et al.

BJA Open 2025 Vol. 14 Pages 100407

BACKGROUND: Early postoperative complication risk prediction would enhance perioperative surveillance and resource allocation. Reports have described brief submaximal cardiopulmonary exercise testing (CPET) for the routine assessment of cardiopulmonary disease. Compared with conventional CPET, it can be performed in 6 min and is used to predict peak CPET measurements. We aimed to determine whether submaximal CPET-derived measures outperform structured surveys in early postoperative complication detection.
METHODS: An institutional review board-approved, single-centre, open-label, clinical device trial was conducted. A total of 101 participants undergoing noncardiac surgery, aged >60 yr, with revised cardiac risk index </=2, self-reported metabolic equivalents >4 (METs in ml O(2) kg(-1) min(-1); self-endorsed reliably climbing two flights of stairs), were enrolled. Participants completed a subjective METs assessment, Duke Activity Status Index, and submaximal CPET that derived peak oxygen uptake (VO(2), ml O(2)kg(-1) min(-1)), METs, and gas exchange-derived pulmonary capacitance (GXCAP, in ml O(2) beat(-1) kPa(-1)). Elastic net regularisation machine learning identified feature importance among study measures for the primary endpoint (Postoperative Morbidity Survey [POMS] >/=1), secondary endpoints (cardiac, pulmonary and renal domains of the POMS [POMS-CPR >/=1]), and length of stay. Adjusted multivariable regression models were used to identify significance.
RESULTS: Of 101 participants, 53 (52.4%) had POMS >/=1. GXCAP to peak VO(2) slope (GXCAP-VO(2)) was associated with POMS >/=1 (OR(adj) 0.94; 95% CI 0.89-0.99; P=0.011) and increasing length of stay (OR(adj) 0.98; 95% CI 0.96-0.99; P=0.01). GXCAP-VO(2) slope (OR(adj) 0.93; 95% CI 0.88-0.99; P=0.015) was associated with POMS-CPR >/=1.
CONCLUSIONS: Compared with structured surveys (subjective METs or Duke Activity Status Index) or conventional peak CPET values (VO(2) or METs), a novel measure, GXCAP-VO(2) slope, offered superior early postoperative complication discrimination in low-morbidity subjects. These preliminary findings support GXCAP-VO(2) slope as a compelling investigational target for early postoperative complication risk, supporting the use of CPET to enhance early postoperative complication prediction. CLINICAL TRIAL REGISTRATION: NCT05743673.