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.

Blumer V; Inova Schar Heart and Vascular, Falls Church, Virginia, USA, & many other institutions worldwide
Januzzi JL Jr; Liu Y; Butler J; Ezekowitz JA;Rosenstock J; Del Prato S; Tang WHW; Urbinati A; Zannad F; Lewis GD; Solomon SD; Hedge S; Ibrahim NE;
Lam CSP;

JACC. Heart failure [JACC Heart Fail] 2025 Apr 23. The ARISE-HF trial
Date of Electronic Publication: 2025 Apr 23.

Background: Diabetic cardiomyopathy (DbCM) is a significant cause of heart failure (HF) in individuals with type 2 diabetes mellitus. Although sex differences are noted in HF patients, it is unclear if such differences exist in those with DbCM and whether sex-based differences affect treatment responses.
Objectives: This analysis focuses on sex differences in baseline characteristics of study participants with DbCM at high risk for progression to overt HF and sex-based treatment responses to high-dose AT-001, a novel aldose reductase inhibitor.
Methods: The ARISE-HF trial was a Phase 3, randomized, international, placebo-controlled study designed to evaluate the efficacy and safety of AT-001 in study participants with DbCM.
Results: Of 691 participants, 348 (50.4%) were women. At baseline, women had higher N-terminal pro-B-type natriuretic peptide concentrations (92 vs 60 ng/L; P &lt; 0.001), lower peak oxygen uptake (13.87 vs 17.59 mL/kg/min; P &lt; 0.001), shorter cardiopulmonary exercise testing durations (8.47 vs 11.05 minutes; P &lt; 0.001), and worse quality of life and health status (Kansas City Cardiomyopathy Questionnaire overall summary score 87.79 vs 92.55; P &lt; 0.001; Physical Activity Scale for the Elderly score 137.87 vs 171.09; P &lt; 0.001) compared with men. Despite these differences, there were no significant sex differences in the efficacy or tolerability of high-dose AT-001 compared with placebo. The placebo-corrected oxygen uptake change was 0.26 for women and 0.27 for men (P = 0.58), and changes from baseline to month 15 in Kansas City Cardiomyopathy Questionnaire and Physical Activity Scale for the Elderly scores showed no significant sex differences (all P &gt; 0.05).
Conclusions: Despite baseline differences between women and men with DbCM, the efficacy and safety of high-dose AT-001 are comparable across sexes. These findings highlight the presence of sex-specific characteristics in DbCM and underscore the importance of further research to understand potential sex-specific mechanisms. (Aldose Reductase Inhibition for Stabilization of Exercise Capacity in Heart Failure Trial [ARISE-HF]; NCT04083339).

Romanowicz J;  Section of Cardiology, Children’s Hospital Colorado and University of Colorado Anschutz,  USA.
Park S; Bunn J; Jacobsen RM; Fonseca B; Zablah JE; Englund EK; Barker AJ; A.Davidson JA;

Journal of cardiovascular magnetic resonance : official journal of the Society for Cardiovascular Magnetic Resonance [J Cardiovasc Magn Reson] 2025 May 04, pp. 101907.
Date of Electronic Publication: 2025 May 04.

Background: Accumulation of progressive extracardiac disease is nearly universal for patients with single ventricle heart disease palliated to a Fontan circulation; however, etiologies are poorly understood. Limited flow reserve in the Fontan circulation may underlie extracardiac disease found in Fontan physiology through reduced oxygen and nutrient delivery to the tissues. This study aimed to determine regional flow volumes and oxygen delivery to key organ systems in children and adolescents with a Fontan circulation.
Methods: In 17 Fontan subjects and 14 biventricular controls, regional arterial flow volumes to the carotid, celiac, superior mesenteric, renal, and iliac arteries were quantified with MRI. Arterial oxygen content was calculated using subject hemoglobin level and pulse oximetry, and regional oxygen delivery was calculated using regional flow volume and oxygen content for the above listed arteries. Cardiac output was measured from ascending aorta flow, systemic blood flow from the caval veins, and aorto-pulmonary collateral flow was calculated as the difference between the two. Flows were compared between groups (t-test) and associations were analyzed between flows and with maximal exercise performance on clinical cardiopulmonary exercise testing (Pearson correlation).
Results: On average, renal and iliac arterial flows were lower in the Fontan group, compared to controls. Carotid, celiac, and superior mesenteric arterial flows were preserved in the Fontan group. Arterial oxygen content was equivalent between groups, and thus, regional oxygen delivery followed the same pattern as regional flows. Cardiac output was no different between groups, but systemic blood flow was lower in Fontans due to loss of flow to aorto-pulmonary collaterals. Systemic blood flow correlated with iliac flow such that those with the lowest systemic flow had the least amount of iliac flow. Celiac arterial flow correlated with percent-predicted peak oxygen consumption (VO2) on exercise testing.
Conclusions: Our results are consistent with a limited flow reserve in the Fontan circulation with sacrifice of iliac arterial flow as global systemic blood flow decreases. Importantly, these data were measured with subjects supine and at rest. Future work requires the addition of exercise to determine how flow to specific organs is affected by increasing metabolic demand from the extremities.