In heart failure, oxygen uptake and cardiac output measurements at peak and during exercise are important in defining heart failure severity and prognosis. Several cardiopulmonary exercise test-derived parameters have been proposed to estimate stroke volume during exercise, including the oxygen pulse (oxygen uptake/heart rate). Data comparing measured stroke volume and the oxygen pulse or stroke volume estimates from the oxygen pulse at different stages of exercise in a sizeable population of healthy individuals and heart failure patients are lacking. We analysed 1007 subjects, including 500 healthy and 507 heart failure patients, who underwent cardiopulmonary exercise testing with stroke volume determination by the inert gas rebreathing technique. Stroke volume measurements were made at rest, submaximal (∼50% of exercise) and peak exercise. At each stage of exercise, stroke volume estimates were obtained considering measured haemoglobin at rest, predicted exercise-induced haemoconcentration and peripheral oxygen extraction according to heart failure severity. A strong relationship between oxygen pulse and measured stroke volume was observed in healthy and heart failure subjects at submaximal (R² = 0.6437 and R² = 0.6723, respectively), and peak exercise (R² = 0.6614 and R² = 0.5662) but not at rest. In healthy and heart failure subjects, agreement between estimated and measured stroke volume was observed at submaximal (–3 ± 37 and –11 ± 72 ml, respectively) and peak exercise (1 ± 31 and 6 ± 29 ml, respectively) but not at rest. In heart failure patients, stroke volume estimation and oxygen pulse during exercise represent stroke volume, albeit with a relevant individual data dispersion so that both can be used for population studies but cannot be reliably applied to a single subject. Accordingly, whenever needed stroke volume must be measured directly.

Evaluation of arterial carbon dioxide pressure (PaCO₂) and dead space to tidal volume ratio (V_D/V_T) during exercise is important for the identification of exercise limitation causes in heart failure (HF). However, repeated sampling of arterial or arterialized ear lobe capillary blood may be clumsy. The aim of our study was to estimate PaCO₂ by means of a non-invasive technique, transcutaneous PCO₂ (PtCO₂), and to verify the correlation between PtCO₂ and PaCO₂ and between their derived parameters, such as V_D/V_T, during exercise in HF patients. 29 cardiopulmonary exercise tests (CPET) performed on a bike with a ramp protocol aimed at achieving maximal effort in ≈10 min were analyzed. PaCO₂ and PtCO₂ values were collected at rest and every 2 min during active pedaling. The uncertainty of PCO₂ and V_D/V_T measurements were determined by analyzing the error between the two methods. The accuracy of PtCO₂ measurements vs. PaCO₂ decreases towards the end of exercise. Therefore, a correction to PtCO₂ that keeps into account the time of the measurement was implemented with a multiple regression model. PtCO₂ and V_D/V_T changes at 6, 8 and 10 min vs. 2 min data were evaluated before and after PtCO₂ correction. PtCO₂ overestimates PaCO₂ for high timestamps (median error 2.45, IQR −0.635–5.405, at 10 min vs. 2 min, p-value = 0.011), while the error is negligible after correction (median error 0.50, IQR = −2.21–3.19, p-value > 0.05). The correction allows removing differences also in PCO₂ and V_D/V_T changes. In HF patients PtCO₂ is a reliable PaCO₂ estimation at rest and at low exercise intensity. At high exercise intensity the overall response appears delayed but reproducible and the error can be overcome by mathematical modeling allowing an accurate estimation by PtCO₂ of PaCO₂ and V_D/V_T.

Periodic repetition of right heart catheterization (RHC) in pulmonary arterial hypertension (PAH) can be challenging. We evaluated the correlation between RHC and cardiopulmonary exercise test (CPET) aiming at CPET use as a potential noninvasive tool for hemodynamic burden evaluation. One hundred and forty‐four retrospective PAH patients who had performed CPET and RHC within 2 months were enrolled. The following analyses were performed: (a) CPET parameters in hemodynamic variables tertiles; (b) position of hemodynamic parameters in the peak end‐tidal carbon dioxide pressure (P_ETCO₂) versus ventilation/carbon dioxide output (VE/VCO₂) slope scatterplot, which is a specific hallmark of exercise respiratory abnormalities in PAH; (c) association between CPET and a hemodynamic burden score developed including mean pulmonary arterial pressure (mPAP), pulmonary vascular resistance (PVR), cardiac index, and right atrial pressure. VE/VCO₂ slope and peak P_ETCO₂ significantly varied in mPAP and PVR tertiles, while peak oxygen uptake (peak VO₂) and O₂ pulse varied in the tertiles of all hemodynamic parameters. P_ETCO₂ versus VE/VCO₂ slope showed a strong hyperbolic relationship (R² = 0.7627). Patients with peak P_ETCO₂ > median (26 mmHg) and VE/VCO₂ slope < median (44) presented lower mPAP and PVR (p < 0.005) than patients with peak P_ETCO₂ < median and VE/VCO₂ slope > median. Multivariate analysis individuated peak VO₂ (p = 0.0158) and peak P_ETCO₂ (p = 0.0089) as hemodynamic score independent predictors; the formula 11.584 − 0.0925 × peak VO₂ − 0.0811 × peak P_ETCO₂ best predicts the hemodynamic score value from CPET data. A significant correlation was found between estimated and calculated scores (p < 0.0001), with a precise match for patients with mild‐to‐moderate hemodynamic burden (76% of cases). The results of the present study suggest that CPET could allow to estimate the hemodynamic burden in PAH patients.

The mechanisms underlying the effects of dapagliflozin in heart failure with reduced ejection fraction (HFrEF) are not yet fully understood. This study aims to evaluate the effect of the drug on cardiorespiratory function by assessing alveolar–capillary membrane characteristics, sleep apnea, pulmonary and cardiac performance in stable HFrEF patients. Seventy-three patients with stable HFrEF were enrolled, with 66 completing the six-month follow-up. Analyses included assessment of the alveolar–capillary membrane by diffusion capacity, including its membrane diffusion and capillary volume components and measurements of proSP-B in the blood, an emerging biomarker of alveolar–capillary membrane function. Pulmonary function tests, overnight respiratory monitoring, and echocardiographic parameter collection were also conducted. After 6 months, a reduction in circulating proSP-B levels was observed (32.65 ± 13.36 at baseline vs. 30.86 ± 12.45 AU at 6 months, p for trend 0.0092), accompanied by improvements in echocardiographic parameters (left ventricle ejection fraction and pulmonary pressures). Pulmonary function tests and overnight respiratory monitoring showed no significant changes in lung diffusion, spirometry, or obstructive sleep apnea (apnea hypopnea index from 5.0 [1.1–16.6] at baseline to 6.2 [0.7–13.8]/h; p = n.s.). A significant reduction in central sleep apnea (CSA) was noted in the 13 patients with at least one CSA at baseline (15 [3–48] vs. 0 [0–18.5]/h, p = 0.017). Dapagliflozin demonstrates both hemodynamic and non-hemodynamic effects, particularly improving alveolar–capillary membrane function. This study highlights the multifactorial benefits of dapagliflozin in patients with stable HFrEF and the potential of proSP-B as a sensitive marker for evaluating therapeutic response.