BACKGROUND: Recent guidelines redefined exercise pulmonary hypertension as a mean pulmonary artery pressure/cardiac output (mPAP/CO) slope >3 mm Hg·L ⁻¹ ·min ⁻¹ . A peak systolic pulmonary artery pressure >60 mm Hg during exercise has been associated with an increased risk of cardiovascular death, heart failure rehospitalization, and aortic valve replacement in aortic valve stenosis. The prognostic value of the mPAP/CO slope in aortic valve stenosis remains unknown. METHODS: In this prospective cohort study, consecutive patients (n=143; age, 73±11 years) with an aortic valve area ≤1.5 cm ² underwent cardiopulmonary exercise testing with echocardiography. They were subsequently evaluated for the occurrence of cardiovascular events (ie, cardiovascular death, heart failure hospitalization, new-onset atrial fibrillation, and aortic valve replacement) during a follow-up period of 1 year. Findings were externally validated (validation cohort, n=141). RESULTS: One cardiovascular death, 32 aortic valve replacements, 9 new-onset atrial fibrillation episodes, and 4 heart failure hospitalizations occurred in the derivation cohort, whereas 5 cardiovascular deaths, 32 aortic valve replacements, 1 new-onset atrial fibrillation episode, and 10 heart failure hospitalizations were observed in the validation cohort. Peak aortic velocity (odds ratio [OR] per SD, 1.48; P =0.036), indexed left atrial volume (OR per SD, 2.15; P =0.001), E/e’ at rest (OR per SD, 1.61; P =0.012), mPAP/CO slope (OR per SD, 2.01; P =0.002), and age-, sex-, and height-based predicted peak exercise oxygen uptake (OR per SD, 0.59; P =0.007) were independently associated with cardiovascular events at 1 year, whereas peak systolic pulmonary artery pressure was not (OR per SD, 1.28; P =0.219). Peak V o ₂ (percent) and mPAP/CO slope provided incremental prognostic value in addition to indexed left atrial volume and aortic valve area ( P <0.001). These results were confirmed in the validation cohort. CONCLUSIONS: In moderate and severe aortic valve stenosis, mPAP/CO slope and percent-predicted peak V o ₂ were independent predictors of cardiovascular events, whereas peak systolic pulmonary artery pressure was not. In addition to aortic valve area and indexed left atrial volume, percent-predicted peak V o ₂ and mPAP/CO slope cumulatively improved risk stratification.

Background: We investigated the role of the dynamic changes of pulmonary congestion, as assessed by sonographic B-lines, as a tool to stratify prognosis in patients admitted for acute heart failure with reduced and preserved ejection fraction (HFrEF, HFpEF). Methods: In this multicenter, prospective study, lung ultrasound was performed at admission and before discharge by trained investigators, blinded to clinical findings. Results: We enrolled 208 consecutive patients (mean age 76 [95% confidence interval, 70–84] years), 125 with HFrEF, 83 with HFpEF (mean ejection fraction 32% and 57%, respectively). The primary composite endpoint of cardiovascular death or HF re-hospitalization occurred in 18% of patients within 6 months. In the overall population, independent predictors of the occurrence of the primary endpoint were the number of B-lines at discharge, NT-proBNP levels, moderate-to-severe mitral regurgitation, and inferior vena cava diameter on admission. B-lines at discharge were the only independent predictor in both HFrEF and HFpEF subgroups. A cut-off of B-lines > 15 at discharge displayed the highest accuracy in predicting the primary endpoint (AUC = 0.80, p < 0.0001). Halving B-lines during hospitalization further improved event classification (continuous net reclassification improvement = 22.8%, p = 0.04). Conclusions: The presence of residual subclinical sonographic pulmonary congestion at discharge predicts 6-month clinical outcomes across the whole spectrum of acute HF patients, independent of conventional biohumoral and echocardiographic parameters. Achieving effective pulmonary decongestion during hospitalization is associated with better outcomes.

Cardiopulmonary exercise testing combined with exercise stress Echocardiography (CPET-ESE) is an advanced diagnostic modality for evaluating cardiovascular disease and tailoring patient-specific treatment strategies. By integrating metabolic, ventilatory, and hemodynamic data with real-time imaging, CPET-ESE offers a comprehensive assessment of cardiovascular function under physiological stress. CPET provides detailed insights into metabolic and ventilatory performance, while ESE allows for the dynamic visualisation of cardiac structure and function during exercise. This review outlines the physiological foundations and core parameters of CPET and ESE, emphasising their complementary roles in cardiovascular diagnostics and prognostication and exploring their clinical value for evaluating unexplained dyspnoea and exercise-induced hemodynamic abnormalities. CPET-ESE plays a pivotal role in detecting subtle hemodynamic abnormalities, assessing functional capacity, and contributing to earlier diagnosis, targeted interventions, and improved clinical outcomes.

BACKGROUND: Managing clinically significant primary mitral regurgitation is challenging. Right ventricular–pulmonary arterial coupling, assessed with tricuspid annular plane systolic excursion (TAPSE) and systolic pulmonary artery pressure (sPAP) ratio, reflects right ventricular adaptability to afterload. This international multicenter cohort study aimed to evaluate the prognostic value of rest TAPSE/sPAP and exercise TAPSE (exTAPSE)/sPAP in primary mitral regurgitation. METHODS: Between January of 2019 and December of 2023, 211 patients assigned to a derivation cohort (64±12 years of age, 40% women) and 146 patients assigned to a validation cohort (66±13 years of age, 39% women), all of whom had moderate or severe primary mitral regurgitation, no or discordant symptoms, and no left ventricular systolic dysfunction or atrial fibrillation, underwent semisupine cycle–ergometry cardiopulmonary exercise testing combined with exercise echocardiography. TAPSE/sPAP was measured at rest and at intermediate (defined as the first ventilatory threshold) and peak exercise. The primary end point was a composite of cardiovascular death, unplanned cardiovascular hospitalizations, and new atrial fibrillation. RESULTS: In the derivation cohort, 48 patients reached the composite outcome (median follow-up, 24 months [interquartile range, 12–51]). Intermediate and peak exTAPSE/sPAP were strongly correlated ( r =0.84; P <0.001), with intermediate exTAPSE/sPAP offering superior feasibility (98% versus 92%) with comparable prognostic accuracy to peak exTAPSE/sPAP (area under the receiver operating characteristic curve, 0.794 [0.730–0.849] versus 0.765 [0.698–0.823]) and therefore was used as the exercise TAPSE/sPAP measure. Patients with a reduced rest TAPSE/sPAP (cutoff 0.8 mm/mm Hg) and intermediate exTAPSE/sPAP (cutoff 0.6 mm/mm Hg) had a lower event-free survival (log-rank P <0.0001). Intermediate exTAPSE/sPAP and percent-predicted peak VO ₂ were independently associated with the primary end point (hazard ratio, 0.64 [0.51–0.80] per 0.1 mm/mm Hg increase [ P <0.001] and hazard ratio, 2.03 [1.05–3.93] if <80% [ P =0.04], respectively) and had incremental prognostic value beyond age, left atrial volume index, mitral regurgitation severity, rest TAPSE/sPAP, and mitral valve intervention (time-dependent covariable). Similar results were found when rest and intermediate exTAPSE/sPAP were included in the multivariable model as categorical measures. Validation in an independent cohort confirmed the consistent and robust performance of both multivariable models, irrespective of whether TAPSE/sPAP was modeled as a continuous or categorical variable. CONCLUSIONS: Exercise right ventricular–pulmonary arterial coupling, particularly intermediate exTAPSE/sPAP, is a robust and feasible measure independently associated with adverse outcomes, and provides prognostic information beyond resting variables and cardiorespiratory fitness, potentially refining risk stratification and guiding management in patients with primary mitral regurgitation.

BACKGROUND: Moderate and severe tricuspid regurgitation (TR) is associated with poor outcomes, yet current grading systems do not fully capture circulatory heterogeneity. We investigate the relationship of cardiac index (CI) with rest-exercise hemodynamics, metabolic and inflammatory profiles, and clinical outcomes in moderate and severe TR. METHODS: We prospectively enrolled 300 outpatients with atrial secondary, nonatrial secondary, and lead-associated moderate and severe TRs without ≥moderate left-sided valve disease. All underwent comprehensive laboratory profiling and ultrasound evaluation at rest and during cardiopulmonary exercise. Patients were stratified by CI tertiles and followed clinically (primary end point: all-cause mortality or heart failure hospitalization). RESULTS: CI decreased with TR severity but showed wide interindividual variability. In patients with low CI, severe forward flow limitation was associated with more advanced right ventricle-pulmonary arterial uncoupling and biatrial dysfunction ( P <0.05 versus the other tertiles), identifying a hypodynamic-uncoupled profile. Conversely, high CI identified a hyperdynamic-congestive phenotype characterized by advanced congestion, reduced systemic vascular resistance, and heightened systemic inflammation, metabolic-nutritional derangements, and mitochondrial dysfunction ( P <0.05 versus the other tertiles). Intermediate CI showed the most favorable hemodynamic and laboratory profile. A U-shaped relationship between CI and adverse outcomes was observed, with the lowest risk at intermediate values. This pattern persisted across TR severity, cause, staging systems, and adiposity categories ( P <0.05 for all). CONCLUSIONS: In moderate and severe TRs, CI profiling captures cardiac and extracardiac determinants of flow and independently predicts outcomes beyond conventional TR grading and staging. Both low and high CIs identify high-risk patients, while an intermediate CI indicates a balanced, prognostically favorable state. CI profiling may refine risk stratification, guide individualized treatment strategies, and optimize patient selection and timing for tricuspid valve interventions.