Journal Article

Beyond the slope: prognostic utility of the VE/VCO 2 intercept in chronic heart failure

Emdin, Michele, Sinagra, Gianfranco, Pezzuto, Beatrice, Apostolo, Anna, Contini, Mauro C, Cosimo, Carriere, Campodonico, Jeness, Tricarico, Lucia, Castiglione, Vincenzo, Vignati, Carlo, Senni, Michele, Magrì, Damiano, Mapelli, Massimo, Agostoni, Piergiuseppe, Galotta, Arianna, Baracchini, Nikita, Cattadori, Gaia, Felli, Luca, Sciomer, Susanna, Grosdani, Stefano, Passino, Claudio, Iorio, Annamaria, Willixhofer, Robin, Barbato, Emanuele, Correale, Michele, Mattavelli, Irene, Palermo, Pietro, Salvioni, Elisabetta, Capovilla, Teresa Maria, Rubbo, Filippo Maria, Abete, Raffaele, Fiori, Emiliano

2026

Overview

Cardiopulmonary exercise testing (CPET) parameters are used for heart failure (HF) prognostication. While the ventilation to carbon dioxide production (VE/VCO ) slope ≥34 identifies high risk, patients with intermediate values remain heterogeneous. The VE/VCO Y-intercept, reflecting dead space ventilation at rest and its changes during effort, may refine prognostication. We retrospectively analysed 2642 HF. Follow-up was 26 (9-63) months. The study endpoint was the composite of all-cause death, urgent transplant or left ventricular assist device implantation. Median age was 62 (53-70) years and left ventricular ejection fraction (LVEF) 33% (27%-39%). 27% of patients were New York Heart Association class III-IV. During follow-up, 534 events occurred. Both VE/VCO slope and peakVO were associated with outcome in univariable and multivariable models (HR 1.04, 95% CI 1.03 to 1.06; HR 0.90, 95% CI 0.88 to 0.93, p<0.001, respectively). Y-intercept was not prognostic univariately but added independent value in multivariable models (HR 1.08, 95% CI 1.04 to 1.13, p<0.001). Prognosis and clinical profiles improved from group A (VE/VCO slope ≥34, n=858) to B (28-34, n=943) to C (<28, n=841). Group A versus C patients had lower LVEF (30% (25%-36%) vs 35% (30%-40%), p <0.001), peakVO (12.7 (10.06-15.3) vs 17.7 (14.6-21.6) mL/kg/min, p <0.001) and higher N-terminal pro-B-type natriuretic peptide (1400 (572-3122) vs 454 (174-1081) pg/mL, p <0.001). Only within group B, a high median Y-intercept (B1≥3.9 L/m) clearly identified patients with higher HF severity and worse survival than B2 (<3.9 L/m, log-rank p<0.001). An increase in the VE/VCO slope is associated with a progressive lower survival. Y-intercept enhances risk assessment in HF with intermediate VE/VCO slope values.

• Subject: Aged / Carbon Dioxide - metabolism / Chronic Disease / Exercise Test / Exercise Tolerance / Female / Follow-Up Studies / Heart Failure - diagnosis / Heart Failure - mortality / Heart Failure - physiopathology / Heart Failure - therapy / Heart Transplantation / Heart-Assist Devices / Humans / Male / Middle Aged / Oxygen Consumption - physiology / Predictive Value of Tests / Prognosis / Retrospective Studies / Risk Assessment / Risk Factors / Stroke Volume / Time Factors / Ventricular Function, Left