Beyond the slope: prognostic utility of the VE/VCO2 intercept in chronic heart failure

Aims: Cardiopulmonary exercise testing (CPET) parameters are used for heart failure (HF) prognostication. While the ventilation to carbon dioxide production (VE/VCO2) slope ≥34 identifies high risk, patients with intermediate values remain heterogeneous. The VE/VCO2 Y-intercept, reflecting dead space ventilation at rest and its changes during effort, may refine prognostication. Methods: 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. Results: 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/VCO₂ slope and peakVO₂ 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/VCO2 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%), ptrend<0.001), peakVO₂ (12.7 (10.06-15.3) vs 17.7 (14.6-21.6) mL/kg/min, ptrend<0.001) and higher N-terminal pro-B-type natriuretic peptide (1400 (572-3122) vs 454 (174-1081) pg/mL, ptrend<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). Conclusion: An increase in the VE/VCO2 slope is associated with a progressive lower survival. Y-intercept enhances risk assessment in HF with intermediate VE/VCO₂ slope values.