Agostoni P; Centro Cardiologico Monzino Istituto di Ricovero e
Cura a Carattere Scientifico, Milan, Italy.
Willixhofer R; Galotta A; Rubbo FM; et al

Open Heart. 13(1), 2026 Jun 3

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.