Left ventricular transmural pressure and ventilatory inefficiency during exercise in advanced heart failure

Baseline intracavitary haemodynamic measurements frequently demonstrate an inconsistent relationship with exertional performance. This may reflect an incomplete interpretation of left ventricular (LV) filling pressures. LV transmural pressure difference (ΔP_TM = LV end-diastolic pressure [LVEDP]—right atrial pressure [RAP]) integrates LV filling pressure with right ventricular/pericardial constraint and may provide a composite representation of resting haemodynamic conditions. Ventilatory efficiency, assessed by the minute ventilation-carbon dioxide production (V_E/VCO₂) slope during cardiopulmonary exercise testing (CPET), is a leading representation of cardiopulmonary reserves and a powerful prognostic marker in heart failure (HF). Whether ΔP_TM is associated with exercise ventilatory efficiency beyond conventional resting filling pressure measurements remains unclear.

We retrospectively studied 422 patients with advanced HF (LVEF ≤25%) who underwent right-heart catheterization and CPET. ΔP_TM was analysed both continuously and by tertiles. The primary outcome was V_E/VCO₂ slope; peak VO₂ was a secondary outcome. Bayesian multivariable regression models were adjusted using a directed acyclic graph-derived confounder set. Sensitivity analyses compared ΔP_TM with LVEDP and RAP modelled individually and jointly.

Among 422 patients (mean age 51.3 ± 10.8 years; 62 [14.7%] female), higher ΔP_TM was independently associated with a lower V_E/VCO₂ slope (posterior mean β = −0.34 per mmHg; 95% credible interval [CrI] −0.58 to −0.11; 99.7% posterior probability of a negative association). Unadjusted V_E/VCO₂ slope decreased from 40.2 (31.7–67.1) in the lowest ΔP_TM tertile to 34.9 (30.6–44.8) in the highest tertile (P = .029). The adjusted posterior predictive difference between the highest and lowest ΔP_TM tertiles was −4.42 units (95% CrI −7.85 to −0.62). Following multivariable adjustment, ΔP_TM showed no significant association with peak VO₂ (posterior mean β = +0.06; 95% CrI −0.02 to +0.14). Neither LVEDP nor RAP, modelled individually or jointly, demonstrated independent associations with ventilatory efficiency.

Resting ΔP_TM was inversely associated with the V_E/VCO₂ slope during exercise, whereas no independent association was observed with peak VO₂. Compared with individual left- or right-sided filling pressures, ΔP_TM provides a parsimonious summary of the balance between left-sided distending pressure and right-sided constraint associated with ventilatory efficiency in advanced HF.