Left ventricular transmural pressure and ventilatory inefficiency during exercise in advanced heart failure
B Kultursay, S Tanyeri, M Karacam, D Mutlu, B Guven, S C Efe, G S Halil, O Y Akbal, C Dogan, M K Kirali, R D Acar, E AslangerAbstract
Background
Conventional resting filling pressures fail to predict exercise capacity and cardiovascular reserves. On the other hand, ventilatory efficiency, assessed by the VE/VCO₂ slope during cardiopulmonary exercise testing (CPET), is a powerful functional and prognostic marker in heart failure (HF). This discrepancy may reflect an incomplete interpretation of LVEDP as a surrogate for left ventricular (LV) preload. LV transmural pressure difference (ΔPTM = left ventricular end-diastolic pressure [LVEDP] − right atrial pressure [RAP]) accounts for external constraint and may better reflect effective preload. Whether ΔPTM improves the prediction of exercise ventilatory efficiency remains unclear.
Methods
We retrospectively studied 422 patients with advanced systolic HF (LVEF ≤25%) who underwent right-heart catheterization, CPET, and echocardiography within one week. ΔPTM was calculated as LVEDP − RAP and analyzed both continuously and by tertiles. The primary outcome was ventilatory efficiency (VE/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 ΔPTM with LVEDP and RAP modeled individually and jointly.
Results
Higher ΔPTM was independently associated with better ventilatory efficiency, reflected by a lower VE/VCO₂ slope (posterior mean β −0.35; 95% credible interval −0.63 to −0.07; 99.2% posterior probability of a negative association). Patients in the highest ΔPTM tertile had markedly lower VE/VCO₂ slopes than those in the lowest tertile (median difference −4.48 units; 95% credible interval −8.21 to −0.89). In contrast, LVEDP and RAP showed weaker, inconsistent, or null associations with ventilatory efficiency. Neither ΔPTM nor LVEDP was meaningfully associated with peak VO₂.
Conclusion
ΔPTM is inversely associated with ventilatory efficiency during exercise and outperforms conventional resting filling pressures in explaining VE/VCO₂ abnormalities. These findings suggest that impaired effective preload is preferentially expressed through a transmural pressure-based framework for interpreting exercise hemodynamics.Figure1For image description, please refer to the figure legend and surrounding text.Figure2For image description, please refer to the figure legend and surrounding text.