Beyond filling pressures: transmural pressure gradient and disease progression in advanced heart failure

Objective Conventional resting hemodynamic variables often show poor concordance with outcomes in advanced heart failure (HF). This study investigated whether the left ventricular transmural pressure difference ΔPTM, which accounts for external constraint by the pericardium and right ventricle (RV), provides superior prognostic value compared to traditional filling pressures. Methods We retrospectively analyzed 420 patients with advanced systolic HF (LVEF<25%) undergoing heart transplantation (HTx) evaluation. ΔPTM was calculated as the difference between left ventricular end-diastolic pressure (LVEDP) and right atrial pressure (RAP) obtained via invasive right-heart catheterization. The primary endpoint was a composite of all-cause mortality, left ventricular assist device (LVAD) implantation, or HTx over a median follow-up of 871 days. Results Patients in the lowest ΔPTM tertile (≤ 9 mmHg) exhibited significantly higher event rates for the composite endpoint compared to the highest tertile (≥ 16 mmHg; log-rank p<0.01). After adjustment for confounders, each 1-mmHg increase in ΔPTM was associated with a 4% risk reduction for the composite outcome (HR: 0.96; 95% CI: 0.93–0.99; p=0.006). Notably, ΔPTM was primarily associated with markers of disease progression—specifically LVAD implantation (p=0.012)—rather than isolated all-cause mortality (p>0.05). Discrimination metrics showed that ΔPTM -based models outperformed models incorporating RAP or LVEDP alone. Conclusions In advanced HF, the transmural pressure gradient is an independent predictor of long-term outcomes, particularly disease progression necessitating mechanical circulatory support. By integrating left- and right-sided filling pressures, ΔPTM provides a physiologically grounded index of effective preload that captures clinical deterioration more effectively than conventional pressure-based measures.Figure1Figure2