Uncoupling between intravascular and distending pressures leads to underestimation of circulatory congestion in obesity

Aims: Patients with obesity frequently present with dyspnoea. Biomarkers that reflect wall stress are often used to evaluate circulatory congestion and help determine whether dyspnoea is of cardiac causes. Patients with obesity display greater external restraint on the heart, which may alter relationships between intravascular pressures and stress markers. Methods and results: Subjects with unexplained dyspnoea (n = 212) underwent cardiac catheterization with simultaneous echocardiography. Blood sampling was performed in a subset (n = 58). Relationships between echocardiographic and blood biomarkers of circulatory congestion and directly-measured haemodynamics were compared between participants with severe obesity [body mass index (BMI) ≥35 kg/m², Group B) and those without (BMI <35 kg/m², Group A). Circulatory congestion was assessed by pulmonary capillary wedge pressure (PCWP), and vascular distending pressure was assessed by left ventricular transmural pressure (LVTMP). As compared to Group A, participants in Group B displayed higher PCWP relative to N-terminal pro-B-type natriuretic peptide, mid-regional pro-atrial natriuretic peptide, troponin T, and growth differentiation factor-15 (all p < 0.01). In contrast, the relationships between LVTMP and the biomarkers were superimposable. Echocardiographic biomarkers revealed the same pattern: PCWP was higher for any E/e′ ratio in Group B compared to Group A, but the relationship between LVTMP and E/e′ was similar. In contrast, levels of C-terminal pro-endothelin-1 and mid-regional pro-adrenomedullin were more robustly correlated with PCWP (r = 0.67 and r = 0.62, both p < 0.0001), with no differential relationship based upon BMI. Conclusions: Non-invasive haemodynamic markers underestimate circulatory congestion in patients with obesity, an effect that appears related to uncoupling between cardiac wall stress and intravascular pressures. This may lead to systematic under-recognition of congestion in patients with obesity.