Right ventricular (RV) morphometric and ventriculo-vascular (VV) coupling patterns in patients with advanced pulmonary arterial hypertension (PAH) undergoing parenteral treprostinil therapy

Increased RV wall thickness relative to cavity size is an adaptation to lower wall tension in PAH. However, this remodeling may lead to an attenuated response to therapy. We examined RV structural morphology in relation to VV coupling in patients with advanced PAH undergoing dose escalation of treprostinil. RV pressure-volume analysis was performed in 17 PAH patients during treatment with parenteral treprostinil. This was used to derive RV afterload (Ea, pulmonary arterial elastance), systolic contractile function (Ees , end-systolic elastance) and diastolic ventricular stiffness (β). Cardiac MRI short axis cine projections were used to calculate RV mass, RVEF, and wall thickness index (WTI). Pulmonary resistance-compliance product (RC time) was used as a measure of incremental pulsatile load. Treprostinil dose was 41 ± 3 ng/kg/min by 3 mo. Patients presented with RV failure (RVEF 23±3.0%) and RV hypertrophy (mass 88.7±14.0 gm). Baseline β was related WTI (ρ=0.6, p high >0.05 vs β low . β high had higher Ea but similar Ees/Ea at baseline (2.75±0.37 vs 1.66±0.23 mmHg/ml and 0.77±0.17 vs 0.77±0.16). By 3 mo., Ea improved in both groups (1.77±0.28 vs 1.12±0.12 mmHg/ml, p=0.02) but Ees/Ea remained lower in β high (0.53±0.1) vs β low (0.86±0.2). RC time was similar at baseline (0.58±0.02 vs 0.62±0.05 sec.) and remained unchanged on therapy. Increased VV stiffening is associated with increased WTI and an attenuated treatment response to treprostinil in patients with advanced PAH. Improvements in afterload are likely related to changes in pulmonary resistance vessels.