Aims This study investigated the relationship between right ventricular (RV) structure and function and survival in idiopathic pulmonary arterial hypertension (IPAH). Methods and resultsIn 64 patients, cardiac magnetic resonance, right heart catheterization, and the six-minute walk test (6MWT) were performed at baseline and after 1-year follow-up. RV structure and function were analysed as predictors of mortality. During a mean follow-up of 32 months, 19 patients died. A low stroke volume (SV), RV dilatation, and impaired left ventricular (LV) filling independently predicted mortality. In addition, a further decrease in SV, progressive RV dilatation, and further decrease in LV end-diastolic volume (LVEDV) at 1-year follow-up were the strongest predictors of mortality. According to Kaplan-Meier survival curves, survival was lower in patients with an inframedian SV index 25 mL/m 2 , a supramedian RV end-diastolic volume index !84 mL/m 2 , and an inframedian LVEDV 40 mL/m 2 . Conclusions The RV contains prognostic information in IPAH. A large RV volume, low SV, and a reduced LV volume are strong independent predictors of mortality and treatment failure.

After PAH-targeted therapy, RV function can deteriorate despite a reduction in PVR. Loss of RV function is associated with a poor outcome, irrespective of any changes in PVR.

I diopathic pulmonary arterial hypertension (PAH) is a rare but fatal disease with a survival rate of 58% at 3 years. Present therapy is unable to normalize pulmonary arterial pressures, and PAH patients ultimately develop right heart failure. Editorial see p 1999 Clinical Perspective on p 2025Previous studies have demonstrated that PAH patients have reduced systolic function as measured by right ventricular Background-The role of right ventricular (RV) diastolic stiffness in pulmonary arterial hypertension (PAH) is not well established. Therefore, we investigated the presence and possible underlying mechanisms of RV diastolic stiffness in PAH patients. Methods and Results-Single-beat RV pressure-volume analyses were performed in 21 PAH patients and 7 control subjects to study RV diastolic stiffness. Data are presented as mean±SEM. RV diastolic stiffness (β) was significantly increased in PAH patients (PAH, 0.050±0.005 versus control, 0.029±0.003; P<0.05) and was closely associated with disease severity. Subsequently, we searched for possible underlying mechanisms using RV tissue of PAH patients undergoing heart/lung transplantation and nonfailing donors. Histological analyses revealed increased cardiomyocyte cross-sectional areas (PAH, 453±31 μm 2 versus control, 218±21 μm 2 ; P<0.001), indicating RV hypertrophy. In addition, the amount of RV fibrosis was enhanced in PAH tissue (PAH, 9.6±0.7% versus control, 7.2±0.6%; P<0.01). To investigate the contribution of stiffening of the sarcomere (the contractile apparatus of RV cardiomyocytes) to RV diastolic stiffness, we isolated and membrane-permeabilized single RV cardiomyocytes. Passive tension at different sarcomere lengths was significantly higher in PAH patients compared with control subjects (>200%; P interaction <0.001), indicating stiffening of RV sarcomeres. An important regulator of sarcomeric stiffening is the sarcomeric protein titin. Therefore, we investigated titin isoform composition and phosphorylation. No alterations were observed in titin isoform composition (N2BA/N2B ratio: PAH, 0.78±0.07 versus control, 0.91±0.08), but titin phosphorylation in RV tissue of PAH patients was significantly reduced (PAH, 0.16±0.01 arbitrary units versus control, 0.20±0.01 arbitrary units; P<0.05). In addition, these measures are highly sensitive to the confounding effects of increased preload and afterload and are therefore not reliable in the setting of PAH. 4 On the other hand, the gold standard of measuring load-independent diastolic stiffness by pressure-volume (PV) analysis is not without risk in PAH patients because it requires temporal preload reduction. Conclusions-RV3 In left heart failure, this was circumvented by the development of single-beat analyses of diastolic PV relationship. 5,6 However, it is unclear whether this analysis could also be used for the RV in PAH.There are several possible contributing factors explaining RV diastolic stiffness in PAH. Hypertrophy and fibrosis are known to increase ventricular stiffness.7 However, RV diastolic stiffn...