Clinical relevance of right ventricular diastolic stiffness in pulmonary hypertension

Abstract

Right ventricular (RV) diastolic stiffness is increased in pulmonary arterial hypertension (PAH) patients. We investigated whether RV diastolic stiffness is associated with clinical progression and assessed the contribution of RV wall thickness to RV systolic and diastolic stiffness.Using single-beat pressure-volume analyses, we determined RV end-systolic elastance (Ees), arterial elastance (Ea), RV-arterial coupling (Ees/Ea), and RV end-diastolic elastance (stiffness, Eed) in controls (n=15), baseline PAH patients (n=63) and treated PAH patients (survival >5 years n=22 and survival <5 years n=23).We observed an association between Eed and clinical progression, with baseline Eed >0.53 mmHg·mL -1 associated with worse prognosis (age-corrected hazard ratio 0.27, p=0.02). In treated patients, Eed was higher in patients with survival <5 years than in patients with survival >5 years (0.91±0.50 versus 0.53 ±0.33 mmHg·mL -1 , p<0.01). Wall-thickness-corrected Eed values in PAH patients with survival >5 years were not different from control values (0.76±0.47 versus 0.60±0.41 mmHg·mL -1 , respectively, not significant), whereas in patients with survival <5 years, values were significantly higher (1.52 ±0.91 mmHg·mL -1 , p<0.05 versus controls). RV diastolic stiffness is related to clinical progression in both baseline and treated PAH patients. RV diastolic stiffness is explained by the increased wall thickness in patients with >5 years survival, but not in those surviving <5 years. This suggests that intrinsic myocardial changes play a distinctive role in explaining RV diastolic stiffness at different stages of PAH. @ERSpublications Right ventricular diastolic stiffness is related to clinical progression in both baseline and treated PAH patients

Right Ventricular Myocardial Stiffness in Experimental Pulmonary Arterial Hypertension

“… 2 More recently, we demonstrated that increased RV diastolic stiffness is associated with worse outcome in patients with PAH. 3 Therefore, diastolic dysfunction is likely to be of clinical relevance. Whether RV diastolic stiffness is restricted to idiopathic pulmonary arterial hypertension or is also present in other disorders that are associated with elevated RV pressure is currently unclear.…”

“… 1 Although it is known for some years that RV systolic adaptation is of clinical importance, it has just recently became clear that RV diastolic stiffness increases and may contribute to disease progression in PAH. 2 , 3 In addition, we have previously shown that RV diastolic stiffness was closely associated with a doubling in sarcomere-derived cardiomyocyte stiffness and increased myocardial fibrosis in end-stage PAH patients. 2 , 4 …”

Assessment of Right Ventricular Function in the Research Setting: Knowledge Gaps and Pathways Forward. An Official American Thoracic Society Research Statement

“…Coupling of RV function to afterload has an inevitable diastolic component (2,161,182). Diastolic stiffness may be a predictor of outcomes in severe PH (183,184). Please see the online supplement for a summary of RV diastolic function assessment.…”

Looking backwards: is it time to assess veno-atrial interactions in pulmonary arterial hypertension?

“…RV end-diastolic elastance or stiffness is emerging as an important clinical predictor of outcomes. An increase in RV diastolic stiffness significantly associates with increased mortality and lung transplantation in patients with pulmonary hypertension [10,15]. A significant decrease in RV diastolic stiffness has been found in patients on 3 months of intravenous prostacyclin therapy PAH [16].…”

“…A significant decrease in RV diastolic stiffness has been found in patients on 3 months of intravenous prostacyclin therapy PAH [16]. These clinical methods to assess RV diastolic stiffness rely on invasive assessments of RV diastolic pressure and the use of the single-beat method [10,15,17], whereas venous backflow fraction can be measured non-invasively using CMR alone. Few studies have addressed the "veno-atrial" interactions but recent work investigates the role of right atrial function in PAH using echocardiography and CMR imaging [18][19][20][21].…”