Relation between right ventricular wall stress, fibrosis, and function in right ventricular pressure loading

Abstract

Right ventricle (RV) pressure loading can lead to RV fibrosis and dysfunction. We previously found increased RV, septal hinge-point and left ventricle (LV) fibrosis in experimental RV pressure loading. However, the relation of RV wall stress to biventricular fibrosis and dysfunction is incompletely defined. Rabbits underwent progressive pulmonary artery banding (PAB) over 3 wk with hemodynamics, echocardiography, and myocardial samples obtained at a terminal experiment at 6 wk. An additional group received PAB and treatment with an endothelin receptor antagonist. The endocardial and epicardial borders of short-axis echo images were traced and analyzed with invasive pressures to yield regional end-diastolic (ED) and end-systolic (ES) wall stress. To increase clinical translation, computer model-derived wall stress was compared with Laplace wall stress. The relation of wall stress with fibrosis (picrosirius red staining) and ventricular function was analyzed. ED wall stress in all regions and RV and LV free-wall ES wall stress were increased in PAB rabbits versus sham animals. Laplace wall stress correlated well with computational models. In PAB, fibrosis was highest in the RV free wall, then septal hinge regions, and lowest in the septum and LV free wall. Fibrosis was moderately related to ED ( r = 0.47, P = 0.0011), but not ES wall stress. RV ED wall stress was strongly related to echo indexes of function (strain rate: r = 0.71, P = 0.048; E′, r = −0.75, P = 0.0077; tricuspid annular plane systolic excursion: r = 0.85, P = 0.0038) and RV fractional area change ( r = 0.77, P = 0.027). ED, more than ES, wall stress is related moderately to fibrosis and strongly to function in experimental RV pressure loading, especially at the septal hinge-point regions, where fibrosis is prominent. This suggests that wall stress partially links RV pressure loading, fibrosis, and dysfunction and may be useful to follow clinically. NEW & NOTEWORTHY Biventricular fibrosis and dysfunction impact outcomes in RV pressure loading, but their relation to wall stress is poorly defined. Using a pulmonary artery band rabbit model, we entered echocardiography and catheter data into a computer model to yield regional end-diastolic (EDWS) and end-systolic (ESWS) wall stress. EDWS, more than ESWS, correlated with fibrosis and dysfunction, especially at the fibrosis-intense septal hinge-point regions. Thus, wall stress may be clinically useful in linking RV pressure loading to regional fibrosis and dysfunction.

Reversal of right ventricular pressure loading improves biventricular function independent of fibrosis in a rabbit model of pulmonary artery banding

“…In a recent study using the rabbit PAB model we found that the severity of RV wall stress is moderately related to RV fibrosis and to the degree of RV dysfunction (Gold et al., 2020). In a mouse PAB model, the degree of fibrosis correlated with echo measures of diastolic function such as e′ (Egemnazarov et al., 2015).…”

Valvular heart disease: shifting the focus to the myocardium

“…95–97 However, combined pressure and volume overload is common in these patients whose overall myocardial remodelling and insult are amplified. 95 , 97 Pressure-volume overload may lead also to RV ischaemia which further enhances myocardial fibrosis development. These structural changes all lead ultimately to impaired RV functional parameters which underlies the poor outcomes of these patients.…”

COPD maintenance medication is linked to left atrial size: Results from the COSYCONET cohort

“…An increase of ventricular wall stress is usually rated as being unfavourable for clinical state [20,21], as well as symptoms and prognosis. For instance, increased ventricular wall stress is associated with adverse cardiac remodelling [22,23] and increased risk of arrhythmia [24][25][26][27]. Thus, a reduction of the cardiac filling impairment in COPD by respiratory maintenance medication may contribute to a reduction of symptoms and an improvement of physical capacity [11].…”