Right ventricular remodeling in idiopathic pulmonary arterial hypertension: adaptive versus maladaptive morphology

Badagliacca, Roberto; Poscia, Roberto; Pezzuto, Beatrice; Nocioni, Martina; Mezzapesa, Mario; Francone, Marco; Giannetta, Elisa; Papa, Silvia; Gambardella, Cristina; Sciomer, Susanna; Volterrani, Maurizio; Fedele, Francesco; Vizza, Carmine Dario

doi:10.1016/j.healun.2014.11.002

Cited by 74 publications

(69 citation statements)

References 37 publications

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“…Speckle tracking-derived strain of the RV in patients with PH has been shown to be depressed in proportion to haemodynamic severity and decreased ejection fraction or 6-min walk distance [21] and to be sensitive to therapeutic interventions [21,22] as well as to the occurrence of cardiovascular events [23]. More recently, this novel imaging modality allowed disclosure of regional differences between apical, mid and base segments which were prominent yet not detected by conventional measures of function such as TAPSE in patients with systemic sclerosis compared with controls [24].…”

Section: Discussionmentioning

confidence: 99%

Right ventricular dyssynchrony and exercise capacity in idiopathic pulmonary arterial hypertension

et al. 2017

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Survival in patients with pulmonary arterial hypertension (PAH) is determined by right ventricular (RV) function adaptation to afterload. How altered RV function impacts on exercise capacity in PAH is not exactly known.104 idiopathic PAH (IPAH) patients aged 52±14 years underwent a diagnostic right heart catheterisation, a comprehensive echocardiography including two-dimensional speckle tracking for RV dyssynchrony evaluation and a cardiopulmonary exercise test. Multivariate analyses were performed to identify independent predictors of peak oxygen uptake (peak ' ).A first multivariate analysis of only resting haemodynamic variables identified cardiac index, right atrial (RA) pressure and pulmonary arterial compliance as independent predictors, with low predictive capacity (r=0.31; p<0.001). A second multivariate analysis model which considered only echocardiographic parameters but without RV dyssynchrony, identified RV fractional area change (FAC) and RA area as independent predictors with still low predictivity (r=0.35; p<0.001). Adding RV dyssynchrony to the second model increased its predictivity (r=0.48; p<0.001). Repetition of the three multivariate analyses in patients with preserved RVFAC confirmed that inclusion of RV dyssynchrony results in the highest predictive capability of peak ' (r=0.53; p=0.001).A comprehensive echocardiography with speckle tracking-derived assessment of the heterogeneity of RV contraction improves the prediction of aerobic exercise capacity in IPAH.

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Section: Discussionmentioning

confidence: 99%

Right ventricular dyssynchrony and exercise capacity in idiopathic pulmonary arterial hypertension

et al. 2017

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“…Accordingly, the growth stimuli have been taken to be a deviation from homeostatic stress and stretch along the myofiber direction for the case of concentric and eccentric hypertrophy, respectively [26,27], based on the understanding that the growth mechanism attempts to restore the respective growth stimulus. However, pathophysiology of PAH (and perhaps other structural heart diseases) is not limited to only one phenotype of hypertrophy, and although concentric hypertrophy could be initially prevalent, it may quickly transition to an eccentric phenotype depending on organ-level cardiac demands [9,[28][29][30]. As such, studies that could shed light into the time-evolution of hypertrophy phenotype along PAH progression are essential in developing G&R frameworks with versatile growth stimuli accounting for different phases (e.g., asymptomatic, compensatory, and decompensatory) of heart remodeling.…”

Section: Introductionmentioning

confidence: 99%

Interactions Between Structural Remodeling and Hypertrophy in the Right Ventricle in Response to Pulmonary Arterial Hypertension

Avazmohammadi¹,

Mendiola²,

Li³

et al. 2019

Journal of Biomechanical Engineering

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Pulmonary arterial hypertension (PAH) exerts substantial pressure overload on the right ventricle (RV), inducing RV remodeling and myocardial tissue adaptation often leading to right heart failure. The associated RV free wall (RVFW) adaptation involves myocardial hypertrophy, augmented intrinsic contractility, collagen fibrosis, and structural remodeling in an attempt to cope with pressure overload. If RVFW adaptation cannot maintain the RV stroke volume (SV), RV dilation will prevail as an exit mechanism, which usually decompensates RV function, leading to RV failure. Our knowledge of the factors determining the transition from the upper limit of RVFW adaptation to RV decompensation and the role of fiber remodeling events such as extracellular fibrosis and fiber reorientation in this transition remains very limited. Computational heart models that connect the growth and remodeling (G&R) events at the fiber and tissue levels with alterations in the organ-level function are essential to predict the temporal order and the compensatory level of the underlying mechanisms. In this work, building upon our recently developed rodent heart models (RHM) of PAH, we integrated mathematical models that describe volumetric growth of the RV and structural remodeling of the RVFW. The time-evolution of RV remodeling from control and post-PAH time points was simulated. The results suggest that the augmentation of the intrinsic contractility of myofibers, accompanied by an increase in passive stiffness of RVFW, is among the first remodeling events through which the RV strives to maintain the cardiac output. Interestingly, we found that the observed reorientation of the myofibers toward the longitudinal (apex-to-base) direction was a maladaptive mechanism that impaired the RVFW contractile pattern and advanced along with RV dilation at later stages of PAH. In fact, although individual fibers were more contractile post-PAH, the disruption in the optimal transmural fiber architecture compromised the effective contractile function of the RVFW, contributing to the depressed ejection fraction (EF) of the RV. Our findings clearly demonstrate the critical need for developing multiscale approaches that can model and delineate relationships between pathological alterations in cardiac function and underlying remodeling events across fiber, cellular, and molecular levels.

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“…The RV sensitivity to afterload is heightened compared to the left ventricle (LV) and increased RV afterload can dramatically reduce stroke volume, thus RV dilation might adapt to maintain cardiac output, leading to a decreased RV ejection fraction (RVEF). Indeed, PAH patients show impaired RV longitudinal systolic function, assessed by RV free wall strain, and RV dyssynchrony [9]. Thus, RV dysfunction could be attributable to many factors including RVEF, RV strain, and RV dyssynchrony, and in PAH, although such dysfunction may be induced mainly by the progressive elevation of PVR, the effects of increased afterload on RV remodeling could be diverse, even in the same degree of PAH, probably due to different levels of contractile reserve and myocardial damage.…”

Section: Introductionmentioning

confidence: 99%

Prognostic value of three-dimensional echocardiographic right ventricular ejection fraction in patients with pulmonary arterial hypertension

et al. 2016

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BackgroundRight ventricular (RV) function is an independent predictor of clinical outcomes in patients with pulmonary arterial hypertension (PAH). However, it remains controversial which RV parameter should be measured as an appropriate index for the treatment of PAH. The aim of this study was to identify the most useful parameter that correlates with hemodynamics and predicts clinical outcomes in PAH.ResultsMost of the clinical and echocardiographic RV parameters were significantly correlated with pulmonary vascular resistance (PVR) as well as mean pulmonary arterial pressure (mPAP). Among these, three dimensional right ventricular ejection fraction (3DRVEF) showed the strongest hemodynamic correlation, followed by 6-minute walk distance. Receiver operating characteristic analysis of association with cardiac events including death, hospitalization, and intervention revealed a greater area under the curve for 3DRVEF than for mPAP (0.78 vs. 0.74). Kaplan-Meier analysis showed that patients with 3DRVEF less than 38% had significantly shorter event-free survival than those with greater than 38% (P = 0.0007). Finally, the Cox proportional hazards analysis revealed that 3DRVEF, but not mPAP, was an independent predictor of clinical events in PAH.Materials and MethodsEighty-six consecutive patients were enrolled in this study. RV hemodynamic parameters were measured by right heart catheterization (RHC). RV function was assessed using two-dimensional speckle-tracking echocardiography and three-dimensional transthoracic echocardiography (3DTTE) to evaluate RV free wall global strain (RVFS) and RVEF.ConclusionsRVEF measured by 3DTTE could be a useful parameter for noninvasively assessing RV hemodynamics and predicting the clinical outcomes in PAH patients.

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Right ventricular remodeling in idiopathic pulmonary arterial hypertension: adaptive versus maladaptive morphology

Cited by 74 publications

References 37 publications

Right ventricular dyssynchrony and exercise capacity in idiopathic pulmonary arterial hypertension

Right ventricular dyssynchrony and exercise capacity in idiopathic pulmonary arterial hypertension

Interactions Between Structural Remodeling and Hypertrophy in the Right Ventricle in Response to Pulmonary Arterial Hypertension

Prognostic value of three-dimensional echocardiographic right ventricular ejection fraction in patients with pulmonary arterial hypertension

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