Right ventricular stroke work correlates with outcomes in pediatric pulmonary arterial hypertension

Abstract

Pulmonary arterial hypertension (PAH) is characterized by elevated pulmonary artery pressures (PAP) and pulmonary vascular resistance (PVR). Optimizing treatment strategies and timing for transplant remains challenging. Thus, a quantitative measure to predict disease progression would be greatly beneficial in treatment planning. We devised a novel method to assess right ventricular (RV) stroke work (RVSW) as a potential biomarker of the failing heart that correlates with clinical worsening. Pediatric patients with idiopathic PAH or PAH secondary to congenital heart disease who had serial, temporally matched cardiac catheterization and magnetic resonance imaging (MRI) data were included. RV and PA hemodynamics were numerically determined by using a lumped parameter (circuit analogy) model to create pressure-volume (P-V) loops. The model was tuned using optimization techniques to match MRI and catheterization derived RV volumes and pressures for each time point. RVSW was calculated from the corresponding P-V loop and indexed by ejection fraction and body surface area (RVSW) to compare across patients. Seventeen patients (8 boys; median age = 9.4 years; age range = 4.4-16.3 years) were enrolled. Nine were clinically stable; the others had clinical worsening between the time of their initial matched studies and their most recent follow-up (mean time = 3.9 years; range = 1.1-8.0 years). RVSW and the ratio of pulmonary to systemic resistance (Rp:Rs) values were found to have more significant associations with clinical worsening within one, two, and five years following the measurements, when compared with PVR index (PVRI). A receiver operating characteristic analysis showed RVSW outperforms PVRI, Rp:Rs and ejection fraction for predicting clinical worsening. RVSW correlates with clinical worsening in pediatric PAH, shows promising results towards predicting adverse outcomes, and may serve as an indicator of future clinical worsening.

Comparison of Right Ventricular Function Between Patients With and Without Pulmonary Hypertension Owing to Left-Sided Heart Disease: Assessment Based on Right Ventricular Pressure–Volume Curves

“…It has been reported in pediatric patients with pulmonary arterial hypertension (PAH). 33 In patients with PAH, the RV-PVC generally becomes larger and shifts toward the right with increasing RV stroke work as the clinical condition worsens. 33 This is caused by an increase in mPAP as a consequence of increased resistance and RV dilation to preserve SV in the advanced phase.…”

Multilevel and multifidelity uncertainty quantification for cardiovascular hemodynamics

“…This factor can be changed to target different variances and, by extension, different accuracies for the QoIs, as accuracy is a function of variance. The formulae for the optimal number of samples needed for extrapolation are given by (13), (18), and (20) for the MLMC, MFMC, and MLMF estimators, respectively.…”

“…We introduced the process of extrapolation to estimate the additional number of simulations of each model and fidelity needed to improve the estimator variance by a factor . The formulae for the optimal Outlet Flow Model TAWSS MC MLMC MLMF MLMF MC MLMC MLMF MLMF 3D-1D 3D-1D-0D 3D-1D 3D-1D- number of samples needed for extrapolation are given by (13), (18), and (20) for the MLMC, MFMC, and MLMF estimators, respectively. These formulae have been used successfully for applications such as engine nozzles, scramjets, and wind turbines [47,69].…”

“…These include computing fractional flow reserve for patients with coronary stenoses [5] and assessing differences in the hemodynamic and mechanical response of arterial and venous grafts towards determining cause of vein graft failure [6]. Computational models have also been applied to congenital heart disease for prognosis and treatment planning, from testing designs for surgical interventions of single ventricle congenital heart disease [7-9] to thrombotic risk assessment for Kawasaki disease [10][11][12], and assessment of disease progression and mechanical stimuli in pulmonary hypertension [13,14]. Hemodynamic studies are also used for additional disease cases, such as analyzing blood flow patterns in abdominal aortic aneurysms [15,16] and predicting the development and rupture of cerebral aneurysms [17][18][19].Realistic three-dimensional hemodynamic simulations require segmentation of vascular anatomies from medical image data, followed by numerical solution of the equations governing blood flow in elastically deformable vessels.…”

Genotypes and Phenotypes: Making Progress Toward a Precision Medicine Approach in Pediatric Pulmonary Hypertension

“…50 Yang et al used computational modeling to include both hemodynamic and MRI data in a calculation of RV stroke work, which outperformed both pulmonary vascular resistance and RVEF in predicting clinical worsening in a cohort of children with PAH. 51 In addition to the absolute values, the rate of change of RV stroke work may be particularly helpful to predict clinical worsening in the individual patient (Figure 3). While these studies suggest additive value of MRI in routine clinical assessment, there remains significant variability in current clinical practice.…”