skip to main content


Title: Pulmonary vascular distensibility with passive leg raise is comparable to exercise and predictive of clinical outcomes in pulmonary hypertension
Abstract

Pulmonary vascular distensibility (α) is a marker of the ability of the pulmonary vasculature to dilate in response to increases in cardiac output, which protects the right ventricle from excessive increases in afterload. α measured with exercise predicts clinical outcomes in pulmonary hypertension (PH) and heart failure. In this study, we aim to determine if α measured with a passive leg raise (PLR) maneuver is comparable to α with exercise. Invasive cardiopulmonary exercise testing (iCPET) was performed with hemodynamics recorded at three stages: rest, PLR and peak exercise. Four hemodynamic phenotypes were identified (2019 ECS guidelines): pulmonary arterial hypertension (PAH) (n = 10), isolated post‐capillary (Ipc‐PH) (n = 18), combined pre‐/post‐capillary PH (Cpc‐PH) (n = 15), and Control (no significant PH at rest and exercise) (n = 7). Measurements of mean pulmonary artery pressure, pulmonary artery wedge pressure, and cardiac output at each stage were used to calculate α. There was no statistical difference between α‐exercise and α‐PLR (0.87 ± 0.68 and 0.78 ± 0.47% per mmHg, respectively). The peak exercise‐ and PLR‐based calculations of α among the four hemodynamic groups were: Ipc‐PH = Ex: 0.94 ± 0.30, PLR: 1.00 ± 0.27% per mmHg; Cpc‐PH = Ex: 0.51 ± 0.15, PLR: 0.47 ± 0.18% per mmHg; PAH = Ex: 0.39 ± 0.23, PLR: 0.34 ± 0.18% per mmHg; and the Control group: Ex: 2.13 ± 0.91, PLR: 1.45 ± 0.49% per mmHg. Patients withα ≥ 0.7% per mmHg had reduced cardiovascular death and hospital admissions at 12‐month follow‐up. In conclusion, α‐PLR is feasible and may be equally predictive of clinical outcomes as α‐exercise in patients who are unable to exercise or in programs lacking iCPET facilities.

 
more » « less
NSF-PAR ID:
10445864
Author(s) / Creator(s):
 ;  ;  ;  ;  ;  
Publisher / Repository:
Wiley Blackwell (John Wiley & Sons)
Date Published:
Journal Name:
Pulmonary Circulation
Volume:
12
Issue:
1
ISSN:
2045-8940
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
More Like this
  1. null (Ed.)
    Diastolic dysfunction is a common pathology occurring in about one third of patients affected by heart failure. This condition may not be associated with a marked decrease in cardiac output or systemic pressure and therefore is more difficult to diagnose than its systolic counterpart. Compromised relaxation or increased stiffness of the left ventricle induces an increase in the upstream pulmonary pressures, and is classified as secondary or group II pulmonary hypertension (2018 Nice classification). This may result in an increase in the right ventricular afterload leading to right ventricular failure. Elevated pulmonary pressures are therefore an important clinical indicator of diastolic heart failure (sometimes referred to as heart failure with preserved ejection fraction, HFpEF), showing significant correlation with associated mortality. However, accurate measurements of this quantity are typically obtained through invasive catheterization and after the onset of symptoms. In this study, we use the hemodynamic consistency of a differential-algebraic circulation model to predict pulmonary pressures in adult patients from other, possibly non-invasive, clinical data. We investigate several aspects of the problem, including the ability of model outputs to represent a sufficiently wide pathologic spectrum, the identifiability of the model's parameters, and the accuracy of the predicted pulmonary pressures. We also find that a classifier using the assimilated model parameters as features is free from the problem of missing data and is able to detect pulmonary hypertension with sufficiently high accuracy. For a cohort of 82 patients suffering from various degrees of heart failure severity, we show that systolic, diastolic, and wedge pulmonary pressures can be estimated on average within 8, 6, and 6 mmHg, respectively. We also show that, in general, increased data availability leads to improved predictions. 
    more » « less
  2. Background Despite favorable outcomes of surgical pulmonary artery (PA) reconstruction, isolated proximal stenting of the central PAs is common clinical practice for patients with peripheral PA stenosis in association with Williams and Alagille syndromes. Given the technical challenges of PA reconstruction and the morbidities associated with transcatheter interventions, the hemodynamic consequences of all treatment strategies must be rigorously assessed. Our study aims to model, assess, and predict hemodynamic outcomes of transcatheter interventions in these patients. Methods and Results Isolated proximal and “extensive” interventions (stenting and/or balloon angioplasty of proximal and lobar vessels) were performed in silico on 6 patient‐specific PA models. Autoregulatory adaptation of the cardiac output and downstream arterial resistance was modeled in response to intervention‐induced hemodynamic perturbations. Postintervention computational fluid dynamics predictions were validated in 2 stented patients and quantitatively assessed in 4 surgical patients. Our computational methods accurately predicted postinterventional PA pressures, the primary indicators of success for treatment of peripheral PA stenosis. Proximal and extensive treatment achieved median reductions of 14% and 40% in main PA systolic pressure, 27% and 56% in pulmonary vascular resistance, and 10% and 45% in right ventricular stroke work, respectively. Conclusions In patients with Williams and Alagille syndromes, extensive transcatheter intervention is required to sufficiently reduce PA pressures and right ventricular stroke work. Transcatheter therapy was shown to be ineffective for long‐segment stenosis and pales hemodynamically in comparison with published outcomes of surgical reconstruction. Regardless of the chosen strategy, a virtual treatment planning platform could identify lesions most critical for optimizing right ventricular afterload. 
    more » « less
  3. Abstract

    Right ventricular (RV) failure remains a significant clinical burden particularly during the perioperative period surrounding major cardiac surgeries, such as implantation of left ventricular assist devices (LVADs), bypass procedures or valvular surgeries. Device solutions designed to support the function of the RV do not keep up with the pace of development of left‐sided solutions, leaving the RV vulnerable to acute failure in the challenging hemodynamic environments of the perioperative setting. This work describes the design of a biomimetic, soft, conformable sleeve that can be prophylactically implanted on the pulmonary artery to support RV ventricular function during major cardiac surgeries, through afterload reduction and augmentation of flow. Leveraging electrohydraulic principles, a technology is proposed that is non‐blood contacting and obviates the necessity for drivelines by virtue of being electrically powered. In addition, the integration of an adjacent is demonstrate, continuous pressure sensing module to support physiologically adaptive control schemes based on a real‐time biological signal. In vitro experiments conducted in a pulsatile flow‐loop replicating physiological flow and pressure conditions show a reduction of mean pulmonary arterial pressure of 8 mmHg (25% reduction), a reduction in peak systolic arterial pressure of up to 10 mmHg (20% reduction), and a concomitant 19% increase in diastolic pulmonary flow. Computational simulations further predict substantial augmentation of cardiac output as a result of reduced RV ventricular stress and RV dilatation.

     
    more » « less
  4. Pulmonary hypertension (PH), defined by a mean pulmonary arterial blood pressure above 20 mmHg in the main pulmonary artery, is a cardiovascular disease impacting the pulmonary vasculature. PH is accompanied by chronic vascular remodeling, wherein vessels become stiffer, large vessels dilate, and smaller vessels constrict. Some types of PH, including hypoxia-induced PH (HPH), also lead to microvascular rarefaction. This study analyzes the change in pulmonary arterial morphometry in the presence of HPH using novel methods from topological data analysis (TDA). We employ persistent homology to quantify arterial morphometry for control and HPH mice characterizing normalized arterial trees extracted from micro-computed tomography (micro-CT) images. We normalize generated trees using three pruning algorithms before comparing the topology of control and HPH trees. This proof-of-concept study shows that the pruning method affects the spatial tree statistics and complexity. We find that HPH trees are stiffer than control trees but have more branches and a higher depth. Relative directional complexities are lower in HPH animals in the right, ventral, and posterior directions. For the radius pruned trees, this difference is more significant at lower perfusion pressures enabling analysis of remodeling of larger vessels. At higher pressures, the arterial networks include more distal vessels. Results show that the right, ventral, and posterior relative directional complexities increase in HPH trees, indicating the remodeling of distal vessels in these directions. Strahler order pruning enables us to generate trees of comparable size, and results, at all pressure, show that HPH trees have lower complexity than the control trees. Our analysis is based on data from 6 animals (3 control and 3 HPH mice), and even though our analysis is performed in a small dataset, this study provides a framework and proof-of-concept for analyzing properties of biological trees using tools from Topological Data Analysis (TDA). Findings derived from this study bring us a step closer to extracting relevant information for quantifying remodeling in HPH. 
    more » « less
  5. Abstract

    Pulmonary hypertension (PH), defined as an elevated mean blood pressure in the main pulmonary artery (MPA) at rest, is associated with vascular remodeling of both large and small arteries. PH has several sub‐types that are all linked to high mortality rates. In this study, we use a one‐dimensional (1‐D) fluid dynamics model driven by in vivo measurements of MPA flow to understand how model parameters and network size influence MPA pressure predictions in the presence of PH. We compare model predictions with in vivo MPA pressure measurements from a control and a hypertensive mouse and analyze results in three networks of increasing complexity, extracted from micro‐computed tomography (micro‐CT) images. We introduce global scaling factors for boundary condition parameters and perform local and global sensitivity analysis to calculate parameter influence on model predictions of MPA pressure and correlation analysis to determine a subset of identifiable parameters. These are inferred using frequentist optimization and Bayesian inference via the Delayed Rejection Adaptive Metropolis (DRAM) algorithm. Frequentist and Bayesian uncertainty is computed for model parameters and MPA pressure predictions. Results show that MPA pressure predictions are most sensitive to distal vascular resistance and that parameter influence changes with increasing network complexity. Our outcomes suggest that PH leads to increased vascular stiffness and decreased peripheral compliance, congruent with clinical observations.

     
    more » « less