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Helicity and Vorticity of Pulmonary Arterial Flow in Patients With Pulmonary Hypertension: Quantitative Analysis of Flow Formations.

ABSTRACT: Qualitative and quantitative flow hemodynamic indexes have been shown to reflect right ventricular (RV) afterload and function in pulmonary hypertension (PH). We aimed to quantify flow hemodynamic formations in pulmonary arteries using 4-dimensional flow cardiac magnetic resonance imaging and the spatial velocity derivatives helicity and vorticity in a heterogeneous PH population.Patients with PH (n=35) and controls (n=10) underwent 4-dimensional flow magnetic resonance imaging study for computation of helicity and vorticity in the main pulmonary artery (MPA), the right pulmonary artery, and the RV outflow tract. Helicity and vorticity were correlated with standard RV volumetric and functional indexes along with MPA stiffness assessed by measuring relative area change. Patients with PH had a significantly decreased helicity in the MPA (8 versus 32 m/s2; P<0.001), the right pulmonary artery (24 versus 50 m/s2; P<0.001), and the RV outflow tract-MPA unit (15 versus 42 m/s2; P<0.001). Vorticity was significantly decreased in patients with PH only in the right pulmonary artery (26 versus 45 1/s; P<0.001). Total helicity computed correlated with the cardiac magnetic resonance imaging-derived ventricular-vascular coupling (-0.927; P<0.000), the RV ejection fraction (0.865; P<0.0001), cardiac output (0.581; P<0.0001), mean pulmonary arterial pressure (-0.581; P=0.0008), and relative area change measured at the MPA (0.789; P<0.0001).The flow hemodynamic character in patients with PH assessed via quantitative analysis is considerably different when compared with healthy and normotensive controls. A strong association between helicity in pulmonary arteries and ventricular-vascular coupling suggests a relationship between the mechanical and flow hemodynamic domains.

SUBMITTER: Schafer M

PROVIDER: S-EPMC5779020 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Helicity and Vorticity of Pulmonary Arterial Flow in Patients With Pulmonary Hypertension: Quantitative Analysis of Flow Formations.

Schäfer Michal M Barker Alex J AJ Kheyfets Vitaly V Stenmark Kurt R KR Crapo James J Yeager Michael E ME Truong Uyen U Buckner J Kern JK Fenster Brett E BE Hunter Kendall S KS

Journal of the American Heart Association 20171220 12

<h4>Background</h4>Qualitative and quantitative flow hemodynamic indexes have been shown to reflect right ventricular (RV) afterload and function in pulmonary hypertension (PH). We aimed to quantify flow hemodynamic formations in pulmonary arteries using 4-dimensional flow cardiac magnetic resonance imaging and the spatial velocity derivatives helicity and vorticity in a heterogeneous PH population.<h4>Methods and results</h4>Patients with PH (n=35) and controls (n=10) underwent 4-dimensional fl ...[more]

PMID: 29263034

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Project description:ObjectivesLongitudinal hemodynamic follow-up is important in the management of pulmonary hypertension (PH). This study aimed to evaluate the potential of MR 4-dimensional (4D) flow imaging to predict changes in the mean pulmonary arterial pressure (mPAP) during serial investigations.MethodsForty-four adult patients with PH or at risk of developing PH repeatedly underwent routine right heart catheterization (RHC) and near-term MR 4D flow imaging of the main pulmonary artery. The duration of vortical blood flow along the main pulmonary artery was evaluated from MR 4D velocity fields using prototype software and converted to an MR 4D flow imaging-based mPAP estimate (mPAPMR) by a previously established model. The relationship of differences between RHC-derived baseline and follow-up mPAP values (ΔmPAP) to corresponding differences in mPAPMR (ΔmPAPMR) was analyzed by means of regression and Bland-Altman analysis; the diagnostic performance of ΔmPAPMR in predicting mPAP increases or decreases was investigated by ROC analysis.ResultsAreas under the curve for the prediction of mPAP increases and decreases were 0.92 and 0.93, respectively. With the natural cutoff ΔmPAPMR = 0 mmHg, mPAP increases (decreases) were predicted with an accuracy, sensitivity, and specificity of 91% (91%), 85% (89%), and 94% (92%), respectively. For patients in whom 4D flow allowed a point estimate of mPAP (mPAP > 16 mmHg), ΔmPAPMR correlated strongly with ΔmPAP (r = 0.91) and estimated ΔmPAP bias-free with a standard deviation of 5.1 mmHg.ConclusionsMR 4D flow imaging allows accurate non-invasive prediction and quantification of mPAP changes in adult patients with PH or at risk of developing PH.Trial registrationClinicalTrials.gov identifier: NCT00575692 and NCT01725763 KEY POINTS: • MR 4D flow imaging allows accurate non-invasive prediction of mean pulmonary arterial pressure increases and decreases in adult patients with or at risk of developing pulmonary hypertension. • In adult patients with mean pulmonary arterial pressure > 16 mmHg, MR 4D flow imaging allows estimation of longitudinal mean pulmonary arterial pressure changes without bias with a standard deviation of 5.1 mmHg.

Project description:BACKGROUND:While primarily a right heart disease, pulmonary arterial hypertension (PAH) can impact left heart function and aortic flow through a shifted interventricular septum from right ventricular pressure overload and reduced left ventricular preload, among other mechanisms. In this study, we used phase contrast (PC) MRI and a modest exercise challenge to examine the effects of PAH on systemic circulation. While exercise challenges are typically performed with ultrasound in the clinic, MRI exercise studies allow for more reproducible image alignment, more accurate flow quantification, and improved tissue contrast. METHODS:Six PAH patients and fifteen healthy controls (8 older age-matched, 7 younger) exercised in the magnet bore with an MRI-compatible exercise device that allowed for scanning immediately following cessation of exercise. PC scans were performed in the ascending aorta during a breath hold immediately after modest exercise to non-invasively measure stroke volume (SV), cardiac output (CO), aortic peak systolic flow (PSF), and aortic wall stiffness via relative area change (RAC). RESULTS:Images following exercise showed mild blurring, but were high enough quality to allow for segmentation of the aorta. While SV was approximately 30% lower in PAH patients (SVPAH,rest?=?67?±?16?mL; SVPAH,stress?=?90?±?42?mL) than age-matched controls (SV,older,rest?=?93?±?16?mL; SVolder,stress?=?133?±?40?mL) at both rest and following exercise, CO was similar for both groups following exercise (COPAH,stress?=?10.8?±?5.7?L/min; COolder,stress?=?11.8?±?5.0?L/min). This was achieved through a compensatory increase in heart rate in the PAH subjects (74% increase as compared to 29% in age-matched controls). The PAH subjects also demonstrated reduced aortic peak systolic flow relative to the healthy controls (PSFPAH,rest?=?309?±?52?mL/s; PSFolder,rest?=?416?±?114?mL/s; PSFPAH,stress?=?388?±?113?mL/s; PSFolder,stress?=?462?±?176?mL/s). PAH patients and older controls demonstrated stiffer aortic walls when compared to younger controls (RACPAH,rest?=?0.15?±?0.05; RAColder,rest?=?0.17?±?0.05; RACyoung,rest?=?0.28?±?0.08). CONCLUSIONS:PC MRI following a modest exercise challenge was capable of detecting differences in left heart dynamics likely induced from PAH. These results demonstrated that PAH can have a significant influence on systemic flow, even when the patient has no prior left heart disease. Image quantification following exercise could likely be improved in future studies through the implementation of free-breathing or real-time MRI acquisitions. TRIAL REGISTRATION:Retrospectively registered on 02/26/2018 (TRN: NCT03523910 ).

Project description:Pulmonary arterial hypertension (PAH) is a rare disorder associated with high morbidity and mortality despite currently available treatments. We compared the phosphoproteome of lung tissue from subjects with idiopathic PAH (iPAH) obtained at the time of lung transplant with control lung tissue. The mass spectrometry-based analysis found 60,428 phosphopeptide features from which 6622 proteins were identified. Within the subset of identified proteins there were 1234 phosphopeptides with q < 0.05, many of which are involved in immune regulation, angiogenesis, and cell proliferation. Most notably there was a marked relative increase in phosphorylated (S378) IKZF3 (Aiolos), a zinc finger transcription factor that plays a key role in lymphocyte regulation. In vitro phosphorylation assays indicated that GSK3 alpha and/or GSK3 beta could phosphorylate IKZF3 at S378. Western blot analysis demonstrated increased pIKZF3 in iPAH lungs compared to controls. Immunohistochemistry demonstrated phosphorylated IKZF3 in lymphocytes surrounding severely hypertrophied pulmonary arterioles. In situ hybrization showed gene expression in lymphocyte aggregates in PAH samples. A BCL2 reporter assay showed that IKZF3 increased BCL2 promoter activity and demonstrated the potential role of phosphorylation of IKZF3 in the regulation of BCL mediated transcription. Kinase network analysis demonstrated potentially important regulatory roles of casein kinase 2, cyclin-dependent kinase 1 (CDK1), mitogen-associated protein kinases (MAPKs), and protein kinases (PRKs) in iPAH. Bioinformatic analysis demonstrated enrichment of RhoGTPase signaling and the potential importance of cGMP-dependent protein kinase 1 (PRKG). In conclusion, this unbiased phosphoproteomic analysis demonstrated several novel targets regulated by kinase networks in iPAH, and reinforced the potential role of immune regulation in the pathogenesis of iPAH. The identified up- and down-regulated phosphoproteins have potential to serve as biomarkers for PAH and to provide new insights for therapeutic strategies.

Project description:Inhalation profiles to support use of dry powder inhalers for drug delivery in patients with pulmonary arterial hypertension have not been reported. We aimed to evaluate the inspiratory flow pattern associated with low and medium flow resistance dry powder inhaler devices (RS01-L and RS01-M, respectively) in patients with pulmonary arterial hypertension. This single-center study enrolled patients with pulmonary arterial hypertension associated with connective tissue disease (n = 10) and idiopathic pulmonary arterial hypertension (n = 10) to measure the following inhalation parameters: inspiratory effort (kPa), peak inspiratory flow rate (L/min), inhaled volume (L), and flow increase rate (L/s2) using the two devices. We identified a trend toward higher mean pulmonary artery pressure in the idiopathic pulmonary arterial hypertension group (50 ± 13 mmHg vs. 40 ± 11 mmHg in pulmonary arterial hypertension associated with connective tissue disease; p = 0.077). On average, peak inspiratory flow rate was higher with RS01-L vs. RS01-M (84 ± 19.7 L/min vs. 70.4 ± 13.2 L/min; p = 0.015). In the overall group, no differences between RS01-L and RS01-M were observed for inhaled volume, inspiratory effort, or flow increase rate. Inhaled volume with RS01-L was higher in pulmonary arterial hypertension associated with connective tissue disease vs. idiopathic pulmonary arterial hypertension patients: 1.6 ± 0.4 L vs. 1.3 ± 0.2 L; p = 0.042. For the RS01-L, inhaled volume correlated with forced expiratory volume in one second (r = 0.460, p = 0.030) and forced vital capacity (r = 0.507, p = 0.015). In patients with pulmonary arterial hypertension associated with connective tissue disease using RS01-L, both inspiratory effort and flow increase rate were highly correlated with pulmonary vascular compliance (r = 0.903, p = 0.0001 and r = 0.906, p = 0.0001; respectively); while with RS01-M, inspiratory effort was highly correlated with pulmonary vascular compliance (r = 0.8, p = 0.001). Our data suggest that the use of RS01-L and RS01-M dry powder inhaler devices allowed adequate inspiratory flow in pulmonary arterial hypertension patients. The correlation between flow increase rate and pulmonary vascular compliance in pulmonary arterial hypertension associated with connective tissue disease deserves further investigation.

Dataset Information

Helicity and Vorticity of Pulmonary Arterial Flow in Patients With Pulmonary Hypertension: Quantitative Analysis of Flow Formations.

Publications

Helicity and Vorticity of Pulmonary Arterial Flow in Patients With Pulmonary Hypertension: Quantitative Analysis of Flow Formations.

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