Pulmonary Artery Hemodynamics Research Articles

Making Living-donor Liver Transplantation a Viable Option for Patients With Portopulmonary Hypertension.

Liver transplantation (LT) in patients with significant portopulmonary hypertension (PoPH) is associated with an increased risk of several complications, including graft failure. Graft loss is one of the major reasons. Living donor LT (LDLT) is not routinely performed in the United States in this patient population. In addition, ethical considerations often preclude donation from healthy donors in the setting of a procedure associated with an elevated risk of recipient morbidity and mortality. However, LDLT allows LT to be performed electively, using a superior graft with an improved probability of a good outcome. The key to success in managing these patients is establishing a multidisciplinary team that follows an institutional protocol with clear evaluation and management criteria. These criteria include screening and early diagnosis as well as treatment of PoPH with the goal of optimizing pulmonary arterial hemodynamics and maintaining right ventricular function. Any protocol should include admitting the patient to the hospital a day before surgery for placement of a pulmonary artery catheter to measure and derive relevant hemodynamic variables. A multidisciplinary team should determine the fitness for a transplant a after a careful review of the most up-to-date clinical information. Finally, the team prescribes and executes a plan for optimization and safe perioperative management of the patient. In this report, we discuss our approach to the perioperative management of a patient with significant PoPH who safely underwent LDLT with an excellent postoperative outcome.

Unsupervised physics-informed deep learning for assessing pulmonary artery hemodynamics

Deep learning advancements have significantly benefited medical applications. One such helpful application is noninvasive fractional flow reserve (FFR) evaluation along the pulmonary artery tree, which aids in planning optimal balloon pulmonary angioplasty. This study proposes a surrogate model that employs an unsupervised physics-informed neural network (UPNN) to predict FFR based on pulmonary CT angiography. To ensure the UPNN strictly follows the unique solution of the governing equations, we implemented a hard boundary conditions enforcement approach. Subsequently, a finite difference convolutional filter was developed to enhance connectivity among neighboring points. This allows the neural networks to propagate boundary conditions into the unseen vessel interior and perceive the geometric structure of the computational domain. We also introduced regularization constraints on the three components contributing to pressure drop within the artery tree. A total of 4500 synthetic pulmonary artery trees were used to train the UPNN with impedance outlet boundary conditions. We found that the limits of agreement of FFR trained by UPNN ranged from −0.05 to 0.04 with computational fluid dynamics (CFD) simulation results. The testing results showed that the correlation coefficient between FFR predicted by UPNN and CFD were 96.1% and 94.7% for synthetic and patient-specific data, respectively. Using invasive FFR as reference, the accuracy of FFR predicted by UPNN and CFD was 81.4% and 84.8%, respectively. These results demonstrate that our UPNN-based surrogate model’s performance in evaluating FFR aligns closely with CFD simulations.

Computational Study on the Effects of Valve Orientation on the Hemodynamics and Leaflet Dynamics of Bioprosthetic Pulmonary Valves.

Pulmonary valves do not display a fibrous annulus as do other valves in the heart; thus, pulmonary valves can be implanted at multiple orientations and locations within the right ventricular outflow tract (RVOT). This gives surgeons more freedom when implanting the valve but it also results in uncertainties regarding placement, particularly with respect to valve orientation. We investigate the pulmonary artery hemodynamics and valve leaflet dynamics of pulmonary valve replacements (PVRs) with various orientations via fluid-structure interaction (FSI) models. A canonical model of the branching pulmonary artery is coupled with a dynamic model of a pulmonary valve, and from this we quantify the effect of valve implant orientation on the postvalvular hemodynamics and leaflet dynamics. Metrics such as turbulent kinetic energy (TKE), branch pulmonary artery flow distributions, projected valve opening area (PVOA), and pressure differentials across the valve leaflets are analyzed. Our results indicate that off-axis orientation results in higher pressure forces and flow and energy asymmetry, which potentially have implications for long-term durability of implanted bioprosthetic valves.

Efficient uncertainty quantification in a spatially multiscale model of pulmonary arterial and venous hemodynamics.

Pulmonary hypertension (PH) is a debilitating disease that alters the structure and function of both the proximal and distal pulmonary vasculature. This alters pressure-flow relationships in the pulmonary arterial and venous trees, though there is a critical knowledge gap in the relationships between proximal and distal hemodynamics in disease. Multiscale computational models enable simulations in both the proximal and distal vasculature. However, model inputs and measured data are inherently uncertain, requiring a full analysis of the sensitivity and uncertainty of the model. Thus, this study quantifies model sensitivity and output uncertainty in a spatially multiscale, pulse-wave propagation model of pulmonary hemodynamics. The model includes fifteen proximal arteries and twelve proximal veins, connected by a two-sided, structured tree model of the distal vasculature. We use polynomial chaos expansions to expedite sensitivity and uncertainty quantification analyses and provide results for both the proximal and distal vasculature. We quantify uncertainty in blood pressure, blood flow rate, wave intensity, wall shear stress, and cyclic stretch. The latter two are important stimuli for endothelial cell mechanotransduction. We conclude that, while nearly all the parameters in our system have some influence on model predictions, the parameters describing the density of the microvascular beds have the largest effects on all simulated quantities in both the proximal and distal arterial and venous circulations.

Surgical Modulation of Pulmonary Artery Shear Stress: A Patient-Specific CFD Analysis of the Norwood Procedure.

This study created 3D CFD models of the Norwood procedure for hypoplastic left heart syndrome (HLHS) using standard angiography and echocardiogram data to investigate the impact of shunt characteristics on pulmonary artery (PA) hemodynamics. Leveraging routine clinical data offers advantages such as availability and cost-effectiveness without subjecting patients to additional invasive procedures. Patient-specific geometries of the intrathoracic arteries of two Norwood patients were generated from biplane cineangiograms. "Virtual surgery" was then performed to simulate the hemodynamics of alternative PA shunt configurations, including shunt type (modified Blalock-Thomas-Taussig shunt (mBTTS) vs. right ventricle-to-pulmonary artery shunt (RVPAS)), shunt diameter, and pulmonary artery anastomosis angle. Left-right pulmonary flow differential, Qp/Qs, time-averaged wall shear stress (TAWSS), and oscillatory shear index (OSI) were evaluated. There was strong agreement between clinically measured data and CFD model output throughout the patient-specific models. Geometries with a RVPAS tended toward more balanced left-right pulmonary flow, lower Qp/Qs, and greater TAWSS and OSI than models with a mBTTS. For both shunt types, larger shunts resulted in a higher Qp/Qs and higher TAWSS, with minimal effect on OSI. Low TAWSS areas correlated with regions of low flow and changing the PA-shunt anastomosis angle to face toward low TAWSS regions increased TAWSS. Excellent correlation between clinically measured and CFD model data shows that 3D CFD models of HLHS Norwood can be developed using standard angiography and echocardiographic data. The CFD analysis also revealed consistent changes in PA TAWSS, flow differential, and OSI as a function of shunt characteristics.

Subject-specific one-dimensional fluid dynamics model of chronic thromboembolic pulmonary hypertension

Chronic thromboembolic pulmonary hypertension (CTEPH) develops due to the accumulation of blood clots in the lung vasculature that obstructs flow and increases pressure. The mechanobiological factors that drive progression of CTEPH are not understood, in part because mechanical and hemodynamic changes in the small pulmonary arteries due to CTEPH are not easily measurable. Using previously published hemodynamic measurements and imaging from a large animal model of CTEPH, we applied a subject-specific one-dimensional (1D) computational fluid dynamic (CFD) approach to investigate the impact of CTEPH on pulmonary artery stiffening, time-averaged wall shear stress (TAWSS), and oscillatory shear index (OSI) in extralobar (main, right, and left) pulmonary arteries and intralobar (distal to the extralobar) arteries. Our results demonstrate that CTEPH increases pulmonary artery wall stiffness and decreases TAWSS in extralobar and intralobar arteries. Moreover, CTEPH increases the percentage of the intralobar arterial network with both low TAWSS and high OSI, quantified by the novel parameter φ\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\varphi$$\\end{document}, which is related to thrombogenicity. Our analysis reveals a strong positive correlation between increases in mean pulmonary artery pressure (mPAP) and φ\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\varphi$$\\end{document} from baseline to CTEPH in individual subjects, which supports the suggestion that increased φ\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\varphi$$\\end{document} drives disease severity. This subject-specific experimental–computational framework shows potential as a predictor of the impact of CTEPH on pulmonary arterial hemodynamics and pulmonary vascular mechanics. By leveraging advanced modeling techniques and calibrated model parameters, we predict spatial distributions of flow and pressure, from which we can compute potential physiomarkers of disease progression. Ultimately, this approach can lead to more spatially targeted interventions that address the needs of individual CTEPH patients.

Assessment of Pulmonary Arteries Hemodynamics and Its Relationship With Cardiac Remodeling and Myocardial Fibrosis in Athletes With Four-Dimensional Flow MRI.

Exercise-induced cardiac remodeling (CR) and myocardial fibrosis (MF) can increase cardiovascular risk in athletes. Early detection of pulmonary arterial hemodynamics parameters among athletes may be beneficial in optimizing the frequency of clinical follow-ups. To analyze the hemodynamics of pulmonary arteries and its relationship with CR and MF in athletes using four-dimensional (4D) flow MRI. Prospective. One hundred twenty-one athletes (median age, 24 years; mean exercise per week 10 hours, for mean of 5 years) and twenty-onesedentary healthy controls (median age, 25 years; exercise per week <3 hours, irregular pattern). True fast imaging with steady state free precession, time-resolved 3D Cartesian phase-contrast, and phase sensitive inversion recovery late gadolinium enhancement sequences at 3.0 T. CR was defined as any cardiac parameters exceeding the 99th percentile upper reference limits, encompassing ventricular function, bi-atrium and bi-ventricle diameters, and ventricular wall thickness. MF was visually evaluated by three independent radiologists. 4D flow parameters were assessed in the main, right, and left pulmonary arteries (MPA, RPA, and LPA, respectively) and compared between different groups. Four machine learning (ML) models were developed to differentiate between athletes with and without CR and/or MF. Univariate analysis was used to compare groups. Area under the receiver operating characteristic curve (AUC) was used to assess the performance of the ML models. Athletes had significantly higher WSSmax in the MPA, RPA, and LPA than controls. Athletes with CR and/or MF (N = 30) had significantly lower RPmax from MPA to RPA than those without (N = 91). Among the ML models, the gradient boosting machine model had the highest performance, with an AUC of 0.90. The pulmonary arterial hemodynamics parameters could differentiate CR and/or MF in athletes, which may be potential to assist in optimizing frequency of follow-up. 1 TECHNICAL EFFICACY: Stage 2.

A computational growth and remodeling framework for adaptive and maladaptive pulmonary arterial hemodynamics.

Hemodynamic loading is known to contribute to the development and progression of pulmonary arterial hypertension (PAH). This loading drives changes in mechanobiological stimuli that affect cellular phenotypes and lead to pulmonary vascular remodeling. Computational models have been used to simulate mechanobiological metrics of interest, such as wall shear stress, at single time points for PAH patients. However, there is a need for new approaches that simulate disease evolution to allow for prediction of long-term outcomes. In this work, we develop a framework that models the pulmonary arterial tree through adaptive and maladaptive responses to mechanical and biological perturbations. We coupled a constrained mixture theory-based growth and remodeling framework for the vessel wall with a morphometric tree representation of the pulmonary arterial vasculature. We show that non-uniform mechanical behavior is important to establish the homeostatic state of the pulmonary arterial tree, and that hemodynamic feedback is essential for simulating disease time courses. We also employed a series of maladaptive constitutive models, such as smooth muscle hyperproliferation and stiffening, to identify critical contributors to development of PAH phenotypes. Together, these simulations demonstrate an important step toward predicting changes in metrics of clinical interest for PAH patients and simulating potential treatment approaches.

Assessment of pulmonary artery stiffness by multiparametric cardiac magnetic resonance-surrogate for right heart catheterization.

Cardiac magnetic resonance (CMR) imaging allows for multiparametric assessment of healthy pulmonary artery (PA) hemodynamics. Gender- and aging-associated PA stiffness and pressure alterations have remained clinically unestablished, however may demonstrate epidemiological differences in disease development. The aim of this study is to evaluate the role of CMR as a surrogate for catheter examinations by providing a comprehensive CMR assessment of sex- and age-related reference values for PA stiffness, flow, and pressure. PA hemodynamics were studied between gender and age groups (>/<50 years) using phase-contrast CMR. Corresponding correlation analyses were performed. 179 healthy volunteers with a median age of 32.6 years (range 11.3-68.2) were examined. Males demonstrated increased PA compliance (median [interquartile range] or mean ± standard deviation) (20.8 mm2/mmHg [16.6; 25.8] vs. 19.2 ± 7.1 mm2/mmHg; P < 0.033), higher pulse wave velocity (2.00 m/s [1.35; 2.87] vs. 1.73 m/s [1.19; 2.34]; P = 0.018) and a reduced full width half maximum (FWHM) (219 ± 22 ms vs. 235 ± 23 ms; P < 0.001) than females. Mean, systolic, diastolic PA pressure and pulmonary proportional pulse pressure were significantly elevated for males compared to females (P < 0.001). Older subjects (>50 years) exhibited reduced PA elasticity (41.7% [31.0; 52.9] vs. 66.4% [47.7; 83.0]; P < 0.001), reduced PA compliance (15.4 mm2/mmHg [12.3; 20.7] vs. 21.3 ± 6.8 mm2/mmHg; P < 0.001), higher pulse wave velocity (2.59 m/s [1.57; 3.59] vs. 1.76 m/s [1.24; 2.34]; P < 0.001) and a reduced FWHM (218 ± 29 ms vs. 231 ± 21 ms; P < 0.001) than younger subjects. Velocity-time profiles are dependent on age and gender. PA stiffness indices deteriorate with age. CMR has potential to serve as a surrogate for right heart catheterization.

Pulmonary pulse transit time as the first sign of pulmonary arterial hemodynamics alteration.

Pulmonary pulse transit time as the first sign of pulmonary arterial hemodynamics alteration.

Correlation between serum GDF-15 level and pulmonary vascular morphological changes and prognosis in patients with pulmonary arterial hypertension.

To investigate how serum GDF-15 concentration affects pulmonary artery hemodynamics and pulmonary vascular morphological changes in patients with pulmonary arterial hypertension. A total of 45 patients admitted to our hospital from December 2017 to December 2019, were selected for the study. Pulmonary vascular hemodynamics and pulmonary vascular morphology were detected by RHC and IVUS. Serum GDF-15 levels were detected by enzyme-linked immunosorbent assay (ELISA). Based on the concentration of GDF-15, the patients were divided into two groups-the normal GDF-15 group (GDF-15 <1,200 pg/ml, 12 cases) and the elevated GDF-15 group (GDF-15 ≥1,200 pg/ml, 33 cases). A statistical analysis was performed to compare the effects of normal blood GDF-15 levels and high serum GDF-15 levels on hemodynamics and pulmonary vascular morphology in each group of patients. The average levels of RVP, sPAP, dPAP, mPAP, and PVR in patients with elevated GDF-15 levels were higher than those in patients with normal GDF-15 levels. The difference between the two groups was statistically significant (P < 0.05). The average levels of Vd, elastic modulus, stiffness index β, lesion length, and PAV in the normal GDF-15 group were lower than those in the elevated GDF-15 group. The average levels of compliance, distensibility, and minimum l umen area were higher than those in the elevated GDF-15 group. The difference between the two groups was statistically significant (P < 0.05). The survival analysis results showed that the 1-year survival rate of patients with normal GDF-15 levels and elevated GDF-15 levels was 100% and 87.9%, respectively, and that the 3-year survival rate of patients with normal GDF-15 levels and elevated GDF-15 levels was 91.7% and 78.8%, respectively. The survival rates of the two groups were compared by the Kaplan Meier method, and the difference was not statistically significant (P > 0.05). Patients with pulmonary arterial hypertension with elevated GDF-15 levels have higher pulmonary arterial pressure, higher pulmonary vascular resistance, and more serious pulmonary vascular lesions, which are potentially more harmful. There was no statistically significant difference in survival rates among patients with different serum GDF-15 levels.

Impact of right ventricular-pulmonary arterial coupling on clinical outcomes in patients undergoing transcatheter aortic valve implantation

AimsThe interplay between pulmonary hypertension (PH) and right ventricular (RV) function is reflected in an index of RV function to pulmonary artery (PA) systolic pressure (PASP). The present study aimed to assess the importance of RV-PA coupling on clinical outcomes after transcatheter aortic valve implantation (TAVI). Methods and resultsIn a prospective TAVI registry, clinical outcomes of TAVI patients with RV dysfunction or PH were stratified according to coupling or uncoupling of tricuspid annular plane systolic excursion (TAPSE) to PASP, and compared to those of patients with normal RV function and absence of PH. The median TAPSE/PASP ratio was used to differentiate uncoupling (>0.39) from coupling (<0.39). Among 404 TAVI patients, 201 patients (49.8 %) had RVD or PH at baseline: 174 patients had RV-PA uncoupling, and 27 had coupling at baseline. RV-PA hemodynamics normalized in 55.6 % of patients with RV-PA coupling and in 28.2 % of patients with RV-PA uncoupling, and deteriorated in 33.3 % of patients with RV-PA coupling and in 17.8 % of patients with no RVD, respectively, at discharge. Patients with RV-PA uncoupling after TAVI showed a trend towards an increased risk of cardiovascular death at 1 year as compared to patients with normal RV-function (HRadjusted 2.06, 95 % CI 0.97–4.37). ConclusionAfter TAVI, RV-PA coupling changed in a significant proportion of patients and is a potentially important metric for risk stratification of TAVI patients with RVD or PH. Tweet“Patients with right ventricular dysfunction and pulmonary hypertension are at increased risk of death after TAVI. Integrated right ventricular to pulmonary artery hemodynamics change after TAVI in a significant proportion of patients and is instrumental to refine risk stratification.” Clinical trial registrationhttps://www.clinicaltrials.gov: NCT01368250.

Shikonin improves pulmonary vascular remodeling in monocrotaline‑induced pulmonary arterial hypertension via regulation of PKM2.

Pulmonary arterial hypertension (PAH), a fatal disease with an insidious onset and rapid progression, shows characteristics such as increases in pulmonary circulatory resistance and pulmonary arterial pressure, and progressive right heart failure. Shikonin can reduce right ventricular systolic pressure in chronically hypoxic mice. However, the mechanisms underlying the protective effect of shikonin against PAH pathogenesis have only been sporadically identified. The present study evaluated whether inhibiting the expression of pyruvate kinase M2 (PKM2) contributed to the improvement of pulmonary vascular remodeling in PAH rats induced by monocrotaline (MCT) treatment. Hemodynamic parameters were assessed using echocardiography and right ventricular catheterization. Right ventricular hypertrophy index analysis and hematoxylin and eosin staining were used to evaluate the degree of pulmonary vascular and right heart remodeling. Moreover, PKM2, p‑PKM2, ERK, p‑ERK, glucose transporter 1 (GLUT1), lactate dehydrogenase A (LDHA) protein expression levels were semi‑quantified using western blotting. The expression and distribution of PKM2 were assessed using immunofluorescence microscopy. The present study demonstrated that MCT treatment caused pulmonary arterial hypertension and pulmonary vascular remodeling in experimental rats. Shikonin improved hemodynamics and pulmonary vascular remodeling in MCT‑induced PAH rats, decreased aerobic glycolysis and downregulated PKM2, p‑PKM2, p‑ERK, GLUT 1 and LDHA protein expression levels. Shikonin improved experimental pulmonary arterial hypertension hemodynamics and pulmonary vascular remodeling at least partly through the inhibition of PKM2 and the resultant suppression of aerobic glycolysis. These results provide a novel understanding of possible new treatment targets for PAH.

Alterations of pulmonary vascular afterload in exercise‐induced pre‐ and post‐capillary pulmonary hypertension

Exercise imposes increased pulmonary vascular afterload based on rises in pulmonary artery (PA) wedge pressure, declines in PA compliance, and resistance-compliance time. In health, afterload stress stabilizes during steady-state exercise. Our objective was to examine alterations of these exercise-associated stresses in states of pre- and post-capillary pulmonary hypertension (PH). PA hemodynamics were evaluated at rest, 2 and 7min of steady-state exercise at moderate intensity in patients who exhibited Pre-capillary (n=22) and post-capillary PH (n=22). Patients with normal exercise hemodynamics (NOR-HD) (n=32) were also studied. During exercise in all groups, PA wedge pressure increased at 2min, with no further change at 7min. In post-capillary PH and NOR-HD, increases in PA diastolic pressure and diastolic pressure gradient remained stable at 2 and 7min of exercise, while in pre-capillary PH, both continued to increase at 7 min. The behavior of the diastolic pressure gradient was linearly related to the duration of resistance-compliance time at rest (r2 =0.843) and exercise (r2 =0.760). Exercise resistance-compliance time was longer in pre-capillary PH associated with larger increases in diastolic pressure gradient. Conversely, resistance-compliance time was shortest in post-capillary PH compared to pre-capillary PH and NOR-HD and associated with limited increases in exercise diastolic pressure gradient. During steady-state, modest-intensity exercise-specific patterns of pulmonary vascular afterload responses were observed in pre- and post-capillary PH relative to NOR-HD. Longer resistance-compliance time related to greater increases in PA diastolic pressure and diastolic pressure gradients in pre-capillary PH, while shorter resistance-compliance time appeared to limit these increases in post-capillary PH.

β3 adrenergic agonism: A novel pathway which improves right ventricular-pulmonary arterial hemodynamics in pulmonary arterial hypertension.

Efficacy of therapies that target the downstream nitric oxide (NO) pathway in pulmonary arterial hypertension (PAH) depends on the bioavailability of NO. Reduced NO level in PAH is secondary to "uncoupling" of endothelial nitric oxide synthase (eNOS). Stimulation of β3 adrenergic receptors (β3 ARs) may lead to the recoupling of NOS and therefore be beneficial in PAH. We aimed to examine the efficacy of β3 AR agonism as a novel pathway in experimental PAH. In hypoxia (5 weeks) and Sugen hypoxia (hypoxia for 5 weeks + SU5416 injection) models of PAH, we examined the effects of the selective β3 AR agonist CL316243. We measured echocardiographic indices and invasive right ventricular (RV)-pulmonary arterial (PA) hemodynamics and compared CL316243 with riociguat and sildenafil. We assessed treatment effects on RV-PA remodeling, oxidative stress, and eNOS glutathionylation, an oxidative modification that uncouples eNOS. Compared with normoxic mice, RV systolic pressure was increased in the control hypoxic mice (p < 0.0001) and Sugen hypoxic mice (p < 0.0001). CL316243 reduced RV systolic pressure, to a similar degree to riociguat and sildenafil, in both hypoxia (p < 0.0001) and Sugen hypoxia models (p < 0.03). CL316243 reversed pulmonary vascular remodeling, decreased RV afterload, improved RV-PA coupling efficiency and reduced RV stiffness, hypertrophy, and fibrosis. Although all treatments decreased oxidative stress, CL316243 significantly reduced eNOS glutathionylation. β3 AR stimulation improved RV hemodynamics and led to beneficial RV-PA remodeling in experimental models of PAH. β3 AR agonists may be effective therapies in PAH.

Obstructive sleep apnea and pulmonary hypertension: the pendulum swings again.

Obstructive sleep apnea and pulmonary hypertension: the pendulum swings again.

Using a Fibrinolysis Delivery Catheter in Pulmonary Embolism Treatment for Measurement of Pulmonary Artery Hemodynamics.

Ultrasound-facilitated and catheter-directed low-dose fibrinolysis (EKOS) has shown favorable hemodynamic and safety outcomes in intermediate- to high-risk pulmonary embolism (PE) cases. This prospective single-arm monocentric study assessed the effects of using a delivery catheter for fibrinolysis as a novel approach for acute intermediate- to high-risk patients on pulmonary artery hemodynamics PE. Forty-five patients (41 intermediate-high and 4 high risk) with computer tomography (CT)-confirmed PE underwent EKOS therapy. By protocol, a total of 6 mg of tissue-plasminogen activator (t-PA) was administered over 6 h in the pulmonary artery (unilateral 6 mg or bilateral 12 mg). Unfractionated heparin was provided periprocedurally. The primary safety outcome was death, as well as major and minor bleeding within 48 of procedure initiation and at 90 days. The primary effectiveness outcomes were: 1. to assess the difference in pulmonary artery pressure from baseline to 6 h post-treatment as a primary precise surrogate marker, and 2. to determine the echocardiographic RV/LV ratio from baseline to 48 h and at 90 days post-delivery. Pulmonary artery pressure decreased by 15/6/10 mmHg (p &lt; 0.001). The mean RV/LV ratio decreased from 1.2 ± 0.85 at baseline to 0.85 ± 0.12 at 48 and to 0.76 ± 0.13 at 90 days (p &lt; 0.001). Five patients (11%) died within 90 days of therapy. Pulmonary artery hemodynamics were assessed using a delivery catheter for fibrinolysis, which is reproducible for identifying PE at risk of adverse outcomes. The results matched the right heart catheter results in EKOS and Heparin arm of Ultima trial, thereby confirming the validity of this potential diagnostic tool to assess therapy effectiveness and thereby reduce additional procedure-related complications, hospital residency, and economics. These results stress the importance of having an interdisciplinary team involved in the management of PE to evaluate the quality of life of these patients and this protocol shortens ICU admission to 6 h.

No evidence of pulmonary hypertension revealed in an echographic evaluation of right-sided hemodynamics in hyperthyroid cats.

Hyperthyroidism is a common endocrinopathy affecting middle-aged to elderly cats, with multisystemic repercussions. Hyperthyroid humans show decreased lung compliance and increased cardiac output with subsequent left heart failure leading to pulmonary capillary congestion. Prognosis worsens with the development of increased pulmonary vascular pressures (ie, pulmonary hypertension [PH]) in hyperthyroid humans. The effect of excess thyroid hormone concentration on pulmonary arterial hemodynamics is unknown in cats. Assessing pulmonary vascular pressures in veterinary medicine relies heavily on echocardiographic measurements performed at the level of the heart and pulmonary trunk. This study investigated right-sided cardiac and pulmonary arterial hemodynamics in hyperthyroid cats using echocardiography. Echocardiographic examinations of hyperthyroid cats identified through a bi-institutional database search were reviewed for the determination of systolic pulmonary arterial pressure (PAP) and 20 other metrics. Values were compared with those of a healthy cat group using non-parametric statistical analyses. Systolic PAP could not be determined in 23/26 hyperthyroid and 13/14 healthy cats owing to unmeasurable tricuspid regurgitation flow velocity. Hyperthyroid cats were roughly twice as old (P <0.001) and had 2-4-fold higher respiratory rates (P <0.001) than healthy cats. Hyperthyroid cats showed an increase in acceleration time-to-ejection time ratio of pulmonary flow (1.4-fold, P = 0.001), pulmonary artery velocity time integral (1.2-1.6-fold, P = 0.001), maximal pulmonary velocity (1.3-1.7-fold, P = 0.002), stroke volume (1.5-fold, P = 0.001) and cardiac output (1.6-fold, P <0.001) vs healthy cats. None of the other echocardiographic metrics reached statistical significance. Systolic PAP estimation proved unsuitable as a sole measurement for the assessment of PH in hyperthyroid cats owing to the frequent inability to interrogate tricuspid regurgitant flow velocity. Hyperthyroid cats have altered echocardiographic measures of pulmonary hemodynamics dissimilar to those reported in hyperthyroid humans. Differential effects of thyrotoxic cardiomyopathy on ventricular systolic function may underlie species differences.

Abstract 10998: Pulmonary Artery Pulsatility Measured by Cardiac Magnetic Resonance Imaging in Over 42,000 Participants Reveals Novel Genetic Risk Loci

Introduction: Pulmonary artery (PA) hemodynamics are important predictors of mortality. However, genetic mechanisms underlying increased PA stiffness in diseases such as pulmonary hypertension are poorly understood, and targeted therapies are limited. Evaluation of PA hemodynamics frequently requires invasive right heart catheterization, limiting large-scale studies. This study leveraged cardiac magnetic resonance (CMR) imaging to non-invasively determine and characterize PA pulsatility, an established measure of pulmonary vascular compliance. Methods and Results: A deep-learning neural network was implemented to determine PA pulsatility, defined as the relative cross-sectional area change from diastole to systole, in 42,774 UK Biobank participants (intraclass correlation 0.94-0.96 compared with human readers). The mean (SD) PA pulsatility was 0.36 (0.11), and pulsatility decreased by 0.035 for every decade increase in age. Reduction in pulsatility by 0.1 was associated with the presence of congestive heart failure (OR 1.55 [95% CI 1.37-⁠1.76]), chronic obstructive pulmonary disease (OR 1.41 [1.29-⁠1.53]), or diabetes (OR 1.18 [1.13-⁠1.23]), and PA pulsatility was associated with increased all-cause mortality (HR 1.13 [1.03-1.23]) after adjusting for age and sex and excluding those with CHF or COPD (Fig A-B). A genome-wide association study of 40,496 participants identified loci on chromosomes 2 (top SNP: rs6738973) and 10 (rs2077218) associated with PA pulsatility at genome-wide significance ( p &lt; 5 х 10 –8 ; Fig C). Integrative fine-mapping analyses identified PKDCC and PLCE1 among likely effector genes. Conclusions: This is the first population-based epidemiologic and genomics study of PA pulsatility. Decreased PA pulsatility is associated with advanced age, increased rates of comorbidities, and higher mortality. The genes PKDCC and PLCE1 are among likely effectors of PA pulsatility and warrant further functional investigation.

Urokinase-loaded cyclic RGD-decorated liposome targeted therapy for in-situ thrombus of pulmonary arteriole of pulmonary hypertension.

Backgroud: In-situ thrombosis is a significant pathophysiological basis for the development of pulmonary hypertension (PH). However, thrombolytic therapy for in-situ thrombus in PH was often hampered by the apparent side effects and the low bioavailability of common thrombolytic medications. Nanoscale cyclic RGD (cRGD)-decorated liposomes have received much attention thanks to their thrombus-targeting and biodegradability properties. As a result, we synthesized urokinase-loaded cRGD-decorated liposome (UK-cRGD-Liposome) for therapy of in-situ thrombosis as an exploration of pulmonary hypertensive novel therapeutic approaches. Purpose: To evaluate the utilize of UK-cRGD-Liposome for targeted thrombolysis of in-situ thrombus in PH and to explore the potential mechanisms of in-situ thrombus involved in the development of PH. Methods: UK-cRGD-Liposome nanoscale drug delivery system was prepared using combined methods of thin-film hydration and sonication. Induced PH via subcutaneous injection of monocrotaline (MCT). Fibrin staining (modified MSB method) was applied to detect the number of vessels within-situ thrombi in PH. Echocardiography, hematoxylin-eosin (H & E) staining, and Masson's trichrome staining were used to analyze right ventricular (RV) function, pulmonary vascular remodeling, as well as RV remodeling. Results: The number of vessels with in-situ thrombi revealed that UK-cRGD-Liposome could actively target urokinase to in-situ thrombi and release its payload in a controlled manner in the in vivo environment, thereby enhancing the thrombolytic effect of urokinase. Pulmonary artery hemodynamics and echocardiography indicated a dramatical decrease in pulmonary artery pressure and a significant improvement in RV function post targeted thrombolytic therapy. Moreover, pulmonary vascular remodeling and RV remodeling were significantly restricted post targeted thrombolytic therapy. Conclusion: UK-cRGD-Liposome can restrict the progression of PH and improve RV function by targeting the dissolution of pulmonary hypertensive in-situ thrombi, which may provide promising therapeutic approaches for PH.