Computational Analysis of the Pulmonary Arteries in Congenital Heart Disease: A Review of the Methods and Results.

With the help of computational fluid dynamics (CFD), hemodynamics of the pulmonary arteries (PA's) can be studied in detail and varying physiological circumstances and treatment options can be simulated. This offers the opportunity to improve the diagnostics and treatment of PA stenosis in biventricular congenital heart disease (CHD). The aim of this review was to evaluate the methods of computational studies for PA's in biventricular CHD and the level of validation of the numerical outcomes. A total of 34 original research papers were selected. The literature showed a great variety in the used methods for (re) construction of the geometry as well as definition of the boundary conditions and numerical setup. There were 10 different methods identified to define inlet boundary conditions and 17 for outlet boundary conditions. A total of nine papers verified their CFD outcomes by comparing results to clinical data or by an experimental mock loop. The diversity in used methods and the low level of validation of the outcomes result in uncertainties regarding the reliability of numerical studies. This limits the current clinical utility of CFD for the study of PA flow in CHD. Standardization and validation of the methods are therefore recommended.

4D Flow MRI Estimation of Boundary Conditions for Patient Specific Cardiovascular Simulation.

Accurate image based cardiovascular simulations require patient specific boundary conditions (BCs) for inlets, outlets and vessel wall mechanical properties. While inlet BCs are typically determined non-invasively, invasive pressure catheterization is often used to determine patient specific outlet BCs and vessel wall mechanical properties. A method using 4D Flow MRI to non-invasively determine both patient specific outlet BCs and vessel wall mechanical properties is presented and results for both in vitro validation with a latex tube and an in vivo pulmonary artery stenosis (PAS) stent intervention are presented. For in vitro validation, acceptable agreement is found between simulation using BCs from 4D Flow MRI and benchtop measurements. For the PAS virtual intervention, simulation correctly predicts flow distribution with 9% error compared to MRI. Using 4D Flow MRI to noninvasively determine patient specific BCs increases the ability to use image based simulations as pressure catheterization is not always performed.

Computational Pre-surgical Planning of Arterial Patch Reconstruction: Parametric Limits and In Vitro Validation.

Surgical treatment of congenital heart disease (CHD) involves complex vascular reconstructions utilizing artificial and native surgical materials. A successful surgical reconstruction achieves an optimal hemodynamic profile through the graft in spite of the complex post-operative vessel growth pattern and the altered pressure loading. This paper proposes a new in silico patient-specific pre-surgical planning framework for patch reconstruction and investigates its computational feasibility. The proposed protocol is applied to the patch repair of main pulmonary artery (MPA) stenosis in the Tetralogy of Fallot CHD template. The effects of stenosis grade, the three-dimensional (3D) shape of the surgical incision and material properties of the artificial patch are investigated. The release of residual stresses due to the surgical incision and the extra opening of the incision gap for patch implantation are simulated through a quasi-static finite-element vascular model with shell elements. Implantation of different unloaded patch shapes is simulated. The patched PA configuration is pressurized to the physiological post-operative blood pressure levels of 25 and 45 mmHg and the consequent post-operative stress distributions and patched artery shapes are computed. Stress-strain data obtained in-house, through the biaxial tensile tests for the mechanical properties of common surgical patch materials, Dacron, Polytetrafluoroethylene, human pericardium and porcine xenopericardium, are employed to represent the mechanical behavior of the patch material. Finite-element model is experimentally validated through the actual patch surgery reconstructions performed on the 3D printed anatomical stenosis replicas. The post-operative recovery of the initially narrowed lumen area and post-op tortuosity are quantified for all modeled cases. A computational fluid dynamics solver is used to evaluate post-operative pressure drop through the patch-reconstructed outflow tract. According to our findings, the shorter incisions made at the throat result in relatively low local peak stress values compared to other patch design alternatives. Longer cut and double patch cases are the most effective in repairing the initial stenosis level. After the patch insertion, the pressure drop in the artery due to blood flow decreases from 9.8 to 1.35 mmHg in the conventional surgical configuration. These results are in line with the clinical experience where a pressure gradient at or above 50 mmHg through the MPA can be an indication to intervene. The main strength of the proposed pre-surgical planning framework is its capability to predict the intra-operative and post-operative 3D vascular shape changes due to intramural pressure, cut length and configuration, for both artificial and native patch materials.

Consequences of an early catheter-based intervention on pulmonary artery growth and right ventricular myocardial function in a pig model of pulmonary artery stenosis.

OBJECTIVE: To determine the consequences of an early catheter-based intervention on pulmonary artery (PA) growth and right ventricular (RV) myocardial function in an animal model of branch PA stenosis. BACKGROUND: Acute results and safety profiles of deliberate stent fracture within the pulmonary vasculature have been demonstrated. The long-term impact of early stent intervention and deliberate stent fracture on PA growth and myocardial function is not understood. METHODS: Implantation of small diameter stents was performed in a pig model of left PA stenosis at 6 weeks (10 kg) followed by dilations at 10 (35 kg) and 18 weeks (65 kg) with intent to fracture and implant large diameter stents. Hemodynamics, RV contractility, and 2D/3D angiography were performed with each intervention. The heart and pulmonary vasculature were histologically assessed. RESULTS: Stent fracture occurred in 9/12 and implantation of large diameter stents was successful in 10/12 animals with no PA aneurysms or dissections. The final stented PA segment and distal left PA branch origins equaled the corresponding PA diameters of sham controls. Growth of left PA immediately beyond the stent was limited and there was diffuse fibro-intimal proliferation within the distal left and right PA. RV contractility was diminished in the intervention group and the response to dobutamine occurred uniquely via increases in heart rate. CONCLUSIONS: Early stent intervention in this surgically created PA stenosis model was associated with improved growth of the distal PA vasculature but additional investigation of PA vessel physiology and impact on the developing heart are needed.

A case of vasculopathy of unknown etiology associated with fatal hydrops fetalis and review of the literature on intimomedial mucoid degeneration.

Non-immune hydrops fetalis (NIHF) has a high mortality rate [1]. Many etiologies of NIHF have been identified, including cardiovascular abnormalities, severe anemia, and genetic defects. In patients with cardiovascular etiology, structural malformations lead to fluid accumulation resulting in increased intravascular hydrostatic pressure. We report a fatal case of NIHF in a 31 week gestational age, Caucasian neonate with heart remodeling associated with a stenotic vasculopathy of the right pulmonary artery. The artery revealed partial occlusion with vascular wall abnormalities, including disarrayed smooth muscle fibers, hyperplasia within the tunica media, and myxoid change within the media and intima. Identical vasculopathy was also identified within a mesenteric artery, and this contributed to hemorrhage and early ischemic necrosis of the small intestine, discovered on postmortem examination.

Takayasu's Arteritis with Isolated Pulmonary Artery Involvement in a Middle-Aged Asian Woman with Hepatitis B and Latent Tuberculosis Infection.

We report a rare case of Takayasu's arteritis with isolated pulmonary artery stenosis in the presence of active hepatitis B and latent Mycobacterium tuberculosis infection in a middle-aged Asian woman who initially presented with severe dyspnea on exertion and recurrent syncope, occasional burning chest pains, and fatigue. Therapy of the active hepatitis B and latent M. tuberculosis infection together with a course of methotrexate led to a slight reversal of the symptoms, as angioplasty with or without stenting was not an option. The constellation described here hints at the possible link between hepatitis B and M. tuberculosis infection and the development of Takayasu's arteritis. The case also supports the little evidence available indicating that treatment of active hepatitis B infection could positively influence the course of Takayasu's arteritis.

Interventional therapy in sarcoidosis-associated pulmonary arterial stenosis and pulmonary hypertension.

BACKGROUNDS: Pulmonary sarcoidosis is often complicated by pulmonary hypertension, a complication that is associated with increased disability and mortality. To this point, however, little progress has been made in the treatment of sarcoidosis associated with pulmonary hypertension (SAPH). METHODS: A prospective study was performed on 72 consecutive Chinese sarcoidosis patients followed at an outpatient clinic. The patients were evaluated by Doppler echocardiography and computed tomography pulmonary angiography. SAPH was confirmed by right heart catheterisation. The clinical parameters were compared before and 2 months after treatment with oral glucocorticoids. Eight stage III and IV patients with moderate to severe proximal pulmonary arterial stenosis (PAS) and SAPH underwent interventional therapy (IT) after prednisone treatment and were followed up at 3-month intervals. RESULTS: After 2 months of prednisone treatment, 32 stage III and IV patients continued to display varying degrees of PAS and SAPH. Eight patients underwent IT without severe complications and made improvements in pulmonary arterial pressure, pulmonary vascular resistance, arterial oxygen saturation and WHO functional classification, with the improvements lasting more than 3 months. CONCLUSIONS: PAS caused by external compression in sarcoidosis is a significant reason for SAPH. IT is effective and safe in the treatment of PAS and SAPH.

Upregulation of Transient Receptor Potential Canonical Channels Contributes to Endotoxin-Induced Pulmonary Arterial Stenosis.

BACKGROUND Septic shock is a pathologic condition caused by endotoxin-producing bacteria, and often associated with severe pulmonary hypertension. Inflammation is a major systemic response to endotoxin; however, it is unknown whether endotoxin has a direct impact on pulmonary arteries that contributes to pathogenesis of pulmonary hypertension. MATERIAL AND METHODS Rat pulmonary arteries and primary pulmonary arterial smooth muscle cells (PASMCs) were cultured in vitro and treated with lipopolysaccharide (LPS) and blockers of transient receptor potential canonical (TRPC) channels. Neointimal growth and arterial stenosis were observed on cryosections of cultured pulmonary arteries. Proliferation of PASMCs was examined by a WST-1 (water-soluble tetrazolium salt) assay. Expression of TRPC genes in pulmonary arteries and PASMCs were detected and quantified by real-time polymerase chain reaction and Western blotting. RESULTS LPS significantly induced neointimal growth and stenosis of pulmonary arteries and promoted proliferation of PASMCs. TRPC channel blockers 2-aminoethoxydiphenyl borate and SKF-96365 inhibited LPS-induced remodeling of pulmonary arteries and PASMC proliferation. Expression of TRPC1/3/4/6 was detected in pulmonary arteries and PASMCs. LPS treatment dramatically increased the expression of TRPC3 and TRPC4 at both messenger RNA and protein levels. CONCLUSIONS LPS stimulates stenosis of pulmonary arteries through enhancement of TRPC-mediated Ca2+ entry into PASMCs, which is caused by upregulation of TRPC3 and TRPC4 channels.