Results of the multicenter early feasibility study (EFS) of the Renata Minima stent as treatment for branch pulmonary artery stenosis and coarctation of aorta in infants.

BACKGROUND: Stent implantation has become standard of care in older children and adults for treatment of branch pulmonary artery stenosis (BPAS) and coarctation aorta (CoAo). There are no stents approved or available for infants that have the potential to be dilated to adult diameters. The Minima stent was designed to fulfill this unmet need. METHODS: Multicenter, prospective, nonrandomized early feasibility study evaluating safety and effectiveness of the Minima stent for treatment of BPAS and CoAo. Primary endpoints included: (1) successful deployment across lesion, (2) stenosis relief defined by an increase in angiographic diameter of >50% and (3) freedom from stent explant, embolization or migration at 30 days and 6 months. RESULTS: Between 2/2022 and 5/2022, 10 pts underwent Minima stent implantation with a median age and weight of 9 months (4-43 months) and 7.6 kg (5.1-16.9 kg). Procedural success and predefined stenosis relief was achieved in all cases (CoAo [n = 4], BPAS [n = 6]). Adverse events occurred in 3 pts: transient diminished lower extremity pulse (n = 2), distal stent on-balloon displacement successfully managed in the catheterization suite (n = 1). There were no deaths or major adverse events. All patients were free from stent explant and migration at 30 days and 6 months with no evidence for significant restenosis at latest follow-up. CONCLUSIONS: Implantation of the Renata Minima stent was safe and effective for the treatment of BPAS and CoAo in this small cohort of infants and young children during early follow-up. Based on these early results, an expanded study with longer follow-up is warranted.

The impact of unilateral pulmonary artery stenosis on right ventricular to pulmonary arterial coupling in patients with transposition of the great arteries.

BACKGROUND: Unilateral pulmonary artery (PA) stenosis is common in the transposition of the great arteries (TGA) after arterial switch operation (ASO) but the effects on the right ventricle (RV) remain unclear. AIMS: To assess the effects of unilateral PA stenosis on RV afterload and function in pediatric patients with TGA-ASO. METHODS: In this retrospective study, eight TGA patients with unilateral PA stenosis underwent heart catheterization and cardiac magnetic resonance (CMR) imaging. RV pressures, RV afterload (arterial elastance [Ea]), PA compliance, RV contractility (end-systolic elastance [Ees]), RV-to-PA (RV-PA) coupling (Ees/Ea), and RV diastolic stiffness (end-diastolic elastance [Eed]) were analyzed and compared to normal values from the literature. RESULTS: In all TGA patients (mean age 12 ± 3 years), RV afterload (Ea) and RV pressures were increased whereas PA compliance was reduced. RV contractility (Ees) was decreased resulting in RV-PA uncoupling. RV diastolic stiffness (Eed) was increased. CMR-derived RV volumes, mass, and ejection fraction were preserved. CONCLUSION: Unilateral PA stenosis results in an increased RV afterload in TGA patients after ASO. RV remodeling and function remain within normal limits when analyzed by CMR but RV pressure-volume loop analysis shows impaired RV diastolic stiffness and RV contractility leading to RV-PA uncoupling.

Doppler Echocardiographic Indices Are Specific But Not Sensitive to Predict Pulmonary Artery Occlusion Pressure in Critically Ill Patients Under Mechanical Ventilation.

OBJECTIVES: The objective of this study was to prospectively evaluate the ability of transthoracic echocardiography to assess pulmonary artery occlusion pressure in mechanically ventilated critically ill patients. DESIGN: In a prospective observational study. SETTING: Amiens University Hospital Medical ICU. PATIENTS: Fifty-three mechanically ventilated patients in sinus rhythm admitted to our ICU. INTERVENTION: Transthoracic echocardiography was performed simultaneously to pulmonary artery catheter. MEASUREMENTS AND MAIN RESULTS: Transmitral early velocity wave recorded using pulsed wave Doppler (E), late transmitral velocity wave recorded using pulsed wave Doppler (A), and deceleration time of E wave were recorded using pulsed Doppler as well as early mitral annulus velocity wave recorded using tissue Doppler imaging (E'). Pulmonary artery occlusion pressure was measured simultaneously using pulmonary artery catheter. There was a significant correlation between pulmonary artery occlusion pressure and lateral ratio between E wave and E' (E/E' ratio) (r = 0.35; p < 0.01), ratio between E wave and A wave (E/A ratio) (r = 0.41; p < 0.002), and deceleration time of E wave (r = -0.34; p < 0.02). E/E' greater than 15 was predictive of pulmonary artery occlusion pressure greater than or equal to 18 mm Hg with a sensitivity of 25% and a specificity of 95%, whereas E/E' less than 7 was predictive of pulmonary artery occlusion pressure less than 18 mm Hg with a sensitivity of 32% and a specificity of 81%. E/A greater than 1.8 yielded a sensitivity of 44% and a specificity of 95% to predict pulmonary artery occlusion pressure greater than or equal to 18 mm Hg, whereas E/A less than 0.7 was predictive of pulmonary artery occlusion pressure less than 18 mm Hg with a sensitivity of 19% and a specificity of 94%. A similar predictive capacity was observed when the analysis was confined to patients with EF less than 50%. A large proportion of E/E' measurements 32 (60%) were situated between the two cut-off values obtained by the receiver operating characteristic curves: E/E' greater than 15 and E/E' less than 7. CONCLUSIONS: In mechanically ventilated critically ill patients, Doppler transthoracic echocardiography indices are highly specific but not sensitive to estimate pulmonary artery occlusion pressure.

Stent interventions for pulmonary artery stenosis improve bi-ventricular flow efficiency in a swine model.

BACKGROUND: Branch pulmonary artery (PA) stenosis (PAS) commonly occurs in patients with congenital heart disease (CHD). Prior studies have documented technical success and clinical outcomes of PA stent interventions for PAS but the impact of PA stent interventions on ventricular function is unknown. The objective of this study was to utilize 4D flow cardiovascular magnetic resonance (CMR) to better understand the impact of PAS and PA stenting on ventricular contraction and ventricular flow in a swine model of unilateral branch PA stenosis. METHODS: 18 swine (4 sham, 4 untreated left PAS, 10 PAS stent intervention) underwent right heart catheterization and CMR at 20 weeks age (55 kg). CMR included ventricular strain analysis and 4D flow CMR. RESULTS: 4D flow CMR measured inefficient right ventricular (RV) and left ventricular (LV) flow patterns in the PAS group (RV non-dimensional (n.d.) vorticity: sham 82 ± 47, PAS 120 ± 47; LV n.d. vorticity: sham 57 ± 5, PAS 78 ± 15 p < 0.01) despite the PAS group having normal heart rate, ejection fraction and end-diastolic volume. The intervention group demonstrated increased ejection fraction that resulted in more efficient ventricular flow compared to untreated PAS (RV n.d. vorticity: 59 ± 12 p < 0.01; LV n.d. vorticity: 41 ± 7 p < 0.001). CONCLUSION: These results describe previously unknown consequences of PAS on ventricular function in an animal model of unilateral PA stenosis and show that PA stent interventions improve ventricular flow efficiency. This study also highlights the sensitivity of 4D flow CMR biomarkers to detect earlier ventricular dysfunction assisting in identification of patients who may benefit from PAS interventions.

Pulmonary artery and lung parenchymal growth following early versus delayed stent interventions in a swine pulmonary artery stenosis model.

OBJECTIVES: Compare lung parenchymal and pulmonary artery (PA) growth and hemodynamics following early and delayed PA stent interventions for treatment of unilateral branch PA stenosis (PAS) in swine. BACKGROUND: How the pulmonary circulation remodels in response to different durations of hypoperfusion and how much growth and function can be recovered with catheter directed interventions at differing time periods of lung development is not understood. METHODS: A total of 18 swine were assigned to four groups: Sham (n = 4), untreated left PAS (LPAS) (n = 4), early intervention (EI) (n = 5), and delayed intervention (DI) (n = 5). EI had left pulmonary artery (LPA) stenting at 5 weeks (6 kg) with redilation at 10 weeks. DI had stenting at 10 weeks. All underwent right heart catheterization, computed tomography, magnetic resonance imaging, and histology at 20 weeks (55 kg). RESULTS: EI decreased the extent of histologic changes in the left lung as DI had marked alveolar septal and bronchovascular abnormalities (p = .05 and p < .05 vs. sham) that were less prevalent in EI. EI also increased left lung volumes and alveolar counts compared to DI. EI and DI equally restored LPA pulsatility, R heart pressures, and distal LPA growth. EI and DI improved, but did not normalize LPA stenosis diameter (LPA/DAo ratio: Sham 1.27 ± 0.11 mm/mm, DI 0.88 ± 0.10 mm/mm, EI 1.01 ± 0.09 mm/mm) and pulmonary blood flow distributions (LPA-flow%: Sham 52 ± 5%, LPAS 7 ± 2%, DI 44 ± 3%, EI 40 ± 2%). CONCLUSION: In this surgically created PAS model, EI was associated with improved lung parenchymal development compared to DI. Longer durations of L lung hypoperfusion did not detrimentally affect PA growth and R heart hemodynamics. Functional and anatomical discrepancies persist despite successful stent interventions that warrant additional investigation.

First in man study of a new semi-open cell design Zephyr cobalt-chromium stent in large vessels and conduits.

OBJECTIVES: We present a first-in-man clinical use of a new hybrid design stent in stenosed large vessels. Its unique C and S polylinks prevent foreshortening without compromising its strength. Its thin profile permits use of smaller introducer sheaths. BACKGROUND: Stent angioplasty is widely employed in large vessel and conduit stenosis. These procedures are associated with difficulties due to large stent profiles, stent fractures, foreshortening and recoil. Cobalt chromium stents have high tensile strengths compared to stainless steel stents. METHODS: A retrospective analysis of feasibility and safety of a new Cobalt chromium stent in large vessels namely aorta, pulmonary arteries and outflow conduits was done from two institutions. Demographic patient details, procedural results, complications and medium term follow-up were analyzed. Stent recoil, foreshortening, fractures were assessed. RESULTS: Twenty patients including three with aortic coarctations, seven with stenosed conduits and 10 with pulmonary artery stenosis underwent stent angioplasty using 23 stents. Three stents were deployed to expand further a previously implanted stent. Procedure was successful in all patients, lumen increased by 150-300%, gradients reduced in all patients. There was no stent recoil, foreshortening or fractures. There were no complications. At a follow up of 3-27 months, there were no stent related complications and the gradients remained stable. CONCLUSIONS: The new Zephyr stent was useful in a wide variety of stenotic lesions involving large vessels including those that were previously stented. Lack of stent recoil and foreshortening seems to be an advantage for this new stent that needs validation in larger multicenter studies.

Proximal pressure reducing effect of wave reflection in the pulmonary circulation disappear in obstructive disease: insight from a rabbit model.

Locating the site of increased resistance within the vascular tree in pulmonary arterial hypertension could assist in both patient diagnosis and tailoring treatment. Wave intensity analysis (WIA) is a wave analysis method that may be capable of localizing the major site of reflection within a vascular system. We investigated the contribution of WIA to the analysis of the pulmonary circulation in a rabbit model with animals subjected to variable occlusive pulmonary disease. Animals were embolized with different sized microspheres for 6 wk ( n = 10) or underwent pulmonary artery (PA) ligation for 6 wk ( n = 3). These animals were compared with a control group ( n = 6) and acutely embolized animals ( n = 4). WIA was performed and compared with impedance-based methods to analyze wave reflections. The control group showed a relatively high extent of reflected waves (15.7 ± 10.6%); reflections had a net effect of pressure reduction during systole, suggesting an open-end reflector. The pattern of wave reflection was not different in the group with partial PA ligation (12.4 ± 4.1%). In the chronically embolized group, wave reflection was not observed (3.6 ± 1.5%). In the acute embolization group, wave reflection was more prominent (37.3 ± 12.6%), with the appearance of a novel wave increasing pressure, suggesting the appearance of a closed-end reflector. Wave reflections of an open-end type are present in the normal rabbit pulmonary circulation. However, the pattern and nature of reflections vary according to the extent of pulmonary vascular occlusion. NEW & NOTEWORTHY The study proposes an original framework of a complementary analysis of wave reflections in the time domain and in the frequency domain. The methodology was used in the pulmonary circulation with different forms of chronic obstructions. The results suggest that the pulmonary vascular tree generates a reflection pattern that could actually assist the heart during ejection, and chronic obstruction significantly modifies the pattern.

Utility of the Medtronic microvascular plug™ as a transcatheter implantable and explantable pulmonary artery flow restrictor in a swine model.

BACKGROUND: A surgical pulmonary artery band (PAB) is used to control excessive pulmonary blood flow for certain congenital heart diseases. Previous attempts have been made to develop a transcatheter, implantable pulmonary flow restrictor (PFR) without great success. We modified a microvascular plug (MVP) to be used as a PFR. The objectives of this study were to demonstrate feasibility of transcatheter implantation and retrieval of the modified MVP as a PFR, and compare PA growth while using the PFR versus PAB. METHODS AND RESULTS: The PFR was implanted in eight newborn piglets in bilateral branch pulmonary arteries (PAs). Immediately post-PFR implantation, the right ventricular systolic pressure increased from a median of 20-51 mmHg. Transcatheter retrieval of PFR was 100% successful at 3, 6, and 9 weeks and 50% at 12-weeks post-implant. A left PAB was placed via thoracotomy in four other newborn piglets. Debanding was performed 6-weeks later via balloon angioplasty. On follow-up, the proximal left PA diameters in the PFR and the PAB groups were similar (median 8 vs. 7.1 mm; p = 0.11); albeit the surgical band sites required repeat balloon angioplasty secondary to recurrent stenosis. By histopathology, there was grade II vessel injury in two pigs immediately post-retrieval of PFR that healed by 12 weeks. CONCLUSIONS: Transcatheter implantation and retrieval of the MVP as a PFR is feasible. PA growth is comparable to surgical PAB, which is likely to require reinterventions. The use of the MVP as a PFR in humans has to be trialed before recommending its routine use.

Premounted stents for branch pulmonary artery stenosis in children: A short term solution.

OBJECTIVE: Define outcomes of premounted stent implantation (PMS) for branch pulmonary artery stenosis (BPAS). BACKGROUND: PMS for BPAS in children raises concern of long term viability, with limited maximal expansion. METHODS: We reviewed our cardiac database over an 11-year period ending in 2013. Primary endpoint was need for surgical stent intervention (SSI). Other endpoints included acute results and repeat interventions (RI). RESULTS: 82 PMS were implanted in 60 children for BPAS. Median weight was 6.3 (25th -75th 4.6-9.8) kg. Median stent diameter was 6 (range 4-9) mm. Acutely, vessel diameter improved from 2.0 (25th -75th 1.6-3.4) to 5.0 (25th -75th 4.2-5.9) mm (p < 0.001), pressure gradient decreased from 41 (25th -75th 29-50) to 11 (25th -75th 7-18) mmHg (n = 47, p < 0.001), RV:Ao pressure ratio decreased from 100% (25th -75th 85-110%) to 59% (25th -75th 49-74%) (n = 40, p < 0.001). Freedom from SSI was 81% at 1 year and 35% at 5 years. Freedom from RI was 50% at 1 year and 14% at 5 years. 86% of PMS underwent SSI during a concomitant planned cardiac surgery. 45% patients had stent redilation, improving stent diameter from 4.6 (25th -75th 4.1-5.4) to 5.7 (25th -75th 4.9-7) mm (p < 0.001). 1 stent (3%) was able to be fractured longitudinally. CONCLUSIONS: PMS is an effective short term solution for BPAS in children. PMS is associated with expected early need for transcatheter reintervention to accommodate for growth, but also has high rates of SSI.

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.

Maldistribution of pulmonary blood flow in patients after the Fontan operation is associated with worse exercise capacity.

BACKGROUND: Maldistribution of pulmonary artery blood flow (MPBF) is a potential complication in patients who have undergone single ventricle palliation culminating in the Fontan procedure. Cardiovascular magnetic resonance (CMR) is the best modality that can evaluate MPBF in this population. The purpose of this study is to identify the prevalence and associations of MPBF and to determine the impact of MPBF on exercise capacity after the Fontan operation. METHODS: This retrospective single-center study included all patients after Fontan operation who had maximal cardiopulmonary exercise test (CPET) and CMR with flow measurements of the branch pulmonary arteries. MPBF was defined as > 20% difference in branch pulmonary artery flow. Exercise capacity was measured as percent of predicted oxygen consumption at peak exercise (% predicted VO2). Linear and logistic regression models were used to determine univariate and multivariable predictors of exercise capacity and correlates of MPBF, respectively. RESULTS: A total of 147 patients who had CMR between 1999 and 2017 were included (median age at CMR 21.8 years [interquartile range (IQR) 16.5-30.6]) and the median time between CMR and CPET was 2.8 months [IQR 0-13.8]. Fifty-three patients (36%) had MPBF (95% CI 29-45%). The mean % predicted VO2 was 63 ± 16%. Patients with MPBF had lower mean % predicted VO2 compared to patients without MPBF (60 ± 14% versus 65 ± 16%, p = 0.04). On multivariable analysis, a lower % predicted VO2 was independently associated with longer time since Fontan, higher ventricular mass-to-volume ratio, and MPBF. On multivariable analysis, only compression of the branch pulmonary arteries by the ascending aorta or aortic root was associated with MPBF (OR 6.5, 95% CI 5.6-7.4, p < 0.001). CONCLUSION: In patients after the Fontan operation, MPBF is common and is independently associated with lower exercise capacity. MPBF was most likely to be caused by pulmonary artery compression by the aortic root or the ascending aorta. This study identifies MPBF as an important risk factor and as a potential target for therapeutic interventions in this fragile patient population.

Pulmonary Perfusion Using Intrabronchial Capnography in Pulmonary Artery Stenosis.

Stenting at the flow-limiting segment can improve the ventilation-perfusion ratio in patients with central airway stenosis. However, there is no quantitative examination for assessing the perfusion status during interventional bronchoscopy. Intrabronchial capnography can estimate regional gas exchange by measuring carbon dioxide concentration. We herein report a case of bilateral bronchial stenosis where stenting was able to improve ventilation-perfusion ratio using intrabronchial capnography. A 44-year-old man was admitted to our institution with orthopnea. Chest computed tomography showed an extrinsic compression at the bilateral main bronchus and right pulmonary artery due to a mediastinal mass. After introduction of general anesthesia, arterial oxygen tension suddenly decreased in the supine position. After initial stenting, an increase was seen in ventilation at the right lung; however, a ventilation-perfusion mismatch occurred due to an increase in dead-space ventilation at the right pulmonary artery stenosis. Intrabronchial capnography was an effective modality to confirm the regional perfusion status during interventional bronchoscopy in real time.

Twenty years of experience with intraoperative pulmonary artery stenting.

OBJECTIVES: To describe our 20-year experience with intraoperative pulmonary artery (PA) stent placement and evaluate long-term patient outcomes, specifically the need and risk factors for reintervention. BACKGROUND: Intraoperative PA stent placement is an alternative to surgical patch arterioplasty and percutaneous angioplasty or stent placement to treat branch PA stenosis. METHODS: We performed a retrospective review of all intraoperative PA stents placed at our institution from 1994-2013. Patient and stent characteristics and outcome data were collected. Risk factors associated with reintervention were identified using univariate cox regression analysis. RESULTS: Eighty-one PA stents were placed in 68 patients. The procedural complication rate was 4.4%. During a median follow-up period of 6 years (interquartile range [IQR] 0.9-12.7), 30 patients (44%) underwent reintervention on the stented PA with a median time to first reintervention of 2.6 years (IQR 0.7-4.4 years). The first reintervention was surgical in 30% and catheter-based in 70%. Risk factors for reintervention included age < 18 months (Hazard ratio [HR] 2.97, P = 0.005) and body surface area < 0.47 m2 (HR 3.20, P = 0.003) at the time of stent implantation, and the presence of multiple aortopulmonary collaterals in patients with tetralogy of Fallot (HR 4.61, P = 0.003). CONCLUSIONS: Intraoperative PA stent implantation is a safe and effective alternative to percutaneous stent implantation and offers several advantages, including the ability to implant adult-size stents in small patients while avoiding injury to peripheral vessels, to position stents to facilitate future percutaneous stent redilation, and to access the PAs directly, which eliminates radiation exposure. © 2017 Wiley Periodicals, Inc.

Reference Levels for Central Venous Pressure and Pulmonary Artery Occlusion Pressure Monitoring in the Lateral Position.

OBJECTIVE: To investigate reference levels for central venous pressure or pulmonary artery occlusion pressure monitoring in a lateral position. DESIGN: Retrospective observational study. SETTING: A tertiary university hospital. PARTICIPANTS: A total of 204 adults who underwent chest computed tomography scan in the 90° lateral position from November 2006 to February 2015. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Distances from the mid-sternum to the uppermost and lowermost blood levels of both atria were measured. Ratios of the distance from the bottom of the thorax to the uppermost and the lowermost blood levels of both atria to the largest diameter of the thorax were calculated. There were significant differences between the distances from the mid-sternum to the uppermost and the lowermost blood levels of the right atrium and those of the left atrium in the right and left lateral positions, respectively. There were significant differences in the uppermost (3.3±0.1 cm; 95% confidence interval [CI] 3.1-3.5) and the lowermost (4.4±0.1 cm; 95% CI 4.2-4.7) blood levels of the right atrium between the right and left lateral positions. Although the uppermost (1.5±0.1 cm; 95% CI 1.3-1.8) and the lowermost (0.4±0.1 cm; 95% CI 0.2-0.6) blood levels of the left atrium between the right and left lateral positions showed differences, their extent was smaller than the right atrium. The uppermost and the lowermost blood levels of the right atrium lay lower than those of the left atrium in the 90° right lateral position. In contrast, in the 90° left lateral position, the uppermost and the lowermost blood levels of the right atrium lay higher than those of the left atrium. CONCLUSIONS: When monitoring the central venous pressure and pulmonary artery occlusion pressure with patients in the lateral position, changes in the blood level of both atria should be considered when releveling the reference transducer.

Dynamic four-dimensional CT angiography for the assessment of pulmonary perfusion in an adult patient with pulmonary artery occlusion and major aortopulmonary collateral after multistage repair of Fallot's Pentalogy.

Dynamic CT angiography provides haemodynamic assessment combined with detailed information on complex cardiac anatomy in patients with congenital malformations such as multistage correction of Fallot's Pentalogy.

Effects of Proximal Pulmonary Artery Occlusion on Pulsatile Right Ventricular Afterload in Rats.

BACKGROUND: In patients with proximal pulmonary artery (PA) thromboembolism, an increased PA resistance contributes to abnormal right ventricular (RV) afterload. However, the effects of proximal thromboembolism on the dynamic properties of RV afterload, which is determined by PA impedance, have not been analyzed quantitatively. The present study aimed to identify changes in PA impedance after the pulmonary perfusion volume was greatly reduced by unilateral proximal PA occlusion. METHODS AND RESULTS: Ten male Sprague-Dawley rats were used. PA flow and pressure waveforms were recorded during irregular pacing, before and 10 min after left PA occlusion. PA impedance was parameterized by using a three-element Windkessel model consisting of peripheral resistance (RP), arterial compliance (CP) and characteristic impedance (ZC). After proximal PA occlusion, PA impedance modulus increased over a frequency range of interest.ZCincreased significantly (after PA occlusion vs. baseline: 0.128±0.016 vs. 0.074±0.010 mmHg·min/ml, P<0.001), whereasCPandRPdid not change significantly. CONCLUSIONS: Proximal PA occlusion increasedZCwith the attenuation ofRPincrease andCPdecrease predicted from the decreased pulmonary perfusion volume. The insignificant changes inRPandCPindicate that a recruitment phenomenon may result in this attenuation. The existence of compensation by a recruitment mechanism suggests the relative importance of increasedZCin defining abnormal RV afterload in patients with proximal PA thromboembolism. (Circ J 2016; 80: 2010-2018).

Morphological and Hemodynamic Effectiveness of Stenting for Pulmonary Artery Stenosis　- Subanalysis of JPIC Stent Survey.

BACKGROUND: Percutaneous stenting for branch pulmonary artery stenosis is an established interventional choice in congenital heart disease. The apparent morphologic change in the vessel diameter often differs from the hemodynamic result. METHODS AND RESULTS: We performed a subanalysis of the data from the Japanese Society of Pediatric Interventional Cardiology (JPIC) stent survey. The factors that may have contributed to morphologic effectiveness included reference vessel diameter (RVD), minimum lumen diameter (MLD) and percent diameter stenosis (%DS) and the relation between morphologic and hemodynamic effectiveness was evaluated in 206 lesions treated with stenting. We defined a "50% increase in MLD" as "morphologically effective", while "achievement of either a reduced pressure gradient greater than 50% or an increase of perfusion ratio to the affected side to the contralateral side greater than 20%" as "hemodynamically effective". Morphologic effectiveness was achieved in 84% of patients. Before stenting, %DS was significantly larger, while RVD was smaller in the "effective" group than in the "non-effective" group. The cutoff value for effective stenting was 51% for %DS and 14.7 mm for RVD before stenting. Hemodynamic effectiveness was obtained more often in the "morphologic effective" group. CONCLUSIONS: RVD and %DS were the 2 main contributors to acute morphologic effectiveness. There was a significant relationship between "morphologic effectiveness" and "hemodynamic effectiveness", judging from increased perfusion of the affected lung and/or decreased pressure gradient. (Circ J 2016; 80: 1852-1856).

A probabilistic neural twin for treatment planning in peripheral pulmonary artery stenosis.

The substantial computational cost of high-fidelity models in numerical hemodynamics has, so far, relegated their use mainly to offline treatment planning. New breakthroughs in data-driven architectures and optimization techniques for fast surrogate modeling provide an exciting opportunity to overcome these limitations, enabling the use of such technology for time-critical decisions. We discuss an application to the repair of multiple stenosis in peripheral pulmonary artery disease through either transcatheter pulmonary artery rehabilitation or surgery, where it is of interest to achieve desired pressures and flows at specific locations in the pulmonary artery tree, while minimizing the risk for the patient. Since different degrees of success can be achieved in practice during treatment, we formulate the problem in probability, and solve it through a sample-based approach. We propose a new offline-online pipeline for probabilistic real-time treatment planning which combines offline assimilation of boundary conditions, model reduction, and training dataset generation with online estimation of marginal probabilities, possibly conditioned on the degree of augmentation observed in already repaired lesions. Moreover, we propose a new approach for the parametrization of arbitrarily shaped vascular repairs through iterative corrections of a zero-dimensional approximant. We demonstrate this pipeline for a diseased model of the pulmonary artery tree available through the Vascular Model Repository.

Estimating pulmonary arterial remodeling via an animal-specific computational model of pulmonary artery stenosis.

Pulmonary artery stenosis (PAS) often presents in children with congenital heart disease, altering blood flow and pressure during critical periods of growth and development. Variability in stenosis onset, duration, and severity result in variable growth and remodeling of the pulmonary vasculature. Computational fluid dynamics (CFD) models enable investigation into the hemodynamic impact and altered mechanics associated with PAS. In this study, a one-dimensional (1D) fluid dynamics model was used to simulate hemodynamics throughout the pulmonary arteries of individual animals. The geometry of the large pulmonary arteries was prescribed by animal-specific imaging, whereas the distal vasculature was simulated by a three-element Windkessel model at each terminal vessel outlet. Remodeling of the pulmonary vasculature, which cannot be measured in vivo, was estimated via model-fitted parameters. The large artery stiffness was significantly higher on the left side of the vasculature in the left pulmonary artery (LPA) stenosis group, but neither side differed from the sham group. The sham group exhibited a balanced distribution of total distal vascular resistance, whereas the left side was generally larger in the LPA stenosis group, with no significant differences between groups. In contrast, the peripheral compliance on the right side of the LPA stenosis group was significantly greater than the corresponding side of the sham group. Further analysis indicated the underperfused distal vasculature likely moderately decreased in radius with little change in stiffness given the increase in thickness observed with histology. Ultimately, our model enables greater understanding of pulmonary arterial adaptation due to LPA stenosis and has potential for use as a tool to noninvasively estimate remodeling of the pulmonary vasculature.

Pulmonary Hypertension Induced by Right Pulmonary Artery Occlusion: Hemodynamic Consequences of Bmpr2 Mutation.

BACKGROUND: The primary genetic risk factor for heritable pulmonary arterial hypertension is the presence of monoallelic mutations in the BMPR2 gene. The incomplete penetrance of BMPR2 mutations implies that additional triggers are necessary for pulmonary arterial hypertension occurrence. Pulmonary artery stenosis directly raises pulmonary artery pressure, and the redirection of blood flow to unobstructed arteries leads to endothelial dysfunction and vascular remodeling. We hypothesized that right pulmonary artery occlusion (RPAO) triggers pulmonary hypertension (PH) in rats with Bmpr2 mutations. METHODS AND RESULTS: Male and female rats with a 71 bp monoallelic deletion in exon 1 of Bmpr2 and their wild-type siblings underwent acute and chronic RPAO. They were subjected to full high-fidelity hemodynamic characterization. We also examined how chronic RPAO can mimic the pulmonary gene expression pattern associated with installed PH in unobstructed territories. RPAO induced precapillary PH in male and female rats, both acutely and chronically. Bmpr2 mutant and male rats manifested more severe PH compared with their counterparts. Although wild-type rats adapted to RPAO, Bmpr2 mutant rats experienced heightened mortality. RPAO induced a decline in cardiac contractility index, particularly pronounced in male Bmpr2 rats. Chronic RPAO resulted in elevated pulmonary IL-6 (interleukin-6) expression and decreased Gdf2 expression (corrected P value<0.05 and log2 fold change>1). In this context, male rats expressed higher pulmonary levels of endothelin-1 and IL-6 than females. CONCLUSIONS: Our novel 2-hit rat model presents a promising avenue to explore the adaptation of the right ventricle and pulmonary vasculature to PH, shedding light on pertinent sex- and gene-related effects.