Pulmonary Arteries In Patients Research Articles

RUNX2 is stabilised by TAZ and drives pulmonary artery calcification and lung vascular remodelling in pulmonary hypertension due to left heart disease.

Calcification is common in chronic vascular disease, yet its role in pulmonary hypertension due to left heart disease is unknown. Here, we probed for the role of runt-related transcription factor-2 (RUNX2), a master transcription factor in osteogenesis, and its regulation by the HIPPO pathway transcriptional coactivator with PDZ-binding motif (TAZ) in the osteogenic reprogramming of pulmonary artery smooth muscle cells and vascular calcification in patients with pulmonary hypertension due to left heart disease. We similarly examined its role using an established rat model of pulmonary hypertension due to left heart disease induced by supracoronary aortic banding. Pulmonary artery samples were collected from patients and rats with pulmonary hypertension due to left heart disease. Genome-wide RNA sequencing was performed, and pulmonary artery calcification assessed. Osteogenic signalling via TAZ and RUNX2 was delineated by protein biochemistry. In vivo, the therapeutic potential of RUNX2 or TAZ inhibition by CADD522 or verteporfin was tested in the rat model. Gene ontology term analysis identified significant enrichment in ossification and osteoblast differentiation genes, including RUNX2, in pulmonary arteries of patients and lungs of rats with pulmonary hypertension due to left heart disease. Pulmonary artery calcification was evident in both patients and rats. Both TAZ and RUNX2 were upregulated and activated in pulmonary artery smooth muscle cells of patients and rats. Co-immunoprecipitation revealed a direct interaction of RUNX2 with TAZ in pulmonary artery smooth muscle cells. TAZ inhibition or knockdown decreased RUNX2 abundance due to accelerated RUNX2 protein degradation rather than reduced de novo synthesis. Inhibition of either TAZ or RUNX2 attenuated pulmonary artery calcification, distal lung vascular remodelling and pulmonary hypertension development in the rat model. Pulmonary hypertension due to left heart disease is associated with pulmonary artery calcification that is driven by TAZ-dependent stabilisation of RUNX2, causing osteogenic reprogramming of pulmonary artery smooth muscle cells. The TAZ-RUNX2 axis may present a therapeutic target in pulmonary hypertension due to left heart disease.

In vivo study of pulmonary artery remodeling and pulsatility in long Fontan patient

Abstract Background Pulmonary vasculopathy associated with Fontan circulation is a relatively unexplored entity that could have clinical and therapeutic implications. Purpose Our aim was to evaluate the physiology of the pulmonary artery in patients with Fontan circulation using conventional right heart catheterization (RHC) and intravascular ultrasound (IVUS). Methods From December 2022 to January 2024, data from all consecutive Fontan patients undergoing RHC were prospectively collected at a tertiary referral center for adult congenital heart disease. Pressures and pulmonary artery wall high-definition IVUS recordings (OptiCrossTM, 60 MHz, Boston Scientific) were recorded at rest and during apnea. Pathological Fontan pressure was defined when as exceeding 15 mmHg. IVUS pulsatility index was defined as [(systolic lumen area - diastolic lumen area)/(diastolic lumen area) ×100], Peterson's elastic modulus as (pulmonary pulse pressure/IVUS pulsatility index), and area of wall thickness as [(wall area - lumen area)/(lumen area) x100)]. In the literature, the mean ± standard deviation (SD) normal values of elastic modulus and wall thickness area have been reported as 21 ± 1.7 mmHg and 1.4 ± 1.3%, respectively, in healthy patients without pulmonary hypertension (1: doi: 10.1186/s12931-017-0568-z). We define an alteration in intrinsic pulmonary arterial wall viscoelastic properties as an elastic modulus > 70 mmHg, and we define structural pulmonary wall remodeling as an increase in wall thickness area greater than 5%. Results 13 patients were studied. Median age was 28.1 years interquartile range (IQR) (25.6- 41.4), 7 (53.9%) were female, and 4 (30,8%) were in functional New York Heart Associtation (NYHA) class I. RHC and pulmonary arterial wall IVUS values are presented in Figure 1. 6 (46.2%) had Fontan abnormal pressures at rest. All patients showed minimal pulse pressure in the pulmonary arteries synchronized with heart rate, median pulmonary pulse pressure (IQR) 3 (2-4) mmHg. This pulsatility was detected in the IVUS study in all patients, pulsatility index (median (IQR) 4.8 (3.3-10.1)) and elastic modulus (median (IQR) 51.5 (20.5-101.6) mmHg). All of them had some degree of structural pulmonary wall remodeling (>5% wall thickness area), and 10 (76.9%) of them had marked remodeling (> 10%). The median (IQR) of wall thickness area was 13.6 (10.5-18.3) % (Figure 2). We think that the pseudo-normality of the elastic modulus is due to a low pulmonary pulse pressure, however, structural remodeling could be secondary to the endothelial dysfunction present and described in arteries with very low pulsatility. Conclusions The IVUS evaluation of the pulmonary artery in Fontan patients may be useful for revealing significant information regarding pulmonary physiology. Pulmonary wall thickening has been observed, providing insight into altered structural remodeling of the pulmonary arteries in this population.

Estrogen Oppositely Regulates Pulmonary Hypertension via METTL3/PFKFB3 Under Normoxia and Hypoxia.

Despite extensive investigation into estrogen's role in pulmonary hypertension (PH) development, its effects-whether beneficial or detrimental-remains contentious. This study aimed to elucidate estrogen's potential role in PH under normoxic and hypoxic conditions. Utilizing norfenfluramine- and hypoxia-induced rat models of PH, the study evaluated the impact of 17β-estradiol (E2) on PH progression. E2 promoted PH development under normoxia while providing protection under hypoxia. Mechanistically, under normoxia, E2 upregulated methyltransferase-like 3 (METTL3) gene transcription and protein via an estrogen response element-dependent pathway, which in turn elevated the m6A methylation and translational efficiency of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase isoform 3 (PFKFB3) mRNA, leading to increased PFKFB3 protein levels and enhanced proliferation and migration of pulmonary artery smooth muscle cells (PASMCs). Conversely, under hypoxia, E2 downregulated METTL3 transcription through a hypoxia response element-dependent mechanism, driven by elevated hypoxia-induced factor 1α (HIF-1α) levels, resulting in reduced PFKFB3 protein expression and diminished PASMCs proliferation and migration. Both METTL3 and PFKFB3 proteins are upregulated in the pulmonary arteries of patients with PAH. Collectively, these findings suggest that E2 exerts differential effects on PH progression via dual regulation of the METTL3/PFKFB3 protein under normoxic and hypoxic conditions, positioning the METTL3/PFKFB3 protein as a potential therapeutic target for PH treatment.

Investigation of pulmonary artery and circulating endothelin-1 expression in dogs with pulmonary hypertension secondary to myxomatous mitral valve disease.

Pulmonary hypertension (PH) is a condition characterized by abnormally elevated pressure in the pulmonary vasculature. It is a common complication of myxomatous mitral valve disease (MMVD) in dogs. Several vasoactive substances, including endothelin-1 (ET-1), have been suggested to contribute to pathological changes in the pulmonary arteries of patients with PH. This study aimed to examine the local and systemic expression of ET-1 in dogs with PH secondary to MMVD. Lung tissues were collected from 20 client-owned dogs during the first stage of the study and divided into three groups: normal dogs (n = 5), MMVD dogs (n = 8), and MMVD+PH dogs (n = 7). The expression of ET-1 and endothelin A receptor (ETAR) in the pulmonary arteries was determined using immunohistochemistry. Blood samples were collected from 61 client-owned dogs for the second stage of the study and divided into three groups: normal (n = 22), MMVD (n = 20), and MMVD+PH (n = 19). Plasma ET-1 concentration was measured using a sandwich enzyme-linked immunosorbent assay. There was no difference in ET-1 and ETAR expression in the pulmonary arteries among the three groups. Similarly, there was no difference in the plasma ET-1 concentration between the groups. In addition, no correlation was found between the immunohistochemical expression of ET-1 and ETAR and the thickness of the pulmonary arteries or between the plasma ET-1 level and echocardiographic variables. The lack of difference in the expression of ET-1 and ETAR in the pulmonary arteries and in the circulating ET-1 concentration among the studied groups suggests that ET-1 may not be related to the pathological development of PH secondary to MMVD in dogs. Due to the small sample size in this study, further research is needed to confirm these findings.

Resistin predicts disease severity and survival in patients with pulmonary arterial hypertension

BackgroundAbnormal remodeling of distal pulmonary arteries in patients with pulmonary arterial hypertension (PAH) leads to progressively increased pulmonary vascular resistance, followed by right ventricular hypertrophy and failure. Despite considerable advancements in PAH treatment prognosis remains poor. We aim to evaluate the potential for using the cytokine resistin as a genetic and biological marker for disease severity and survival in a large cohort of patients with PAH.MethodsBiospecimens, clinical, and genetic data for 1121 adults with PAH, including 808 with idiopathic PAH (IPAH) and 313 with scleroderma-associated PAH (SSc-PAH), were obtained from a national repository. Serum resistin levels were measured by ELISA, and associations between resistin levels, clinical variables, and single nucleotide polymorphism genotypes were examined with multivariable regression models. Machine-learning (ML) algorithms were applied to develop and compare risk models for mortality prediction.ResultsResistin levels were significantly higher in all PAH samples and PAH subtype (IPAH and SSc-PAH) samples than in controls (P < .0001) and had significant discriminative abilities (AUCs of 0.84, 0.82, and 0.91, respectively; P < .001). High resistin levels (above 4.54 ng/mL) in PAH patients were associated with older age (P = .001), shorter 6-min walk distance (P = .001), and reduced cardiac performance (cardiac index, P = .016). Interestingly, mutant carriers of either rs3219175 or rs3745367 had higher resistin levels (adjusted P = .0001). High resistin levels in PAH patients were also associated with increased risk of death (hazard ratio: 2.6; 95% CI: 1.27–5.33; P < .0087). Comparisons of ML–derived survival models confirmed satisfactory prognostic value of the random forest model (AUC = 0.70, 95% CI: 0.62–0.79) for PAH.ConclusionsThis work establishes the importance of resistin in the pathobiology of human PAH. In line with its function in rodent models, serum resistin represents a novel biomarker for PAH prognostication and may indicate a new therapeutic avenue. ML-derived survival models highlighted the importance of including resistin levels to improve performance. Future studies are needed to develop multi-marker assays that improve noninvasive risk stratification.

A Case Report: A Successful Management of Extrinsic Compression of the Left Main Coronary Artery by a Dilated Pulmonary Artery in Patients with Pulmonary Arterial Hypertension

Extrinsic compression of the left main coronary artery (LMCA) by a dilated pulmonary artery can be life threatening in pulmonary arterial hypertension patients; however, it can be treated with percutaneous coronary intervention. In this case report, we presented a successful treatment with the stenting of the LMCA stenosis associated with extrinsic compression of LMCA by a dilated pulmonary artery.

GRK2-YAP signaling is implicated in pulmonary arterial hypertension development.

Pulmonary arterial hypertension (PAH) is characterized by excessive proliferation of small pulmonary arterial vascular smooth muscle cells (PASMCs), endothelial dysfunction, and extracellular matrix remodeling. G protein-coupled receptor kinase 2 (GRK2) plays an important role in the maintenance of vascular tone and blood flow. However, the role of GRK2 in the pathogenesis of PAH is unknown. GRK2 levels were detected in lung tissues from healthy people and PAH patients. C57BL/6 mice, vascular smooth muscle cell-specific Grk2 -knockout mice ( Grk2ΔSM22 ), and littermate controls ( Grk2flox/flox ) were grouped into control and hypoxia mice ( n =8). Pulmonary hypertension (PH) was induced by exposure to chronic hypoxia (10%) combined with injection of the SU5416 (cHx/SU). The expression levels of GRK2 and Yes-associated protein (YAP) in pulmonary arteries and PASMCs were detected by Western blotting and immunofluorescence staining. The mRNA expression levels of Grk2 and Yes-associated protein ( YAP ) in PASMCs were quantified with real-time polymerase chain reaction (RT-PCR). Wound-healing assay, 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT) assay, and 5-Ethynyl-2'-deoxyuridine (EdU) staining were performed to evaluate the proliferation and migration of PASMCs. Meanwhile, the interaction among proteins was detected by immunoprecipitation assays. The expression levels of GRK2 were upregulated in the pulmonary arteries of patients with PAH and the lungs of PH mice. Moreover, cHx/SU-induced PH was attenuated in Grk2ΔSM22 mice compared with littermate controls. The amelioration of PH in Grk2ΔSM22 mice was accompanied by reduced pulmonary vascular remodeling. In vitro study further confirmed that GRK2 knock-down significantly altered hypoxia-induced PASMCs proliferation and migration, whereas this effect was severely intensified by overexpression of GRK2 . We also identified that GRK2 promoted YAP expression and nuclear translocation in PASMCs, resulting in excessive PASMCs proliferation and migration. Furthermore, GRK2 is stabilized by inhibiting phosphorylating GRK2 on Tyr86 and subsequently activating ubiquitylation under hypoxic conditions. Our findings suggest that GRK2 plays a critical role in the pathogenesis of PAH, via regulating YAP expression and nuclear translocation. Therefore, GRK2 serves as a novel therapeutic target for PAH treatment.

Pulmonary blood flow in children with univentricular heart and unilateral diaphragmatic paralysis.

Spontaneous breathing has an important effect on pulmonary arterial blood flow in patients with Glenn/Fontan circulation. Unilateral diaphragmatic paralysis (DP) is a frequent complication after heart surgery in congenital heart disease. The aim of this study was to investigate the influence of unilateral DP on blood flow distribution in the pulmonary arteries with Glenn/Fontan circulation. Magnetic resonance phase-contrast imaging was used to evaluate stroke volume index (SVI) in the left and right pulmonary arteries in patients with Glenn/Fontan circulation with unilateral DP. Data for 18 patients with univentricular heart and unilateral DP were analysed, 8 in the Glenn stage and 10 in the Fontan stage. Ten patients had right-sided DP, and 8 had left-sided DP. A diaphragmatic plication was performed in 7 patients. The control group consisted of 36 patients with Glenn (n = 16)/Fontan (n = 20) circulation without DP. In both left- and right-sided DP, the SVI to the ipsilateral side was significantly lower than in controls [2.81 (1.45-4.50) ml/m2 left vs 11.97 (7.36-16.37) ml/m2 in controls, P < 0.0002; 8.2 (4.49-12.64) ml/m2 with right vs 12.64 (9.66-16.61) ml/m2 in controls; P = 0.0284]. The SVI to the contralateral side showed a slight but non-significant increase in the presence of unilateral DP. Unilateral DP in patients with Glenn/Fontan circulation has a negative impact on pulmonary arterial SVI on the side of the paralysis.

Pulmonary artery wave intensity analysis in pulmonary hypertension associated with heart failure and reduced left ventricular ejection fraction.

Wave intensity analysis (WIA) uses simultaneous changes in pressure and flow velocity to determine wave energy, type, and timing of traveling waves in the circulation. In this study, we characterized wave propagation in the pulmonary artery in patients with pulmonary hypertension associated with left-sided heart disease (PHLHD) and the effects of dobutamine. During right heart catheterization, pressure and velocity data were acquired using a dual-tipped pressure and Doppler flow sensor wire (Combowire; Phillips Volcano), and processed offline using customized Matlab software (MathWorks). Patients with low cardiac output underwent dobutamine challenge. Twenty patients with PHLHD (all heart failure with reduced left ventricular ejection fraction) were studied. Right ventricular systole produced a forward compression wave (FCW), followed by a forward decompression wave (FDW) during diastole. Wave reflection manifesting as backward compression wave (BCW) following the FCW was observed in 14 patients. Compared to patients without BCW, patients with BCW had higher mean pulmonary artery pressure (28.7 ± 6.12 vs. 38.6 ± 6.5 mmHg, p = 0.005), and lower pulmonary arterial capacitance (PAC: 2.88 ± 1.75 vs. 1.73 ± 1.16, p = 0.002). Pulmonary vascular resistance was comparable. Mean pulmonary artery pressure of 34.5 mmHg (area under the curve [AUC]: 0.881) and PAC of 2.29 mL/mmHg (AUC: 0.833) predicted BCW. The magnitude of the FCW increased with dobutamine (n = 11) and correlated with pulmonary artery wedge pressure. Wave reflection in PHLHD is more likely at higher pulmonary artery pressures and lower PAC and the magnitude of reflected waves correlated with pulmonary artery wedge pressure. Dobutamine increased FCW but did not affect wave reflection.

Effect of CPAP therapy on the reperfusion lung injury after transluminal balloon angioplasty of the pulmonary arteries in patients with chronic thromboembolic pulmonary hypertension

Aim. To evaluate the effect of non-invasive ventilation (NIV) in CPAP (continuous positive airway pressure) mode on the development of reperfusion pulmonary edema after percutaneous balloon pulmonary angioplasty (BPA) in patients with chronic thromboembolic pulmonary hypertension (CTEPH).Materials and methods. The study included 70 patients with CTEPH who underwent the first stage of BPA. Prevention of reperfusion edema was carried out using NIV in the CPAP mode starting from the early postoperative period in combination with oxygen and diuretic therapy (as nedeed). The presence and severity of pulmonary edema was assessed based on clinical signs and data from computed tomography or chest radiography.Results. Patients after BPA were on CPAP therapy: average pressure: 10.0±0,7 hPa. During 1st day, the average time of use was: 990±417 minutes. Prolongation of CPAP therapy &gt;1 day occurred in 26 (37%) patients. Depending on the severity of reperfusion edema to the lungs, patients were divided into 2 groups: group 1 (grade 1, n=42) and group 2 (grade 3-4, n=12). During the observation period, there were no cases of severe reperfusion edema (grade 5), and no cases required the use of invasive ventilation or extracorporeal membrane oxygenation. No complications of CPAP therapy were recorded. The number of PA segments and ΔPFG did not differ, but the PEPSI index was higher in group 2: 41,9 [16,0; 57,9] vs 80.5 [52,5; 111,25], p=0,0146. The number of days before discharge after BPA in patients of group 2 was higher: 4.0 [3,9; 5,5] vs 7,0 [4,6; 10,0] days, p=0,013. Despite the development of reperfusion edema, before discharge the SpO2 values in group 2 were comparable to the baseline: 93,0 [89,9; 94,2] vs 93,0 [89,7; 94,4]Conclusion. Preventive use of NIV in the CPAP mode, starting from the early postoperative period, is safe and makes it possible to achieve optimal clinical results in patients even with moderate and severe lung reperfusion edema after large volumes of surgical intervention.

Modified central shunt in pulmonary atresia with diminutive pulmonary arteries.

The commonly used central shunt (i.e. direct connection of the divided main pulmonary artery to the ascending aorta) to facilitate the growth of the diminutive branch pulmonary artery in patients with pulmonary atresia with major aortopulmonary collateral arteries can cause main pulmonary artery distortion, and subsequent disproportional branch pulmonary artery flow and growth. This report describes a novel technique of shunt construction to minimize pulmonary artery torque and tension by using a modified central shunt constructed from autologous pericardium that is anastomosed in an end-to-side fashion to the lateral aspect of the ascending aorta. This shunt will serve as an intermediary conduit to facilitate the main pulmonary artery anastomosis while minimizing torque and tension on the main pulmonary artery. The tension-free connection between the main pulmonary artery and the aorta enabled by the modified central shunt supports proportional pulmonary artery flow and growth in patients with pulmonary atresia, ventricular septal defect, or multiple aortopulmonary collateral arteries and concomitant diminutive native pulmonary arteries.

Surgical and transcatheter pulmonary valve replacement in patients with repaired tetralogy of Fallot: cardiac magnetic resonance imaging characteristics and morphology of right ventricular outflow tract.

Pulmonary valve replacement is recommended in patients with repaired tetralogy of Fallot based on cardiac magnetic resonance imaging (MRI) criteria. This procedure is performed by surgical or transcatheter approaches. We aimed to investigate the differences in preprocedural MRI characteristics (volume, function, strain) and morphology of the right ventricular outflow tract and branch pulmonary arteries in patients for whom surgical or transcatheter pulmonary valve replacementwas planned. Cardiac MRI of 166 patients with tetralogy of Fallot were analyzed. Of these, 36 patients for whompulmonary valve replacement was plannedwere included. Magnetic resonance imaging characteristics, right ventricular outflow tract morphology, branch pulmonary artery flow distribution and diameter were compared between surgical and transcatheter groups. Spearman correlation and Kruskal-Wallis tests were performed. Circumferential and radial MRI strain for the right ventricle were lower in thesurgical group (P=0.045and P=0.046, respectively). The diameter of the left pulmonary artery was significantly lower (P=0.021) and branch pulmonary artery flow and diameter ratio were higher (P=0.044and P = 0.002, respectively) in the transcatheter group. There was a significant correlation between right ventricular outflow tract morphology and right ventricular end-diastolic volume indexand global circumferential and radial MRI strain (P=0.046, P=0.046and P= 0.049, respectively). Preprocedural MRI strain, right-to-left pulmonary artery flow, diameter ratio and morphological features of the right ventricular outflow tract were significantly different betweenthe two groups. A transcatheter approach may be recommended for patients with branch pulmonary artery stenosis, since both pulmonary valve replacement and branch pulmonary artery stenting can be performed in the same session.

The state of systolic and diastolic myocardial functions in patients with severe obstructive sleep apnea and their dynamics during CPAP therapy

Aim. To evaluate the change in the parameters of systolic and diastolic myocardial functions in patients with severe obstructive sleep apnea (OSA) syndrome before and after CPAP therapy.&#x0D; Materials and methods. Forty eight patients with severe OSA aged 4574 years were examined. All patients underwent questionnaires, echocardiography with tissue Dopplerography, speckle-tracking echocardiography. At the end of the three-month course of CPAP therapy, the patients were re-examined, followed by a comparative analysis of the data obtained.&#x0D; Results. In patients with severe OSA after CPAP therapy, the ejection fraction of the left ventricle and the amplitude of systolic displacement of the fibrous ring of the tricuspid valve significantly increased, which indicated an increase in the relative capacity of the ventricular myocardium. The performed CPAP therapy had a positive effect on the diastolic function of the myocardium of both ventricles, which was manifested in an increase in the ratio of peak rates of early and late transmitral and transtricuspidal diastolic flows. The rate of transtricuspidal regurgitation and systolic pressure in the pulmonary artery decreased in dynamics.&#x0D; Conclusion. The use of CPAP therapy improves systolic and diastolic heart function, leads to a decrease in systolic pressure in the pulmonary artery in patients with severe OSA. The results obtained substantiate the importance of early initiation of CPAP therapy in the complex treatment of patients with OSA.

Construction and Validation of a Benchtop Model for Testing of Mechanical Thrombectomy Devices for Pulmonary Embolism.

This study aims to define the process of designing and manufacturing 3D printed and glass models of the pulmonary artery (PA) and utilizing them in a test bed for evaluation of devices for mechanical thrombectomy of pulmonary embolism (PE). Patient derived computed tomography angiography (CTA) images of the PA were digitally converted into a hollowed-out structure and translated into clear 3D printed and glass models. A test bed was created using a peristaltic pump and silicone tubing connected to the models. Human clot analogs were then prepared and injected within the models. Thrombectomy testing was done using clinically used predicates and baseline characteristics of the models were evaluated by independent interventionalists. The mean sizes of the main pulmonary artery (MPA) for the 3D printed model and glass model were 30.4mm and 29.2mm, mimicking those of the patient's PA obtained on CTA. Heterogeneous human clot analogs were created with fibrin composition ranging from 60 to 30%. Mechanical thrombectomy was successfully attempted by independent interventionalists. Both the 3D printed, and glass model were appraised as very good for multiple attributes. A complete test bed using 3D printed and glass models of the PA with human clot analogs was created for testing of mechanical thrombectomy devices for PE.

Abstract 10395: Atherosclerotic Lesion in Chronic Thromboembolic Pulmonary Hypertension is Associated With Prolonged Symptom Duration

Background: The cause of atherosclerotic lesions in the pulmonary artery of patients with chronic thromboembolic pulmonary hypertension (CTEPH) remains unclear. We aimed to discuss the clinical characteristics of CTEPH patients with atherosclerotic lesions and further explore the unique metabolic pathway of atherosclerosis in the pulmonary artery. Methods: Following detailed pathological examination of the pulmonary endarterectomy (PEA) specimen, CTEPH patients were divided into two age- and sex-matched groups, those with and without atherosclerotic lesion (n=25 each), and their clinical characteristics were compared. Untargeted metabolomics were used to determine the different metabolites in the proximal lesions of the pulmonary artery. Results: 27.2% (25/92) of all PEA specimens were found with atherosclerotic lesions. Patients with atherosclerotic lesions were more likely to have a history of symptomatic embolism than those without atherosclerotic lesion (88% vs. 56%, P=0.012), including pulmonary embolism and deep venous thrombosis. Patients with atherosclerotic lesions were found to have longer symptom duration (8.0±6.5 vs. 4.7±4.2, P=0.039) and a lower rate of residual pulmonary hypertension after PEA than those without atherosclerotic lesion (40% vs. 56%). However, the existence of atherosclerotic lesion was not associated with pre-operative hemodynamic parameters and cardiac function. Metabolomic profiling revealed that the formation of atherosclerotic lesion in CTEPH is closely related to glycine, serine and threonine metabolic axes involved in cellular aging and energy metabolism. Conclusions: The occurrence of atherosclerotic lesions in the pulmonary artery of CTEPH was associated with symptomatic thromboembolic history and extended symptom duration. The results suggested a new link between atherosclerotic lesions and aberrant amino acid metabolism in the context of CTEPH. Further investigations focused on atherosclerotic lesion and pulmonary vascular remodeling may provide novel insight into the pathophysiology and new therapeutic strategies for CTEPH.

Correlation between Pulmonary Artery Pressure and Vortex Duration Determined by 4D Flow MRI in Main Pulmonary Artery in Patients with Suspicion of Chronic Thromboembolic Pulmonary Hypertension (CTEPH).

Chronic thromboembolic pulmonary hypertension (CTEPH) is one of the causes of pulmonary hypertension (PH) and requires invasive measurement of the mean pulmonary artery pressure (mPAP) during right heart catheterisation (RHC) for the diagnosis. 4D flow MRI could provide non-invasive parameters to estimate the mPAP. Twenty-five patients with suspected CTEPH underwent cardiac MRI. Mean vortex duration (%), pulmonary distensibility, right ventricular volumes and function were measured using 4D flow MRI and cine sequences, and compared with the mPAP measured by RHC. The mPAP measured during RHC was 33 ± 16 mmHg (10–66 mmHg). PH (defined as mPAP > 20 mmHg) was present in 19 of 25 patients (76%). A vortical flow was observed in all but two patients (92%) on 4D flow images, and vortex duration showed good correlation with the mPAP (r = 0.805; p < 0.0001). Youden index analysis showed that a vortex duration of 8.6% of the cardiac cycle provided a 95% sensitivity and an 83% specificity to detect PH. Reliability for the measurement of vortex duration was excellent for both intra-observer ICC = 0.823 and inter-observer ICC = 0.788. Vortex duration could be a useful parameter to non-invasively estimate mPAP in patients with suspected CTEPH.

Abnormal flow conduction through pulmonary arteries is associated with right ventricular volume and function in patients with repaired tetralogy of Fallot: does flow quality affect afterload?

Flow through the proximal pulmonary arteries (PAs) of patients with repaired Tetralogy of Fallot (TOF) is known to be highly disordered and associated with significant regurgitation. The purpose of this study was to evaluate 4D-Flow MRI-derived viscous energy loss [Formula: see text])-as a result of non-efficient flow propagation, and relate this parameter to standard right ventricular (RV) size and function markers in patients with repaired TOF. Thirty-five patients with TOF and 14 controls underwent comprehensive 4D-Flow MRI evaluation for qualitative flow analysis and to calculate [Formula: see text] in the main and right pulmonary arteries. Sampled [Formula: see text] indices were correlated with the MRI-derived RV size and functional indices. All patients with TOF exhibited abnormal, supra-physiologic helical/vortical formations in the PAs. Patients with TOF had significantly increased peak systolic [Formula: see text] (8.0 vs 0.5 mW, p < 0.001), time-averaged [Formula: see text] (2.5 vs. 0.2 mW, p < 0.001), and peak systolic [Formula: see text] indexed to stroke volume (0.082 vs. 0.012 mW/mL, p < 0.001). [Formula: see text] indexed to stroke volume correlated with the RV end-diastolic volume (R = 0.68, p < 0.001), end-systolic volume (R = 0.62, p < 0.001), ejection fraction (R = -0.45, p = 0.002), and cardiac index (R = 0.45, p = 0.002). The mean estimated energy loss due to [Formula: see text] with regard to input RV mechanical power was 4.7%. This study demonstrates that patients with repaired TOF have highly abnormal flow conduction through the PAs which result into extensive viscous energy loss. This significant flow-mediated energy loss is associated with the RV volume and function, and might represent considerable loss of mechanical power generated by each cardiac cycle. Future studies are required to assess whether the abnormal flow conduction adds to the RV afterload and remodeling. • Abnormal flow patterns through proximal pulmonary arteries in patients with TOF are associated with excessive viscous energy loss. • Inefficient flow conduction is associated with the RV dilation and reduced function and might contribute to the RV adaptive remodeling.

Correlation of qanadli obstruction index (QOI) and atrial size on CT pulmonary angiography (CTPA) in patients with pulmonary thromboembolism

BackgroundPulmonary thromboembolism (PTE) is a potentially fatal and life-threatening variation of venous thromboembolism (Faghihi Langroudi et al. in Radiol Res Pract 2:1–6, 2019). Computed Tomography Pulmonary Angiography (CTPA) has been proven to be an invaluable first-line diagnostic tool in the early identification of pulmonary thromboembolism (Aviram et al. J Thromb Haemost 9(2):293–299, 2011; Ghaye et al. in RadioGraphics. 26 1 23 39, 2006). Preliminary studies have suggested the correlation between atrial size and clot burden in the pulmonary arteries in patients with pulmonary thromboembolism (Faghihi Langroudi et al. in Radiol Res Pract 2:1–6, 2019; Aviram et al. J Thromb Haemost 9(2):293–299, 2011). Clot burden is calculated by applying the CTPA dependent score—Qanadli Obstruction Index (QOI)/Pulmonary Arterial Obstruction Index (PAOI) in the pulmonary arteries.ResultsThere was a significant negative correlation between left atrial/right atrial area, left atrial/right atrial short axis and left atrial/right atrial long axis with the PAOI, especially the left atrial/right atrial area ratio and left atrial/right atrial short axis ratio, which showed the most significant negative correlation. Additionally, an LA/RA area of ≤ 0.60 correlated with a PAOI of > 20 and an obstruction percentage of > 50%, which can serve as a predictor of right ventricular dysfunction.ConclusionsThese atrial dimensions can serve as additional early parameters that reflect changes in the cardiac morphology in response to the clot load within the pulmonary arteries, and can thus contribute towards a more comprehensive risk assessment in patients with acute pulmonary thrombo-embolism.

Quantification of vortex flow in pulmonary arteries of patients with chronic thromboembolic pulmonary hypertension

PurposeThis study proposes an objective method of quantifying the vortex flow in pulmonary arteries to compare the duration of its presence before and after balloon pulmonary angioplasty (BPA) in patients with chronic thromboembolic pulmonary hypertension (CTEPH). MethodsThoracic 4D-flow magnetic resonance imaging was performed in 28 CTEPH patients before and after BPA. Planes were set in pulmonary arteries to evaluate volume flow rate (VFR), the duration, and area of backward flow in the pulmonary trunk, which is a component of the vortex flow. The full width at half maximum (FWHM) of the peak of the time course of VFR of backward flow was assessed to quantify the duration of the vortical flow. ResultsAlthough overall flow patterns after BPA appeared to be the same as the one before BPA, significant decreases in the FWHM, area, and VFR of the backward flow after BPA were found (FWHM: before, 1.88 × 10−1 ± 1.51 × 10−2 [cardiac cycle] vs. after, 1.65 × 10−1 ± 1.86 × 10−2 [cardiac cycle]; area ratio: before, 2.67 × 10−1 ± 1.30 × 10−2 vs. after, 2.38 × 10−1 ± 1.31 × 10−2; VFR: before, 13.6 ± 2.21 [mL/s] vs. after, 11.3 ± 2.36 [mL/s]). ConclusionBPA promoted significant decreases in the FWHM, area, and VFR of backward flow in the pulmonary trunk, thereby facilitating efficient blood transport. The tendencies for these changes were to be larger for cases where BPA more greatly decreased the pressure. The results suggest that the FWHM, area, and VFR are useful indicators for the noninvasive evaluation of the therapeutic effects of BPA.

Effectiveness of Bilateral Pulmonary Artery Banding in Patients with Hypoplastic Left Heart Syndrome and Congenital Heart Defects with A Functional Single Ventricle: A Single-Center Retrospective Study

Background: Bilateral banding of the branches of the pulmonary artery in patients with hypoplastic left heart syndrome (HLHS) and other duct dependent critical neonatal heart malformations can significantly reduce the incidence of severe complications in the postoperative period, especially in severely unstable patients. In our study we compared different surgical techniques of bilateral pulmonary artery banding (PAB) in respect to their success in balancing systemic and pulmonary blood flow. Methods: We included 44 neonates with a HLHS and congenital heart diseases (CHD) with a functional single ventricle underwent a hybrid operation: bilateral PAB and patent ductus arteriosus stenting. The hybrid surgery for method No. 1 is performed as a one-stage procedure, together with patent ductus arteriosus (PDA) stenting. After median sternotomy, two Gore-Tex 1–2 mm wide bands with a diameter of 3–3.5 mm are put. When we apply method No. 2 then the thread is used to create bands. Method No. 3 is distinguished by intraoperative assessment of blood flow at the site of narrowing of the branches of the pulmonary artery and optional stenting of the PDA. The cuff for banding is made of Gore-Tex tubing. Effectiveness when applying method Nos. 1 and 2 is assessed by the change in invasive blood pressure and oxygen saturation after narrowing of the branches of the pulmonary artery. Also, with these techniques PDA stenting by inserting the introducer via pulmonary artery trunk is performed. Results: HLHS with mitral or aortic valve atresia or both was present in 19 patients (43.1%), with severe left heart obstruction resulting in PDA dependent systemic circulation in 16 babies (36.4%). CHD with single ventricle physiology occurred in 9 patients (20.5%). 14 babies (31.8%) undergo the procedure following the method No. 1, 8 patients (18.2%) method No. 2 and 22 patients (50%) method No. 3. Qp/Qs = 1/1 was achieved in 30 patients (30/44, 68.1%): as a result of the method No. 1 was achieved in 5 patients (5/14, 35.7%), method No. 2 in 4 patients (4/8, 50%), method No. 3 in 21 patients (21/22, 95.5%). Multivariate regression analysis revealed that method No. 3 significantly increases the chances of hemodynamic efficacy operations (OR = 35.0; p = 0.005; CI (95%) 3–411.5). Conclusion: Application of the operation technique No. 3 in combination with the intraoperative assessment of blood flow parameters at the site of banding of the branches of the pulmonary artery are the most optimal criteria for achieving Qp/Qs = 1/1. If there are signs of restriction at the level of the foramen ovale, atrioseptostomy should be done in the second stage after bilateral pulmonary banding.