Pulmonary Artery Acceleration Time Research Articles

Right Atrial Strain in Pediatric Pulmonary Hypertension-A Prospective Observational Study.

Right ventricular (RV) afterload due to elevated pulmonary arterial (PA) pressure in pulmonary hypertension (PH) causes long-term right atrial (RA) remodeling and dysfunction. RA function has been shown to correlate with PA pressures and outcome in both adult and pediatric patients with PH. We studied the role of RA strain in estimating PA pressures in congenital heart disease (CHD)-associated PH. Children below 12years undergoing elective repair of CHD with left-to-right shunts and echocardiographic evidence of PH were included. RA reservoir, conduit and contractile strain along with conventional measures of RV function and PA pressure were measured using transthoracic echocardiography after induction of anaesthesia. Pre-and post-repair invasive PA pressures were measured after surgical exposure. 51 children with a median age of 24months (range 4-144months) were included, most of whom were undergoing VSD closure. Contractile RA strain showed good correlation with pre-repair systolic PA pressure in mmHg (r = 0.59, 95%CI 0.37-0.75) or expressed as a percentage of SBP (r = 0.67, 95%CI 0.49-0.80). It also predicted persistent postoperative PH as well as pre-repair pulmonary artery acceleration time and right ventricular systolic pressure measured from tricuspid regurgitation jet. The trends of correlation observed suggest a possible prognostic role of RA strain in ACHD with PH and potential utility in its echocardiographic assessment. The observed findings merit deeper evaluation in larger cohorts.

Effect of maternal asthma on fetal pulmonary artery Doppler parameters: a case-control study.

To compare fetal pulmonary artery Doppler parameters between pregnant women with asthma and healthy pregnant women. This prospective, cross-sectional study was conducted on 50 pregnant women diagnosed with asthma and 61 healthy pregnant women. Fetal pulmonary artery Doppler parameters and the fetal main pulmonary artery acceleration time/ejection time (PATET) ratio were compared between the study and control groups. Thereafter, the study group was divided into two subgroups as non-severe and severe asthma. PATET ratio was compared between the subgroups. The fetal main pulmonary artery acceleration time was 25 ms in pregnant women with asthma and 33 ms in the healthy group, indicating a statistically significant difference (p=0.001). The acceleration time/ejection time ratio was statistically lower in the asthma group (0.185 vs. 0.240, p<0.001). The acceleration time/ejection time ratio was 0.172 in patients with severe asthma and 0.195 ms in the non-severe study group (p=0.156). In the maternal asthma group, the PATET ratio of those who went to the NICU due to respiratory distress was also 0.188, and the PATET ratio of those who went to the NICU for other reasons was 0.269 (p=0.053). Fetal pulmonary artery acceleration time and PATET decreased statistically in pregnant women with severe or non-severe asthma. Maternal asthma is associated with changes in pulmonary Doppler parameters in the fetus.

ВЛИЯНИЕ ПЕРЕНЕСЕННОЙ НОВОЙ КОРОНАВИРУСНОЙ ИНФЕКЦИИ НА СТРУКТУРНО-ФУНКЦИОНАЛЬНЫЕ ПАРАМЕТРЫ ПРАВЫХ ОТДЕЛОВ СЕРДЦА И ЛЕГОЧНУЮ ГЕМОДИНАМИКУ У БОЛЬНЫХ ХРОНИЧЕСКОЙ ОБСТРУКТИВНОЙ БОЛЕЗНЬЮ ЛЕГКИХ

Abstract. Introduction. This paper presents the interim results of a prospective clinical study, in which we studied the long-term influence of 2019 novel coronavirus infection (2019-nCoV) on pulmonary-cardiac relationships in patients with chronic obstructive pulmonary disease. Aim: Studying the effect provided by the previous 2019-nCoV on the structural and functional parameters of the right ventricle of the heart and on pulmonary hemodynamics in patients with chronic obstructive pulmonary disease. Materials and Methods. Over the years 2021-2023, we examined 43 patients with stable chronic obstructive pulmonary disease, having a history of 2019-nCoV by transthoracic echocardiography. The study consisted of two control points: on day 8-12 in the hospital and the follow-up visit to the clinic 12 months after 2019-nCoV. The study included a control group of 30 stable chronic obstructive pulmonary disease patients having no 2019-nCoV history. Results and Discussion. We found that the structural and functional strains of the right heart are aggravated in the acute period of 2019-nCoV in patients with chronic obstructive pulmonary disease. Thus, as compared to the control group, the maximum right atrium width (p&lt;0.05), right ventricle anterior wall thickness (p&lt;0.05), and basal right ventricle diameter values were significantly higher. Echocardiographic signs of right ventricle diastolic dysfunction Type 1 were found in 36,3% of cases and Type 2 in 23.3%. Pulmonary artery diameter and mean pulmonary artery pressure were higher than in those of the control group, as well. In 44% of patients, the value of pulmonary artery acceleration time was less than 105 ms (χ2 = 4.59; p&lt;0.05). Persistently high linear and volumetric right atrium and right ventricle indicators were registered in patients after 12 months of follow-up. Signs of the Type 1 diastolic dysfunction were found in 62.7% of patients. There was a tendency to decrease the mean pulmonary artery pressure and pulmonary artery acceleration time values. Conclusions. Thus, according to echocardiography, the combination of chronic obstructive pulmonary disease and 2019-nCoV leads to the aggravation of right ventricle diastolic dysfunction and the progression of pulmonary hypertension. These signs persisted for a long time (12 months).

Relationship between Plasma D-Dimer Level and Pulmonary Hypertension as well as Right Ventricle Dysfunction in Patient Post Pneumonia COVID-19

Background: High rate of coagulopathy and pulmonary thromboembolism in coronavirus disease 2019 (COVID-19), which is represented by an increase in plasma D-Dimer levels is believed to be related to pulmonary hypertension (PH) and right ventricle (RV) dysfunction. Objective: To evaluate the relationship between plasma D-Dimer levels with PH and RV dysfunction assessed from transthoracic echocardiography (TTE) in patients post COVID-19 pneumonia. Methods: Observational research with a cross-sectional design. Estimated mean pulmonary arterial pressure (mPAP) was calculated from Mahan's formula obtained from pulmonary artery acceleration time (PAAT) and RV function was assessed from RV free wall strain (RV FWS), tricuspid annular plane systolic excursion (TAPSE), and fractional area change (FAC). D-Dimer levels during hospitalisation were obtained from medical records and actual D-Dimer was obtained at the time of echocardiography. Results: Total 40 patients post-COVID-19 pneumonia underwent TTE in a median of 11 days after negative PCR. There was a significant correlation between peak D-Dimer levels with mPAP (r=0.526, p&lt;0.001), RV FWS (r=-0.506, p=0.001), TAPSE (r=-0.498, p=0.001), and FAC (r=0.447, p=0.004). Multivariate analysis found peak D-Dimer ≥4530 µg/L independently associated with PH with odds ratio (OR) 6.6, (95% CI 1.1-10; p=0.048), but not with RV dysfunction. Conclusion: Peak D-Dimer level correlates with echocardiographic parameters of RV function and mPAP in patients with COVID-19 infection. Peak D-Dimer ≥4530 µg/L might increase risk of PH, but not RV dysfunction in patient post pneumonia COVID-19.

Impact of cord clamping on haemodynamic transition in term newborn infants

ObjectiveTo assess the haemodynamic consequences of cord clamping (CC) in healthy term infants.DesignCohort study.SettingTertiary maternity hospital.Patients46 full-term vigorous infants born by caesarean section.InterventionsEchocardiography was performed before CC, immediately after CC...

Shape of Pulmonary Artery Doppler Flow Profile and Right Ventricular Hemodynamics in Neonates

To characterize pulmonary artery Doppler flow profile (PAFP) patterns among infants receiving care in neonatal intensive care units (NICUs) and to examine the association of PAFP patterns with pulmonary and right ventricular (RV) hemodynamics. This is a retrospective study at two tertiary NICUs over 4 years that included neonates who demonstrated a complete tricuspid regurgitation envelope on targeted neonatal echocardiography (TNE). Separate personnel reviewed TNEs to characterize PAFP patterns, divide cohort into PAFP groups, and measure quantitative indices of RV hemodynamics (RV systolic pressure [RVSP], pulmonary artery acceleration time [PAAT] and its ratio with RV ejection time [RVET/PAAT], tricuspid annular plane systolic excursion [TAPSE] and RV output [RVO]), for intergroup comparisons. We evaluated TNEs from 186 neonates with median (IQR) gestational age of 28.5 weeks (25.9-35.9) weeks. Four distinct PAFP patterns were identified: A. near-isosceles triangle (22%), B. right-angled triangle (29%), C. notching (40%), and D. low peak velocity (<0.4 m/s; 9%). Groups A-C demonstrated a stepwise worsening in all indices of PH, while pattern D was associated with lower TAPSE and RVO. Using common definitions of pulmonary hypertension (PH), pattern A performed best to rule out PH [sensitivity range 81-90%] and pattern C for diagnosing PH [specificity range 63-78%]. Inspection of PAFP is a simple bedside echocardiography measure that provides clinically meaningful information on underlying RV hemodynamics and may aid in screening and monitoring of patients for PH in NICUs.

Contribution of Mitochondrial Reactive Oxygen Species to Chronic Hypoxia-Induced Pulmonary Hypertension.

Pulmonary hypertension (PH) resulting from chronic hypoxia (CH) occurs in patients with chronic obstructive pulmonary diseases, sleep apnea, and restrictive lung diseases, as well as in residents at high altitude. Previous studies from our group and others demonstrate a detrimental role of reactive oxygen species (ROS) in the pathogenesis of CH-induced PH, although the subcellular sources of ROS are not fully understood. We hypothesized that mitochondria-derived ROS (mtROS) contribute to enhanced vasoconstrictor reactivity and PH following CH. To test the hypothesis, we exposed rats to 4 weeks of hypobaric hypoxia (PB ≈ 380 mmHg), with control rats housed in ambient air (PB ≈ 630 mmHg). Chronic oral administration of the mitochondria-targeted antioxidant MitoQ attenuated CH-induced decreases in pulmonary artery (PA) acceleration time, increases in right ventricular systolic pressure, right ventricular hypertrophy, and pulmonary arterial remodeling. In addition, endothelium-intact PAs from CH rats exhibited a significantly greater basal tone compared to those from control animals, as was eliminated via MitoQ. CH also augmented the basal tone in endothelium-disrupted PAs, a response associated with increased mtROS production in primary PA smooth muscle cells (PASMCs) from CH rats. However, we further uncovered an effect of NO synthase inhibition with Nω-nitro-L-arginine (L-NNA) to unmask a potent endothelial vasoconstrictor influence that accentuates mtROS-dependent vasoconstriction following CH. This basal tone augmentation in the presence of L-NNA disappeared following combined endothelin A and B receptor blockade with BQ123 and BQ788. The effects of using CH to augment vasoconstriction and PASMC mtROS production in exogenous endothelin 1 (ET-1) were similarly prevented by MitoQ. We conclude that mtROS participate in the development of CH-induced PH. Furthermore, mtROS signaling in PASMCs is centrally involved in enhanced pulmonary arterial constriction following CH, a response potentiated by endogenous ET-1.

Prostaglandin-E1 infusion in persistent pulmonary hypertension of the newborn.

Neonates with persistent pulmonary hypertension of the newborn (PPHN) can present with hypoxia and right ventricular dysfunction with resultant inadequate oxygen delivery and end-organ damage. This study describes the use of prostaglandin-E1 (PGE) for ductal patency to preserve right ventricular systolic function and limit afterload in newborns with PPHN. This is a retrospective cohort study that follows the hemodynamics, markers of end-organ perfusion, length of therapeutics, and echocardiographic variables of 57 newborns who used prostglandin-E1 in the setting of PPHN. Tachycardia, lactic acidosis, and supplemental oxygen use improved following PGE initiation. Fractional area change (FAC), to assess right ventricular systolic function, and pulmonary arterial acceleration time indexed to right ventricular ejection time (PAAT/RVET), to assess right ventricular afterload, also improved over three time points relative to PGE use (before, during, and after). Overall, we described the safety and utility of PGE in newborns with severe PPHN for stabilization while allowing natural disease progression.

Abstract 14869: The Role of Female Sex Hormones in Dimorphism of the Immune System in Group 1 Pulmonary Hypertension

Background: The right ventricle (RV) fails in pulmonary arterial hypertension (PAH) in part due to inflammation. In male PAH, RV CCR2 + macrophages induce inflammation via NLRP3 inflammasome. Since PAH males have worse outcomes, a cardioprotective role of the female sex hormones is suggested. Hypothesis: Ovariectomy (OVX) in females recapitulates the males’ disease severity by increasing RV inflammation. NLRP3 inhibition ameliorates RV function in male and OVX rats with monocrotaline (MCT)-induced PAH. Methods: PAH was induced with MCT (60mg/kg) in male, female, and OVX female Sprague Dawley rats. 10 days post-MCT, rats (n=6/sex) were treated with the NLRP3 inhibitor, MCC950 (6mg/Kg/day). Control and MCT rats were studied (n=4/sex/group). RV function was assessed by echocardiography and high-fidelity hemodynamics. Inflammatory (His48 lo CD43 lo CCR2 + ) monocytes were quantified via flow cytometry, RV macrophages (CD68 + CCR2 + ) and mitochondrial morphology were quantified by confocal microscopy. RV fibrosis and hypertrophy were measured. Results: MCT rats had higher RV systolic pressure (RVSP), reduced pulmonary artery acceleration time (PAAT), cardiac output (CO), and tricuspid annular plane systolic excursion (TAPSE) vs. controls (Table). The RV end-diastolic pressure (RVEDP) was high in MCT males, while RV-free wall thickening was reduced in males and OVX. MCC950 improved CO in MCT males but reduced RVSP in males and OVX. The number of CCR2 + inflammatory monocytes ( p=0.065 ) and RV macrophages ( p=0.007 ) was higher in MCT males. Fragmented mitochondria ( p=0.004 ), RV fibrosis ( p&lt;0.0001) and cardiomyocyte hypertrophy ( p&lt;0.0001 ) were present only in MCT males. MCC950 reduced fibrosis ( p=0.006 ) and hypertrophy ( p&lt;0.0001) in males. MCC950 tended to improve hemodynamics in OVX. Conclusion: RV inflammation is most severe in males, and female sex hormones are cardioprotective. Inhibition of the NLRP3 is beneficial in MCT males and trend to benefit OVX.

Timely PAH Identification in Adults With Repaired Congenital Heart Disease? The ACHD-QuERI Registry Insights

BackgroundThe Quality Enhancement Research Initiative (QuERI) in adults with congenital heart disease (ACHD) was developed to improve detection of pulmonary arterial hypertension (PAH) after repair of systemic-to-pulmonary arterial shunt lesions. ObjectivesThis study sought to standardize use of accepted criteria for PAH diagnosis and evaluate utility in at-risk patients with ACHD. MethodsPatients ≥18 years of age with ACHD repaired ≥1 year before enrollment and with additional risk factors for developing PAH were eligible. History, physical examination, electrocardiogram, transthoracic echocardiogram, World Health Organization functional class, and 6-minute walk distance were evaluated at baseline and yearly for 3 years. Pop-up reminders of patient-specific evidence-based recommendations for PAH detection appeared during data entry. ResultsAmong 217 eligible patients, mean age (enrollment) was 44.0 ± 15.9 years, 72.3% were women, and 82.0% were World Health Organization functional class I. Electrocardiogram was performed in >80% and TTE in >70% of patients annually; capture of required transthoracic echocardiography (TTE) measures and alignment between study- and core-center interpretation improved over time, with more frequent assessment of pulmonary arterial flow acceleration time and documentation of right ventricular outflow tract Doppler notching. Approximately 40% of patients had ≥2 high-risk features for PAH on TTE, but only 7% (6/82) underwent right heart catheterization (RHC). Using current definitions, 2 patients were confirmed by RHC to have a diagnosis of PAH (maximum follow-up 3 years). ConclusionsA structured protocol may improve screening for patients with repaired ACHD at risk of developing PAH. RHC may be underutilized in patients with ACHD with TTE findings suggestive of PAH. (Adult Congenital Heart Disease Registry [QuERI]; NCT01659411)

Cardiopulmonary physiological effects of diuretic therapy in preterm infants with chronic pulmonary hypertension.

Using targeted neonatal echocardiography (TNE) to examine cardiopulmonary physiological impact of diuretics in preterm infants with chronic pulmonary hypertension (cPH). Retrospective study comparing TNE indices pre- and ≤2 weeks (post) of initiating diuretic therapy in infants born <32 weeks gestational age with cPH. Twenty-seven neonates with mean gestational age, birthweight and interval between pre-post diuretic TNE of 27.0 ± 2.8 weeks, 859 ± 294 grams, and 7.8 ± 3.0 days respectively were studied. Diuretics was associated with improvement in pulmonary vascular resistance [pulmonary artery acceleration time (PAAT); 34.27(9.76) vs. 40.24(11.10)ms, p = 0.01), right ventricular (RV) ejection time:PAAT ratio [5.92(1.66) vs. 4.83(1.14), p < 0.01)], RV fractional area change [41.6(9.8) vs. 46.4(6.5%), p = 0.03)] and left ventricular myocardial performance index [0.55(0.09) vs. 0.41(0.23), p < 0.01)]. Post-treatment, frequency of bidirectional/right-to-left inter-atrial shunts decreased significantly (24% vs. 4%, p = 0.05). Primary diuretic treatment in neonates with cPH may result in improvement in PVR, RV and LV function and compliance.

Assessment of Myocardial Function in Infants of Mothers with Gestational Diabetes Mellitus Using Deformation Imaging over the First Year of Age

To assess serial myocardial performance and pulmonary vascular resistance (PVR) in infants of mothers with gestational diabetes mellitus (GDM) over the first year of life. This was a prospective, observational study. Echocardiography was performed at birth, 6months, and 1year of age. Pulmonary artery acceleration time and left ventricular (LV) eccentricity index provided surrogate measurements of PVR. Biventricular function was assessed by tissue Doppler imaging and deformation analysis. Fifty infants of mothers with GDM were compared with 50 controls with no difference in gestation (38.9±0.8 weeks vs 39.3±0.9weeks; P=.05) or birthweight (3.55±0.49 kg vs 3.56±0.41kg; P=.95). At 1 year of age, the pulmonary artery acceleration time was lower (70±11 vs 79±10; P=.01) in the GDM group. LV global longitudinal strain (24.7±1.9 vs 28.8±1.8 %; P<.01), LV systolic strain rate (1.8±0.2 vs 2.1±0.3 1/s; P<.01), and RV free wall strain (31.1±4.8 vs 34.6±3.9 %; P<.01) were lower in the GDM cohort at 1year of age (all P values adjusted for gestation, mode of delivery, and maternal body mass index). Our findings demonstrate higher indices of PVR and lower biventricular function in infants ofmothers with GDM compared with controls at each time point assessed in this study over the first year of life.

A neonatal rat model of pulmonary vein stenosis

ObjectivesPulmonary vein stenosis (PVS), one of the most challenging clinical problems in congenital heart disease, leads to secondary pulmonary arterial hypertension (PAH) and right ventricular (RV) hypertrophy. Due to the lack of a rodent model, the mechanisms underlying PVS and its associated secondary effects are largely unknown, and treatments are minimally successful. This study developed a neonatal rat PVS model with the aim of increasing our understanding of the mechanisms and developing possible treatments for PVS.MethodsPVS was created at postnatal day 1 (P1) by banding pulmonary veins that receive blood from the right anterior and mid lobes. The condition was confirmed using echocardiography, computed tomography (CT), gross anatomic examination, hematoxylin and eosin (H&E) staining, fibrosis staining, and immunofluorescence. Lung and RV remodeling under the condition of PVS were evaluated using H&E staining, fibrosis staining, and immunofluorescence.ResultsAt P21, echocardiography revealed a change in wave form and a decrease in pulmonary artery acceleration time—indicators of PAH—at the transpulmonary valve site in the PVS group. CT at P21 showed a decrease in pulmonary vein diameter in the PVS group. At P30 in the PVS group, gross anatomic examination showed pulmonary congestion, H&E staining showed wall thickening and lumen narrowing in the upstream pulmonary veins, and immunofluorescence showed an increase in the smooth muscle layers in the upstream pulmonary veins. In addition, at P30 in the PVS group, lung remodeling was evidenced by hyperemia, thickening of pulmonary small vessel walls and smooth muscle layers, and reduction of the number of alveoli. RV remodeling was evidenced by an increase in RV free wall thickness.ConclusionsA neonatal rat model of PVS was successfully established, showing secondary lung and RV remodeling. This model may serve as a useful platform for understanding the mechanisms and treatments for PVS.

Demographic, clinical, and echocardiographic factors associated with residual perfusion defects beyond six months after pulmonary embolism

BackgroundResidual perfusion defects (RPD) after pulmonary embolism (PE) are common. Primary aimThis study aimed to determine the prevalence of RPD in a cohort diagnosed with PE 6–72 months earlier, and to determine demographic, clinical, and echocardiographic variables associated with RPD. MethodsPatients aged 18–75 years with prior PE, confirmed by computed tomography pulmonary angiography 6–72 months earlier, were included. Participants (N = 286) completed a diagnostic work-up consisting of transthoracic echocardiography and ventilation/perfusion scintigraphy. Demographic, clinical, and echocardiographic characteristics between participants with RPD and those without RPD were explored in univariate analyses using t-test or Mann-Whitney U test. Multiple logistic regression analysis was used to assess the association between selected variables and RPD. ResultsRPD were detected in 72/286 patients (25.2 %, 95 % CI:20.5 %–30.5 %). Greater tricuspid annular plane systolic excursion (TAPSE) (adjusted odds ratio (aOR) 1.10, 95 % CI:1.00–1.21, p = 0.048) at echocardiographic follow-up, greater thrombotic burden at diagnosis, as assessed by mean bilateral proximal extension of the clot (MBPEC) score 3–4 (aOR 2.08, 95 % CI:1.06–4.06, p = 0.032), and unprovoked PE (aOR 2.25, 95 % CI:1.13–4.48, p = 0.021) were independently associated with increased risk of RPD, whereas increased pulmonary artery acceleration time was associated with a lower risk of RPD (aOR 0.72, 95 % CI:0.62–0.83, p < 0.001, per 10 ms). Dyspnoea was not associated with RPD. ConclusionRPD were common after PE. Reduced pulmonary artery acceleration time and greater TAPSE on echocardiography at follow-up, greater thrombotic burden at diagnosis, and unprovoked PE were associated with RPD.

Quantitative Measures of Right Ventricular Size and Function by Echocardiogram Correlate with Cardiac Catheterization Hemodynamics in Congenital Diaphragmatic Hernia

To evaluate associations between cardiac catheterization (cath) hemodynamics, quantitative measures of right ventricular (RV) function by echocardiogram, and survival in patients with congenital diaphragmatic hernia (CDH). This single-center retrospective cohort study enrolled patients with CDH who underwent index cath from 2003 to 2022. Tricuspid annular plane systolic excursion z score, RV fractional area change, RV free wall and global longitudinal strain, left ventricular (LV) eccentricity index, RV/LV ratio, and pulmonary artery acceleration time were measured from preprocedure echocardiograms. Associations between hemodynamic values, echocardiographic measures, and survival were evaluated by Spearman correlation and Wilcoxon rank sum test, respectively. Fifty-three patients (68% left-sided, 74% liver herniation, 57% extracorporeal membrane oxygenation, 93% survival) underwent cath (39 during index hospitalization, 14 later) including device closure of a patent ductus arteriosus in 5. Most patients (n=31, 58%) were on pulmonary hypertension treatment at cath, most commonly sildenafil (n=24, 45%) and/or intravenous treprostinil (n=16, 30%). Overall, hemodynamics were consistent with precapillary pulmonary hypertension. Pulmonary capillary wedge pressure was >15mm Hg in 2 patients (4%). Lower fractional area change and worse ventricular strain were associated with higher pulmonary artery pressure while higher LV eccentricity index and higher RV/LV ratio were associated with both higher pulmonary artery pressure and higher pulmonary vascular resistance. Hemodynamics did not differ based on survival status. Worse RV dilation and dysfunction by echocardiogram correlate with higher pulmonary artery pressure and pulmonary vascular resistance on cath in this CDH cohort. These measures may represent novel, noninvasive clinical trial targets in this population.

Macitentan in the Young-Mid-term Outcomes of Patients with Pulmonary Hypertensive Vascular Diseasetreated in a Pediatric Tertiary Care Center.

Pulmonary hypertension (PH) is a severe hemodynamic condition with high morbidity and mortality. Approved targeted therapies are limited for pediatric subjects, and treatments are widely adopted from adult algorithms. Macitentan is a safe and effective drug used for adult PH, but data on pediatric patients are limited. In this prospective single-center study, we investigated mid- and long-term effects of macitentan in children with advanced pulmonary hypertensive vascular disease. Twenty-four patients were enrolled in the study for treatment with macitentan. Efficacy was determined by echo parameters and brain natriuretic peptide levels (BNP) at 3months and 1year. For detailed analysis, the entire cohort was subgrouped into patients with congenital heart disease-related PH (CHD-PH) and non-CHD-PH patients, respectively. Mean age of the patients was 10.7±7.6 years; median observation period was 36months. Twenty of 24 patients were on additional sildenafil and/or prostacyclins. Two of 24 patients discontinued because of peripheral edema. Within the entire cohort, BNP levels and all echo measures such as right ventricular systolic pressure (RVSP), right ventricular end-diastolic diameter (RVED), tricuspid annular plane systolic excursion (TAPSE), pulmonary velocity time integral (VTI), and pulmonary artery acceleration time (PAAT) improved significantly after 3months (p ≤ 0.01), whereas in the long term significant improvement persisted for BNP levels (-16%), VTI (+14%) and PAAT (+11%) (p<0.05). By subgroup analysis, non-CHD PH patients showed significant improvements in BNP levels (-57%) and all echo measures (TAPSE +21%, VTI +13%, PAAT +37%, RVSP -24%, RVED -12%) at 3months (p≤0.01), whereas at 12months, improvements persisted (p<0.05) except for RVSP and RVED (nonsignificant). In CHD-PH patients, none of the measures changed (nonsignificant). 6-MWD (distance walked in 6 minutes)slightly increased but was not statistically evaluated. Data presented herein account for the largest cohort of severely affected pediatric patients receiving macitentan. Overall, macitentan was safe and associated with significant beneficial effects and sustained positive signals after 1year, albeit in the long term disease progression remains a major concern. Our data suggest limited efficacy in CHD-related PH, whereas favorable outcomes were mainly driven by improvements in patients with PH not related to CHD. Larger studies are needed to verify these preliminary results and to prove efficacy of this drug in different pediatric PH entities.

Comparison of echocardiographic pulmonary flow Doppler markers in patients with massive or submassive acute pulmonary embolism and control group: A cross-sectional study.

Computed tomography angiography (CTA) is the gold standard for the diagnosis of massive (MPE) and submassive pulmonary embolism (SMPE). Ultrasound has not been accepted as a diagnostic tool. We aim to evaluate the pattern of pulmonary Doppler echocardiography in patients with pulmonary embolism (PE). From 2020 to 2022, 30 patients with acute MPE or SMPE confirmed by CTA and normal pulmonary pressures were selected. A control group was created with 30 individuals without PE. All patients had an echocardiography Doppler study of the pulmonary flow with a focus on early systolic notching (ESN), McConnell's (MC) sign, Right ventricular outflow tract velocity time integral (RVOTVTI), segmental thickness variability (STV), right ventricular end-diastolic diameter (RVEDD), tricuspid regurgitation (TR) gradient, pulmonary artery pressure (PAP), and acceleration (AT) or ejection time (ET). ESN was identified in 96.6% of PE patients and 0% of the control group (p < 0.001). In comparison with the control group, STV (p < 0.001), RVOT VTI (p < 0.001), ET (p = 0.04), and AT (p < 0.001) values were lower in patients with PE while RVEDD, TR gradient, PAP, ESN, MC sign, and d-shape were higher (p < 0.001). Identification of the ESN pattern and AT/ET < 0.4 showed excellent predictive ability for MPE and SMPE with a sensitivity of 97.0% and 100%, specificity of 99.0% and 97%, and an area under the ROC curve of 0.967 (95% CI 0.914-1.00) and 0.933 (95% CI 0.844-1.00), respectively. Doppler echocardiography with particular attention to ESN, may be a suitable noninvasive method for the diagnosis of MPE and SMPE. Further studies with more sample sizes are needed to confirm its diagnostic benefit.

Phosphodiesterase type 9 opposes relaxation of mouse pulmonary artery but does not influence chronic hypoxia-induced pulmonary hypertension in mouse

PDE9 is a phosphodiesterase which has recently emerged as a regulator of cGMP in cardiac and vascular myocytes. Its contribution in vasculature is, however, unclear. We sought to investigate PDE9 expression and function in mouse pulmonary artery by comparing wild type (WT) and PDE9-deficient, Pde9a(-/-), mice. We also addressed the hypothesis that PDE9 could represent a new therapeutic target to treat pulmonary arterial hypertension, a severe, deadly disease. PDE9 expression was examined in mouse tissues and human pulmonary artery from subjects with or without pulmonary arterial hypertension using RT-PCR and immunoblots. Relaxant responses were studied in mouse pulmonary arteries mounted on a myograph and contracted with phenylephrine. A challenge with 21-day, 10% O2-hypoxia was used as a model of pulmonary hypertension in mice and was compared to normoxia. Right ventricle and pulmonary artery morphology and function were determined by echocardiography, right ventricle catheterization and gravimetric analysis. PDE9 protein and Pde9a transcript were detected in human and mouse pulmonary arteries, respectively. Pulmonary arteries from Pde9a(-/-) mice displayed more potent relaxant responses to acetylcholine, to the NO donor diethylamine NONOate and to atrial natriuretic peptide than vessels from WT animals. Following hypoxia, Pde9a expression was increased in lung and right ventricle from WT mice. PDE9 deficiency failed to ameliorate pulmonary hypertension hemodynamic criteria, namely higher right ventricular systolic pressure and lower echocardiographic pulmonary arterial acceleration time. Right ventricle hypertrophy, reflected by increased Fulton index, right ventricle thickness and fetal genes expression, were also similar in Pde9a(-/-) and WT groups. PDE9 is expressed in pulmonary artery and takes part in the relaxant responses mediated by the cGMP pathway. The ablation of Pde9a in mouse, however, does not prevent the development of pulmonary hypertension in a 21-day hypoxia model, nor does it attenuate right ventricle deleterious remodeling.

Assessment of fetal pulmonary artery Doppler indices in pregnant women with rheumatoid arthritis and ankylosing spondylitis.

To investigate fetal pulmonary artery Doppler parameters in pregnant women with rheumatoid arthritis (RA) and ankylosing spondylitis (AS). This case-control study included 24 pregnant women diagnosed with 13 AS and 11 RA and 48 healthy pregnant women at 29-30 weeks of gestation. The demographic and clinical features were recorded, including disease type and duration, attacks during pregnancy, and medications. Pulmonary artery acceleration time (AT), ejection time (ET), and pulmonary artery acceleration time to ejection time (PATET) ratio were measured by manual trace with spectral Doppler ultrasound. A shorter pulmonary AT and lower PATET ratio were found in the case group (34.8 ± 2.3, p < 0.001, 0.18 ± 0.02, p < 0.001, respectively). When comparing the groups that had an attack during pregnancy and had not, there were no significant differences in the pulmonary artery indices. We also demonstrated a moderate correlation between maternal disease years and the PATET ratio (r = -0.562, p = 0.004). This is the first study to evaluate the effect of RA and AS on fetal pulmonary indices. Maternal inflammation might affect pulmonary development and circulation. Fetal pulmonary Doppler indices can be used to obtain further information about neonatal respiratory morbidities in rheumatological disorders.

Role of Pulmonary Artery Acceleration Time in Infants of Diabetic Mothers in assessement of Pulmonary Artery Pressure

Role of Pulmonary Artery Acceleration Time in Infants of Diabetic Mothers in assessement of Pulmonary Artery Pressure