Pulmonary Artery Flow Research Articles

Prognostic Value of Reflux of Contrast into the Inferior Vena Cava and Hepatic Veins on CT Pulmonary Angiography in Patients of Pulmonary Embolism

A pulmonary embolism (PE) that obstructs pulmonary arterial blood flow is a medical emergency. Its early detection and appropriate management can be lifesaving. CT pulmonary angiography (CTPA) is currently in use as a standard tool for diagnosis of PE. This study was performed to determine the prognostic accuracy of contrast reflux into the inferior vena cava (IVC) and hepatic veins on CTPA in patients suffering from acute PE. Materials and Methods The study was composed of 285 patients between 15 to 85 years of age that had filling defects in pulmonary arteries on CTPA that were consistent with those of a pulmonary embolism. The extent of contrast reflux into the IVC and hepatic veins was determined on the basis of a Groves scale. The patients were followed for a period of 30 days. Results Of 285 total patients, 200 (70.17%) survived the post PE period of 30 days and were labeled as survivors. The other 85 (29.83%) patients did not survive the 30-day duration and were called non-survivors. The sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy of IVC contrast reflux grading were 65.8%, 90%, 73.68%, 86.12 % and 82.8 % respectively. Conclusion We conclude that IVC contrast reflux grading assessed on helical CT is a beneficial tool for predicting prognosis in cases of acute PE.

Comprehensive Neonatal Cardiac, Feed and Wrap, Non-contrast, Non-sedated, Free-breathing Compressed Sensing 4D Flow MRI Assessment.

Cardiac MRI is an important imaging tool in congenital cardiac disease, but its use has been limited in the neonatal population as general anesthesia has been needed for breath-holding. Technological advances in four-dimensional (4D) flow MRI have now made nonsedated free-breathing acquisition protocols a viable clinical option, but the method requires prospective validation in neonates. To test the feasibility of compressed sensing (CS) 4D flow MRI in the neonatal population and to compare with standard previously validated two-dimensional (2D) phase-contrast (PC) flow MRI. Prospective, cohort, image quality. A total of 14 healthy neonates (median [range] age: 2.5 [0-80] days; 8 male). Noncontrast 2D cine gradient echo sequence with through-plane velocity encoding (PC) sequence and compressed sensing (CS) three-dimensional (3D), time-resolved, cine phase-contrast MRI with 3D velocity-encoding (4D flow MRI) at 3 T. Aortic 2D PC, and aortic, pulmonary trunk and superior vena cava CS 4D flow MRI were acquired using the feed and wrap technique (nonsedated) and quantified using commercially available software. Aortic flow and peak velocity were compared between methods. Internal consistency of 4D flow MRI was determined by comparing mean forward flow of the main pulmonary artery (MPA) vs. the sum of left and right pulmonary artery flows (LPA and RPA) and by comparing mean ascending aorta forward flow (AAo) vs. the sum of superior vena cava (SVC) and descending aorta flows (DAo). Flow and peak-velocity comparisons were assessed using paired t-tests, with P < 0.05 considered significant, and Bland-Altman analysis. Interobserver and intraobserver agreement and internal consistency were analyzed by intraclass correlation co-efficient (ICC). There was no statistically significant difference between ascending aortic forward flow between 2D PC and CS 4D Flow MRI (P=0.26) with a bias of 0.11 mL (-0.59 to 0.82 mL) nor peak velocity (P =0.11), with a bias of -5cm/sec and (-26 to 16 cm/sec). There was excellent interobserver and intraobserver agreement for each vessel (interobserver ICC: AAo 1.00; DAo 0.94, SVC 0.90, MPA 0.99, RPA 0.98, LPA 0.96; intraobserver ICC: AAo 1.00; DAo 0.99, SVC 0.98, MPA 1.00, RPA 1.00, LPA 0.99). Internal consistency measures showed excellent agreement for both mean forward flow of main pulmonary artery vs. the sum of left and right pulmonary arteries (ICC: 0.95) and mean ascending aorta forward flow vs. the sum of superior vena cava and descending aorta flows (ICC: 1.00). Sedation-free neonatal feed and wrap MRI is well tolerated and feasible. CS 4D flow MRI quantification is similar to validated 2D PC free-breathing imaging with excellent interobserver and intraobserver agreement. 1 TECHNICAL EFFICACY: Stage 2.

Echocardiographic Assessment of Pulmonary Hypertension in Neonates with Congenital Diaphragmatic Hernia Using Pulmonary Artery Flow Characteristics.

Background: Assessment of pulmonary hypertension (PH) is essential in neonates with congenital diaphragmatic hernia (CDH). Echocardiography is widely established to quantify PH severity, but currently used parameters have inherent limitations. The aim of our study was to investigate the prognostic utility of the index of the pulmonary artery acceleration time to the right ventricular ejection time (PAAT:ET) in CDH neonates assessed using echocardiography. Methods: PAAT:ET values were prospectively measured in CDH neonates on admission, on day of life (DOL) 2 and DOL 5–7. Optimal cut-off values to predict mortality and need for ECMO were calculated and PAAT:ET values were compared between non-ECMO survivors, ECMO-survivors, and ECMO-non-survivors. Results: 87 CDH neonates were enrolled and 39 patients required ECMO therapy. At baseline, PAAT:ET values were significantly lower in ECMO patients compared to non-ECMO patients (p < 0.001). ECMO survivors and ECMO non-survivors had similar values at baseline (p = 0.967) and DOL 2 (p = 0.124) but significantly higher values at DOL 5–7 (p = 0.003). Optimal PAAT:ET cut-off for predicting ECMO was 0.290 at baseline and 0.310 for predicting non-survival in patients on ECMO at DOL 5–7. Conclusion: PAAT:ET is a feasible parameter for early risk assessment in CDH neonates.

Quantitative cardiopulmonary magnetic resonance imaging in neonatalcongenital diaphragmatic hernia.

Pulmonary arterial hypertension, impaired cardiac function and lung hypoplasia are common in infants with congenital diaphragmatic hernia (CDH) and are associated with increased morbidity and mortality. Robust noninvasive methods to quantify these abnormalities in early infancy are lacking. To determine the feasibility of MRI to quantify cardiopulmonary hemodynamics and function in infants with CDH and to investigate left-right blood flow and lung volume discrepancies. We conducted a prospective MRI study of 23 neonates (isolated left CDH: 4 pre-repair, 7 post-repair, 3 pre- and post-repair; and 9 controls) performed on a small-footprint 1.5-tesla (T) scanner. We calculated MRI-based pulmonary arterial blood flow, left ventricular eccentricity index, cardiac function and lung volume. Using the Wilcoxon rank sum test for continuous data and Fisher exact test for categorical data, we made pairwise group comparisons. The right-to-left ratios for pulmonary artery blood flow and lung volume were elevated in pre-repair and post-repair CDH versus controls (flow: P&lt;0.005; volume: P&lt;0.05 pre-/post-repair). Eccentricity index at end-systole significantly differed between pre-repair and post-repair CDH (P&lt;0.01) and between pre-repair CDH and controls (P&lt;0.001). Cardiopulmonary MRI is a viable method to serially evaluate cardiopulmonary hemodynamics and function in critically ill infants and is useful for capturing left-right asymmetries in pulmonary blood flow and lung volume.

Divergent effects of initial ventilation with delayed cord clamping on systemic and pulmonary arterial flows in the birth transition of preterm lambs.

A current view that delayed cord clamping (DCC) results in greater haemodynamic stability at birth than immediate cord clamping (ICC) is based on comparison of DCC vs. ICC followed by an asphyxial (∼2min) cord clamp-to-ventilation (CC-V) interval. More recent data suggest that relatively minor perinatal differences in heart rate and blood pressure fluctuations exist between DCC and ICC with a non-asphyxial (<45s) CC-V interval, but it is unknown how ventricular output and central arterial blood flow effects of DCC compare with those of non-asphyxial ICC. Anaesthetized preterm fetal lambs instrumented with flow probes on major central arteries were ventilated for 97 (7) s (mean (SD)) before DCC at birth (n=10), or underwent ICC 40 (6) s before ventilation (n=10). Compared to ICC, initial ventilation and DCC was accompanied by (1) redistribution of a similar level of ascending aortic flow away from cephalic arteries and towards the aortic isthmus after ventilation; (2) a lower right ventricular output after cord clamping that was redistributed towards the lungs, thereby maintaining the absolute contribution of this output to a similar increase in pulmonary arterial flow after birth; and (3) a lower descending thoracic aortic flow after birth, related to a more rapid decline in phasic right-to-left ductal flow only partially offset by increased aortic isthmus flow. However, systemic arterial flows were similar between DCC and non-asphyxial ICC within 5min after birth. These findings suggest that compared to non-asphyxial ICC, initial ventilation with DCC transiently redistributed central arterial flows, resulting in lower perinatal systemic arterial, but not pulmonary arterial, flows. KEY POINTS: A current view that delayed cord clamping (DCC) results in greater haemodynamic stability at birth than immediate cord clamping (ICC) is based on comparison of DCC vs. ICC with an asphyxial (∼2min) cord clamp-to-ventilation (CC-V) interval. Recent data suggest that relatively minor perinatal differences in heart rate and blood pressure fluctuations exist between DCC and ICC with a non-asphyxial (<45s) CC-V interval, but how central arterial blood flow effects of DCC compare with those of non-asphyxial ICC is unknown. Anaesthetized preterm fetal lambs instrumented with central arterial flow probes underwent initial ventilation for ∼90s before DCC at birth, or ICC for ∼40s before ventilation. Compared to non-asphyxial ICC, initial ventilation with DCC redistributed central blood flows, resulting in lower systemic, but not pulmonary, arterial flows during this period of transition. This flow redistribution was transitory, however, with systemic arterial flows similar between DCC and non-asphyxial ICC within minutes after birth.

Coronavirus 2019 in a Morbidly Obese Patient: ECMO or No ECMO?

IntroductionCoronavirus 2019 (COVID-19) can lead to Acute Respiratory Distress Syndrome (ARDS), necessitating prolonged mechanical ventilation and the use of extracorporeal membrane oxygenation (ECMO). A Body Mass Index (BMI) higher than 30 kg/m2 is associated with an increased risk of developing ARDS along with greater morbidity, length of stay, and duration of mechanical ventilation in the intensive care unit. There is limited data on utilizing ECMO support in the morbidly obese population.Case ReportA 51-year-old female with a history of chronic obstructive pulmonary disease and extreme obesity with BMI of 54 kg/m2 presented with a complaint of worsening shortness of breath. She was afebrile with a temperature of 97F, tachypneic with a rate of 32, and hypoxic with oxygen saturation in the 80′s. Chest x-ray showed severe bilateral interstitial airspace opacities (figure 1). Transthoracic echocardiogram showed an ejection fraction of 55-60%. She tested positive for COVID-19 and was promptly started on dexamethasone and remdesivir. Her respiratory status continued to decline and she was intubated on day 6. Despite being on 100% Fio2, her hypoxemia persisted. We proceeded to cannulate veno-venous ECMO via the right internal jugular vein and right femoral vein. Over the next several days, her ARDS status continued to improve drastically along with oxygenation. On Day 13, she was successfully de-cannulated with no complications. The patient recovered well and was discharged to an acute rehabilitation facility.SummaryECMO has several advantages including direct pulmonary artery flow improving oxygenation and ventilation, early mobility once off the ventilator, and survival benefit. The use of veno-arterial ECMO should also be considered in the setting of severe respiratory failure accompanied by severe heart failure or right ventricular dysfunction. This case highlights the importance of considering ECMO as a feasible therapeutic option in the morbidly obese patient population with COVID-19 as it can be life-saving.

Clinical Feasibility of Structural and Functional MRI in Free‐Breathing Neonates and Infants

Evaluation of structural lung abnormalities with magnetic resonance imaging (MRI) has previously been shown to be predictive of clinical neonatal outcomes in preterm birth. MRI during free-breathing with phase-resolved functional lung (PREFUL) may allow for complimentary functional information without exogenous contrast. To investigate the feasibility of structural and functional pulmonary MRI in a cohort of neonates and infants with no cardiorespiratory disease. Macrovascular pulmonary blood flows were also evaluated. Prospective. Ten term infants with no clinically defined cardiorespiratory disease were imaged. Infants recruited from the general population and neonatal intensive care unit (NICU) were studied. T1 -weighted VIBE, T2 -weighted BLADE uncorrected for motion. Ultrashort echo time (UTE) and 3D-flow data were acquired during free-breathing with self-navigation and retrospective reconstruction. Single slice 2D-gradient echo (GRE) images were acquired during free-breathing for PREFUL analysis. Imaging was performed at 3T. T1 , T2 , and UTE images were scored according to the modified Ochiai scheme by three pediatric body radiologists. Ventilation/perfusion-weighted maps were extracted from free-breathing GRE images using PREFUL analysis. Ventilation and perfusion defect percent (VDP, QDP) were calculated from the segmented ventilation and perfusion-weighted maps. Time-averaged cardiac blood velocities from three-dimensional-flow were evaluated in major pulmonary arteries and veins. Intraclass correlation coefficient (ICC). The ICC of replicate structural scores was 0.81 (95% CI: 0.45-0.95) across three observers. Elevated Ochiai scores, VDP, and QDP were observed in two NICU participants. Excluding these participants, mean ± standard deviation structural scores were 1.2 ± 0.8, while VDP and QDP were 1.0% ± 1.1% and 0.4% ± 0.5%, respectively. Main pulmonary arterial blood flows normalized to body surface area were 3.15 ± 0.78 L/min/m2 . Structural and functional pulmonary imaging is feasible using standard clinical MRI hardware (commercial whole-body 3T scanner, table spine array, and flexible thoracic array) in free-breathing infants. 2 TECHNICAL EFFICACY: Stage 1.

Feasibility of Echocardiographic Estimation of Pulmonary Artery Stiffness in Horses

Pulmonary artery stiffness (PAS) is an index of pulmonary artery elasticity that permits to evaluate the pulmonary vascular bed in humans. It can early detect an increase in pulmonary artery stiffness as a consequence of remodeling of the vessel wall caused by chronic pulmonary and congenital heart diseases. This remodeling can occur also in horses with chronic respiratory diseases. Thus, PAS could be a useful echocardiographic parameter also in horses. However, in literature, there are no studies regarding PAS in horses. The aim of this study is to evaluate the feasibility of PAS in horses. Fifteen healthy horses were included in this prospective study. Maximal frequency shift and acceleration time were measured from the pulsed-wave Doppler trace of the pulmonary artery flow, obtained from the right parasternal short-axis view at the level of the pulmonary artery, and then PAS was calculated as the ratio of Maximal frequency shift to acceleration time. The low variability assessed for intra- and inter-observer variability, day-to-day variability and image acquisition variability suggests that PAS can be measured consistently in horses. Further studies could be useful to assess the clinical usefulness of PAS in unhealthy horses, such as those affected by chronic respiratory diseases.

Four-dimensional flow CMR in tetralogy of fallot: current perspectives.

Tetralogy of Fallot is the most common cyanotic congenital heart defect, accounting for 10% of all CHD. Despite most patients now surviving well into adulthood, morbidity and mortality rates continue to be high. Surgical and percutaneous pulmonary valve replacement are procedures that are performed to prevent long-term complications from occurring. Unfortunately, pulmonary valve replacement based on current CMR criteria does not prevent postoperative ventricular arrhythmia, heart failure, and sudden cardiac death. Thus, a more advanced and comprehensive hemodynamic evaluation is needed to better understand right ventricular (dys)function in tetralogy of Fallot patients and to optimize the timing of valve replacement. Recently, four-dimensional flow CMR has emerged as a promising and non-invasive imaging technique that can provide comprehensive quantitative evaluation of flow in an entire volume within the chest in a single imaging session. With velocity-encoding in all three spatial directions throughout the complete cardiac cycle, it can provide analysis of cardiac, pulmonary artery and aortic flow volumes, flow velocities, flow patterns, as well as more advanced hemodynamic parameters. Four-dimensional flow CMR could therefore provide insights into the complex hemodynamics of tetralogy of Fallot and could potentially provide novel criteria for pulmonary valve replacement in these patients. The aim of this review is to provide an overview of available research on four-dimensional flow CMR research in tetralogy of Fallot patients.

4D flow cardiovascular magnetic resonance recovery profiles following pulmonary endarterectomy in chronic thromboembolic pulmonary hypertension

BackgroundFour-dimensional flow cardiovascular magnetic resonance imaging (4D flow CMR) allows comprehensive assessment of pulmonary artery (PA) flow dynamics. Few studies have characterized longitudinal changes in pulmonary flow dynamics and right ventricular (RV) recovery following a pulmonary endarterectomy (PEA) for patients with chronic thromboembolic pulmonary hypertension (CTEPH). This can provide novel insights of RV and PA dynamics during recovery. We investigated the longitudinal trajectory of 4D flow metrics following a PEA including velocity, vorticity, helicity, and PA vessel wall stiffness.MethodsTwenty patients with CTEPH underwent pre-PEA and > 6 months post-PEA CMR imaging including 4D flow CMR; right heart catheter measurements were performed in 18 of these patients. We developed a semi-automated pipeline to extract integrated 4D flow-derived main, left, and right PA (MPA, LPA, RPA) volumes, velocity flow profiles, and secondary flow profiles. We focused on secondary flow metrics of vorticity, volume fraction of positive helicity (clockwise rotation), and the helical flow index (HFI) that measures helicity intensity.ResultsMean PA pressures (mPAP), total pulmonary resistance (TPR), and normalized RV end-systolic volume (RVESV) decreased significantly post-PEA (P < 0.002). 4D flow-derived PA volumes decreased (P < 0.001) and stiffness, velocity, and vorticity increased (P < 0.01) post-PEA. Longitudinal improvements from pre- to post-PEA in mPAP were associated with longitudinal decreases in MPA area (r = 0.68, P = 0.002). Longitudinal improvements in TPR were associated with longitudinal increases in the maximum RPA HFI (r=-0.85, P < 0.001). Longitudinal improvements in RVESV were associated with longitudinal decreases in MPA fraction of positive helicity (r = 0.75, P = 0.003) and minimum MPA HFI (r=-0.72, P = 0.005).ConclusionWe developed a semi-automated pipeline for analyzing 4D flow metrics of vessel stiffness and flow profiles. PEA was associated with changes in 4D flow metrics of PA flow profiles and vessel stiffness. Longitudinal analysis revealed that PA helicity was associated with pulmonary remodeling and RV reverse remodeling following a PEA.

Clinical Application of 4D Flow MR Imaging to Pulmonary Hypertension.

Pulmonary hypertension (PH) is characterized by elevated pulmonary arterial pressure (PAP). Although right-heart catheterization is the gold standard method for the diagnosis of PH by definition, various less-invasive imaging tests have been used for screening, detection of underlying diseases-causing PH, and monitoring of diseases. Among them, 4D flow MRI is an emerging and unique imaging test that allows for comprehensive visualization of blood flow in the right heart and proximal pulmonary arteries. The characteristic blood flow pattern observed in patients with PH is vortical flow formation in the main pulmonary artery. Recent studies have proposed the use of these findings to determine not only the presence of PH but also estimate the mean PAP. Other applications of 4D flow MRI for PH include measurement of wall shear stress, helicity, and 3D flow balance in the pulmonary arteries. It is worth noting that 4D flow has also the potential for longitudinal follow-ups. In this review, the clinical definition of PH, summary of conventional imaging tests, characteristics of pulmonary arterial flow as shown by 4D flow MRI, and clinical application of 4D flow MRI in the management of patients with PH will be discussed.

Estimation of Pulmonary Arterial Wave Reflection by Echo-Doppler: A Preliminary Study in Dogs With Experimentally-Induced Acute Pulmonary Embolism.

Background: Pulmonary arterial (PA) wave reflection provides additional information for assessing right ventricular afterload, but its applications is hampered by the need for invasive pressure and flow measurements. We tested the hypothesis that PA pressure and flow waveforms estimated by Doppler echocardiography could be used to quantify PA wave reflection.Methods: Doppler echocardiographic images of tricuspid regurgitation and right ventricular outflow tract flow used to estimate PA pressure and flow waveforms were acquired simultaneously with direct measurements with a dual sensor-tipped catheter under various hemodynamic conditions in a canine model of pulmonary hypertension (n = 8). Wave separation analysis was performed on echo-Doppler derived as well as catheter derived waveforms to separate PA pressure into forward (Pf) and backward (Pb) pressures and derive wave reflection coefficient (RC) defined as the ratio of peak Pb to peak Pf.Results: Wave reflection indices by echo-Doppler agreed well with corresponding indices by catheter (Pb: mean difference = 0.4 mmHg, 95% limits of agreement = −4.3 to 5.0 mmHg; RC: bias = 0.13, 95% limits of agreement = −0.25 to 0.26). RC correlated negatively with PA compliance.Conclusion: This echo-Doppler method yields reasonable measurement of reflected wave in the pulmonary circulation, paving the way to a more integrative assessment of pulmonary hemodynamics in the clinical setting.

The value of outflow tract flow tracing in early pregnancy in the screening of structural malformations of fetal cardiac great arteries.

BackgroundTo explore the application value of outflow tract “〥” blood flow in screening fetal cardiac macrovascular structural malformations in early pregnancy.MethodsA total of 3,356 pregnant women who underwent nuchal translucency (NT) screening during early pregnancy in the prenatal diagnosis center of General Hospital of Ningxia Medical University from January 2017 to December 2018 were taken as the research objects, and the fetuses were systematically screened by ultrasound. The display of four chamber cardiac blood flow, X-shaped blood flow of main pulmonary artery, V-shaped blood flow of three vessel trachea and “〥” shaped blood flow of outflow tract were observed and recorded. Fetal autopsy was performed after informed consent of those who terminated pregnancy. Follow up of fetuses and physical examination of newborns.ResultsA total of 3,356 cases underwent NT examination in early pregnancy, with an average age of 29.18±4.55 years and crown-rump length (CRL) (6.62±0.89 cm). A total of 66 cases of congenital heart disease (CHD) were detected, and the detection rate was 1.97%. There were 15 cases of conus trunk malformation, accounting for 22.7% of the total incidence of CHD. The sensitivity and the receiver operating characteristic (ROC) curve area (AUC =0.659) of “〥” blood flow of outflow tract in early pregnancy were higher than those of “X” Cross blood flow of main pulmonary artery and “V” blood flow of three vessel trachea.Conclusions“〥” Doppler superimposed blood flow in the outflow tract has high sensitivity in the screening of fetal cardiac macrovascular malformations, and has good predictive value for CHD. It can be used as a standard to evaluate whether fetal heart is accompanied by conus trunk malformation.

Abstract 11209: KER-012, a Novel Modified ActrII Ligand Trap, Attenuated Cardiac Pathology in a Pulmonary Arterial Banding Model of Right Ventricle Overload

Pulmonary arterial hypertension (PAH) is a debilitating disorder, characterized by right ventricle (RV) pressure overload, cardiac hypertrophy, and progressive RV dysfunction. PAH is associated with unbalanced TGFß signaling, favoring signaling of SMAD2/3 and opposing SMAD1/5/9. The result is an increase in vascular proliferation and disruption of vascular homeostasis. KER-012 is a modified ActRII ligand trap designed to inhibit ligands that signal through SMAD2/3 to promote restoration of vascular homeostasis. To investigate the cardio-protective effects of RKER-012, a research version of KER-012, we evaluated the effect of treatment in a pulmonary arterial banding (PAB) model. In this study, 8-week-old, male C57BL/6 mice underwent sham or PAB surgery to increase RV pressure and induce cardiac remodeling. The sham cohort received vehicle (VEH) treatment and PAB mice received either vehicle (VEH) or 10 mg/kg RKER-012 twice weekly for 3 weeks. Relative to sham mice, all PAB mice had elevated pulmonary arterial pressures on day 1 (all ps&lt;0.0001) that persisted until day 21 (all ps&lt;0.01), indicating that the PAB procedure was effective. VEH PAB mice also exhibited diminished cardiac function, including increased end systolic pressure volume relationship (ESPVR; +79.3%; p&lt;0.001) and increased myocardial performance index (MPI; +45.6%; p&lt;0.0001) compared to Sham VEH. Additionally, VEH PAB mice had markers of cardiac remodeling, including increased Fulton Indices (+54.8%; p&lt;0.0001), increased RV free wall thickness (RVFWT; +95.8%; p&lt;0.0001) and increased cardiac fibrotic tissue (+529.9%; p&lt;0.0001). In contrast, RKER-012 treatment was cardioprotective and prevented changes in cardiac function and tissue remodeling. In treated mice, there was a trend for decreased ESPVR (-14.2%), decreased MPI (-13.2%, p&lt;0.01), decreased Fulton Index (-13.5%; p&lt;0.01), and decreased RVFWT (-22.9%; p&lt;0.0001) compared to VEH PAB. Treated mice also had reduced cardiac fibrotic tissue (-38.9%, p&lt;0.01). Taken together, these data provide evidence that KER-012 has the potential to reduce cardiac remodeling and improve cardiac performance in pathologies involving constricted pulmonary arterial blood flow and could provide benefit in diseases such as PAH.

Pulmonary Vascular Resistance Estimated by Echocardiography in Dogs With Myxomatous Mitral Valve Disease and Pulmonary Hypertension Probability.

Post-capillary pulmonary hypertension (PH) is a life-threatening complication in dogs with myxomatous mitral valve disease (MMVD). An increase in pulmonary vascular resistance (PVR) is associated with post-capillary PH progression. In humans, PVR estimated by echocardiography (PVRecho) enables the non-invasive assessment of PVR in patients with PH. This study aimed to evaluate the clinical utility of PVRecho in dogs with MMVD, PH probability, and right-sided congestive heart failure (R-CHF). Dogs with MMVD and detectable tricuspid valve regurgitation were included in the study. Dogs were classified into three PH probability groups (low/intermediate/high) and according to the presence or absence of R-CHF. All dogs underwent echocardiographic measurements for right ventricular (RV) morphology and function. PVRecho was calculated by two methods using tricuspid valve regurgitation velocity and velocity–time integral of the pulmonary artery flow (PVRecho and PVRecho2). RV size indicators were significantly higher with a higher probability of PH. RV strain and velocity–time integral of the pulmonary artery flow in the high probability group were significantly lower than those in the other groups. Tricuspid valve regurgitation velocity, PVRecho, and PVRecho2 were significantly higher with an increase in PH probability. Logistic regression analysis revealed a significant association between the presence of R-CHF and increased PVRecho2 and end-diastolic RV internal dimension normalized by body weight. PVRecho and PVRecho2 showed significant differences among the PH probability groups. These non-invasive variables may be useful for the diagnosis and stratification of PH and the determination of the presence of R-CHF in dogs with MMVD.

Angiostatic Peptide, Endostatin, Predicts Severity in Pediatric Congenital Heart Disease-Associated Pulmonary Hypertension.

BackgroundEndostatin, an angiogenic inhibitor, is associated with worse pulmonary arterial hypertension (PAH) outcomes in adults and poor lung growth in children. This study sought to assess whether endostatin is associated with disease severity and outcomes in pediatric PAH.Methods and ResultsSerum endostatin was measured in cross‐sectional (N=160) and longitudinal cohorts (N=64) of pediatric subjects with PAH, healthy pediatric controls and pediatric controls with congenital heart disease (CHD) (N=54, N=15), and adults with CHD associated PAH (APAH‐CHD, N=185). Outcomes, assessed by regression and Kaplan‐Meier analysis, included hemodynamics, change in endostatin over time, and transplant‐free survival. Endostatin secretion was evaluated in pulmonary artery endothelial and smooth muscle cells. Endostatin was higher in those with PAH compared with healthy controls and controls with CHD and was highest in those with APAH‐CHD. In APAH‐CHD, endostatin was associated with a shorter 6‐minute walk distance and increased mean right atrial pressure. Over time, endostatin was associated with higher pulmonary artery pressure and pulmonary vascular resistance index, right ventricular dilation, and dysfunction. Endostatin decreased with improved hemodynamics over time. Endostatin was associated with worse transplant‐free survival. Addition of endostatin to an NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide) based survival analysis improved risk stratification, reclassifying subjects with adverse outcomes. Endostatin was secreted primarily by pulmonary artery endothelial cells.ConclusionsEndostatin is associated with disease severity, disease improvement, and worse survival in APAH‐CHD. Endostatin with NT‐proBNP improves risk stratification, better predicting adverse outcomes. The association of elevated endostatin with shunt lesions suggests that endostatin could be driven by both pulmonary artery flow and pressure. Endostatin could be studied as a noninvasive prognostic marker, particularly in APAH‐CHD.

A computational model of contributors to pulmonary hypertensive disease: impacts of whole lung and focal disease distributions.

Pulmonary hypertension has multiple etiologies and so can be difficult to diagnose, prognose, and treat. Diagnosis is typically made via invasive hemodynamic measurements in the main pulmonary artery and is based on observed elevation of mean pulmonary artery pressure. This static mean pressure enables diagnosis, but does not easily allow assessment of the severity of pulmonary hypertension, nor the etiology of the disease, which may impact treatment. Assessment of the dynamic properties of pressure and flow data obtained from catheterization potentially allows more meaningful assessment of the strain on the right heart and may help to distinguish between disease phenotypes. However, mechanistic understanding of how the distribution of disease in the lung leading to pulmonary hypertension impacts the dynamics of blood flow in the main pulmonary artery and/or the pulmonary capillaries is lacking. We present a computational model of the pulmonary vasculature, parameterized to characteristic features of pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension to help understand how the two conditions differ in terms of pulmonary vascular response to disease. Our model incorporates key features known to contribute to pulmonary vascular function in health and disease, including anatomical structure and multiple contributions from gravity. The model suggests that dynamic measurements obtained from catheterization potentially distinguish between distal and proximal vasculopathy typical of pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension. However, the model suggests a non-linear relationship between these data and vascular structural changes typical of pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension which may impede analysis of these metrics to distinguish between cohorts.

Prediction of Fetal Lung Maturity by Fetal Pulmonary Artery Doppler in Cases of Severe Pre-Eclampsia

Background: Severe pre-eclampsia occurring remote from the term is a decision-making dilemma for the obstetrician, the general recommendation is that women with severe pre-eclampsia should be delivered to avoid maternal complications; others recommend prolonging pregnancy in most cases of severely premature pre-eclamptic gestation until the development of fetal lung maturity, development of fetal or maternal distress, or achievement of gestational age of 34 to 36-week of gestation. The cut-off level of pulmonary artery acceleration time to ejection time ratio [PAT/ET] that determines fetal lung maturity in cases of severe pre-eclampsia [PE] is not determined yet.Aim of the work: To study the Doppler indices of the main fetal pulmonary artery and their role in predicting respiratory distress syndrome [RDS] in severe pre-eclampsia.Patients and Methods: A prospective longitudinal cohort research was designed in which 102 pregnant women with PE were chosen and fetal pulmonary artery flow velocity data were acquired by Doppler ultrasound and linked with the development of neonatal RDS.Results: The AT/ET ratio in the fetal pulmonary artery velocity waveform was found to be directly related to the development of newborn RDS. A cut-off value of 0.3 resulted in a sensitivity of 71.4%, specificity of 79.7%, and total accuracy of 77.5%.Conclusion: A high AT/ET ratio in the fetal pulmonary artery is related to the future development of RDS in neonates of mothers with severe pre-eclampsia, implying that fetal pulmonary artery Doppler ultrasound may be a valuable tool in the identification of fetal lung maturity in situations of severe pre-eclampsia.

Impact of maternal late gestation undernutrition on surfactant maturation, pulmonary blood flow and oxygen delivery measured by magnetic resonance imaging in the sheep fetus.

Restriction of fetal substrate supply has an adverse effect on surfactant maturation in the lung and thus affects the transition from in utero placental oxygenation to pulmonary ventilation ex utero. The effects on surfactant maturation are mediated by alteration in mechanisms regulating surfactant protein and phospholipid synthesis. This study aimed to determine the effects of late gestation maternal undernutrition (LGUN) and LGUN plus fetal glucose infusion (LGUN+G) compared to Control on surfactant maturation and lung development, and the relationship with pulmonary blood flow and oxygen delivery ( ) measured by magnetic resonance imaging (MRI) with molecules that regulate lung development. LGUN from 115 to 140days' gestation significantly decreased fetal body weight, which was normalized by glucose infusion. LGUN and LGUN+G resulted in decreased fetal plasma glucose concentration, with no change in fetal arterial compared to control. There was no effect of LGUN and LGUN+G on the mRNA expression of surfactant proteins (SFTP) and genes regulating surfactant maturation in the fetal lung. However, blood flow in the main pulmonary artery was significantly increased in LGUN, despite no change in blood flow in the left or right pulmonary artery and to the fetal lung. There was a negative relationship between left pulmonary artery flow and to the left lung with SFTP-B and GLUT1 mRNA expression, while their relationship with VEGFR2 was positive. These results suggest that increased pulmonary blood flow measured by MRI may have an adverse effect on surfactant maturation during fetal lung development. KEY POINTS: Maternal undernutrition during gestation alters fetal lung development by impacting surfactant maturation. However, the direction of change remains controversial. We examined the effects of maternal late gestation maternal undernutrition (LGUN) on maternal and fetal outcomes, signalling pathways involved in fetal lung development, pulmonary haemodynamics and oxygen delivery in sheep using a combination of molecular and magnetic resonance imaging (MRI) techniques. LGUN decreased fetal plasma glucose concentration without affecting arterial . Surfactant maturation was not affected; however, main pulmonary artery blood flow was significantly increased in the LGUN fetuses. This is the first study to explore the relationship between in utero MRI measures of pulmonary haemodynamics and lung development. Across all treatment groups, left pulmonary artery blood flow and oxygen delivery were negatively correlated with surfactant protein B mRNA and protein expression in late gestation.

Transcatheter closure of silent patent ductus arteriosus for prevention of endocarditis is justified

A diagnosis of ductal infective endocarditis (DIE) usually relies on the clinical histories of infectious syndrome, results of blood cultures and echocardiography. It remains a therapeutic challenge. The prognosis is still poor. Is the prevention of infective endarteritis a valid reason to always close the isolated silent PDA in childhood? The question is not yet eluded [1] , [2] , [3] , [4] . We present the case of six years old girl with DIE developed after dental procedure. The patient was managed by combined medical and early surgery with favorable evolution. A six year old girl was admitted to our service with tachypnea, fatigue and fever lasting for seven days. The patient had dental procedures few days earlier. The physical examination revealed a temperature at 40 °C and a left subclavian murmur. The acute phase marker levels were significantly elevated and β-hemolytic group A streptococcus was grown in his blood culture. Echocardiography revealed vegetations with the diameter of 10 mm on the left side of the PDA ( Fig. 1 ) with turbulent flow in the left pulmonary artery. Treatment with ceftriaxone 200 mg/kg/day and gentamycin 5 mg/kg/day was started then readapted according to antibiogram. The operation was performed on day 15 of antibiotherapy ( Fig. 2 a and b), whom was continued for 4 weeks. The fever did not return and the clinical course of the patient was stable; the final echocardiogram revealed the absence of left ventricular dilatation with a correct systolic function, normal pulmonary pressure. She was discharged four weeks after the surgical cardiac procedure. Infective endarteritis (IE) complicating PDA is very rare nowadays and the risk is very low especially in the industrialized world. Indeed, standardized management by a skilled multidisciplinary team with expertise in imaging, surgery and intensive care has proven to decrease mortality [3] , [4] , [5] , [6] , [7] . Primary prevention is vital. Even though it was not clear if the closure of a small PDA was beneficial, routine closure of any PDA in children and young adults appeared reasonable. The reasons for this recommendation included the risk of infective endocarditis and low-or-zero morbidity from closure, especially when using a transcatheter device [8] , [9] .