Increase In Pulmonary Blood Flow Research Articles

Pulmonary hypertension secondary to valvular heart disease: a state-of-the-art review.

Pulmonary hypertension (PH) is a common disease affecting up to 1% of the population and at least 50% of patients diagnosed with heart failure (HF) (Hoeper et al. in Lancet Respir Med 4(4):306-322, 2016). It is estimated that PH is present in 15% to 60% of patients with valvular heart disease (VHD) which can result from an increase in pulmonary blood flow and subsequently in pulmonary venous congestion and pulmonary vascular resistance (PVR). It is important to identify the severity of PH in patients with VHD to appropriately risk stratify and manage these patients (Magne et al. in JACC Cardiovasc Imaging 8(1):83-99, 2015). In this review, we examine the diagnostic criteria for PH and its pathophysiology. We also focus on the growing evidence supporting the presence of PH secondary to VHD and describe the contemporary surgical and medical therapeutic interventions in this patient population (Fig.1).

MRI Characterization of Blood Flow and Oxygen Delivery in the Fetal Sheep whilst Exposed to Sildenafil Citrate

Introduction: Newborns exposed to sildenafil citrate (SC) in utero have increased rates of persistent pulmonary hypertension. The mechanism behind this has not yet been fully elucidated. We aimed to utilize a combination of clinically relevant MRI techniques to comprehensively characterize the haemodynamics of the fetal sheep whilst under the influence of SC. We hypothesized that these MRI techniques would detect SC-induced increases in pulmonary blood flow and oxygen delivery prior to birth. Methods: At 116–117 days gestational age (term, 150 days), pregnant Merino ewes (n = 9) underwent fetal catheterization surgery. MRI scans were performed during a basal state and then repeated during a constant umbilical vein infusion of SC to measure blood flow and oxygenation within the major vessels of the fetal circulation using phase-contrast-MRI and T₂ oximetry. Results: Right and left ventricular cardiac outputs were not different between states. Pulmonary blood flow increased during the SC state resulting in elevated pulmonary oxygen delivery. Right to left heart shunting through the foramen ovale was reduced without reducing cerebral oxygen delivery. Conclusion: SC induces alterations to pulmonary haemodynamics in utero; a characteristic that if maintained may underlie or act as a precursor towards the elevated rates of poor pulmonary outcomes after birth. These MRI techniques are the first to comprehensively characterize sildenafil’s direct impact on the pulmonary vasculature and its indirect detriment to the flow of oxygen-rich blood through the foramen ovale.

Surgical correction of total anomalous pulmonary venous return in an adult patient

BackgroundTotal anomalous pulmonary venous return (TAPVR) is rare congenital heart disease. Most TAPVRs require surgical corrections in the neonatal period and survival to adulthood without surgical correction is extremely rare. Most untreated patients with large atrial septal defects and no pulmonary venous obstruction have pulmonary vascular damage from pulmonary over circulation.Case presentation44-year-old TAPVR patient admitted to our medical center. A snowman-shaped heart, including cardiomegaly and an increase in pulmonary blood flow, was seen in the chest X-ray. A large-sized (around 3 cm) atrial septal defect with dilated right atrium, right ventricle, and pulmonary artery was detected on echocardiography. Heart computed tomography was performed for further evaluation, and supra-cardiac type TAPVR without any obstructive lesion was identified.ConclusionsTAPVR in an adult patient is extremely rare, and this patient was treated successfully with surgical correction and is doing well. A sinus rhythm and mild mitral valve regurgitation have remained during 2.5 years of outpatient follow-up.

The Paradox of Pulmonary Vascular Resistance: Restoration of Pulmonary Capillary Recruitment as a Sine Qua Non for True Therapeutic Success in Pulmonary Arterial Hypertension.

Exercise-induced increases in pulmonary blood flow normally increase pulmonary arterial pressure only minimally, largely due to a reserve of pulmonary capillaries that are available for recruitment to carry the flow. In pulmonary arterial hypertension, due to precapillary arteriolar obstruction, such recruitment is greatly reduced. In exercising pulmonary arterial hypertension patients, pulmonary arterial pressure remains high and may even increase further. Current pulmonary arterial hypertension therapies, acting principally as vasodilators, decrease calculated pulmonary vascular resistance by increasing pulmonary blood flow but have a minimal effect in lowering pulmonary arterial pressure and do not restore significant capillary recruitment. Novel pulmonary arterial hypertension therapies that have mainly antiproliferative properties are being developed to try and diminish proliferative cellular obstruction in precapillary arterioles. If effective, those agents should restore capillary recruitment and, during exercise testing, pulmonary arterial pressure should remain low despite increasing pulmonary blood flow. The effectiveness of every novel therapy for pulmonary arterial hypertension should be evaluated not only at rest, but with measurement of exercise pulmonary hemodynamics during clinical trials.

Health Supervision for Children and Adolescents With Down Syndrome.

Health Supervision for Children and Adolescents With Down Syndrome.

The adding value of fluid challenge and balloon occlusion tests in patients with atrial septal defect

Abstract Background Careful, step-wise assessment is required in all patients with an atrial septal defect (ASD) to exclude pre-existing pulmonary vascular disease or left ventricular disease. Fluid challenge test (FCT) and balloon occlusion testing (BOT) may unmask left ventricular disease and challenge the pulmonary circulation, but their complementary role in the evaluation of patients with “operable” ASD is not well established. Aim To evaluate the haemodynamic changes of the pulmonary circulation by FCT and BOT in ASD patients undergoing percutaneous closure according to the current guidelines. Methods Consecutive patients selected for percutaneous ASD closure underwent invasive hemodynamic assessment at baseline and after BOT, FCT and both. Results Fifty patients (mean age 47.3±11.7 years, 72% female) were included. All patients had a pulmonary-to-systemic flow ratio (QP/QS) ≥1.5, pulmonary vascular resistance (PVR) <5 WU and pulmonary arterial wedge pressure (PAWP) <15 mmHg. Individuals with a PVR ≥2 WU at baseline were older, more symptomatic, with a higher baseline systemic vascular resistance compared to the lower PVR group (PVR <2 WU; p<0.0001). The response of Qp/Qs to FCT was different between groups (p<0.0001, Figure 1). Patients with a lower baseline PVR experienced an increase in Qp/Qs, which remained above 1.5 in all patients, whereas in almost all (90%) patients with a higher baseline PVR, the Qp/Qs fell to below 1.5. FCT caused a marked increase in pulmonary blood flow of almost 2 liters (p<0.0001) accompanied by increases in PAWP (p<0.0001). BOT led to a modest increase in PAWP (Δ1.5 [−1.0–7.0] mmHg, p<0.0001). FCT added to BOT caused a further increase in PAWP and Qs (both p<0.0001), while PVR was unchanged (p>0.1). No difference was observed in the PAWP response to FCT, BOT or both between groups; no patients reached a PAWP ≥18 mmHg following FCT or BOT alone, but 4 (8%) patients did following the addition of FCT to BOT. No acute clinical adverse events were experienced by any patients. Conclusions None of the reported ASD patients presented with FCT criteria of post-capillary PH (that is a PAWP >18 mmHg). Even small rises in PVR may have significant implications on cardiovascular haemodynamics. In fact, patients with PVR <2 WU showed an increase in Qp/Qs, which remained above 1.5 in all patients, suggesting that they still had a distensible pulmonary circulation, whereas in almost all patients with a PVR ≥2 WU, the Qp/Qs fell to below 1.5. Funding Acknowledgement Type of funding sources: None. Figure 1

Respiratory morbidity in children with congenital heart disease

ObjectiveTo evaluate the respiratory outcome in children with congenital heart disease (CHD), considering recent management procedures and the CHD pathophysiology. Design and SettingClinical and functional respiratory outcome were evaluated in 8-year-old children with isolated CHD followed up from birth in the prospective population-based EPICARD cohort. PatientsChildren were assigned to two groups, based on the pathophysiology of the CHD: CHDs with left-to-right shunt (n = 212) and CHDs with right outflow tract obstruction (n = 113). ResultsCurrent wheezing episodes were observed in 15% of the children with isolated CHD and left-to-right shunt, and 11% of the children with isolated CHD and right outflow tract obstruction (not significant). Total lung capacity (TLC) was the only respiratory function parameter that significantly differed between the two groups. It was lower in children with left-to-right shunt (88.72 ± 0.65% predicted) than in those with right outflow tract obstruction (91.84 ± 0.96, p = 0.006). In multivariate analysis, CHD with left-to-right shunt (coeff. [95% CI]: -3.17 [-5.45; -0.89]) and surgery before the age of 2 months (-6.52 [-10.90; -2.15]) were identified as independent factors associated with significantly lower TLC values. ConclusionLower TLC remains a long-term complication in CHD, particularly in cases with left-to-right shunt and in patients requiring early repair. These findings suggest that an increase in pulmonary blood flow may directly impair lung development.

Fluid challenge and balloon occlusion testing in patients with atrial septal defects

IntroductionCareful, stepwise assessment is required in all patients with atrial septal defect (ASD) to exclude pulmonary vascular or left ventricular (LV) disease. Fluid challenge and balloon occlusion may unmask LV...

Non-invasive MRI Derived Hemodynamic Simulation to Predict Successful vs. Unsuccessful Catheter Interventions for Branch Pulmonary Artery Stenosis: Proof-of-Concept and Experimental Validation in Swine.

This study assessed the ability of hemodynamic simulations to predict the success of catheter interventions in a swine model of branch pulmonary artery stenosis (bPAS). bPAS commonly occurs in congenital heart disease and is often managed with catheter based interventions. However, despite technical success, bPAS interventions do not lead to improved distal pulmonary blood flow (PBF) distribution in approximately 1/3rd of patients. New tools are needed to better identify which patients with bPAS would most benefit from catheter interventions. For 13 catheter intervention cases in swine with surgically created left PAS (LPAS), PA pressures from right heart catheterization (RHC) and PBF distributions from MRI were measured before and after catheter interventions. Hemodynamic simulations with a reduced order computational fluid dynamics (CFD) model were performed using non-invasive PBF measurements derived from MRI, and then correlated with changes in invasive measures of hemodynamics and PBF distributions before and after catheter intervention to relieve bPAS. Compared to experimentally measured changes in left PBF distribution, simulations had a small bias (3.4 ± 11.1%), moderate agreement (ICC = 0.69 [0.24-0.90], 0.71 [0.23-0.91]), and good diagnostic capability to predict successful interventions (> 20% PBF increase) (AUC 0.83 [0.59-1.0]). Simulations had poorer prediction of changes in stenotic pressure gradient (ICC = 0.28 [- 0.33 to 0.73], r = 0.57 [- 0.04 to 0.87]) and MPA systolic pressure (ICC = 0.00 [- 0.52 to 0.53], r = 0.29 [- 0.32 to 0.72]). While there was only weak to moderate agreement between predicted and measured changes in PA pressures and pulmonary blood flow distributions, hemodynamic simulations did show good diagnostic value for predicting successful versus unsuccessful catheter based interventions to relieve bPAS. The results of this proof of concept study are promising and should encourage future development for using hemodynamic models in planning interventions for patients with bPAS.

Birth is Associated with Reduced Coronary Capacity in Sheep

The transition from fetal to neonatal life is among the most universal and rapid changes in physiology encountered in mammalian life. In this study, we sought to directly characterize the effects of birth on the function and capacity of the coronary vasculature in a large animal model of cardiac development. We hypothesized that significant increases in coronary reserve and oxygen delivery would accompany the increased demands placed on the myocardium by the challenges of postnatal life, including dramatic increases in pulmonary blood flow, left ventricular preload, and cardiac output. Near term fetuses (N = 7), and term-born lambs (N = 5) of mixed western breed ewes were instrumented with catheters (aortic arch, right atrium, left atrium), inflatable occluders (inferior vena cava, postductal thoracic aorta), and a Transonic flow probe (left circumflex coronary artery). Studies (unanesthetized) were carried out at least 3 days later (135-136 days gestation (term = 147 days)) or 5-6 d postnatal. Pressure-flow relationships were determined at rest or at maximal adenosine-induced hyperemia. The mass of myocardium served by the artery from which flow was measured was determined by postmortem Evan's Blue perfusion; all reported flow values are normalized to this mass. Cardiac work is the double product of driving (aortic minus right atrial) pressure. We define coronary conductance as the slope of the pressure-flow relationships, and coronary flow reserve as the fold change in coronary flow between resting and hyperemic conductance. Differences between fetuses and neonates were assessed by the Mann-Whitney U-test and considered significant when p < 0.05. Basal cardiac work was significantly greater after birth, as heart rate and driving pressure were 1.3 and 1.6-fold greater in neonate than fetus (p = 0.009, p = 0.003, respectively). Resting coronary flow was 1.8-fold lower in the neonate than the fetus (p = 0.048). Despite a 1.6-fold increase in arterial blood oxygen content (p = 0.006), baseline oxygen delivery per work in the neonate was less than half that in the fetus (p = 0.005; Figure 1A). Pressure-flow relationships (Figure 1B) likewise showed a reduction in coronary conductance from fetus to neonate both at rest (2.3-fold, p = 0.073) and with adenosine hyperemia (2-fold, p = 0.048). Estimated hyperemic coronary flow at resting daily pressures were decreased by 1.6-fold in the neonate (p = 0.03). Coronary flow reserve was similar between fetuses and lambs (p = 1; Figure 1C). Despite the increased cardiac demands of postnatal life, these results suggest that there is not an increase in coronary reserve or capacity following birth. Rather, we find evidence of lower resting and maximal coronary flow in the postnatal period such that flow reserve is maintained. This evidence of an actively regulated decrease in coronary capacity shows the functional consequence of a known reduction in capillary to fiber ratio occurring in the myocardium between birth and maturity. Future studies of myocardial perfusion focusing on microvascular structure and function are therefore warranted.

Impact of Acute and Chronic Hypoxia-Ischemia on the Transitional Circulation.

The transition from intrauterine life to extrauterine existence encompasses significant cardiorespiratory adaptations. These include rapid lung aeration and increase in pulmonary blood flow (PBF). Perinatal asphyxia and fetal growth restriction can severely hamper this transition. Hypoxia is the common denominator in these 2 disease states, with the former characterized by acute insult and the latter by utero-placental insufficiency and a chronic hypoxemic state. Both may manifest as hemodynamic instability. In this review, we emphasize the role of physiologic-based cord clamping in supplementing PBF during transition. The critical role of lung aeration in initiating pulmonary gas exchange and increasing PBF is discussed. Physiologic studies in animal models have enabled greater understanding of the mechanisms and effects of various therapies on transitional circulation. With data from sheep models, we elaborate instrumentation for monitoring of cardiovascular and pulmonary physiology and discuss the combined effect of chest compressions and adrenaline in improving transition at birth. Lastly, physiologic adaptation influencing management in human neonatal cohorts with respect to cardiac and vascular impairments in hypoxic-ischemic encephalopathy and growth restriction is discussed. Impairments in right ventricular function and vascular mechanics hold the key to prognostication and understanding of therapeutic rationale in these critically ill cohorts. The right ventricle and pulmonary circulation seem to be especially affected and may be explored as therapeutic targets. The role of comprehensive assessments using targeted neonatal echocardiography as a longitudinal, reliable, and easily accessible tool, enabling precision medicine facilitating physiologically appropriate treatment choices, is discussed.

Dilatable Pulmonary Artery Banding Palliation in Congenital Heart Disease

Surgical pulmonary artery banding (PAB) has been limited in practice because of later requirement for surgical removal or adjustment. The aim of this study is to describe our experience creating a dilatable PAB via transcatheter balloon dilation (TCBD) in congenital heart disease (CHD) patients. Retrospective chart review of adjustable PAB-outline anatomical variants palliated and patient outcomes. Sixteen patients underwent dilatable PAB-median age 52 days (range 4-215) and weight 3.12 kg (1.65-5.8). Seven (44%) of the patients were premature, 11 (69%) had ventricular septal defect(s) with pulmonary over-circulation, four (25%) atrioventricular septal defects, and four (25%) single ventricle physiology. Subsequent to the index procedure: five patients have undergone intracardiac complete repair, six patients remain well palliated with no additional intervention, and four single ventricles await their next palliation. One patient died from necrotizing enterocolitis (unrelated to PAB) and one patient required a pericardiocentesis postoperatively. Five patients underwent TCBD of the PAB without complication-Two had one TCBD, two had two TCBD, and another had three TCBD. The median change in saturation was 14% (complete range 6-22) and PAB diameter 1.7 mm (complete range 1.1-5.2). Median time from PAB to most recent outpatient follow-up was 868 days (interquartile range 190-1,079). Our institution has standardized a PAB technique that allows for transcatheter incremental increases in pulmonary blood flow over time. This methodology has proven safe and effective enough to supplant other institutional techniques of limiting pulmonary blood flow in most patients-allowing for interval growth or even serving as the definitive palliation.

Prenatal prediction of neonatal haemodynamic adaptation after maternal hyperoxygenation

The reactivity of the pulmonary vascular bed to the administration of oxygen is well established in the post-natal circulation. The vasoreactivity demonstrated by the fetal pulmonary artery Doppler waveform in response to maternal hyperoxia has been investigated. We sought to investigate the relationship between the reactivity of the fetal pulmonary arteries to hyperoxia and subsequent neonatal cardiac function in the early newborn period.MethodsThis explorative study with convenience sampling measured pulsatility index (PI), resistance index (RI), acceleration time (AT), and ejection time (ET) from the fetal distal branch pulmonary artery (PA) at baseline and following maternal hyperoxygenation (MH). Oxygen was administered for 10 min at a rate of 12 L/min via a partial non-rebreather mask. A neonatal functional echocardiogram was performed within the first 24 h of life to assess ejection fraction (EF), left ventricular output (LVO), and neonatal pulmonary artery AT (nPAAT). This study was conducted in the Rotunda Hospital, Dublin, Ireland.ResultsForty-six women with a singleton pregnancy greater than or equal to 31 weeks’ gestational age were prospectively recruited to the study. The median gestational age was 35 weeks. There was a decrease in fetal PAPI and PARI following MH and an increase in fetal PAAT, leading to an increase in PA AT:ET. Fetuses that responded to hyperoxygenation were more likely to have a higher LVO (135 ± 25 mL/kg/min vs 111 ± 21 mL/kg/min, p < 0.01) and EF (54 ± 9% vs 47 ± 7%,p = 0.03) in the early newborn period than those that did not respond to MH prenatally. These findings were not dependent on left ventricular size or mitral valve (MV) annular diameter but were related to an increased MV inflow. There was no difference in nPAAT.ConclusionThese findings indicate a reduction in fetal pulmonary vascular resistance (PVR) and an increase in pulmonary blood flow and left atrial return following MH. The fetal response to hyperoxia reflected an optimal adaptation to postnatal life with rapid reduction in PVR increasing measured cardiac output.

Persistent Pulmonary Hypertension of the Newborn: Pathophysiological Mechanisms and Novel Therapeutic Approaches.

Persistent pulmonary hypertension of the newborn (PPHN) is one of the main causes of neonatal morbidity and mortality. It is characterized by sustained elevation of pulmonary vascular resistance (PVR), preventing an increase in pulmonary blood flow after birth. The affected neonates fail to establish blood oxygenation, precipitating severe respiratory distress, hypoxemia, and eventually death. Inhaled nitric oxide (iNO), the only approved pulmonary vasodilator for PPHN, constitutes, alongside supportive therapy, the basis of its treatment. However, nearly 40% of infants are iNO resistant. The cornerstones of increased PVR in PPHN are pulmonary vasoconstriction and vascular remodeling. A better understanding of PPHN pathophysiology may enlighten targeted and more effective therapies. Sildenafil, prostaglandins, milrinone, and bosentan, acting as vasodilators, besides glucocorticoids, playing a role on reducing inflammation, have all shown potential beneficial effects on newborns with PPHN. Furthermore, experimental evidence in PPHN animal models supports prospective use of emergent therapies, such as soluble guanylyl cyclase (sGC) activators/stimulators, l-citrulline, Rho-kinase inhibitors, peroxisome proliferator-activated receptor-γ (PPAR-γ) agonists, recombinant superoxide dismutase (rhSOD), tetrahydrobiopterin (BH4) analogs, ω-3 long-chain polyunsaturated fatty acids (LC-PUFAs), 5-HT2A receptor antagonists, and recombinant human vascular endothelial growth factor (rhVEGF). This review focuses on current knowledge on alternative and novel pathways involved in PPHN pathogenesis, as well as recent progress regarding experimental and clinical evidence on potential therapeutic approaches for PPHN.

Watershed phenomena during extracorporeal life support and their clinical impact: a systematic in vitro investigation.

AimsExtracorporeal life support (ECLS) during acute cardiac failure restores haemodynamic stability and provides life‐saving cardiopulmonary support. Unfortunately, all common cannulation strategies and remaining pulmonary blood flow increase left‐ventricular afterload and may favour pulmonary congestion. The resulting disturbed pulmonary gas exchange and a residual left‐ventricular action can contribute to an inhomogeneous distribution of oxygenated blood into end organs. These complex flow interactions between native and artificial circulation cannot be investigated at the bedside: only an in vitro simulation can reveal the underlying activities. Using an in vitro mock circulation loop, we systematically investigated the impact of heart failure, extracorporeal support, and cannulation routes on the formation of flow phenomena and flow distribution in the arterial tree.Methods and resultsThe mock circulation loop consisted of two flexible life‐sized vascular models (aorta and vena cava) driven by two paracorporeal assist devices, resistance elements, and compliance reservoirs to mimic the circulatory system. Several large‐bore antegrade and retrograde access ports allowed connection to an ECLS system for extracorporeal support. With four degrees of extracorporeal support—that for cardiac failure, early recovery, late recovery, and weaning—we investigated aortic blood flow velocity, blood flow, and mixing zones using colour‐coded Doppler ultrasound in the aorta and its corresponding branches. Full retrograde extracorporeal support (3–4 L/min) perfused major portions of the aorta but did not reach the supra‐aortic branches and ascending aorta, resulting in an area in the thoracic aorta demonstrating nearly stagnant blood flow velocities during cardiogenic shock and early recovery (0 ± 4 cm/s; −10 ± 15 cm/s, respectively) confined by two watersheds at the aortic isthmus and renal artery origin. Even increased ECLS flow was unable to shift the watershed towards the aortic arch. Antegrade support resulted in homogeneous flow distribution during all stages of cardiac failure but created a markedly negative flow vector in the ascending aorta during cardiogenic shock and early recovery with increased afterload.ConclusionsOur systematic fluid‐mechanical analysis confirms the clinical assumption that despite restoring haemodynamic stability, extracorporeal support generates an inhomogeneous distribution of oxygenated blood with an inadequate supply to end organs and increased left‐ventricular afterload with absent ventricular unloading. End‐organ supply may be monitored by near‐infrared spectroscopy, but an obviously non‐controllable watershed emphasizes the need for additional measures: pre‐pulmonary oxygenation with a veno‐arterial‐venous ECLS configuration can allow a transpulmonary passage of oxygenated blood, providing improved end‐organ supply.

Surfactant for pulmonary haemorrhage in neonates.

In the 1960s and 1970s, pulmonary haemorrhage (PH) occurred mainly in full-term infants with pre-existing illness with an incidence of 1.3 per 1000 live births. Risk factors for PH included severity of illness, intrauterine growth restriction, patent ductus arteriosus (PDA), coagulopathy and the need for assisted ventilation. Presently, PH occurs in 3% to 5% of preterm ventilated infants with severe respiratory distress syndrome (RDS) who often have a PDA and have received surfactant. The cause of PH is thought to be due to rapid lowering of intrapulmonary pressure, which facilitates left to right shunting across a PDA and an increase in pulmonary blood flow. Retrospective case reports and one prospective uncontrolled study have shown promising results for surfactant in treating PH. To evaluate the effect of surfactant treatment compared to placebo or no intervention on mortality and morbidities in neonates with PH. For this update The Cochrane Library, Issue 2, 2012; MEDLINE; EMBASE; CINAHL; Clinicaltrials.gov; Controlled-trials.com; proceedings (2000 to 2011) of the Annual Meetings of the Pediatric Academic Societies (Abstracts2View) and Web of Science were searched on 8 February 2012. Randomised or quasi-randomised controlled trials that evaluated the effect of surfactant in the treatment of PH in intubated term or preterm (< 37 weeks) neonates with PH. Infants were included up to 44 weeks' postmenstrual age. The interventions studied were intratracheal instillation of surfactant (natural or synthetic, regardless of dose) versus placebo or no intervention. If studies were identified by the literature search, the planned analyses included risk ratio, risk difference, number needed to treat to benefit or to harm for dichotomous outcomes, and mean difference for continuous outcomes, with their 95% confidence intervals. A fixed-effect model would be used for meta-analyses. The risk of bias for included trials would be assessed. Heterogeneity tests, including the I2 statistic, would be performed to assess the appropriateness of pooling the data and the results would be reported. No trials were identified. No randomised or quasi-randomised trials that evaluated the effect of surfactant in PH were identified. Therefore, no conclusions from such trials can be drawn. In view of the promising results from studies with less strict study designs than a randomised controlled trial, there is reason to conduct further trials of surfactant for the treatment of PH in neonates.

Effects of Interatrial Shunt on Pulmonary Vascular Function in Heart Failure With Preserved Ejection Fraction

BackgroundImplantation of an interatrial shunt device (IASD) in patients with heart failure (HF) reduces left atrial hypertension by shunting oxygenated blood to the right heart and lungs. The attendant increases in pulmonary blood flow (Qp) and oxygen content may alter pulmonary vascular function, while left-to-right shunting might compromise systemic perfusion. ObjectivesThe authors hypothesized that IASD would improve indexes of pulmonary artery (PA) function at rest and during exercise in HF patients without reducing systemic blood flow (Qs). MethodsThis is a pooled analysis from 2 trials assessing the effects of the IASD on resting and exercise hemodynamics in HF patients (n = 79) with EF ≥40% with baseline and repeated hemodynamic evaluation between 1 and 6 months. Patients with pulmonary vascular resistance (PVR) >4 WU or right ventricular dysfunction were excluded. ResultsQp and PA oxygen content increased by 27% and 7% following IASD. These changes were associated with salutary effects on pulmonary vascular function (17% reduction in PVR, 12% reduction in PA elastance [pulmonary Ea], and 24% increase in PA compliance). Qp increased during exercise to a greater extent following IASD compared with baseline, which was associated with reductions in exercise PVR and pulmonary Ea. Patients with increases in PA compliance following IASD experienced greater improvements in supine exercise duration. There was no reduction in Qs following IASD at rest or during exercise. ConclusionsImplantation of an IASD improves pulmonary vascular function at rest and during exercise in selected patients with HF and EF ≥40%, without compromising systemic perfusion. Further study is warranted to identify underlying mechanisms and long-term pulmonary hemodynamic effects of IASD. (REDUCE LAP-HF Trial [REDUCE LAP-HF]; NCT01913613; and REDUCE LAP-HF Randomized Trial I [REDUCE LAP-HF I]; NCT02600234)

P4371Right ventricular remodeling during the first weeks of life in healthy neonates

Abstract Background The right ventricle (RV) serves as the dominant ventricle in utero. The transition from fetal to post-natal circulation at birth involves marked structural and functional cardiac changes including a large increase in pulmonary blood flow and closure of fetal shunts. Little is known about how the transitional circulation influences RV structure and function in healthy neonates during the first weeks of life. The purpose of this study was to systematically assess RV remodeling in a large, unselected cohort of healthy neonates. Methods Transthoracic echocardiograms of unselected neonates &lt;26 days old without any signs of structural cardiac abnormalities performed between April 1st, 2016 and August 12th, 2017, were consecutively included from the Copenhagen Baby Heart study until at least 90 neonates per day were included. Left parasternal long-axis RV anterior end-diastolic wall thickness and short-axis RV outflow tract end-diastolic diameter were measured offline by one sonographer according to recommendations by the American Society of Echocardiography. RV parameters were corrected for body surface area (BSA). Comparisons were made by T-tests and correlations were computed using univariate linear regression. Results A total of 3,412 echocardiograms were assessed, of which 414 were excluded due to age ≥26 days (n=159), presence of cardiac abnormality (n=179), or suboptimal parasternal views (n=76). Thus, a total of 2,998 (48% male) were included for analysis. Age, weight, and length at examination were (mean±SD) 11.1±7.5 days, 3.6±0.6 kg, and 52±2.6 cm, respectively. BSA-corrected mean (95% CI) end-diastolic outflow tract diameter and end-diastolic anterior wall thickness according to age are presented (Figure). There was a small age-related reduction in end-diastolic RV outflow tract diameter (r2=0.018, p&lt;0.001), whereas the BSA-corrected end-diastolic anterior wall thickness decreased by 35% (from 14.2 to 9.2 mm/m2, p&lt;0.001) from birth to day 25. Figure 1. Mean (95% CI) BSA-corrected end-diastolic RV anterior wall thickness and end-diastolic RV outflow tract diameter. P-value for correlation. Conclusion RV remodeling during the first 25 days of life in unselected neonates included a small decrease in RV outflow tract diameter and a 35% decrease in anterior wall thickness.

Issues in cardiopulmonary transition at birth

The transition from fetal to newborn life involves a complex series of physiological events that commences with lung aeration, which is thought to involve 3 mechanisms. Two mechanisms occur during labour, Na+ reabsorption and fetal postural changes, and one occurs after birth due to pressure gradients generated by inspiration. However, only one of these mechanisms, fetal postural changes, involves the loss of liquid from the respiratory system. Both other mechanisms involve liquid being reabsorbed from the airways into lung tissue. While this stimulates an increase in pulmonary blood flow (PBF), in large quantities this liquid can adversely affect postnatal respiratory function. The increase in PBF (i) facilitates the onset of pulmonary gas exchange and (ii) allows pulmonary venous return to take over the role of providing preload for the left ventricle, a role played by umbilical venous return during fetal life. Thus, aerating the lung and increasing PBF before umbilical cord clamping (known as physiological based cord clamping), can avoid the loss of preload and reduction in cardiac output that normally accompanies immediate cord clamping.

EXPRESS: Parameters associated with outcome in pediatric patients with congenital heart disease and pulmonary hypertension subjected to combined vasodilator and surgical treatments.

Management of pediatric pulmonary hypertension associated with congenital heart disease (PHT‐CHD) is challenging. Some patients have persistently elevated pulmonary artery pressure (PAP) after cardiac surgery, an undesired condition that is difficult to predict. We investigated the value of clinical, hemodynamic, and histopathological data in predicting the outcome in a prospective cohort. Patients with PHT‐CHD received sildenafil orally pre‐ and postoperatively for six months and then were subjected to a catheter study. Thirty‐three patients were enrolled (age range = 4.6–37.0 months). Pulmonary vascular resistance (PVR) was 4.9 (range = 3.9–7.2) Wood units × m2 (median with IQR). Twenty‐two patients had a ≥ 20% decrease in PVR and pulmonary‐to‐systemic vascular resistance ratio (PVR/SVR) in response to inhaled nitric oxide (NO). The response was directly related to the degree of medial hypertrophy of pulmonary arterioles (P &lt; 0.05) (morphometric analysis, intraoperative lung biopsy). Subsequently, five of the non‐responders had a ≥ 30% increase in pulmonary blood flow in response to sildenafil (3.0 [2.0–4.0] mg/kg/day). Six months after surgery, PAP and PVR were significantly lower (P &lt; 0.001 vs. baseline), even in seven patients with Heath‐Edwards grade III/IV pulmonary vascular lesions (P = 0.018), but still abnormal in 12 individuals (&gt;25 mmHg and &gt;3.0 U × m2, respectively). A preoperative PVR/SVR of ≥24% during NO inhalation and a wall thickness of arteries accompanying respiratory bronchioli of ≥4.7 (Z score) were identified, respectively, as risk and protection factors for abnormal postoperative hemodynamics (hazard ratio [95% CI] = 1.09 [1.01–1.18], P = 0.036; and 0.69 [0.49–0.98], P = 0.040, respectively). Thus, in PHT‐CHD patients receiving oral sildenafil pre‐ and post‐surgical repair of cardiac lesions, mid‐term postoperative outcome is predictable to some extent.