Pulmonary Vascular Resistance In Children Research Articles

International practice heterogeneity in pre-transplant management of pulmonary hypertension related to pediatric left heart disease.

Elevated pulmonary vascular resistance (PVR) in the setting of left heart failure may contribute to poor outcomes after pediatric heart transplant (HTx), but peri-transplant management is variable. We sought to characterize international practice by surveying physicians at pediatric HTx centers. We received 49 complete responses from 39 centers in 16 countries. Most respondents are pediatric cardiologists (90%), practice at centers offering heart (86%) and lung (55%) transplant, and perform pre-HTx acute vasoreactivity testing (AVT, 88%) in patients with elevated PVR. Half (51%) reported defining a PVR cutoff for HTx eligibility as ≤6WU m2 (56%) post-AVT (84%). The highest post-AVT PVR ever accepted for HTx ranged from 3-14.4 (median 6) WU m2 . To treat elevated pre-transplant PVR, phosphodiesterase type 5 inhibitors are most common (65%) followed by oxygen (31%), nitric oxide (14%), endothelin receptor antagonists (11%), and prostacyclins (6%). Nearly a third (31%) do not routinely use pulmonary vasodilators without implantation of a left ventricular assist device (LVAD). Case scenarios highlight treatment variability: in a restrictive cardiomyopathy scenario, HTx listing with post-transplant vasodilator therapy was favored, whereas in a Shone's complex patient with fixed PVR, LVAD ± pulmonary vasodilators followed by repeat catheterization was most common. Management of dilated cardiomyopathy with reactive PVR was variable. Most continue vasodilator therapy until HTx (16%), PVR normalizes (16%) or ≤6 months. Management of elevated PVR in children awaiting HTx is heterogenous. Evidence-based guidelines are needed to allow for longitudinal determination of optimal outcomes and standardized care.

International Practice Heterogeneity in Pediatric Left Heart Disease Related Pulmonary Hypertension

<h3>Purpose</h3> Elevated pulmonary vascular resistance (PVR) in left heart disease contributes to poor outcomes after pediatric heart transplant (HT). Medical management of high PVR pre-HT is controversial and insufficiently described. <h3>Methods</h3> We sought to characterize practice internationally by surveying physicians at pediatric HT centers via ISHLT and other networks. <h3>Results</h3> We received 49 complete responses from 39 centers in 16 countries. The majority of respondents were pediatric cardiologists (90%) practicing at centers offering pediatric heart (86%) and lung (55%) transplant. In patients with left heart failure and elevated baseline PVR, most centers (88%) perform acute vasoreactivity testing (AVT) during catheterization. Only half (51%) have established a maximum PVR for transplant eligibility, with most citing 6 WU*m² or lower (80%) [range 4-8 WU], obtained after AVT (84%). The highest post-AVT PVR ever listed ranged from 4-14.4, median 6 WU*m² (Figure). Pre-HT, phosphodiesterase 5 inhibitors are most frequently used to treat high PVR (65%); however, 31% never use pulmonary vasodilators. Implantation of a left ventricular assist device (LVAD) increases likelihood of medical therapy for PVR, though timing of initiation (pre- vs post-HT) and duration of therapy varies. Case scenarios demonstrate HT listing with post-transplant pulmonary vasodilator therapy is the favored approach for restrictive cardiomyopathy and elevated PVR, whereas LVAD +/- pulmonary vasodilators is favored for patients with dilated cardiomyopathy or postop LV dysfunction and high PVR, regardless of vasoreactivity. Most continue vasodilator therapy until PVR normalizes or short term (<6 months) post-transplant. <h3>Conclusion</h3> Practice regarding medical management of elevated PVR in children awaiting HT is heterogenous, with variable use of pulmonary vasodilators and a wide range of acceptable PVR cutoffs. Evidence-based guidelines are needed to ensure standardized care and equitable organ allocation.

Pulmonary vascular resistance in children and adults. When should we index for body surface area?

Pulmonary vascular resistance in children and adults. When should we index for body surface area?

Parameters of Right Ventricular Function Reveal Ventricular-Vascular Mismatch as Determined by Right Ventricular Stroke Work versus Pulmonary Vascular Resistance in Children with Pulmonary Hypertension

Right ventricular (RV) failure, a determinant of outcomes in pulmonary hypertension (PH), occurs when the right ventricle cannot compensate for increased afterload. The authors showed that RV stroke work (RVSW) can be estimated in children with PH as the product of stroke volume and RV pressure and is related to adverse outcomes. The aim of this study was to test the hypothesis that ventricular-vascular (VV) mismatch (high afterload and low RVSW) is associated with echocardiographic measures of RV performance and adverse outcomes. Invasive hemodynamic data and concurrent echocardiograms were reviewed. Fifty subjects with PH were included. Four groups were created by dividing the patients using median RVSW and median pulmonary vascular resistance. For each group, tricuspid annular plane systolic excursion, fractional area change, myocardial performance index, and anterior RV wall thickness were determined. Both major (i.e., death) and minor (i.e., worsening World Health Organization class) clinical outcomes were tabulated. Groups were compared using the Kruskal-Wallis or Fisher exact test. Patients in the high pulmonary vascular resistance/low RVSW cohort (VV mismatch) had the worst RV dysfunction: median tricuspid annular plane systolic excursion, 0.8cm (interquartile range, 0.7-0.8cm; P=.0002); median fractional area change, 0.29% (interquartile range, 0.27%-0.30%; P=.004); median myocardial performance index, 0.622 (interquartile range, 0.548-0.789; P=.0004). This group had the highest incidence of adverse outcomes: major events in 40%, minor events in 80%, and syncope in 60%. VV mismatch in pediatric PH can be assessed using RVSW and pulmonary vascular resistance and is associated with RV performance and adverse events. RVSW increases in compensated high-afterload states and falls as the right ventricle fails to meet increased load; thus, VV matching status may be a sensitive predictor of outcomes in pediatric PH.

Noninvasive Echocardiographic Measures of Pulmonary Vascular Resistance in Children and Young Adults with Cardiomyopathy

Patients with cardiomyopathy (CM) are at increased risk for pulmonary hypertension (PH). Data are lacking on the use of noninvasive PH measures by echocardiography in patients with CM. The aim of this study was to evaluate the correlation between Doppler-derived echocardiographic indices and catheterization-based measurement of pulmonary vascular resistance (PVR) in children and young adults with CM. Imaging studies were retrospectively reviewed from pediatric patients with CM who underwent both echocardiography and cardiac catheterization within a 72-hour period. The ratio of peak tricuspid regurgitation velocity to right ventricular outflow tract velocity-time integral, the S/D ratio, and right ventricular myocardial performance index were correlated with invasive PVR. Receiver operating characteristic curves were developed to determine cutoffs for detecting PVR ≥ 6 indexed Wood units, a value associated with higher heart transplantation risk. Twenty-three patients with CM (median age, 11.7years; range, 0.5-21years) met the criteria for analysis,the majority (n=17 [74%]) of whom had dilated CM. Linear regression showed significant correlations between echocardiography-based ratio of peak tricuspid regurgitation velocity to right ventricular outflow tract velocity-time integral, S/D ratio, and right ventricular myocardial performance index versus invasive PVR (r=0.84, r=0.72, and r=0.72, respectively, P<.001). All echocardiographic measures showed high sensitivity, specificity, and predictive values to detect PVR ≥ 6 indexed Wood units, with ratio of peak tricuspid regurgitation velocity to right ventricular outflow tract velocity-time integral demonstrating the highest area under the curve (0.958; 95% CI, 0.866-1). Right-sided Doppler-derived echocardiographic indices correlate with PVR measured by cardiac catheterization in children and young adults with CM. These parameters may serve as useful adjuncts in serial assessment of right ventricular hemodynamics in this population.

Treatment of pulmonary hypertension

The therapeutic approach to the management of pulmonary hypertension (PH) is based on strategies to decrease pulmonary vascular resistance (PVR) whilst ensuring optimal cardiorespiratory support to improve oxygenation. The goal is to maintain appropriate systemic blood pressure, ensure oxygen release to tissues and minimize lesions induced by oxygen and ventilation. Inhaled nitric oxide (iNO) remains the mainstay of treatment for this condition. As an inhaled agent it reaches the alveolar space and diffuses into the vascular smooth muscle of the adjacent pulmonary arteries where it causes vasodilation by increasing guanosine monophosphate (cGMP) levels without affecting systemic vascular tone. Although iNO significantly reduces the need for extracorporeal membrane oxygenation, almost 25-40% of iNO-treated infants are considered iNO non–responders. A complementary vasodilatory pathway in the lung is mediated by cyclic adenosine monophosphate (cAMP); prostacyclin stimulates adenylyl cyclase in vascular smooth muscle cells and causes an increase in intracellular cAMP and vasodilation of the systemic and pulmonary circulatory systems. If given as an inhaled drug the vasodilatory effects of prostacyclin tend to be limited to the pulmonary circulation, making this strategy appealing when acute pulmonary vasodilation is needed. [1] Inhibition of the cGMP-degrading phosphodiesterase (PDE5) and inhibition of the cAMP-degrading phosphodiesterase (PDE3) are two other promising therapies. Sildenafil is a PDE5 inhibitor, the predominant PDE isoform in the lung responsible for the breakdown of cGMP. It acts by enhancing NO-mediated vasodilation and may facilitate iNO discontinuation in infants with critical illness.[2] Milrinone is a PDE3 inhibitor with inotropic and vasodilatory effects; it improves the left ventricular cardiac function both directly and by reducing systemic afterload and exerts also important effects on the pulmonary vasculature by reducing PVR. It may be a plausible agent for treating patients with PH and impaired myocardial function. [3] One of the most potent vasoconstrictors described in the pulmonary vasculature is Endothelin-1 (ET-1). Inhibition of ET-1 mediated vasoconstriction could be achieved by administration of an endothelin receptor antagonist (Bosentan). Bosentan lowers pulmonary artery pressure and PVR in children with diverse causes of PH and may improve oxygenation in neonates with persistent pulmonary hypertension; it has also been successfully used as an adjunctive treatment for children receiving long-term prostacyclin therapy.

Real-time magnetic resonance assessment of septal curvature accurately tracks acute hemodynamic changes in pediatric pulmonary hypertension.

This study assesses the relationship between septal curvature and mean pulmonary artery pressure and indexed pulmonary vascular resistance in children with pulmonary hypertension. We hypothesized that septal curvature could be used to estimate right ventricular afterload and track acute changes in pulmonary hemodynamics. Fifty patients with a median age of 6.7 years (range, 0.45-16.5 years) underwent combined cardiac catheterization and cardiovascular magnetic resonance. The majority had idiopathic pulmonary arterial hypertension (n=30); the remaining patients had pulmonary hypertension associated with repaired congenital heart disease (n=17) or lung disease (n=3). Mean pulmonary artery pressure and pulmonary vascular resistance were acquired at baseline and during vasodilation. Septal curvature was measured using real-time cardiovascular magnetic resonance. There was a strong correlation between mean pulmonary artery pressure and SCmin at baseline and during vasodilator testing (r=-0.81 and -0.85, respectively; P<0.01). A strong linear relationship also existed between pulmonary vascular resistance and minimum septal curvature indexed to cardiac output both at baseline and during vasodilator testing (r=-0.88 and -0.87, respectively; P<0.01). Change in septal curvature metrics moderately correlated with absolute change in mean pulmonary artery pressure and pulmonary vascular resistance, respectively (r=0.58 and -0.74; P<0.01). Septal curvature metrics were able to identify vasoresponders with a sensitivity of 83% (95% confidence interval, 0.36-0.99) and a specificity of 91% (95% confidence interval, 0.77-0.97), using the Sitbon criteria. Idiopathic pulmonary arterial hypertension subgroup analysis revealed 3 responders with ΔSCmin values of 0.523, 0.551, and 0.568. If the middle value of 0.551 is taken as a cutoff, the approximate sensitivity would be 67% and the specificity would be 93%. Septal curvature metrics are able to estimate right ventricular afterload and track acute changes in pulmonary hemodynamics during vasodilator testing. This suggests that septal curvature could be used for continuing assessment of load in pulmonary hypertension.

Accuracy of Doppler-Derived Indices in Predicting Pulmonary Vascular Resistance in Children With Pulmonary Hypertension Secondary to Congenital Heart Disease With Left-to-Right Shunting

This study aimed to evaluate the accuracy of Doppler echocardiography-derived indices in children with pulmonary hypertension secondary to congenital heart disease with left-to-right shunting. Doppler-derived indices including the acceleration time corrected (AcTc), deceleration time corrected, deceleration index, peak velocity, heart-rate-corrected inflection time (InTc), and a new index (the acceleration slope [Acc = peak flow velocity/AcTc]) were measured from the pulmonary artery (PA) systolic flow curve before and after 100 % oxygen administration in the main, left, and right PAs of 33 children. The acquired data were compared between low and high pulmonary vascular resistance (PVR) groups and between responders and nonresponders to the vasoreactivity test. The AcTc values differed significantly between the low and high PVR groups before and after oxygen administration in the main (P = 0.032 and <0.001, respectively), right (P = 0.011 and <0.001, respectively), and left (P < 0.001 and <0.001, respectively) PAs. The AcTc cutoff point in the main PA was 3.44 before oxygen administration (81% sensitivity and 91% specificity). The InTc in the main PA and its changes differed significantly between the low and high PVR groups before and after oxygen administration and between the responders and nonresponders (P = 0.016, 0.046, and 0.021, respectively). The velocity changes of the PA in the main PA differed significantly between the responders and nonresponders to oxygen administration (P < 0.001). The Acc and its changes differed significantly between the low and high PVR groups after oxygen administration and between the responders and nonresponders to oxygen administration (P = 0.044 and 0.006, respectively). Doppler echocardiographic examination using PA systolic flow indices in addition to PA reactivity testing is a promising technique for assessing PVR in children with congenital heart disease.

Noninvasive assessment of elevated pulmonary vascular resistance in children with pulmonary hypertension secondary to congenital heart disease: A comparative study between five different Doppler indices

BackgroundPulmonary vascular resistance (PVR) is an important hemodynamic parameter in patients with congenital heart disease (CHD). Noninvasive estimation of PVR represents an attractive alternative to invasive measurements. MethodsThe study included 175 patients with pulmonary hypertension (PH) secondary to CHD. All patients underwent full echocardiographic study and invasive hemodynamic measurements. The study population was then subdivided into four subgroups. Each of the following Doppler indices was measured in one of these four subgroups: peak tricuspid regurgitant velocity (TRV), the ratio of the TRV to the velocity time integral of the right ventricular outflow tract (TRV/TVIRVOT), peak velocity of tricuspid annular systolic motion (TSm), heart rate corrected acceleration time and infliction time of the proximal left pulmonary artery (ATc, InTc). The data obtained was correlated with invasive PVR measurement. An ROC curve analysis was done to generate cutoff points with the highest balanced sensitivity and specificity to predict PVR>6WU/m2. The receiver operating characteristics (ROC) curves were compared with each other to determine the most reliable cutoff point in predicting elevated PVR>6WU/m2. ResultsThere was a significant correlation between both the TRV and TSm and invasive measurement of PVR (r=−0.511, 0.387 and P value=0.0002, 0.006 respectively). The TSm and TRV cutoff values were the most reliable to predict elevated PVR>6 WU/m2. A TSm cutoff value of ⩽16.16cm/s provided the best balanced sensitivity (85.7%) and specificity (66.7%) to determine PVRCATH>6 WU/m2. A cutoff value less than 7.62cm/s had 100% specificity to predict PVRCATH>6 WU/m2. A TRV cutoff value of >3.96m/s provided the best balanced sensitivity (66.7%) and specificity (100%) to determine PVRCATH>6 WU/m2. Both TRV and TSm had the highest area under the ROC curve among the 5 DOPPLER indices studied. ConclusionPrediction of elevated PVR in children with PH secondary to CHD could be achieved noninvasively using a number of Doppler indices. Among the five Doppler indices examined in the current study, the peak TRV and the TSm of the lateral tricuspid annulus had the highest balanced sensitivity and specificity to predict PVRI>6 WU/m2.

Accuracy of Doppler-Derived Estimation of Pulmonary Vascular Resistance in Congenital Heart Disease: An Index of Operability

Pulmonary vascular resistance (PVR) is a critical and essential parameter during the assessment and selection of modality of treatment in patients with congenital heart disease (CHD) accompanied by pulmonary arterial hypertension (PAH). Cardiac catheterization is the "gold standard" but is an invasive method for PVR measurement. A noninvasive and reliable method for estimation of PVR in children has been a major challenge and most desirable during past decades, especially for those who need repeated measurements. In a prospective study and among consecutive patients who were referred for cardiac catheterizations, PVR was calculated as the ratio of the transpulmonary pressure gradient (∆P) to the amount of the pulmonary flow (QP) accordingly for 20 patients with CHD and high PAH. Subsequently and noninvasively, PVR was assessed for these patients by a Doppler echocardiography-derived index defined as the ratio of the tricuspid regurgitation velocity (TRV(m/s)) to the velocity time integral (VTI(cm)) of the right-ventricular outflow tract (RVOT). There was a good correlation between PVR measured at catheterization (PVR(cath)) and TRV/VTI(m) ratio; the mean of three measurements of VTI (VTI(m)) with R (2) = 0.53 (p = 0.008). In addition, a TRV/VTI(m) value of 0.2 provided a sensitivity of 71.4% and a specificity of 100% for PVR >6 Woods units (WU) as well as sensitivity of 90% and specificity of 90% for a PVR equal to 8 WU. PVR value between 6 and 8 WU by catheterization has been considered as a cut-off point for intervention in children with left-to-right shunts and PAH. In conclusion, Doppler-derived TRV/VTI(m) ratio is a reliable index that may be helpful as a supplementary diagnostic tool for the selection of modality of treatment and follow-up of patients with PAH and increased PVR.

Perioperative Management of the Pediatric Cardiac Transplantation Patient

The major diagnoses carried by children undergoing cardiac transplantation worldwide are congenital heart defects, cardiomyopathies, and retransplantation. The leading diagnosis in infancy is congenital heart disease, whereas cardiomyopathy predominates in older children. In view of this wide spectrum of diagnoses, the perioperative management of these children requires medical, interventional, and surgical expertise in treatment of complex congenital heart defects, end-stage heart failure, and cardiac transplantation. According to the Pediatric Heart Transplantation Survey database, the majority of children listed for cardiac transplantation eventually require higher levels of cardiac support before transplantation. The team caring for these children should be prepared to escalate support in a timely fashion in order to avoid end-organ dysfunction or a catastrophic event that will remove the patient from the cardiac transplantation list. The first step is advanced hemodynamic monitoring in a specialized pediatric cardiac intensive care unit and initiation of inotropic support. Further escalation of care should be based on careful analysis of the hemodynamic profile, end-organ function, and biochemical markers of perfusion and myocardial stress. A patient who continues to deteriorate in spite of inotropic support requires positive pressure ventilation, and if deterioration continues, mechanical circulatory support is initiated. Cardiac transplantation is a challenging operation, and even more so in children with complex congenital heart defects. The abnormal cardiovascular anatomy requires planning and anticipation of possible pitfalls as hypoplasia of the aortic arch, abnormal pulmonary arteries, and abnormal systemic and pulmonary venous connections. The time required to remove adhesions in children with prior cardiac operations increases the ischemic time of the graft and the risk of primary graft dysfunction. Assessment of pulmonary vascular resistance in children with congenital heart defects is problematic, and even children with a normal transpulmonary gradient and pulmonary vascular resistance are at increased risk of postoperative pulmonary hypertension and right ventricular graft failure. The postoperative course is directly linked to the patient's preoperative physical condition and perioperative course. The induction of immunosuppression and the use of plasmapheresis in children with a positive cross-match may lead to further hemodynamic compromise. If severe primary graft dysfunction evolves, early initiation of extracorporeal membranous oxygenator is indicated to avoid irreversible end-organ dysfunction.

Quantitative Assessment of Pulmonary Vascular Resistance and Reactivity in Children with Pulmonary Hypertension Due to Congenital Heart Disease Using a Noninvasive Method: New Doppler-Derived Indexes

We assessed the usefulness of transthoracic Doppler-derived indexes obtained in the proximal pulmonary artery (PA) branch for estimating pulmonary vascular resistance (PVR) in 45 children with congenital heart disease (CHD) and 23 normal control subjects. The acceleration time, inflection time (InT), deceleration index, and peak velocity, which were measured from the systolic PA flow velocity curve obtained at the sites of the main PA, and right and left PA, were compared with the PVR in patients with CHD. In addition, changes in either Doppler-derived indexes or PVR during 100% oxygen administration were compared in 22 patients showing a baseline PVR >or=4.6 U/m(2) (high PVR). The heart-rate-corrected InT (InTc) values obtained in the left PA in the high PVR group were significantly lower than those in the main PA (4.7 +/- 1.5 vs. 7.5 +/- 3.0; p < 0.001). The InTc obtained from the left PA separated patients with high and low PVR (4.7 +/- 1.4 vs. 9.9 +/- 2.4; p < 0.001) and no significant differences in InTc were found between the low PVR and the control groups. An increase in InTc to >6 during 100% oxygen administration for the high PVR group indicated good PA reactivity with a sensitivity of 93%, specificity of 100%, and agreement of 95% (kappa = 0.83). Moreover, this InTc index correlated inversely with PVR (r = -0.80). In conclusion, our method can noninvasively separate high and low PVR and assess the PA reactivity for high PVR in children with CHD.

Ketamine Does Not Increase Pulmonary Vascular Resistance in Children with Pulmonary Hypertension Undergoing Sevoflurane Anesthesia and Spontaneous Ventilation

The use of ketamine in children with increased pulmonary vascular resistance is controversial. In this prospective, open label study, we evaluated the hemodynamic responses to ketamine in children with pulmonary hypertension (mean pulmonary artery pressure >25 mm Hg). Children aged 3 mo to 18 yr with pulmonary hypertension, who were scheduled for cardiac catheterization with general anesthesia, were studied. Patients were anesthetized with sevoflurane (1 minimum alveolar anesthetic concentration [MAC]) in air while breathing spontaneously via a facemask. After baseline catheterization measurements, sevoflurane was reduced (0.5 MAC) and ketamine (2 mg/kg IV over 5 min) was administered, followed by a ketamine infusion (10 microg x kg(-1) x min(-1)). Catheterization measurements were repeated at 5, 10, and 15 min after completion of ketamine load. Data at various time points were compared (ANOVA, P < 0.05). Fifteen patients (age 147, 108 mo; median, interquartile range) were studied. Diagnoses included idiopathic pulmonary arterial hypertension (5), congenital heart disease (9), and diaphragmatic hernia (1). At baseline, median (interquartile range) baseline pulmonary vascular resistance index was 11.3 (8.2) Wood units; 33% of patients had suprasystemic mean pulmonary artery pressures. Heart rate (99, 94 bpm; P = 0.016) and Pao2 (95, 104 mm Hg; P = 007) changed after ketamine administration (baseline, 15 min after ketamine; P value). There were no significant differences in mean systemic arterial blood pressure, mean pulmonary artery pressure, systemic or pulmonary vascular resistance index, cardiac index, arterial pH, or Paco2. In the presence of sevoflurane, ketamine did not increase pulmonary vascular resistance in spontaneously breathing children with severe pulmonary hypertension.

The endothelin antagonist BQ123 reduces pulmonary vascular resistance after surgical intervention for congenital heart disease

Objective: Postoperative pulmonary hypertension in children after surgical intervention for congenital heart disease has been attributed to failure of the pulmonary endothelium to provide adequate vasodilation. Although we have shown that the impaired vasodilatory component attributable to the l-arginine-nitric oxide pathway is almost completely reversible, a nonrestorable component persists, implying an additional vasoconstrictive mechanism in postoperative pulmonary endothelial dysfunction. In this study of children after surgical intervention for congenital heart disease, we measured endothelin-1 levels and used BQ123, a selective endothelin-A receptor antagonist, together with inhaled nitric oxide to discriminate dysfunctional pulmonary endothelial vasodilation from endothelin-mediated pulmonary vasoconstriction. Methods: All children were examined early after surgical intervention in the intensive care unit. Pulmonary vascular resistance (with respiratory mass spectrometry), as well as arterial and venous endothelin-1 levels (measured by means of a quantitative enzyme-linked immunosorbent assay), were determined in 7 children (age range, 3.3-13.7 months; median age, 6.3 months) with intracardiac shunting defects at baseline and during ventilation with a fraction of inspired oxygen of 0.65, with additional BQ123 (0.1 mg/kg infused over 20 minutes), and with inhaled nitric oxide (20 ppm). Results: Pulmonary vascular resistance decreased from 7.7 ± 3.4 at baseline to 6.1 ± 2.8 Woods units · m−2 (P =.022) at a fraction of inspired oxygen of 0.65 and to 4.7 ± 2.7 Woods units · m−2 (P =.013) during BQ123 infusion. Inhaled nitric oxide had no further effect on pulmonary vascular resistance. Left atrial endothelin-1 levels (1.35-5.12 pg/mL; mean, 2.4 pg/mL) correlated significantly with the decrease in pulmonary vascular resistance in response to BQ123 infusion (r2 = 0.89, P =.003). Conclusion: Postoperative elevation of pulmonary vascular resistance in children after surgical intervention for congenital heart disease is responsive to endothelin-A blockade with BQ123. Increased levels of endothelin-1 predict the response to this therapy, which might become an important addition to the clinical armamentarium in postoperative pulmonary hypertensive disease.J Thorac Cardiovasc Surg 2002;124:435-41

Comparison of hyperventilation and inhaled nitric oxide for pulmonary hypertension after repair of congenital heart disease

Pulmonary hypertension is associated with congenital heart lesions with increased pulmonary blood flow. Acute increases in pulmonary vascular resistance (PVR) occur in the postoperative period after repair of these defects. These increases in PVR can be ablated by inducing an alkalosis with hyperventilation (HV) or bicarbonate therapy. Studies have shown that these patients also respond to inhaled nitric oxide (iNO), but uncertainty exists over the relative merits and undesirable effects of HV and iNO. Alkalosis and iNO are equally effective in reducing PVR and pulmonary artery pressure (PAP) in children with pulmonary hypertension after open heart surgery. Critical care unit of a tertiary care pediatric hospital. Prospective, randomized, crossover design. Twelve children with a mean PAP > 25 mm Hg at normal pH after biventricular repair of congenital heart disease. Patients were assigned to receive iNO or HV (pH > 7.5) in random order, and the effect on hemodynamics was measured. Each treatment was administered for 30 mins with a 30-min washout period between treatments. Finally, both treatments were administered together to look for a possible additive effect. Cardiac output and derived hemodynamic parameters using the dye dilution technique. Hyperventilation, achieved by an increase in ventilator rate without a change in mean airway pressure, decreased Pa(CO2) from a mean (SD) of 43.7+/-5.3 to 32.3+/-5.4 mm Hg and increased pH from 7.40+/-0.04 to 7.50+/-0.03. This significantly altered both pulmonary and systemic hemodynamics with a reduction in PAP, PVR, central venous pressure, and cardiac output and an increase in systemic vascular resistance. In comparison, iNO selectively reduced PAP and PVR only. The reduction in PVR was comparable between treatments, although addition of iNO to HV resulted in a small additional reduction in PVR. An additional decrease in PAP was seen when HV was added to iNO, attributable to a reduction in cardiac output rather than a further decrease in PVR. Inhaled NO and HV are both effective at lowering PAP and PVR in children with pulmonary hypertension after repair of congenital heart disease. The selective action of iNO on the pulmonary circulation offers advantages over HV because a decrease in cardiac output and an increase in SVR are undesirable in the postoperative period.

Doppler-derived pulmonary regurgitation velocity is a non-invasive index of pulmonary vascular resistance in children with congenital heart disease

Doppler-derived pulmonary regurgitation velocity is a non-invasive index of pulmonary vascular resistance in children with congenital heart disease

Doppler-derived Pulmonary Regurgitation Velocity Is a Non-invasive Index of Pulmonary Vascular Resistance in Children With Congenital Heart Disease

Doppler-derived Pulmonary Regurgitation Velocity Is a Non-invasive Index of Pulmonary Vascular Resistance in Children With Congenital Heart Disease

Doppler echocardiographic evaluation of pulmonary vascular resistance in children with congenital heart disease

Noninvasive assessment of pulmonary vascular resistance has not been well defined. Cardiac catheterization findings in 33 patients with congenital heart disease (mean age 1.4 years) were compared with Doppler echocardiographic parameters. The right ventricular pre-ejection period (RVPEP), ejection time (RVET), and the ratio RVPEP RVET correlated better with pulmonary vascular resistance than with pulmonary artery pressure. A highly significant correlation with a small standard error of estimate (SEE) was demonstrated between pulmonary vascular resistance and a newly derived parameter RVPEP/velocity time integral (VTI) [ r = 0.87, p < 0.0001, SEE = 2]. An RVPEP VTI value of <0.4 seconds/meter (M) was able to select patients with pulmonary vascular resistance <3 Wood Unit · M 2, even in the presence of pulmonary artery hypertension caused by increased pulmonary blood flow, with 97% accuracy (100% sensitivity, and 92% specificity). An RVPEP VTI value of 0.4 to 0.6 seconds/M identified patients with pulmonary vascular resistance between 3 to 7.5 Wood Unit · M 2 with 91% accuracy, and a value of ≥0.6 seconds/M selected patients with total pulmonary vascular resistance ≥7.5 Wood Unit · M 2 with 94% accuracy.

Effect of inhaled nitric oxide on raised pulmonary vascular resistance in children with congenital heart disease.

To study the short-term effects of inhaled nitric oxide in infants and young children with congenital heart disease. A supraregional referral centre for children with congenital heart disease. 22 infants and children aged 3-32 months (median age 5 months) with congenital heart disease undergoing preoperative cardiac catheterisation. All but one infant had intracardiac shunt lesions and 13 had increased pulmonary vascular resistance. During catheterisation the patients inhaled nitric oxide in a concentration of 40 parts per million in room air. Pulmonary and systemic haemodynamic variables were evaluated by means of measured oxygen consumption and the Fick principle before and after 10 minutes' exposure to nitric oxide. Inhaled nitric oxide did not affect the systemic circulation. There was a significant reduction in the pulmonary vascular resistance, but only in the 13 infants with pulmonary hypertension, in whom pulmonary vascular resistance was reduced by 34% from 8.6 (4.6) mm Hg.min.m2.l-1 (mean (SD)) to 5.7 (3.5) mm Hg.min.m2.l-1. The pulmonary circulation in infants with normal pulmonary vascular resistance was not affected. No statistically significant increase in methaemoglobin was seen, though there were large individual differences. No other side effects were seen. The present study shows that in infants with congenital heart disease inhaled nitric oxide reduced pathologically increased pulmonary vascular resistance without affecting systemic circulation and without important side effects with brief exposure.

Evaluation of the Responsiveness of Elevated Pulmonary Vascular Resistance in Children by Doppler Echocardiography

Evaluation of the Responsiveness of Elevated Pulmonary Vascular Resistance in Children by Doppler Echocardiography