A Belgian consensus on sotatercept for the treatment of pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is a rare disease affecting the small pulmonary vessels, ultimately leading to right ventricular failure and death. Current treatment options target three different pathways (endothelin, nitric oxide/cGMP and prostacyclin pathways). Despite their demonstrated efficacy, these therapies (commonly used in combination) do not cure the disease which is why novel pathways beyond the traditional 'big three' are being developed. Sotatercept is a ligand trap for multiple proteins within the TGF-ß superfamily that was recently approved in the US for the treatment of PAH. Unlike currently available therapies, sotatercept has the potential to act as an anti-remodelling agent rather than a vasodilator. The safety and efficacy of subcutaneous (SC) sotatercept have been established in two multicentre, placebo-controlled randomised-controlled trials. The compound has been shown to consistently improve a variety of measurable endpoints, including exercise capacity, haemodynamics, quality of life and delay of clinical worsening. The drug appears to have an acceptable safety profile, although it is associated with an increased risk in developing telangiectasia and biological changes affecting platelet counts and haemoglobin. This study reviews the current evidence on SC sotatercept and provides a Belgian perspective on its place in the future treatment strategy for PAH.

Percutaneous pulmonary aspiration thrombectomy in an adolescent fontan patient using a large-bore system.

We describe the safe and effective percutaneous pulmonary thrombectomy in an 18-year-old female with a Fontan circulation using the FlowTriever® device (Inari Medical®, Irvine, US). Aspiration thrombectomy of both pulmonary arteries was performed using 24 and 16 F FlowTriever® catheters retrieving large amounts of thrombus material resulting in near total angiographic recanalization.

Evolution of Natural Myocardial Shear Wave Behavior in Young Hearts: Determinant Factors and Reproducibility Analysis.

BACKGROUND: Myocardial diastolic function assessment in children by conventional echocardiography is challenging. High-frame rate echocardiography facilitates the assessment of myocardial stiffness, a key factor in diastolic function, by measuring the propagation velocities of myocardial shear waves (SWs). However, normal values of natural SWs in children are currently lacking. The aim of this study was to explore the behavior of natural SWs among children and adolescents, their reproducibility, and the factors affecting SW velocities from childhood into adulthood. METHODS: One hundred six healthy children (2-18 years of age) and 62 adults (19-80 years of age) were recruited. High-frame rate images were acquired using a modified commercial scanner. An anatomic M-mode line was drawn along the ventricular septum, and propagation velocities of natural SWs after mitral valve closure were measured in the tissue acceleration-coded M-mode display. RESULTS: Throughout life, SW velocities after mitral valve closure exhibited pronounced age dependency (r = 0.73; P < .001). Among the pediatric population, SW velocities correlated significantly with measures of cardiac geometry (septal thickness and left ventricular end-diastolic dimension), local hemodynamics (systolic blood pressure), and echocardiographic parameters of systolic and diastolic function (global longitudinal strain, mitral E/e' ratio, isovolumic relaxation time, and mitral deceleration time) (P < .001). In a multivariate analysis including all these factors, the predictors of SW velocities were age, mitral E/e', and global longitudinal strain (r = 0.81). CONCLUSIONS: Natural myocardial SW velocities in children can be detected and measured. SW velocities showed significant dependence on age and diastolic function. Natural SWs could be a promising additive tool for the assessment of diastolic function among children.

Mitral valve replacement in children: balancing durability and risk with mechanical and bioprosthetic valves.

OBJECTIVES: To investigate if there is still a place for bioprosthetic mitral valve replacement in children by comparing the prosthetic durability and transplant-free survival after bioprosthetic and mechanical mitral valve replacement. METHODS: We reviewed all mitral valve replacements in children between 1981 and 2020. Bioprosthetic mitral valve replacement cases were individually matched to mechanical mitral valve replacement cases. The incidence rate of a 2nd replacement was calculated using the cumulative incidence function that considered death or transplantation as a competing risk. RESULTS: The median age at implantation was 3.6 years (interquartile range 0.8-7.9) for the bioprosthetic valve cohort (n = 28) and 3 years (interquartile range 1.3-7.8) for the mechanical valve cohort (n = 28). Seven years after bioprosthetic mitral valve replacement, the cumulative incidence of death or transplantation was 17.9% [95% confidence interval (CI) 6.3-34.1] and the cumulative incidence of a 2nd replacement was 63.6% (95% CI 39.9-80.1). Seven years after mechanical mitral valve replacement, the cumulative incidence of death or transplantation was 28.6% (95% CI 13.3-46) and the cumulative incidence of a 2nd replacement was 10.7% (95% CI 2.6-25.5). Fifteen years after mechanical mitral valve replacement, the cumulative incidence of death or transplantation was 33.6% (95% CI 16.2-52.1) and the cumulative incidence of a 2nd replacement was 41.1% (95% CI 18.4-62.7). The cumulative incidence curves for bioprosthetic and mechanical mitral valve replacement were statistically different for a 2nd valve replacement (P < 0.001) but not for death or transplantation (P = 0.33). CONCLUSIONS: There is no difference in transplant-free survival after bioprosthetic and mechanical mitral valve replacement in children. The lifespan of bioprosthetic mitral valves remains limited in children because of structural valve failure due to calcification. After 15 years, 40% of mechanical valves were replaced, primarily because of patient-prosthesis mismatch related to somatic growth.

Case report: Cardiac intimal sarcoma in a young child.

Undifferentiated mesenchymal tumors from the intimal layer (intimal sarcomas) are rare within the ventricles and exceptional in children. A rare case of an intimal sarcoma located in the right ventricle in a young child is presented with need for urgent surgical resection due to mechanical flow obstruction. Tumor cells showed amplification of MDM2 gene and a homozygous loss of CDKN2A on 9p21. A review of the literature regarding primary cardiac malignancies and intimal sarcoma in children is provided.

Reversal of Right Ventricular Remodeling After Correction of Pulmonary Regurgitation in Tetralogy of Fallot.

In the sheep model with pathophysiologic changes similar to patients with repaired TOF, severe PR leads to fibrotic changes in the RV. Pulmonary valve replacement reverses these fibrotic changes. Early valve replacement led to a quick RV recovery, and in time there was no difference in outcome between early and late valve replacement. These data support the benefit of valve replacement for RV function and suggest that there is a margin in the timing of the surgery. The fibrotic changes correlated well with the circulating biomarker PICP, which can have an added value in the clinical follow-up of patients with repaired TOF.

Stent expansion of restrictive Fontan conduits to nominal diameter and beyond.

BACKGROUND: Mechanical factors may cause bottlenecks in a Fontan circuit. Extracardiac conduits (ECC) are placed at a young age, but the materials do not allow growth. Restriction in ECC dimensions may deteriorate the function of the circuit. AIMS: This study aimed to evaluate the feasibility and safety of stent expansion of an ECC to the nominal dimension at the time of implant and, if possible, beyond nominal. METHODS: Retrospective, single-center observational review of all ECC Fontan patients who received a stent to expand a previously placed surgical conduit. RESULTS: A total of 44 restrictive conduits were stented over a 14-year study period with a median of 11.8 (interquartile ranges [IQR]: 9.1-13.8) years after ECC placement. Cross-sectional areas were a median of 30% (IQR: 21-42) smaller than the originally placed ECC; there was no gradient in 23/44 patients and in 21/44, a minimal gradient of 1.3 ± 0.5 (range 1-3 mmHg). All conduits could be enlarged with a significant (p < 0.0001) increase in diameter from 13.6 ± 1.8 to 19.2 ± 1.2 mm, corresponding to a median cross-sectional area increase of 171% (IQR: 153-220). In three patients where the conduits were not contracted, expansion of between 127% and 165% was obtained. There were no conduit ruptures and only one minor complication. CONCLUSIONS: ECC in some Fontan patients become smaller than nominal over time, usually without overt symptoms. The dimensions of ECC's can be safely and significantly increased to nominal or even beyond employing stenting. It allows adjustment of ECC dimensions to compensate for somatic growth.

Functional brain maturation and sleep organisation in neonates with congenital heart disease.

OBJECTIVE: Neonates with Congenital Heart Disease (CHD) have structural delays in brain development. To evaluate whether functional brain maturation and sleep-wake physiology is also disturbed, the Functional Brain Age (FBA) and sleep organisation on EEG during the neonatal period is investigated. METHODS: We compared 15 neonates with CHD who underwent multichannel EEG with healthy term newborns of the same postmenstrual age, including subgroup analysis for d-Transposition of the Great Arteries (d-TGA) (n = 8). To estimate FBA, a prediction tool using quantitative EEG features as input, was applied. Second, the EEG was automatically classified into the 4 neonatal sleep stages. Neonates with CHD underwent neurodevelopmental testing using the Bayley Scale of Infant Development-III at 24 months. RESULTS: Preoperatively, the FBA was delayed in CHD infants and more so in d-TGA infants. The FBA was positively correlated with motor scores. Sleep organisation was significantly altered in neonates with CHD. The duration of the sleep cycle and the proportion of Active Sleep Stage 1 was decreased, again more marked in the d-TGA infants. Neonates with d-TGA spent less time in High Voltage Slow Wave Sleep and more in Tracé Alternant compared to healthy terms. Both FBA and sleep organisation normalised postoperatively. The duration of High Voltage Slow Wave Sleep remained positively correlated with motor scores in d-TGA infants. INTERPRETATION: Altered early brain function and sleep is present in neonates with CHD. These results are intruiging, as inefficient neonatal sleep has been linked with adverse long-term outcome. Identifying how these rapid alterations in brain function are mitigated through improvements in cerebral oxygenation, surgery, drugs and nutrition may have relevance for clinical practice and outcome.

Heart failure related to adult congenital heart disease: prevalence, outcome and risk factors.

AIMS: Information on the prevalence, outcome and factors associated with heart failure in patients with adult congenital heart disease (CHD) (ACHD-HF) is lacking. We aimed at assessing the prevalence and outcome of ACHD-HF, the variables associated with ACHD-HF, and the differences between major anatomical/pathophysiological ACHD subgroups. METHODS AND RESULTS: We included 3905 patients (age 35.4 ± 13.2 years) under active follow-up in our institution (last visit >2010). Outcome of ACHD-HF cases was compared with sex- and age-matched cases. Univariable and multivariable binary logistic regression with ACHD-HF diagnosis as a dependent variable was performed. Overall prevalence of ACHD-HF was 6.4% (mean age 49.5 ± 16.7 years), but was higher in patients with cyanotic CHD (41%), Fontan circulation (30%), and a systemic right ventricle (25%). All-cause mortality was higher in ACHD-HF cases when compared with controls (mortality rate ratio 4.67 (2.36-9.27); P = 0.0001). In multivariable logistic regression analysis, age at latest follow-up [per 10 years; odds ratio (OR) 1.52; 95% confidence interval (CI) 1.31-1.77], infective endocarditis (OR 4.11; 95%CI 1.80-9.38), history of atrial arrhythmia (OR 3.52; 95%CI 2.17-5.74), pacemaker implantation (OR 2.66; 95% CI 1.50-4.72), end-organ dysfunction (OR 2.41; 95% CI 1.03-5.63), New York Heart Association class (OR 9.28; 95% CI 6.04-14.25), heart rate (per 10 bpm; OR 1.27; 95% CI 1.08-1.50), ventricular dysfunction (OR 3.62; 95% CI 2.54-5.17), and pulmonary hypertension severity (OR 1.66; 95% CI 1.21-2.30) were independently related to the presence of ACHD-HF. Some variables (age, atrial arrhythmia, pacemaker, New York Heart Association, and ventricular dysfunction) were related to ACHD-HF in all anatomical/physiological subgroups, whereas others were not. CONCLUSIONS: ACHD-HF is prevalent especially in complex CHD and is associated with poor prognosis. Our data provide insight in the factors related to ACHD-HF including differences between specific anatomical and physiological subgroups.

Effect of xenon and dexmedetomidine as adjuncts for general anesthesia on postoperative emergence delirium after elective cardiac catheterization in children: study protocol for a randomized, controlled, pilot trial.

BACKGROUND: Emergence delirium, a manifestation of acute postoperative brain dysfunction, is frequently observed after pediatric anesthesia and has been associated with the use of sevoflurane. Both xenon and dexmedetomidine possess numerous desirable properties for the anesthesia of children with congenital heart disease, including hemodynamic stability, lack of neurotoxicity, and a reduced incidence of emergence delirium. Combining both drugs has never been studied as a balanced-anesthesia technique. This combination allows the provision of anesthesia without administering anesthetic drugs against which the Food and Drug Administration (FDA) issued a warning for the use in young children. METHODS/DESIGN: In this phase-II, mono-center, prospective, single-blinded, randomized, controlled pilot trial, we will include a total of 80 children aged 0-3 years suffering from congenital heart disease and undergoing general anesthesia for elective diagnostic and/or interventional cardiac catheterization. Patients are randomized into two study groups, receiving either a combination of xenon and dexmedetomidine or mono-anesthesia with sevoflurane for the maintenance of anesthesia. The purpose of this study is to estimate the effect size for xenon-dexmedetomidine versus sevoflurane anesthesia with respect to the incidence of emergence delirium in children. We will also describe group differences for a variety of secondary outcome parameters including peri-interventional hemodynamics, emergence characteristics, incidence of postoperative vomiting, and the feasibility of a combined xenon-dexmedetomidine anesthesia in children. DISCUSSION: Sevoflurane is the most frequently used anesthetic in young children, but has been indicated as an independent risk factor in the development of emergence delirium. Xenon and dexmedetomidine have both been associated with a reduction in the incidence of emergence delirium. Combining xenon and dexmedetomidine has never been described as a balanced-anesthesia technique in children. Our pilot study will therefore deliver important data required for future prospective clinical trials. TRIAL REGISTRATION: EudraCT, 2018-002258-56. Registered on 20 August 2018. https://www.clinicaltrialsregister.eu.

Can ductus arteriosus morphology influence technique/outcome of stent treatment?

INTRODUCTION: Results and outcomes of ductus arteriosus stenting vary widely. The aim of this study was to determine whether ductus morphology is associated with different procedural outcome. METHODS: Over an 18-year period, 123 patients presented with ductal dependent pulmonary blood flow. Results were retrospectively assessed based on radiographic anatomic features of the ductus arteriosus: Group 1: "straight" ductus arteriosus, typically seen in patients with Pulmonary atresia with intact septum (PA-IVS), Group 2: "intermediate" ductus arteriosus as seen in severe pulmonary stenosis (PS)-single ventricle, Group 3: "vertical" ductus arteriosus typically seen in patients with pulmonary atresia-ventricular septal defect, Group 4: ductus arteriosus arising from the aorta to a single lung, Group 5: ductus arteriosus arising from the innominate/subclavian artery to a single lung, Group 6: ductus arteriosus from innominate/subclavian artery to both lungs. RESULTS: Ductal stenting (DS) was attempted in 98 patients with 99 ducts. Successful stenting was possible in 83 patients. Success of DS was significantly different among the groups (p = .04, F = 5.41). Groups 1, 4, and 5 were "easy" with good success while Groups 2, 3, and 6 were complex and demanding. There were two deaths (after 5 and 7 days, respectively) that could be ascribed to DS. Elective re-interventions were performed in 34 ductuses (40%). Fifty three percent (n = 44/83) of successful ductus stents proceeded to further surgery and 20 ducts closed spontaneously in asymptomatic patients over time. CONCLUSIONS: Ductus arteriosus morphology influences technique and determines complexity, safety, and final outcome of ductus arteriosus stenting.

Percutaneous embolization of lymphatic fistulae as treatment for protein-losing enteropathy and plastic bronchitis in patients with failing Fontan circulation.

BACKGROUND: To determine the feasibility and clinical result of selective embolization of hepatoduodenal or paratracheal lymphatics in Fontan patients with protein-losing enteropathy (PLE) or plastic bronchitis (PB). METHODS: Dilated lymph vessels in periportal (PLE) or paratracheal (PB) position were percutaneously punctured with a 22G Chiba needle. Intralymphatic position was confirmed by water soluble contrast injection with drainage to hepatoduodenal or tracheal fistulae. After flushing with 10% glucose solution, occlusion of hepatoduodenal or paratreacheal lymphatics was effected by injection of 1-4 cc mixture 4/1 of Lipiodol/n-butyl cyanoacrylate (n-BCA; Histoacryl). RESULTS: Seven patients with proven PLE were treated with periportal lymphatic embolization 10.7 (range: 6.6-13.5) years after the Fontan operation. The Fontan operation was performed at a median age of 3.7 (range: 2.9-5.7) years and PLE started a median of 3.1 (range: 0.9-4.7) years later. Five patients required a second procedure 2-8 months later. Complications were limited (spillage of glue in portal branch, transient cholangitis, and caustic duodenal bleeding). Six of seven patients reported significant improvement in quality of life and normalization of albumin levels after limited follow-up (p < .01). One patient (Fontan at 2.9 years; age 16.4 years) had PB for 2 years. Selective transthoracic cone-beam-directed puncture of left and right paratracheal lymphatics with n-BCA embolization of distal lymphatic fistulae resulted in lasting absence of tracheal casts (11 months). CONCLUSIONS: Embolization of periportal/peritracheal lymphatics is a promising technique in Fontan patients with PLE/PB. Larger series are required to determine incidence and reasons of success/failure, with long-term results and effects on liver function.

First report of a successful pediatric heart transplantation from donation after circulatory death with distant procurement using normothermic regional perfusion and cold storage.

Heart transplantation (HT) from donation after circulatory death (DCD) is a promising alternative to expand the heart donor pool. Cold storage can be used in a strategy to successfully retrieve and transplant DCD hearts after reconditioning using normothermic regional perfusion for distant procurement. Herein, we present the first report of a pediatric DCD heart reconditioned with normothermic regional perfusion, preserved using only cold storage while being transported to a neighboring center, and then successfully transplanted after nearly 2 hours of cold static storage. If supported by an appropriate trial, this finding could obviate the need to use expensive perfusion devices for short interhospital distances for DCD heart transportation and stimulate more centers across the world to embrace DCD HT.

The long-term outcome of an isolated vascular ring - A single-center experience.

BACKGROUND AND OBJECTIVES: The aim of this study is to document the long-term outcome of patients with a vascular ring. METHODS: A single-center retrospective review of clinical symptoms was conducted in all patients born between 1980 and 2013, diagnosed with a complete vascular ring and at least 2 years of follow-up. Data were extracted from patient files and clinical symptoms were assessed by questionnaires sent to the parents. Age and diagnostic tools, type of surgery, postoperative complications, and the prevalence of clinical symptoms (stridor at rest, stridor with exercise, cough, exercise intolerance, dysphagia, and frequent respiratory infections) were reviewed. RESULTS: Fifty-one patients were included. The diagnosis was made before the age of 2 in 35/51. Surgery was performed in 41/51 patients with a limited number of reversible complications. The median follow-up was 8 (IQR 5-12) years. After 2 years, 21/51 patients were asymptomatic: 2/7 asymptomatic patients at diagnosis became symptomatic and symptoms resolved in 16/44 initially symptomatic patients. Consequently, 30/51 patients still had symptoms after 2 years. Of these, 16 had partial improvement, 5 stable symptoms, and 9 aggravation of symptoms. After 10 years, 26/36 patients were free of complaints. The most frequent long-term symptom was stridor. CONCLUSION: Surgical treatment of a congenital vascular ring is safe and mostly performed in patients with a double aortic arch. Conservative treatment for patients with little symptoms seems to be justifiable. A considerable number of patients have residual long-term symptoms after surgical relief of the vascular ring.

Percutaneous obliteration of the right ventricle to avoid coronary damage by sinusoids in patients with pulmonary atresia intact ventricular septum during staged single ventricle palliation.

BACKGROUND AND AIMS: Suprasystemic pressure waves can damage the coronary arteries resulting in myocardial ischemia and excess early mortality. We aimed to reduce the coronary pressure wave through the sinusoids by abolishing RV volume with percutaneous devices. METHODS AND RESULTS: Four patients with PA-IVS and coronary sinusoids from the hypertensive rudimentary RV were evaluated at a median age 26.6 months (range: 2.7-51.7). Right ventricle coronary dependent flow to the left ventricular myocardium was excluded. All four patients had dual perfusion with competitive flow from the RV through the sinusoids to the coronary arteries. Devices used were: Amplatzer vascular plug II of 10-16 mm; 27 coils (diameter 5-15 mm) in the oldest patient. Right ventricular angiography after cavity obliteration showed no more significant coronary perfusion through the sinusoids. There were no complications or deaths. Only minor and transient changes in the levels of troponin were observed. Coronary angiography at pre-Fontan evaluation showed no progress of coronary abnormalities in two patients. CONCLUSION: In selected patients with functionally single left ventricle, obliteration of the hypertensive RV cavity by percutaneous devices is safe and abolishes the systolic pressure wave in coronary sinusoids. When performed early, this may halt coronary damage and avoid excess mortality.

Vasoreactive Pulmonary Arterial Hypertension Manifesting With Misleading Epileptic Seizure: Diagnostic and Treatment Pitfalls.

A 5-year-old girl presented with acute nocturnal episodes of loss of consciousness following abdominal pain and crying. Epilepsy was primarily diagnosed but the course of the disease was suggestive of pulmonary hypertension. An adapted invasive assessment of pulmonary pressure and pharmacological challenge allowed for diagnosing vasoreactive pulmonary arterial hypertension. Initial treatment with sildenafil was not effective. Thus, calcium channel blockers were introduced when positive vasoreactivity was confirmed and permitted to stop the occurrence of the syncope and dramatically improved clinical status. At 2 years follow-up she is well without any complaint and in functional class I. Echocardiography shows a slightly enlarged but not hypertrophied right ventricle with a nearly normalized estimated right ventricular pressure. The last catheterization shows subnormal values of pulmonary arterial pressure (mean pulmonary artery pressure: 24 mmHg) and pulmonary vascular resistance (5, 4 Wood units*m2), normalizing with inhaled Nitric Oxide (mean pulmonary artery pressure of 14 mmHg and pulmonary vascular resistance of 1.5 Wood units*m2). Vasoreactive pulmonary arterial hypertension is a rare entity in children but it should not be misdiagnosed with seizures due to the presence of syncopal episodes. According to current knowledge, this form seems to have a better prognosis than non-reactive pulmonary arterial hypertension and the treatment of choice remains as calcium channel blockers. The management of this case was characterized by successive mishaps and potentially harmful mistakes and underscores the potential risk with pediatric PH evaluation in non-expert centers.

Creation of the Fontan circulation in sheep: a survival model.

OBJECTIVES: Patients with a single ventricle survive thanks to the Fontan palliation. Nevertheless, there is a growing number of Fontan patients with progressive heart failure. To validate therapeutic options in these patients, we developed a chronic Fontan large animal model. METHODS: A Fontan circulation was surgically created in 15 sheep. The superior vena cava was anastomosed end-to-side to the pulmonary artery. The inferior vena cava was connected to the pulmonary artery by an ePTFE conduit, and the inferior vena cava-right atrium junction was ligated. RESULTS: Total cavopulmonary connection was successfully performed in all 15 animals. After creation of the Fontan circulation, central venous pressure increased from 4 [interquartile range (IQR) 3-6] mmHg to 16 (IQR 14-17) mmHg, mean arterial blood pressure decreased from 68 (IQR 54-75) mmHg to 52 (IQR 50-61) mmHg and cardiac output decreased from 5.1 (IQR 4.6-6.8) l/min to 1.7 (IQR 1.3-2.7) l/min. Five animals were electively sacrificed after a follow-up period of 21 weeks. CONCLUSIONS: These results demonstrate that it is feasible to create a chronic animal model with unsupported Fontan circulation. This animal model not only opens perspectives to investigate the pathophysiology of the failing Fontan circulation, but also provides the possibility to study therapeutic options such as the effect of mechanical circulatory support in the failing Fontan physiology.

Pulmonary endarterectomy in a 12-year-old boy with multiple comorbidities.

A 10-year-old boy, with multiple comorbidities presented with fever, exertional dyspnea, fatigue and an obliterated brachiocephalic and inferior caval vein. Chronic thromboembolic pulmonary hypertension (CTEPH) was diagnosed. Nadroparine, antibiotics and supplemental oxygen were successfully started. Aged 12 years, supplemental oxygen was permanently needed with progressive exertional dyspnea and fatigue. In the country of residence the patient was considered as inoperable. The right ventricle was severely dilated, hypocontractile and hypertrophic. Mean pulmonary artery pressure (mPAP) was 79 mmHg and cardiac output 2.2 L/min. Pulmonary endarterectomy was uneventful. Four days later, mPAP was 33 mmHg and cardiac output 6.4 L/min. Three months later the boy restarted his education without supplemental oxygen. Six months after surgery right ventricular size and function and mPAP (14 mmHg) were normal. We demonstrated that pulmonary endarterectomy in young aged children is feasible and well-tolerated, even in the presence of severe co-morbidities. CTEPH should be an important diagnostic consideration in symptomatic children with a known hypercoaguable state, a history of thrombo-embolism or venous catheter placement, and/or a diagnosis of pulmonary hypertension. Hesitating to refer children for surgical consideration, or attempting to treat them by medication, only postpones the single potentially curable treatment and may worsen their prognosis.