Paediatric PH is typically associated with a worse prognosis than adult PAH, and while recent advances have described improved outcomes, many challenges still remain. Performing studies in paediatric pulmonary hypertension remains difficult due to the small number of patients but there is an urgent need to share data on this group of patients to improve management and long term outcome of children with PH We thought that it would be of interest to group manuscript in this research topic entitled paediatric pulmonary hypertension. We thought to collect manuscripts discussing pre clinical and clinical data on paediatric pulmonary hypertension.

Hôpitaux universitaires de Genève (HUG)

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Frontiers in Pediatrics

Pediatric Cardiology

Frontiers in Cardiovascular Medicine

Pediatric Pulmonary Hypertension

Pulmonary hypertension (PH) can present at any age from the neonatal period to adulthood. Pediatric PH is similar to adults but differentiates itself as in a growing child the lungs are still developing (<a href="#B1">1</a>). It is a hemodynamic condition defined by an increased pulmonary artery mean pressure above or equal to 25 mmHg (<a href="#B1">1</a>). This can be associated with multiple clinical conditions forming different etiological groups with specific and diverse pathological and pathobiological characteristics (<a href="#B1">1</a>). When implying an abnormal reduction of small pulmonary arteries section due to endothelial dysfunction, medial proliferation, and adventitial fibrosis, the disease is called pulmonary arterial hypertension (PAH). PAH induces typically a severe and devastating PH that leads to right heart failure and premature death.Until recently, the vast majority of studies published on PH were in the adult population but, as highlighted by the series of manuscript published in this issue of frontiers in pediatrics, awareness about pediatric PH is growing. In this line, a specific subgroup was dedicated to pediatrics at the last world symposium on PH with the publication of an excellent summary (<a href="#B1">1</a>). Manuscripts not only on clinical research but also on basic science further highlight the interest in pediatric PH.Epidemiologic data, mainly sourced from national and international registries, have recently been published, but the content of these registries varies depending on the center involved and the inclusion criteria (<a href="#B2">2</a>). Indeed, most of the registries, including centers from developed countries, do not report children with PAH associated with HIV, in contrast to reports coming from developing countries (<a href="#B3">3</a>). This may be due to the absence of this problem in developed countries in association with aggressive antiretroviral therapies or the absence of screening. L’Huillier et al. report the data from a Swiss cohort of patients with HIV (<a href="#B4">4</a>). No patient presented with PH, but screening of PH was not systematically performed. This must be kept in mind when analyzing epidemiologic data.In pediatrics, there is a need and a constant search for non-invasive assessments of PH, mainly because right heart catheterization, whenever it is still considered as the gold standard for hemodynamic evaluation and PH diagnosis is associated with potential risk in this particular population. So, the development of non-invasive tools for hemodynamic evaluation is not only desirable but mandatory in pediatrics. To this purpose, echocardiography gives invaluable information during the follow-up. Jone and Ivy did an excellent review of the current knowledge application of this approach in pediatric PH (<a href="#B5">5</a>) and offer a basis for the remaining work dedicated to validation of most of the discussed parameters. Similarly, Day et al. reported their experience with the use of oxygen and sildenafil for assessment of pulmonary vascular reactivity in children (<a href="#B6">6</a>). The response to vasoreactivity testing is crucial for orientation of treatment strategy as responders can be treated with calcium channel blockers with an excellent survival rate. This was clearly demonstrated in adults (<a href="#B7">7</a>) but we still have to work to define a similar approach in children. Here, a major question still remains: what is the definition of a responder? The manuscript of Day et al. brings some more information with regards to vasoreactivity assessments in pediatric PH.Still in the field of non-invasive assessment and potential markers of disease, Latus et al. reported their experience with the analysis of heart rate variability (HRV) showing that this parameter may be altered in pediatric patients with PH (<a href="#B8">8</a>). HRV may indeed be related to disease severity and serve as an additional marker for PH evaluation.Although there is still no cure for PAH, quality of life and survival have been improved significantly with specific drug therapies (<a href="#B9">9</a>). Nevertheless, management of pediatric PAH remains challenging and depends mainly on results from adult clinical trials, a few specific pediatric studies and pediatric experts’ recommendations. Any additional report of the use of targeted therapies in children is of interest. Siehr et al. reported their experience with the use of sildenafil and concentrated on its potential side effects (<a href="#B10">10</a>). One must remember that a question was raised on the use of sildenafil in children as the STARTS study reported an increased risk of death using high doses (<a href="#B11">11</a>, <a href="#B12">12</a>). This led to a warning from the FDA and the approval of the medium dose by the European Medical Authorities. Even, if Siehr et al. reported no new side effects, they mention that the incidence of vascular, gastrointestinal, and neurologic side effects in pediatric patients on sildenafil therapy was 30%. Side effects were more common in patients on combination therapy with an endothelin receptor antagonist and/or a prostacyclin than in patients on sildenafil monotherapy.Prior to the development of new therapeutic pathways, recognition of all pathobiological pathways involved in the development of pulmonary vascular disease are needed. Van loon et al. (<a href="#B13">13</a>) reported their experience with erythropoietin (EPO) (<a href="#B10">10</a>). In experimental PAH, EPO treatment restored the number of circulating endothelial progenitor cells (EPCs) to control level, improved pulmonary vascular remodeling, and showed important interplay with heme oxygenase (HO) activity. Inhibition of increased HO activity in PAH rats exacerbated progression of pulmonary vascular remodeling, despite the presence of restored number of circulating EPCs. It may be that both EPO-induced HO and EPCs are promising targets to improve the pulmonary vasculature in PAH.Different specific issues related to pediatric PAH have been reported and highlight the need to continue active research in this field. It is of paramount importance to better understand the pathobiology of the disease, its behavior and discover new treatment pathway in order to finally curing this devastating disease.MB wrote the editorial and reviewed most of the research topic manuscript. FL reviewed the content and added own ideas in the editorial; he also read all research topic manuscripts.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Editorial: Pediatric Pulmonary Hypertension

BackgroundPulmonary arterial hypertension (PAH) is a pulmonary vascular disease with a high mortality, characterized by typical angio-proliferative lesions. Erythropoietin (EPO) attenuates pulmonary vascular remodeling in PAH. We postulated that EPO acts through mobilization of endothelial progenitor cells (EPCs) and activation of the cytoprotective enzyme heme oxygenase-1 (HO-1).</sec>MethodsRats with flow-associated PAH, resembling pediatric PAH, were treated with HO-1 inducer EPO in the presence or absence of the selective HO-activity inhibitor tin-mesoporphyrin (SnMP). HO activity, circulating EPCs and pulmonary vascular lesions were assessed after 3 weeks.</sec>ResultsIn PAH rats, circulating EPCs were decreased and HO activity was increased compared to control. EPO treatment restored circulating EPCs and improved pulmonary vascular remodeling, as shown by a reduced wall thickness and occlusion rate of the intra-acinar vessels. Inhibition of HO activity with SnMP aggravated PAH. Moreover, SnMP treatment abrogated EPO-induced amelioration of pulmonary vascular remodeling, while surprisingly further increasing circulating EPCs as compared with EPO alone.</sec>ConclusionIn experimental PAH, EPO treatment restored the number of circulating EPCs to control level, improved pulmonary vascular remodeling, and showed important interplay with HO activity. Inhibition of increased HO activity in PAH rats exacerbated progression of pulmonary vascular remodeling, despite the presence of restored number of circulating EPCs. We suggest that both EPO-induced HO-1 and EPCs are promising targets to ameliorate the pulmonary vasculature in PAH.</sec>

Background: Pulmonary arterial hypertension (PAH) is a pulmonary vascular disease with a high mortality, characterized by typical angio-proliferative lesions. Erythropoietin (EPO) attenuates pulmonary vascular remodeling in PAH. We postulated that EPO acts through mobilization of endothelial progenitor cells (EPCs) and activation of the cytoprotective enzyme heme oxygenase-1 (HO-1).Methods: Rats with flow-associated PAH, resembling pediatric PAH, were treated with HO-1 inducer EPO in the presence or absence of the selective HO-activity inhibitor tin-mesoporphyrin (SnMP). HO activity, circulating EPCs and pulmonary vascular lesions were assessed after 3 weeks.Results: In PAH rats, circulating EPCs were decreased and HO activity was increased compared to control. EPO treatment restored circulating EPCs and improved pulmonary vascular remodeling, as shown by a reduced wall thickness and occlusion rate of the intra-acinar vessels. Inhibition of HO activity with SnMP aggravated PAH. Moreover, SnMP treatment abrogated EPO-induced amelioration of pulmonary vascular remodeling, while surprisingly further increasing circulating EPCs as compared with EPO alone.Conclusion: In experimental PAH, EPO treatment restored the number of circulating EPCs to control level, improved pulmonary vascular remodeling, and showed important interplay with HO activity. Inhibition of increased HO activity in PAH rats exacerbated progression of pulmonary vascular remodeling, despite the presence of restored number of circulating EPCs. We suggest that both EPO-induced HO-1 and EPCs are promising targets to ameliorate the pulmonary vasculature in PAH.

Erythropoietin Attenuates Pulmonary Vascular Remodeling in Experimental Pulmonary Arterial Hypertension through Interplay between Endothelial Progenitor Cells and Heme Oxygenase

BackgroundPulmonary hypertension (PH) is frequently associated with an increase in sympathetic tone. This may adversely affect cardiac autonomic control. Knowledge about the clinical impact of autonomic dysfunction in patients with PH is limited. We aimed to assess whether parameters of heart rate variability (HRV) are related to disease severity in children with PH.</sec>MethodsParameters of HRV [SDNN, standard deviation of normal-to-normal intervals and SDANN, standard deviation of mean values for normal-to-normal intervals over 5 min] were determined from Holter electrocardiograms of 17 patients with PH without active intracardial shunt (10 female, mean age 12.8 ± 8.7 years). Patients were allocated to two groups according to their disease severity: patients with moderate PH [ratio of pulmonary to systemic arterial pressure (PAP/SAP ratio) < 0.75] (n = 11), patients with severe PH (PAP/SAP ratio > 0.75) (n = 6). An additional group of five adolescents with Eisenmenger syndrome (PAP/SAP ratio 1.13 ± 0.36) was included.</sec>ResultsChildren with severe PH had significantly lower values of HRV [SDNN (73.8 ± 21.1 vs. 164.9 ± 38.1 ms), SDANN (62.2 ± 19.0 vs. 139.5 ± 33.3 ms)] compared to patients with moderate PH (p = 0.0001 for all). SDNN inversely correlated with ratio of PAP/SAP of PH patients without shunt (r = −0.82; p = 0.0002). Eisenmenger patients showed no significant difference of HRV [SDNN 157.6 ± 43.2 ms, SDANN 141.2 ± 45.3 ms] compared to patients with moderate PH without shunt (p > 0.05 for all).</sec>ConclusionAccording to our results, children with severe PH may have alterations in HRV. Since HRV appears to be related to disease severity, it may therefore serve as an additional diagnostic marker of PH. Remarkably, although Eisenmenger patients have systemic pulmonary arterial pressures, they seem to have preserved HRV, which might reflect a more favorable autonomic adaptation.</sec>

Background: Pulmonary hypertension (PH) is frequently associated with an increase in sympathetic tone. This may adversely affect cardiac autonomic control. Knowledge about the clinical impact of autonomic dysfunction in patients with PH is limited. We aimed to assess whether parameters of heart rate variability (HRV) are related to disease severity in children with PH.Methods: Parameters of HRV [SDNN, standard deviation of normal-to-normal intervals and SDANN, standard deviation of mean values for normal-to-normal intervals over 5 min] were determined from Holter electrocardiograms of 17 patients with PH without active intracardial shunt (10 female, mean age 12.8 ± 8.7 years). Patients were allocated to two groups according to their disease severity: patients with moderate PH [ratio of pulmonary to systemic arterial pressure (PAP/SAP ratio) &lt; 0.75] (n = 11), patients with severe PH (PAP/SAP ratio &gt; 0.75) (n = 6). An additional group of five adolescents with Eisenmenger syndrome (PAP/SAP ratio 1.13 ± 0.36) was included.Results: Children with severe PH had significantly lower values of HRV [SDNN (73.8 ± 21.1 vs. 164.9 ± 38.1 ms), SDANN (62.2 ± 19.0 vs. 139.5 ± 33.3 ms)] compared to patients with moderate PH (p = 0.0001 for all). SDNN inversely correlated with ratio of PAP/SAP of PH patients without shunt (r = −0.82; p = 0.0002). Eisenmenger patients showed no significant difference of HRV [SDNN 157.6 ± 43.2 ms, SDANN 141.2 ± 45.3 ms] compared to patients with moderate PH without shunt (p &gt; 0.05 for all).Conclusion: According to our results, children with severe PH may have alterations in HRV. Since HRV appears to be related to disease severity, it may therefore serve as an additional diagnostic marker of PH. Remarkably, although Eisenmenger patients have systemic pulmonary arterial pressures, they seem to have preserved HRV, which might reflect a more favorable autonomic adaptation.

Heart Rate Variability is Related to Disease Severity in Children and Young Adults with Pulmonary Hypertension

Since the advent of highly active anti-retroviral therapy, HIV-related mortality has decreased dramatically. As a consequence, patients are living longer, and HIV infection is becoming a chronic disease. Patients and caretakers have to deal with chronic complications of infection and treatment, such as cardiovascular diseases, which now represent an important health issue, even in the pediatric population. Prevalence of pulmonary arterial hypertension (PAH) in the adult HIV population is around 0.4–0.6%, which is around 1000- to 2500-fold more prevalent than in the general population. In recent adult PAH registries, HIV has been identified as the fourth cause of PAH, accounting for approximately 6–7% of cases. Therefore, regular screening is recommended in HIV-infected adults by many experts. If HIV-associated PAH is mainly reported in HIV-infected adults, pediatric cases have also been, albeit rarely, described. This scarcity may be due to a very low PAH prevalence, or due to the lack of systematic cardiovascular screening in pediatric patients. As PAH may manifest only years or decades after infection, a systematic screening should perhaps also be recommended to HIV-infected children. In this context, we retrospectively looked for PAH screening in children included in our national Swiss Mother and Child HIV cohort study. A questionnaire was sent to all pediatric infectious disease specialists taking care of HIV-infected children in the cohort. The questions tried to identify symptoms suggestive of cardiovascular risk factors and asked which screening test was performed. In the 71 HIV-infected children for which we obtained an answer, no child was known for PAH. However, only two had been screened for PAH, and the diagnosis was not confirmed. In conclusion, PAH in HIV-infected children is possibly underestimated due to lack of screening. Systematic echocardiographic evaluation should be performed in HIV-infected children.

Since the advent of highly active anti-retroviral therapy, HIV-related mortality has decreased dramatically. As a consequence, patients are living longer, and HIV infection is becoming a chronic disease. Patients and caretakers have to deal with chronic complications of infection and treatment, such as cardiovascular diseases, which now represent an important health issue, even in the pediatric population. Prevalence of pulmonary arterial hypertension (PAH) in the adult HIV population is around 0.4&#x2013;0.6%, which is around 1000- to 2500-fold more prevalent than in the general population. In recent adult PAH registries, HIV has been identified as the fourth cause of PAH, accounting for approximately 6&#x2013;7% of cases. Therefore, regular screening is recommended in HIV-infected adults by many experts. If HIV-associated PAH is mainly reported in HIV-infected adults, pediatric cases have also been, albeit rarely, described. This scarcity may be due to a very low PAH prevalence, or due to the lack of systematic cardiovascular screening in pediatric patients. As PAH may manifest only years or decades after infection, a systematic screening should perhaps also be recommended to HIV-infected children. In this context, we retrospectively looked for PAH screening in children included in our national Swiss Mother and Child HIV cohort study. A questionnaire was sent to all pediatric infectious disease specialists taking care of HIV-infected children in the cohort. The questions tried to identify symptoms suggestive of cardiovascular risk factors and asked which screening test was performed. In the 71 HIV-infected children for which we obtained an answer, no child was known for PAH. However, only two had been screened for PAH, and the diagnosis was not confirmed. In conclusion, PAH in HIV-infected children is possibly underestimated due to lack of screening. Systematic echocardiographic evaluation should be performed in HIV-infected children.

Pulmonary Arterial Hypertension among HIV-Infected Children: Results of a National Survey and Review of the Literature

Background: Sildenafil, a phosphodiestase type 5 inhibitor, was approved in 2005 for the treatment of pulmonary arterial hypertension (PAH) in adults and is commonly used off-label for pediatric patients. Little is known, however, about sildenafil’s side effects in this population.Methods: Single institution, longitudinal survey-based study performed in an outpatient pediatric cardiology clinic. Pediatric patients on sildenafil [alone or in combination with other pulmonary hypertension (PH) therapies] completed questionnaires regarding frequency of vascular, gastrointestinal, neurologic, and hematologic side effects.Results: Between January 2011 and May 2014, 66 pediatric patients with PH on sildenafil filled out 214 surveys, 32 patients (96 surveys) on monotherapy, and 43 patients (118 surveys) on sildenafil plus an endothelin receptor antagonist (ERA) (bosentan or ambrisentan) and/or a prostacyclin (epoprostenol or treprostinil). Overall, 30% of respondents identified at least one side effect. For all patients on sildenafil, incidence of side effects by system was 37% gastrointestinal, 35% vascular, and 22% neurologic. For patients on sildenafil monotherapy, incidence of side effects by system was 24% gastrointestinal, 21% vascular, and 18% neurologic compared to patients on combination therapy who reported an incidence of 48% gastrointestinal, 45% vascular, and 25% neurologic.Conclusion: Incidence of vascular, gastrointestinal, and neurologic side effect in pediatric patients on sildenafil therapy for PAH was 30%. Side effects were more common in patients on combination therapy with an ERA and/or prostacyclin than in patients on sildenafil monotherapy.

Background: Sildenafil, a phosphodiestase type 5 inhibitor, was approved in 2005 for the treatment of pulmonary arterial hypertension (PAH) in adults and is commonly used off-label for pediatric patients. Little is known, however, about sildenafil’s side effects in this population.Methods: Single institution, longitudinal survey-based study performed in an outpatient pediatric cardiology clinic. Pediatric patients on sildenafil [alone or in combination with other pulmonary hypertension (PH) therapies] completed questionnaires regarding frequency of vascular, gastrointestinal, neurologic, and hematologic side effects.Results: Between January 2011 and May 2014, 66 pediatric patients with PH on sildenafil filled out 214 surveys, 32 patients (96 surveys) on monotherapy, and 43 patients (118 surveys) on sildenafil plus an endothelin receptor antagonist (ERA) (bosentan or ambrisentan) and/or a prostacyclin (epoprostenol or treprostinil). Overall, 30% of respondents identified at least one side effect. For all patients on sildenafil, incidence of side effects by system was 37% gastrointestinal, 35% vascular, and 22% neurologic. For patients on sildenafil monotherapy, incidence of side effects by system was 24% gastrointestinal, 21% vascular, and 18% neurologic compared to patients on combination therapy who reported an incidence of 48% gastrointestinal, 45% vascular, and 25% neurologic.Conclusion: Incidence of vascular, gastrointestinal, and neurologic side effect in pediatric patients on sildenafil therapy for PAH was 30%. Side effects were more common in patients on combination therapy with an ERA and/or prostacyclin than in patients on sildenafil monotherapy.

Reported Sildenafil Side Effects in Pediatric Pulmonary Hypertension Patients

Objective: Right heart catheterization is performed in patients with pulmonary arterial hypertension to determine the severity of disease and their pulmonary vascular reactivity. The acute pulmonary vascular effect of inhaled nitric oxide is frequently used to identify patients who will respond favorably to long-term vasodilator therapy. This study sought to determine whether the acute pulmonary vascular effects of oxygen with nitric oxide and intravenous sildenafil are similar.Methods: A retrospective, descriptive study of 13 individuals with pulmonary hypertension who underwent heart catheterization and acute vasodilator testing was performed. The hemodynamic measurements during five phases (21–53% oxygen, 100% oxygen, 100% oxygen with 20 ppm nitric oxide, 21–51% oxygen, and 21–51% oxygen with 0.05–0.29 mg/kg intravenous sildenafil) of the procedures were compared using analysis of variance. A linear regression analysis and a Bland Altman plot were used to compare the percent change in mean pulmonary arterial pressure and the percent change in pulmonary vascular resistance from baseline with oxygen and nitric oxide, and from baseline with sildenafil.Results: Mean pulmonary arterial pressure and pulmonary vascular resistance acutely decreased with 100% oxygen with nitric oxide and 21–51% oxygen with sildenafil. Pulmonary blood flow during sildenafil was greater than pulmonary blood flow during 100% oxygen and 100% oxygen with nitric oxide. The pH, right atrial pressure, and left atrial pressure did not change during the five phase of heart catheterization. Mean pulmonary arterial pressure (millimeter of mercury, mean ± standard error of the mean) was 38 ± 4 during 21–53% oxygen, 32 ± 3 during 100% oxygen, 29 ± 2 during 100% oxygen with nitric oxide, 37 ± 3 during 21–51% oxygen, and 32 ± 2 during 21–51% oxygen with sildenafil. There was not a significant correlation between the percent change in pulmonary vascular resistance from baseline with oxygen and nitric oxide, and from baseline with sildenafil (r2 = 0.011, p = 0.738). The Bland Altman analysis demonstrated statistical agreement between the effects of oxygen with nitric oxide and sildenafil. However, differences were large enough to limit the interchangeable use of these vasodilators in a clinical setting.Conclusion: Oxygen with nitric oxide and sildenafil decreased pulmonary vascular resistance. However, the pulmonary vascular effects of oxygen and nitric oxide do not reliably predict the acute response to sildenafil. Additional studies are needed to determine whether the acute response to sildenafil can be used to predict the long-term response to treatment with an oral phosphodiesterase V inhibitor.

Objective: Right heart catheterization is performed in patients with pulmonary arterial hypertension to determine the severity of disease and their pulmonary vascular reactivity. The acute pulmonary vascular effect of inhaled nitric oxide is frequently used to identify patients who will respond favorably to long-term vasodilator therapy. This study sought to determine whether the acute pulmonary vascular effects of oxygen with nitric oxide and intravenous sildenafil are similar.
 Methods: A retrospective, descriptive study of 13 individuals with pulmonary hypertension who underwent heart catheterization and acute vasodilator testing was performed. The hemodynamic measurements during five phases (21–53% oxygen, 100% oxygen, 100% oxygen with 20 ppm nitric oxide, 21–51% oxygen, and 21–51% oxygen with 0.05–0.29 mg/kg intravenous sildenafil) of the procedures were compared using analysis of variance. A linear regression analysis and a Bland Altman plot were used to compare the percent change in mean pulmonary arterial pressure and the percent change in pulmonary vascular resistance from baseline with oxygen and nitric oxide, and from baseline with sildenafil.
 Results: Mean pulmonary arterial pressure and pulmonary vascular resistance acutely decreased with 100% oxygen with nitric oxide and 21–51% oxygen with sildenafil. Pulmonary blood flow during sildenafil was greater than pulmonary blood flow during 100% oxygen and 100% oxygen with nitric oxide. The pH, right atrial pressure, and left atrial pressure did not change during the five phase of heart catheterization. Mean pulmonary arterial pressure (millimeter of mercury, mean ± standard error of the mean) was 38 ± 4 during 21–53% oxygen, 32 ± 3 during 100% oxygen, 29 ± 2 during 100% oxygen with nitric oxide, 37 ± 3 during 21–51% oxygen, and 32 ± 2 during 21–51% oxygen with sildenafil. There was not a significant correlation between the percent change in pulmonary vascular resistance from baseline with oxygen and nitric oxide, and from baseline with sildenafil (r2 = 0.011, p = 0.738). The Bland Altman analysis demonstrated statistical agreement between the effects of oxygen with nitric oxide and sildenafil. However, differences were large enough to limit the interchangeable use of these vasodilators in a clinical setting.
 Conclusion: Oxygen with nitric oxide and sildenafil decreased pulmonary vascular resistance. However, the pulmonary vascular effects of oxygen and nitric oxide do not reliably predict the acute response to sildenafil. Additional studies are needed to determine whether the acute response to sildenafil can be used to predict the long-term response to treatment with an oral phosphodiesterase V inhibitor.

Comparison between the Acute Pulmonary Vascular Effects of Oxygen with Nitric Oxide and Sildenafil

Pulmonary hypertension (PH) can be a rapidly progressive and fatal disease. Although right heart catheterization remains the gold standard in evaluation of PH, echocardiography remains an important tool in screening, diagnosing, evaluating, and following these patients. In this article, we will review the important echocardiographic parameters of the right heart in evaluating its anatomy, hemodynamic assessment, systolic, and diastolic function in children with PH.

Pulmonary hypertension (PH) can be a rapidly progressive and fatal disease. Although right heart catheterization remains the gold standard in evaluation of PH, echocardiography remains an important tool in screening, diagnosing, evaluating, and following these patients. In this article, we will review the important echocardiographic parameters of the right heart in evaluating its anatomy, hemodynamic assessment, systolic, and diastolic function in children with PH.