Pediatric pulmonary hypertension registry: Single-center experience from India

Abstract

Background:

Pulmonary hypertension (PH) is a rare and usually irreversible disease, eventually leading to right heart failure (RHF). There are multiple PH registries in adults with PH, but very few pediatric PH registries, especially from developing countries.

Methods:

All children (aged 3 months–18 years) diagnosed with PH were enrolled in the study. PH was defined by standard echocardiographic and cardiac catheterization criteria. We excluded patients with transient or reversible PH, including hyperkinetic PH associated with congenital heart defects (CHDs).

Results:

Our registry included 100 children from June 2019 to January 2024, with an equal gender ratio (male: female = 1:1). Easy fatigability, syncope, and RHF were the most common presenting features. Only 15% of children were classified as idiopathic pulmonary artery hypertension (IPH). The majority (81%) of children belonged to the CHD-pulmonary artery hypertension (CHD-PAH) group (49% Eisenmenger syndrome, 26% CHD with systemic to pulmonary shunt and severe PAH falling in the inoperable category, and 6% had post-operative residual PH). All patients in the IPH group and 42 patients (48.2%) in other PH were on pulmonary vasodilators. The median follow-up duration was 13 months (range: 4–56 months). Overall, there were 5 deaths (5% mortality), with 3 deaths in the IPH (20%) group. Children with CHD-PAH had better functional class, and no patient in this group died.

Conclusions:

The underlying etiology and prognosis in children with PH may differ in the Indian context compared to the Western world. Different centers across India may still face a higher proportion of unoperated CHD due to late referral, a limited number of specialized centers, and financial constraints. Children with IPH have poor long-term outcomes and a high risk of mortality. Multicenter PH registries may provide actual statistics and further insights into the disease.

INTRODUCTION

Pulmonary hypertension (PH) is a progressive disease with a worse prognosis in children. It is an important cause of morbidity and mortality, and it has not been sufficiently characterized in children.[1] It can present at any age, from infancy to adulthood, although the causes differ in children. The definition of PH in children is the same as in adults. It is defined as the mean pulmonary artery pressure of more than 20 mmHg, as per the revised NICE guidelines.[2] PH is divided into idiopathic PH (IPH) and associated PH (APH), the latter of which occurs when PH is related to other disorders. The median survival time after diagnosis was reported to be 10 months in children, compared with 2.8 years in adults. Survival for children with IPH who were candidates for intravenous prostacyclin but could not be treated with this therapy was poor, with a survival of 45% and 29% at 1 and 4 years, respectively.[3]

Current epidemiological data on pediatric PH are mainly derived from registry cohorts, and there are significant differences concerning adult PH epidemiology.[4,5,6] There is a lot of variation due to geographical location, referral patterns, clinical practices, and disease definition. The estimated incidence of sustained PH in all categories is reported to be 4–10 cases per million children per year.[1]

Recent advances in understanding the pathophysiology and management of PH have significantly improved survival.[7,8,9] Still, the disease progression is rapid, especially in children, which can lead to progressive right ventricular (RV) enlargement and dysfunction. PH in children is intrinsically linked to lung growth and development, genetic etiologies coupled with prenatal and postnatal factors.[10] Newer surgical strategies, such as reverse Potts shunt, are beneficial for young children with severe PH and RV failure.[11] At the same time, there are reports regarding the placement of atrial flow regulators across the interatrial septum to decompress the right atrium.[12] There is very limited data regarding pediatric PH in lower-middle-income countries (LMICs). This is single-center data from an Indian tertiary care pediatric cardiac center.

METHODS

Study design

We have an institutional PH registry to enroll all patients with PH, except those with cardiac shunt-related hyperkinetic PH. This study is a retrospective analysis of children from our PH registry. The waiver of consent was obtained from the institutional ethics committee (approval letter no.: SSK0044/V2/APR/2023/IEC-9).

Study population

We included all patients aged 18 years or younger at the time of their initial presentation from the PH registry of our institute. Diagnosis of PH was based upon standard echocardiography and cardiac catheterization criteria.[2] We excluded patients with transient PH, like large left-to-right shunt-associated hyperkinetic PH, and persistent pulmonary hypertension of the newborn.

Data collection and follow-up

The baseline data included clinical details, modified Ross or World Health Organization functional class (depending on age), and medication details. Chest X-ray, electrocardiogram, and echocardiography were performed at baseline in all children. Echocardiography assessment was performed to confirm the diagnosis and to evaluate functional parameters, including tricuspid annular plane systolic excursion, RV fractional area change, pericardial effusion, and inferior vena cava status. The 6-min walk test (6MWT) was performed in patients aged 5 years or older who were able to complete it. A cardiopulmonary exercise test could not be performed due to logistical constraints. All patients were classified into IPH and APH based on their diagnosis. The APH category was further subdivided into congenital heart defect-PH (CHD-PAH) and miscellaneous groups. The CHD-PAH group included Eisenmenger syndrome, shunt lesions with elevated pulmonary vascular resistance (PVR) above operable range, and post-operative residual PH. Eisenmenger syndrome was defined as a large intra- or extracardiac shunt with bidirectional or right to left shunt. Children with severe PH and a coincidental small shunt were included in the IPH group. Computed tomography (CT) angiography was performed in all patients with IPH to exclude abnormalities, such as pulmonary vein stenosis, lung parenchymal/tracheobronchial abnormalities, and portosystemic shunts (Abernethy malformation). Cardiac catheterization was done for assessment of PVR with acute vasodilator testing (AVT) for all children with IPH and patients with shunt lesions with borderline operability. AVT was performed with inhaled Nitric Oxide, and a positive AVT response was defined according to Sitbon criteria.[13] N-terminal brain natriuretic peptide (NT-proBNP) was measured at initial assessment and repeated as needed during follow-up. Children with cardiac shunt lesions and borderline operability were subjected to cardiac catheterization and later included in the CHD-PAH group if found to be inoperable. Patients were followed up at 6-month intervals or sooner if necessary, depending on each patient’s functional class. Patients who were unable to complete at least one follow-up with us were classified as lost to follow-up. Pulmonary vasodilator therapy, either single or dual, was initiated depending upon clinical and laboratory parameters. Medications were escalated based upon clinical deterioration, worsening echocardiography parameters, and a rise in NT pro-BNP levels.

The study’s objectives included (1) Describe clinical parameters and etiology of pediatric PH patients and (2) To assess the response to medications and morbidity and mortality with respect to the underlying etiology of pediatric PH.

Statistical analysis

Statistical analysis was performed using SPSS software. Parametric data were expressed as the mean ± standard deviation, and non-parametric data were expressed as the median with interquartile ranges. Kaplan–Meier survival graphs were plotted, and the Log-rank test was used to compare survival between groups. P < 0.05 was considered significant.

RESULTS

Our study included 100 children with PH in the study period from June 2019 to January 2024, and the study population had equal gender distribution. Fifteen (15%) patients belonged to the IPH group, and the remaining 85 (85%) belonged to the APH group. In the APH group, 2 (2%) had left heart disease, one patient had BPD (bronchopulmonary dysplasia), and one had a portosystemic shunt (Abernethy malformation). The remaining 81 (81%) patients in the APH category belonged to the CHD-PAH group: 49% had Eisenmenger syndrome, 26% had CHD in the inoperable category, and 6% had postoperative residual PH.

Demographic data and clinical profile

Idiopathic pulmonary hypertension group

The median age was 5 years 10 months (range 4 months–17 years) with a slight male preponderance (M: F = 1.1:1). One patient had confirmed Down syndrome. Many (40%) patients were in Class III or higher at presentation [Figure 1a]. The basal oxygen saturation ranged from 85% to 98%. Four patients (26.6%) had a history of syncope, while 3 (20%) children had features of right heart failure (RHF) at the time of presentation. The median 6MWT distance was 400 m (range: 250–500 m). The median NT-pro-BNP was 6010 pg/mL (range: 82–16,408 pg/mL). A CT angiography did not reveal any evidence of thromboembolism or abnormalities in the tracheobronchial system. Nine patients underwent cardiac catheterization, and the mean PA pressures and pulmonary vascular resistance index were 60.1 ± 21.4 mmHg and 20.3 ± 12.1 WU.m², respectively [Table 1]. Only one patient (6.7%) was positive for AVT and was started on calcium channel blockers (CCB). Two patients were very sick and were considered very high risk for cardiac catheterization, and the other four did not consent to the procedure.

Figure 1.

(a) Histogram showing distribution of the patients based upon their functional class in 2 major groups, i.e., congenital heart defect pulmonary hypertension (CHD-PH) and Idiopathic PH (IPH). (b) Histogram showing incidence of the morbidity and mortality in 2 major groups of CHD-PH and IPH

Table 1.

Demographic data of the children included in the pediatric pulmonary hypertension registry

Characteristics	Whole cohort (n=100), n (%)	IPH (n=15), n (%)	CHD-PAH (n=81), n (%)
WHO functional class
I	53 (53)	3 (20)	50 (62.5)
II	38 (38)	6 (40)	29 (35.8)
III	6 (6)	4 (1 died)	1 (1.23)
IV	3 (3)	2 (both died)	1 (1.23)
Syncope (n)	9	4	5
RHF (n)	4	3	1
6MWTD (m)	400 (150–800)	400 (250–500)	400 (150–800)
NT pro-BNP (pg/ml)	273 (20–16408)	6010 (82–16408)	135 (20–215)
Cath	n=20	n=9	n=11
Mean RA pressure (mm Hg)	8.16±2.3	8.01±2.45 (4–12)	8.2±2.4
Mean PA pressure (mm Hg)	59.76±16.62	59.48±16.9	60.39±16.56
PASP/AOSP	0.92±0.31	0.92±0.31	0.93±0.33
PVRi (WoodU.m2)	13.92±10.53	13.97±10.69	14.03±10.68
SVRi (WoodU.m2)	22.75±8.92	22.52±9.03	22.85±9.1
PVR: SVR	0.64±0.39	0.65±0.4	0.64±0.39
Qs (L/min/m2)	3.09±1.07	3.04±1.05	3.1±1.01
PAH medications
Sildenafil	29 (30.52)	9 (75)	20 (24.69)
Tadalafil	5 (5.27)	3 (25)	2 (2.47)
Bosentan	24 (25.26)	3 (25)	21 (25.92)
Ambrisentan	3 (3.2)	1 (8.3)	2 (2.47)
CCB	1 (1.1)	1 (8.3)	0

6MWT: 6-min walk test distance, AOSP: Aortic systolic pressure, CCB: Calcium channel blockers, CHD-PAH: Congenital heart defect associated pulmonary artery hypertension, IPH: Idiopathic pulmonary hypertension, PA: Pulmonary artery, PASP: Pulmonary artery systolic pressure, PVR: Pulmonary vascular resistance, PVRi: PVR index, Qs: Systemic blood flow, RA: Right atrium, RHF: Right heart failure, SVR: Systemic vascular resistance, SVRi: SVR index, PAH: Pulmonary arterial hypertension, WHO: World Health Organization, Nt pro BNP: N-terminal brain natriuretic peptide

Associated pulmonary hypertension group

Most (n = 85) children with PH have an associated etiology. The majority (81%) of patients belonged to the CHD-PAH group (49% Eisenmenger syndrome, 26% CHD in the inoperable category with systemic to pulmonary shunt, and 6% postoperative residual PH). Left heart disease was the etiological factor in 2%, and BPD and portosystemic shunt (Abernethy malformation) in 1% each. The mean age at presentation was 9 ± 5 years in the CHD-PAH group, with a nearly equal gender ratio (M: F = 0.98:1). The distribution of patients by functional class is shown in Figure 1a. Compared to IPH patients, functional class was preserved in the CHD-PAH group, and none of the patients in this category had class IV symptoms. Isolated ventricular septal defect (VSD) was the most common lesion seen in 46.7% of children with CHD-PAH, as shown in Table 2. Collectively, VSD was observed in more than 2/3 of patients. The incidence of syncope was lower in the CHD-PAH group (6.17%) compared to IPH patients (26.6%) [Figure 1b]. Eleven of these children with borderline operability underwent cardiac catheterization. They were considered inoperable due to high PVR and were on medical follow-up. The catheterization details are given in Table 3. There were 6 patients with postoperative persistent PH, and details are shown in Table 4. All of them had PH based upon follow-up echocardiogram, and one underwent cardiac catheterization. Four of these children underwent surgical closure of an intracardiac defect in early infancy and had persistent PH despite timely correction of the underlying shunt.

Table 2.

Distribution of the different types of cardiac lesions in children with congenital heart defect associated pulmonary hypertension (except postoperative residual pulmonary hypertension)

Type of CHD	Total cases	Percentage of ES/shunt lesions
VSD	35	46.7
VSD + PDA	7	9.3
VSD + ASD	7	9.3
PDA	6	8
Single ventricle	6	8
DORV with large VSD	5	6.7
Truncus arteriosus	3	4
TGA with VSD	2	2.7
DORV VSD pulmonary atresia with large AP window	1	1.3
Complete AV canal defect	1	1.3
CTGA with VSD with PDA	1	1.3
AP window	1	1.3

AP window: Aorto-pulmonary window, ASD: Atrial septal defect, CTGA: Corrected transposition of great arteries, DORV: Double outlet right ventricle, PDA: Patent ductus arteriosus, TGA: Transposition of great arteries, VSD: Ventricular septal defect, CHD: Congenital heart defect, ES: Eisenmenger syndrome, AV: Atrioventricular

Table 3.

Cardiac catheterization data of the children among the congenital heart defect associated pulmonary hypertension group with elevated pulmonary vascular resistance

Age	Diagnosis	Saturations	Qp:Qs	PA pressures	PVRi (Woodsu.m2)	PVR:SVR ratio
9 years	Multiple VSDs	98		89/48/69	6.4	0.47
4 years	Large PDA	96 (LL)	1.7	80/34/56	6.2	0.46
10 years	Large VSD	96			6.75	0.5
2 years 6 months	Large VSD	98	1.15	85/34/59	10.2	0.69
10 years	Large VSD	98	1.7	91/39/68	8.6	0.47
6 years 6 months	Large PDA	97 (LL)	1.4	80/43/58	14	0.74
5 years	Large VSD	97			16
6 years	Large VSD and ASD	96	2.3	84/36/56	6.4	0.32
10 years	Large PDA	88 (LL)	0.8	86/54/70	13.1	1.2
4 years 6 months	Large VSD	98	1.9	97/48/73	12.3	0.44
12 years	Truncus arteriosus	81		81/44/54	NA

PA: Pulmonary artery, VSD: Ventricular septal defect, NA: Not available, ASD: Atrial septal defect, PDA: Patent ductus arteriosus, SVR: Systemic vascular resistance, PVR: Pulmonary vascular resistance, PVRi: PVR index, Qs: Systemic blood flow, Qp: Pulmonary blood flow, LL: Left-to-left

Table 4.

Follow-up data of the children who had persistent pulmonary hypertension after cardiac shunt closure

Diagnosis	Age at surgery/device closure	Duration after surgery	PA pressures on ECHO	Pulmonary vasodilators
ASD	1 year 6 months	10 years	PAMP-60	1
PDA	3 years 9 months	4 years	PASP-55	1
VSD	2 years 2 months	1 year	PASP-70	2
VSD closure with aortic arch repair	2 months	6 months	PASP-75	2
VSD	2 years	2 years	PASP-56	1
VSD	7 years	1 year	PASP-70	1

ECHO: Echocardiography, VSD: Ventricular septal defect, ASD: Atrial septal defect, PDA: Patent ductus arteriosus, PA: Pulmonary artery, PAMP: Pulmonary artery mean pressure, PASP: Pulmonary artery systolic pressure

Treatment initiation and maintenance

Idiopathic pulmonary hypertension

Eight (53.3%) patients were on a single pulmonary vasodilator, and 4 (26.7%) were on dual pulmonary vasodilators at the time of presentation. All 15 patients in this group required pulmonary vasodilators on follow-up. Medications were increased in 5 (33.3%) patients during follow-up due to worsening symptoms. On follow-up, a total of 8 (53.3%) of these were on dual pulmonary vasodilators, and one adolescent boy was started on CCB. He responded very well and was weaned off the other two pulmonary vasodilators on follow-up. None of our patients were on prostacyclin analogues due to financial and feasibility reasons.

Associated pulmonary hypertension

In the shunt lesion/ES category, 32 (42.7%) children were on pulmonary vasodilators, out of which 19 were on bosentan and the remaining on sildenafil. Only 2 patients (2.7%) in this group were on dual pulmonary vasodilators. Among the postoperative PH patients, 2 (33.3%) were on dual pulmonary vasodilators, and 4 (66.7%) were on single pulmonary vasodilators at their last follow-up [Table 4]. A child with Abernethy malformation was gradually escalated to dual pulmonary vasodilators due to worsening functional class. This child subsequently underwent transcatheter device closure of the Abernethy malformation. She is doing well at 1-year follow-up on a single medication. Patients with BPD and left heart disease did not receive any pulmonary vasodilators.

Outcome analysis

The mean survival time of all children with PH was 1448.53 ± 148.29 days (95% C.I: 1157.8–1739.2) as shown in Figure 2a. The overall survival probability was 93.8% (±0.03) for the 1^st year and 87.7% (±0.065) from the 2^nd year onward for all patients with pediatric PH. There were 3 (20%) deaths in the IPH group versus 3 (2.35%) in the APH group.

Figure 2.

(a) Survival analysis curves for the whole cohort of children with pulmonary hypertension. (b) Kaplan–Meier survival curves for 2 primary categories of Idiopathic pulmonary hypertension (PH) and Associated PH

Idiopathic pulmonary hypertension

The mean survival time for patients with IPH was 602.6 ± 90.8 days (95% CI: 424.4–780.7), and it was significantly different when compared with the CHD-PAH group (Log rank test-P value-0.006) [Figure 2b]. The survival for 3 months and 1 year was 91.7% and 80.2% respectively, in the IPH group. Three (20%) patients died in this group. These patients were in symptomatic class IV with severe RV dysfunction and syncopal episodes [Table 5]. Three patients were considered for a reversed Potts shunt due to progression of their disease. Out of the two patients, one underwent surgery. They remained in functional class II after surgery, and NT-proBNP levels decreased significantly.

Table 5.

Details of the children in the idiopathic pulmonary hypertension group with mortality

	1	2	3
Age/sex	3 years 8 months/male	11 months/female	5 years 10 months/female
Functional class	III	IV	IV
Syncope	Yes	NA	Yes
RHF	Yes	Yes	Yes
Spo2 (%)	95	82	97
Pulmonary vasodilators	2	2	2
NT pro BNP (pg/ml)	964	9982	6794
RV function	Moderate dysfunction	Moderate dysfunction	Severe dysfunction
PVRi (Woodsu.m2)	10.3	Not done	17.2
SVRi (Woodsu.m2)	20.1	Not done	48.6

SVRi: Systemic vascular resistance index, PVRi: Pulmonary vascular resistance index, RV: Right ventricle, RHF: Right heart failure, SPo₂: Saturation of peripheral oxygen, NA: Not available, Nt pro BNP: N-terminal brain natriuretic peptide

Associated pulmonary hypertension

The mean survival time in the APH group was 1639.11 ± 47.1 days (95% C.I. 1546.8–1731.3). The survival rates for 3 months and 1 year were 100% and 95.6%, respectively, in this group. There were 2 (2.4%) deaths in the APH group. One child had BPD, and the second one had hypoplasia of all 4 pulmonary veins. There was no mortality in CHD-PAH.

DISCUSSION

Disease registries are important sources of information for assessing disease burden and outcomes. The help in identifying risk factors, estimating prognosis, and planning management.[14] There are multiple registries of PH, both disease- and drug-based, but most include adult patients.[15] It is difficult to find the exact incidence and prevalence of pediatric PH in the community due to diagnostic pitfalls and referral bias, especially in LMIC settings. Pediatric PH has a prevalence of 2–3 per million to 25–50 per million in the population, as reported in various studies.[1] Several factors affect prevalence, natural history, and outcomes in children with PH, e.g., access to medical care issues and interventional procedures, lack of awareness of the disease amongst the healthcare providers, and an unevenly distributed healthcare system.

This is a 5-year dataset of patients diagnosed with PH from a single tertiary care pediatric cardiac center. Our study predominantly had patients with APH, viz., Eisenmenger syndrome and large shunts with borderline operability. The PH registry of children and adolescents from Poland, which enrolled 80 patients, also had 67% patients with associated congenital heart defects and 31% IPH.[16] Similarly, the pediatric PAH registry from the Netherlands had 63% of their patients with associated CHD and 29% IPH.[17]

Only 15% of our cohort had IPH. Patients with IPH may be missed in the primary care setting as they have unusual symptoms. The UK PH registry comprised 216 patients, of whom 60 had idiopathic pulmonary arterial hypertension (27.7%), and 156 had APH.[6] As in the Tracking Outcomes and Practice in Paediatric Pulmonary hypertension (TOPP) registry, PH associated with connective tissue disease, human immunodeficiency virus, drugs, or thromboembolism was rare in our study as well.[1] The underrepresentation of other causes of PH in the present study may be due to a lack of awareness of this disease among pediatricians.

Syncope was the major symptom (26.6%) in patients with IPH; 20% of patients in this group had symptoms of RHF. The symptomatology is similar to that of the patients in the TOPP registry. Syncope in children needs to be evaluated systematically, as it may be misdiagnosed and treated as a neuropsychiatric disorder in children. Most of the patients with shunt lesions or Eisenmenger syndrome were in functional class I or II. These observations were also made in conjunction with other registries.[16,17] In the study of symptomatology in pediatric PH by Berger et al., exercise-induced dyspnea was the major symptom, followed by syncope, which was more common in patients with IPH.[1] BPD as a cause for PH was more common in other studies, perhaps due to more awareness and referral bias. We had only one patient with BPD, and this child died during follow-up. We had only one patient with Down syndrome. Compared with other registries, Down syndrome was under-represented in our study.[18] Short stature was an important observation in the Poland registry and may be secondary to a chronic low-output state.[16]

The purpose of AVT in children is to determine the potential for treatment with CCB. It may also help assess operability in children with shunt lesions.[19] Nine out of 15 patients in the IPH group and 11 patients in the APH group with borderline operability underwent cardiac catheterization for AVT. In the IPH group, only one patient was considered a responder according to the Sitbon criteria, and this child was subsequently considered for CCB. Similar observations were made in other studies as well. These children require close monitoring to assess their sustained response to CCB, and they may require repeat cardiac catheterizations to evaluate their progress. All 11 patients with borderline operability had significantly elevated PVR and, hence, could not be considered for surgical closure of the defect; they were under medical follow-up.

Most of the patients were only on oral sildenafil and/or bosentan, as other drugs like inhaled iloprost and intravenous epoprostenol were costly and often unavailable. Most patients in the IPH group were on either a single or a dual pulmonary vasodilator. In the PPH Net registry data, 78% of the IPH group were on PH medications.[20] In the APH group, patients with CHD-PAH were treated with pulmonary vasodilators only if their functional class was greater than II and their oxygen saturation fell to <80% during the 6MWT. Most of these patients were either in functional class I or II and were able to perform their daily activities without limitations. This study again confirms the better outcome of patients with Eisenmenger syndrome or large shunts who are borderline operable. Their functional class is preserved, and most of them may either not require any pulmonary vasodilator or can be managed with a single drug. Advanced medical therapy with pulmonary vasodilators does improve outcomes in Eisenmenger syndrome with functional Class III and above. Still, we currently lack data to support the proactive initiation of such treatment in asymptomatic patients who are in functional Class I or II.[21] Current ESC guidelines recommend initiating endothelin receptor antagonist monotherapy in patients with reduced exercise capacity, defined as a 6MWD of <450 m.[22] There is a debate about whether mildly symptomatic patients with Eisenmenger syndrome and 6MWD >450 meters should be treated proactively with targeted PAH therapy.[23]

The registry by Haworth and Hislop showed higher mortality in the postoperative PH subset.[6] These observations highlight the need for careful evaluation of patients with large shunts with borderline operability before subjecting them to surgery. In patients with PH, identifying the primary etiology is crucial before labeling them as IPH. Abernethy malformation is a congenital porto-systemic shunt that can lead to PH.[24] This anomaly can be safely treated percutaneously in most children. Multiple studies have shown that PH is completely reversible after shunt closure in these patients.[25,26,27]

The median follow-up period in the present study was 13 months. During this follow-up period, three patients in the IPH group died. The 1-, 3-, and 5-year survival rates reported by Haworth and Hislop in the UK survival registry were 85.6%, 79.9%, and 71.9%, respectively.[6] In our study, the average survival time for IPH was 602.6 ± 90.8 days, and the survival rates for 3 months and 1 year were 91.7% and 80.2%, respectively. As compared with IPH, patients in APH had better functional class and survival. Two patients died in the latter group-one with BPD and another with pulmonary vein hypoplasia. There was no mortality in patients in the CHD-PAH group. The survival time was significantly different in IPH when compared with CHD-PAH (Log rank test P = 0.006). In APH, the underlying diagnosis defines the outcome and mortality. Although children with Eisenmenger syndrome did better in terms of functional class and early mortality compared to IPH, their long-term prognosis remains dismal, underlining the need for early detection and timely correction of CHD. The long-term results of IPH have improved compared to the past; however, the outcome remains poor, as indicated by recent data from the TOPP registry. During their analysis, 17.4% died, 3.7% each required lung transplantation and reverse Potts shunt, and 1.2% of children underwent atrial septostomy.[28] In the study by Bobhate et al., 10 patients with PH benefited from reverse Potts shunts, while 6 did not (4 of whom died). Older age, poor functional class, significantly decreased RV function on echocardiography, higher NT-pro-BNP values, elevated right atrial pressures, and lower cardiac index were predictors of poor outcomes in patients who did not benefit from a reverse Potts shunt.[11] Hence, ensuring correct risk stratification, identifying the primary etiology, individualizing therapy for each child, and performing timely palliative procedures are important considerations when managing these children. No patients underwent lung transplant in our study, as facilities are available at only a few centers, and there were affordability issues.

The underrepresentation of PH classes other than IPH and PH associated with CHD indicates the need to build awareness of PH among primary healthcare workers and pediatricians. The frequent coexistence of PH with other comorbidities necessitates a multidisciplinary approach to managing PH in children.

Limitations

This is a single-center, retrospective study with a small number of patients and a short follow-up duration. We did not have data on the dose of different pulmonary vasodilators. A high incidence of CHD-PAH can be a typical PH profile in LMIC; however, multi-center PH registries can provide actual statistics and further insights into the disease.

CONCLUSIONS

It is important to be aware of pediatric PH, which is a progressively fatal disease. Patients with IPH have poor long-term outcomes and a high risk of mortality. Identification of the primary etiology and timely interventions are crucial for determining the long-term outcome in these patients. Different centers across India may still face a higher proportion of unoperated CHD due to late referral, a limited number of specialized centers, and financial constraints. A large proportion of pediatric PH can be prevented if we can offer timely correction to children with CHD. However, older patients with large cardiac shunts need to be carefully evaluated before planning corrective surgery. In those with borderline operability, medical follow-up has a better prognosis compared to those with persistent post-operative PH after complete shunt closure.

Conflicts of interest

There are no conflicts of interest.

Funding Statement

Nil.