Circulation: Heart Failure

AHA SCIENTIFIC STATEMENT

Pulmonary Hypertension in Congenital Heart

Disease: A Scientific Statement From the
American Heart Association
Pei-Ni Jone, MD, FAHA, Chair; D. Dunbar Ivy, MD, FAHA; Amanda Hauck, MD; Tara Karamlou, MD; Uyen Truong, MD;
Ryan D. Coleman, MD; Juan Pablo Sandoval, MD; María Jesús del Cerro Marín, MD; Pirooz Eghtesady, MD, PhD;
Kathryn Tillman, NP; Usha S. Krishnan, MD, FAHA, Vice Chair

ABSTRACT: Patients with pulmonary hypertension associated with congenital heart disease make up an increasing proportion
of the total pulmonary hypertension population who bring with them added complexity because of underlying anatomical
and hemodynamic abnormalities. Currently, no consensus recommendations are available on how to best manage this group
of patients for either the primary cardiologist or pulmonary hypertension subspecialist, including timing of referral. The
purposes of this document are (1) to describe the various pulmonary hypertension groups and subgroups associated with
congenital heart disease, (2) to describe imaging modalities used in patient evaluation, (3) to elucidate medical and surgical
management considerations, (4) to highlight disparities within this population, and (5) to identify gaps and future research
needs of patients with pulmonary hypertension associated with congenital heart disease.

Key Words: AHA Scientific Statements ◼ congenital heart disease ◼ pediatric pulmonary hypertension ◼ prognosis
◼ pulmonary arterial hypertension ◼ treatment
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P
ulmonary hypertension (PH) is now defined as mean
pulmonary artery pressure >20 mm Hg according to
the updated clinical classification from the 6th World
Symposium of Pulmonary Hypertension (WSPH) and
has many causes (Table 1).1 PH can be associated with
various forms of congenital heart disease and can pres-
ent at different ages, depending on the lesion. Pulmo-
nary arterial hypertension (PAH) is a specific subgroup
of PH characterized hemodynamically by the presence of
precapillary PH, including an end-expiratory pulmonary
artery wedge pressure ≤15 mm Hg and pulmonary vas-
cular resistance (PVR) ≥3 Wood units (WU).1 In children,
PVR is indexed as recommended by the pediatric con-
sensus task force.2 In children with complex congenital
heart disease, including univentricular heart, and those
with segmental PH or mixed group 1 and 2 PH, diag-
nosis and management of PH have to be tailored to the
individual patient’s unique anatomical and hemodynamic
condition. The incidence and prevalence of PAH associ-
ated with congenital heart disease were reported to be
2.2 and 15.6 per 1 million, respectively.3,4 The improve-
ments in diagnosis and management of congenital
heart disease have led to increased survival into adult-
hood. This improved survival is accompanied by a signifi-
cant number of associated cardiac sequelae, including
arrhythmias, postoperative valvar and vascular structural
defects, ventricular dysfunction, and PH.
Although expert guidelines are available for PH,
there is a relative lack of definitive levels of evidence
for the management of PH associated with congeni-
tal heart disease. These patients are typically under-
represented in or excluded from clinical studies and
therefore have been the focus of only a small number
of dedicated clinical trials. The limited prospective trial
data means that treatment strategies are often based
on the experience of clinical experts or on findings
from small single-center or unmatched retrospective
data and should be tailored to the individual patient’s
structural and hemodynamic issues. Management of
this cohort can be lesion-specific and can determine
whether the underlying congenital heart disease can
be safely repaired. The purposes of this document
are to review the various PH groups and subgroups
associated with congenital heart disease within the

© 2023 American Heart Association, Inc.

Circulation: Heart Failure is available at www.ahajournals.org/journal/circheartfailure

Circ Heart Fail. 2023;16:e00080. DOI: 10.1161/HHF.0000000000000080 July 2023 642

 Jone et al Pulmonary Hypertension in Congenital Heart Disease

Table 1. Updated Clinical Classification of PH

CLASSIFICATION OF PH ASSOCIATED
1. PAH
WITH CONGENITAL HEART DISEASE
 1.1 IPAH
The classification of PH has evolved to reflect the con-
 1.2 Heritable PAH
genital cardiac lesions important in pediatric PH.5,6 The
 1.3 Drug- and toxin-induced PAH
updated classification, from the 6th WSPH in 2018, modi-
 1.4 PAH associated with: fied both the definition of PH and the characterization of
  1.4.1 Connective tissue disease PH–congenital heart disease in patients with biventricular
  1.4.2 HIV infection and single-ventricle circulations.1,2,7 Four WSPH pathoge-
  1.4.3 Portal hypertension netic groups include forms of PH–congenital heart dis-
  1.4.4 Congenital heart disease ease: group 1, PAH; group 2, PH due to left heart disease;
  
1.4.5 Schistosomiasis group 4, PH with pulmonary artery obstructions; and group
 1.5 PAH long-term responders to calcium channel blockers
5, PH with unclear or multifactorial mechanisms, including
complex congenital heart disease (Figure). Each time the
 1.6 PAH with overt features of venous/capillaries (PVOD/PCH)
involvement classification has been updated, there has been increased
 1.7 Persistent PH of the newborn syndrome
recognition of the fact that congenital heart disease is
complex and cannot fit neatly into 1 group. Thus, although
2. PH due to left-sided heart disease
the 6th WSPH has taken a great leap in addressing this,
 2.1 PH due to heart failure with preserved LVEF
future classifications may include recognition that patients
 2.2 PH due to heart failure with reduced LVEF
can fit into >1 WSPH group and that individualized man-
 2.3 Valvular heart disease agement is vital. Patients may be in 1 group and over time
 2.4 Congenital/acquired cardiovascular conditions leading to may develop characteristics of a different group in the
postcapillary PH
classification compared with their initial presentation. Fur-
3. PH due to lung diseases or hypoxia, or both ther descriptions and diagnostic criteria for PH–congeni-
 3.1 Obstructive lung disease tal heart disease are included in Table 2.
 3.2 Restrictive lung disease Group 1 PAH includes associated PAH–congenital
 3.3 Other lung disease with mixed restrictive/obstructive pattern heart disease, with mean pulmonary artery pressure >20
 3.4 Hypoxia without lung disease mm Hg, pulmonary capillary wedge pressures ≤15 mm Hg,
and indexed PVR (PVRi) ≥3 WU∙m2 (mmHg/L/min/m2).
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 3.5 Developmental lung disorders

4. PH due to pulmonary artery obstructions
The pathophysiology of PAH–congenital heart disease is
variable and complex, affecting management decisions.8
 4.1 Chronic thromboembolic PH
In patients with large shunts, pulmonary vascular disease
 4.2 Other pulmonary artery obstructions
develops secondary to shear stress, endothelial damage,
  4.2.1 Sarcoma (high or intermediate grade) or angiosarcoma
smooth muscle proliferation, remodeling of the vascula-
  4.2.2 Other malignant tumors ture, and ultimately obliteration of the microvasculature,
  4.2.3 Nonmalignant tumors similar to idiopathic PAH (IPAH).2 Pulmonary vasocon-
  4.2.4 Arteritis without connective tissue disease striction is related to endothelial dysfunction, resulting in
  4.2.5 Congenital pulmonary artery stenosis an imbalance between vasodilators, for example, nitric
  
4.2.6 Parasites oxide and prostacyclin, and vasoconstrictors, including
5. PH with unclear or multifactorial mechanisms, or both endothelin-1, vascular endothelial growth factor, sero-
 5.1 Hematological disorders
tonin, and cytokines. At the cellular level, the endothe-
lium, smooth muscle cells, fibroblasts, inflammatory cells,
 5.2 Systemic and metabolic disorders
circulating progenitor endothelial cells, and platelets all
 5.3 Others
contribute to vascular remodeling.9–11 Awareness of the
 5.4 Complex congenital heart disease
role of genetic factors in PAH–congenital heart disease
IPAH indicates idiopathic pulmonary arterial hypertension; LVEF, left ventricular is increasing, with a number of genes being reported,
ejection fraction; PAH, pulmonary arterial hypertension; PCH, pulmonary capil-
lary hemangiomatous; PH, pulmonary hypertension; and PVOD, pulmonary veno- including BMPR2, SOX17, TBX4, and other rare inherited
occlusive disease. variants of NOTCH1, PTPN1, and RAF1, as well as other
Adapted with permission from Simonneau et al.1 Copyright © 2019 The Euro- genes with de novo variants.12,13 PAH–congenital heart
pean Respiratory Society.
disease (group 1.4.4) occurs in left-to-right shunt lesions
with 4 described clinical and hemodynamic profiles:
classification system, imaging modalities used to eval-
uate these patients, and pharmacological and surgical 1. Eisenmenger syndrome (ES) is clinically defined as
management considerations; to highlight disparities unrepaired, unrestrictive congenital heart disease
within this population; and to identify gaps and research in which severe elevation in PVR develops, result-
opportunities for future work. ing in reversal of shunt direction from systemic to

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 Jone et al
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Figure. Different subgroups of pulmonary hypertension in congenital heart disease.
HD indicates heart disease; and PAH, pulmonary arterial hypertension.
pulmonary to predominantly pulmonary to systemic.
The hallmark of ES is cyanosis with consequences
of chronic hypoxemia, including secondary erythro-
cytosis and multisystem involvement.14
2. Unrepaired moderate to large defects with mildly
to moderately elevated PVR with predominantly
left-to-right shunt form the second subgroup of
PAH–congenital heart disease. This group has
considerable heterogeneity in outcome, depending
on the severity and reversibility of vascular remod-
eling.6 Criteria for operability incorporating baseline
hemodynamics and response to acute vasodilator
testing have been proposed (Table 2).15,16 Patients
can be divided into those in whom congenital heart
disease is still possibly repairable (PVR <4 WU∙m2)
and those in whom congenital heart disease is
Circ Heart Fail. 2023;16:e00080. DOI: 10.1161/HHF.0000000000000080
Pulmonary Hypertension in Congenital Heart Disease
likely not repairable with physiology closer to
Eisenmenger physiology (when PVR >8 WU∙m2).2
A third group has an intermediate status (PVR,
4–8 WU∙m2) and should be considered for tar-
geted PH therapy with re-evaluation for operability
on an individual basis.2 Individual clinical charac-
teristics, including age, shunt location, associated
diagnoses, and saturations, must be considered
when determining appropriateness for intervention.
3. PAH with coincidental congenital heart disease
includes the subset of patients with small pretri-
cuspid or posttricuspid shunts associated with
PAH. These defects are considered coincidental
and not causative of the degree of PAH. These
patients have a clinical course and poor survival,
similar to patients with IPAH.2,17,18
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 Jone et al Pulmonary Hypertension in Congenital Heart Disease

Table 2. PH Associated With Congenital Heart Disease

Treatment/manage-
ment considerations/
PH group Description Hemodynamic criteria Examples gaps
Group 1
 PAH–congenital PAH associated with intracardiac and mPAP >20 mm Hg Pretricuspid shunt …
heart disease extracardiac shunt lesions PCWP or LAP ≤15 mm Hg ASD
PVR ≥3 WU∙m2 Partial AVSD
PAPVR
ES PVR ≥SVR …
TAPVR
Reversal from systemic-to-pulmonary shunt PVR generally >10 WU∙m2
Posttricuspid shunt
to bidirectional or reversed shunt Qp<Qs
VSD
Unrepaired congenital heart disease with PVR <4 WU∙m2, Rp/Rs <0.3  AVSD with large ventricular Upper limit of operability
prevalent left-to-right shunt PVR 4–8 WU∙m2, Rp/Rs component not well defined; no level
Repairable* 0.3–0.5 PDA of evidence available
Possibly repairable “gray zone”16 PVR >8 WU∙m2, Rp/Rs >0.5 Aortopulmonary window
Unrepairable Other
TGA
Coincidental congenital heart disease: Similar to IPAH …
Common arterial trunk
PAH out of proportion to defect size or de-
velopment sooner than explained by defect
PAH after surgical repair Similar to IPAH …
Persistent or recurrent PAH after surgery
without significant residual anatomic lesion
Group 2
 PH due to PH associated with elevated left atrial or Isolated postcapillary PH Pulmonary Use of pulmonary
left-sided heart PCWP PCWP or LAP ≥15 mm Hg Venous/LA obstruction vasodilators before repair
disease mPAP >20 mm Hg PVS is not recommended.
PVR <3 WU∙m2 Obstructed TAPVR Use of pulmonary
Supportive findings: Obstructed cor triatriatum vasodilators after repair
DPG <7 mm Hg Mitral stenosis may be beneficial, but
Combined precapillary and Elevated LVEDP associated data are inadequate.
postcapillary PH with congenital heart disease
mPAP >20 mm Hg Bicuspid aortic valve
PCWP or LAP ≥15 mm Hg Subaortic obstruction
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PVR ≥3 WU∙m2 Supravalvular AS

Supportive findings: Aortic arch obstruction
DPG ≥7 mm Hg
Group 4
 PH due to pul- Congenital pulmonary artery stenosis … … Use of pulmonary
monary artery vasodilators is frequently
obstructions ineffective.
Group 5
 PH due to Single ventricle with pulmonary PVR >3 WU∙m2 Single ventricle after Use of pulmonary vasodi-
unclear or hypertensive vascular disease after TPG (mPAP−PCWP)>6 bidirectional Glenn or Fontan lators may be beneficial
multifactorial cavopulmonary anastomosis mm Hg after the Glenn or Fontan
mechanisms procedure.
Segmental PH Segmental mPAP >20 mm Hg PA/VSD with MAPCAs Use of pulmonary
PH vascular disease of varying severity in Elevated segmental PVR, not Isolated (ductal origin) of PA vasodilators is frequently
different lung segments defined Hemitruncus ineffective because of
surgical shunt (Waterston, fixed obstruction in PA/
Potts) to a portion of pulmonary VSD.
vasculature
Large posttricuspid shunt with
branch PA stenosis
AS indicates aortic stenosis; ASD, atrial septal defect; AVSD, atrioventricular septal defect; DPG, diastolic pressure gradient; ES, Eisenmenger syndrome; IPAH, idio-
pathic pulmonary arterial hypertension; LA, left atrium; LAP, left atrial pressure; LVEDP, left ventricular end-diastolic pressure; MAPCA, major aortopulmonary collateral
artery; mPAP, mean pulmonary artery pressure; PA, pulmonary atresia; PAH, pulmonary arterial hypertension; PAPVR, partial anomalous pulmonary venous return; PCWP,
pulmonary capillary wedge pressure; PDA, patent ductus arteriosus; PH, pulmonary hypertension; PVR, pulmonary vascular resistance; PVS, pulmonary vein stenosis;
Qp, pulmonary flow; Qs, systemic flow; Rp, pulmonary resistance; Rs, systemic resistance; SVR, systemic vascular resistance; TAPVR, total anomalous pulmonary venous
return; TPG, transpulmonary gradient; TGA, transposition of the great arteries; VSD, ventricular septal defect; and WU, Wood unit.
*Operability criteria based on expert opinion incorporating patient age, type of defect, comorbidities, baseline, and exertional saturations without definitive evidence
for treat-and-repair strategy.

4. Persistent or recurrent PAH after surgical repair of this category. Although there are data on the use
congenital heart disease is associated with poor of vasoreactivity testing to determine operability,
prognosis.2,17,18 To date, there are no sufficiently these studies have not been proven sufficiently
reliable data to predict which patients will fall into reliable.17,18

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 Jone et al
In group 2 PH, left-sided heart disease is increasingly
recognized as a cause of PH in congenital heart disease
and may progressively develop over time.19 It occurs
in the setting of elevated pulmonary venous pressure,
resulting in a proportional elevation of precapillary pul-
monary artery pressure (isolated postcapillary PH) or PH
in excess of the pulmonary venous hypertension with
associated pulmonary vascular disease (PVR ≥3 WU∙m2),
referred to as combined precapillary and postcapillary
PH.1 Congenital cardiac lesions that belong to WSPH
group 2.4 include those that directly obstruct pulmonary
venous or left atrial flow and those that indirectly result
in left atrial hypertension due to elevated left ventricular
filling pressures (Table 2).2
Group 4.2.5 PH has been classified in the 6th WSPH
classification as a subgroup of PH due to pulmonary
artery obstructions. However, this rare subgroup of pedi-
atric patients has not been evaluated for the presence
of distal pulmonary vascular disease (as may be seen in
chronic thromboembolic PH), and their response to tar-
geted therapy has not been studied (Table 2).
Group 5.4 PH includes PH with unclear or multifacto-
rial mechanisms such as single-ventricle physiology, seg-
mental PH, and scimitar syndrome (Table 2).2
1. Functional single-ventricle circulation encom-
passes anatomical defects with an effective sin-
gle ventricular pump driving both systemic and
pulmonary circulations. Staged palliation, culmi-
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nating in the Fontan repair, directs caval return
directly to the pulmonary arteries, resulting in pas-
sive, nonpulsatile pulmonary blood flow requiring
an unobstructed pathway with low PVR. Patients
with nonpulsatile cavopulmonary flow can develop
microvascular remodeling that results in a failed
Fontan state, which affects survival.20 The PH diag-
nostic definition of mean pulmonary artery pressure
≥20 mm Hg is irrelevant in the Fontan circulation;
instead, pulmonary hypertensive vascular disease
for univentricular circulations is defined as a mean
transpulmonary gradient >6 mm Hg and an PVRi
>3 WU∙m2.21,22 Measurement of PVR is challenging
in this group because of additional sources of pul-
monary blood flow, residual antegrade pulmonary
flow, segmental pulmonary arterial stenoses, and
flow across the Fontan fenestrations.
2. Segmental PH occurs when different lung seg-
ments develop varying degrees of pulmonary
hypertensive vascular disease, with at least 1 seg-
ment of pulmonary vasculature remaining non-
hypertensive.23 There is often an aortic source of
pulmonary blood flow to a portion of the lungs, as
well as the presence of segmental branch pulmo-
nary artery stenosis or the presence of segmental
branch pulmonary artery stenosis, either alone or in
combination with other congenital heart defects.
Circ Heart Fail. 2023;16:e00080. DOI: 10.1161/HHF.0000000000000080
Pulmonary Hypertension in Congenital Heart Disease
3. Scimitar syndrome is a distinct form of partial
anomalous pulmonary venous drainage of right pul-
monary veins to the inferior vena cava with associ-
ated right lung hypoplasia and anomalous systemic
arterial supply to a portion of the right lung. PH can
develop as a result of variable mechanisms, includ-
ing associated congenital heart disease, excessive
pulmonary blood flow, systemic arterial supply of
pulmonary segments, obstructed pulmonary veins,
or their combination.24 Presentation in infancy with
pulmonary hypertensive vascular disease portends
a worse prognosis.25
It is important to recognize that many pediatric patients
may have multiple reasons for PH and simultaneously
have features of different PH groups, as seen in patients
with Down syndrome with PAH–congenital heart dis-
ease. Down syndrome is associated with lung hypoplasia
and alveolar simplification, which is complicated by other
comorbidities such as congenital heart disease, persis-
tent PH of the newborn, thyroid disease, sleep-disordered
breathing, and prematurity, and other vascular disorders
such as Moyamoya disease are common cotravelers.26,27
Biomarkers such as NT-proBNP (N-terminal pro-B-type
natriuretic peptide) and galectin-3 may help distinguish
between children with Down syndrome with and those
without PH.28 Genetic abnormalities in children may pre-
dispose to antiangiogenesis (COL18a1 [endostatin]), a
proinflammatory state (IFNAR1/2 [interferon α/β recep-
tors 1 and 2]), and lung disease, all contributing to PH.27
Future genetic studies will further our understanding of
the role of underlying molecular pathways compared
with physiologically induced mechanisms and their
potential overlap, which could in turn determine poten-
tial responses to therapies and thus lead to even further
modifications of classifications.
SCREENING AND DIAGNOSING PH–
CONGENITAL HEART DISEASE
Clinical Presentation and Initial Testing
Symptoms of PH in children are frequently subtle and may
delay the diagnosis of PAH–congenital heart disease. In
infants, poor feeding, tachypnea, tachycardia, and poor
growth are common. Syncope is rare in ES, but shortness
of breath is common.29 Physical signs may include a loud
split second heart sound, gallop, and holosystolic mur-
mur of tricuspid regurgitation. Edema of the face, hands,
ankles, and hepatomegaly is a later sign of right-sided
heart failure.30 Chest radiographs may provide clues to
the degree of shunting in children with associated PAH–
congenital heart disease. Congested vasculature is often
seen in large left-to-right intracardiac shunts. Oligemia
may be present in patients with restricted blood flow
such as those with ES. However, radiographic findings
July 2023 646
 Jone et al
do not always correlate with disease severity. Evidence
of right ventricular (RV) hypertrophy on ECG is present
in most children with PH. Some studies have suggested
that the specificity (69%) and positive predictive value
(67%) of ECG are low in children with a diagnosis of PH
by echocardiography.31 In a study of 456 children in the
TOPP registry (Tracking Outcomes and Practice in Pae-
diatric Pulmonary Hypertension) with catheterization-
proven PH, no child with PH had a normal chest x-ray,
ECG, and echocardiogram.32
Transthoracic Echocardiography
Transthoracic echocardiography is the first-line cardio-
vascular imaging modality for the diagnosis of PH. It is
the most accessible noninvasive tool used for routine
assessment33–40 and for serial follow-up of PH associ-
ated with congenital heart disease.41,42 Developments
in echocardiography have led to new insights into the
structure and function of the RV and its role in PH.43,44
Conventional echocardiography-based imaging includes
assessment of anatomy in 2 dimensions, hemodynamics
through Doppler echocardiography, and qualitative and
quantitative evaluation of RV and left ventricular func-
tion.35–37,41,45–47 Advanced echocardiography includes
evaluation of right-sided heart size and function, myocar-
dial mechanics, and estimated ratio of RV to pulmonary
arterial coupling.48–56 Table 3 shows the advantages and
limitations of each of echocardiographic techniques used
in pediatric PH. Different echocardiography parameters
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have been found in small studies to be useful in identify-
ing high-risk patients who are likely to develop adverse
clinical outcomes.51,61,67,69,70 Table 4 demonstrates the
echocardiographic views needed to obtain the qualitative
and quantitative parameters in pediatric PH associated
with congenital heart disease.
Cross-Sectional Imaging
Advancements in magnetic resonance imaging and
computed tomography have allowed high-resolution
evaluation and multiplanar reconstruction capabilities
in the diagnosis and screening of PH. Cross-sectional
imaging has become pivotal in consensus statements
on the care of adult and pediatric patients with PH.75,76
Underlying cardiovascular lesions can affect the severity
of PH. Thus, the ability to view structures simultaneously
in all 3 dimensions makes computed tomography/mag-
netic resonance imaging valuable in delineating complex
congenital heart disease, particularly in older patients
with limited acoustic windows. Both computed tomog-
raphy and magnetic resonance angiography can identify
extracardiac lesions such as patent ductus arteriosus
and pulmonary vein anomalies and stenoses. Hemody-
namic data, direction of intracardiac shunting and degree
of shunting, can be calculated from magnetic resonance
imaging phase-contrast imaging. Physiological sequelae,
including pulmonary artery dilation and pulmonary vascu-
lar pruning, are easily identified. Each modality has distinct
Circ Heart Fail. 2023;16:e00080. DOI: 10.1161/HHF.0000000000000080
Pulmonary Hypertension in Congenital Heart Disease
advantages and disadvantages (Table 5). Patients with
metallic prosthetic valves and implanted devices, includ-
ing pacemakers, may not be able to undergo magnetic
resonance imaging scanning because of either the pres-
ence of abandoned leads or metallic artifact obscuring
vital structures of interest. Gadolinium-based magnetic
resonance contrast has the rare risk of nephrogenic sys-
temic fibrosis seen with impaired renal function. Data
have emerged on concentration-dependent retention of
gadolinium in brains of patients who received repeated
gadolinium-based contrast.77,78 Clinical effects in children
are not yet known.
Cardiac Catheterization
Right- and left-sided heart catheterization is consid-
ered the gold standard for measuring hemodynamics
in patients with congenital heart disease and advanced
pulmonary vascular disease, especially to assess oper-
ability.22,79,80 Acute vasoreactivity testing is performed at
the time of catheterization and helps strategize treat-
ment for postoperative PH. When available, inhaled
nitric oxide (20–80 ppm) alone or in combination with
oxygen is considered the preferred agent for vasodila-
tor testing.79,81–83 It is safe and short acting and offers
a better pulmonary vasodilator effect than systemic
agents. However, nitric oxide is not always affordable
and thus is not readily available in all cardiac cath-
eterization laboratories, particularly in low- to middle-
income countries. Alternative vasodilator agents include
intravenous epoprostenol, adenosine, or inhaled vasodi-
lators such as iloprost, treprostinil, milrinone, and nitro-
glycerin.84–88 Acute vasoreactivity testing is considered
positive in patients with shunt lesions when there is a
PVRi/indexed systemic vascular resistance (Rp/Rs)
ratio <0.3 with an increase in pulmonary flow/systemic
flow (Qp/Qs) with inhaled nitric oxide.22,79,89 However,
no prospective studies have identified reliable baseline
hemodynamic or vasodilating test response cutoffs that
predict reversibility after cardiac correction. Cardiac
catheterization and accurate measurement of PVR
can be fraught with error, as described elegantly by
Viswanathan et al,90 and the results should be carefully
considered in patients with segmental perfusion abnor-
malities, streaming, lung disease, and airway issues, all
of which may alter the hemodynamics. Duct occlusion
to determine the feasibility of closure of patent duc-
tus arteriosus and fenestration occlusion in patients
with Fontan circulations are also performed to evaluate
hemodynamics before intervention. Some centers use
ratios of pulmonary artery to systemic artery diastolic
pressure to determine operability, but no large studies
are available to validate such an approach. Furthermore,
cardiac catheterization and the role of acute vasoreac-
tivity testing in persistent or recurrent PAH after repair
or in patients with single-ventricle physiology are less
clear and merit further evaluation.
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 Jone et al Pulmonary Hypertension in Congenital Heart Disease

Table 3. Echocardiographic Parameters Used at Diagnosis of PH and Follow-Up

Echo parameters Interpretation Advantage Limitations References

Echocardiographic parameters to qualitatively assess septal position
 Interventricular Mild, moderate, or severe to indicate the
septal flattening severity of pulmonary hypertension
 End-systolic RV/ >1 may indicate increased risk of adverse
LV ratio events in pediatric PH
 Eccentricity Eccentricity index=D2/D1 where
index D1=diameter 1 and D2=diameter 2
D2/D1>1.16 indicates the presence of PH
Echocardiographic parameters to access hemodynamics
 TR peak velocity RVSP=SPAP= 4(TR max)²+mean RA
(m/s) pressure (mRAP)
If TR velocity is >3m/s, PH may be
suspected.
 S/D ratio >1.4 indicates severity of PH and
increased risk of mortality
 Mean PAP mPAP=4 V(early peak pulmonary
(mm Hg) regurgitation velocity)²+RAP
 Diastolic PAP DPAP=4 V(end-diastolic pulmonary
(mm Hg) regurgitation velocity)²+RAP
 PAAT (ms) Abnormal PAAT values with z score <−2
SDs were predictive of PH.
Echocardiographic parameters to assess biventricular systolic function
 TAPSE (mm) Longitudinal systolic function
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Quick visual assessments when Qualitative 57,58
there is not adequate TR peak Can occur in systole and diastole,
velocity to estimate RVSP depending on pressure or volume overload
Poor validation with clinically relevant
measures
Easy to obtain clinically Cannot be used in patients with left- 59
to-right shunts
Easy to measure Cannot be measured when the LV is 52
obliterated
Easy to obtain 75% of TR is measurable 60
Modest correlation with systolic
pulmonary artery pressure
Easy to measure from TR velocity Requires the presence of defined TR 61
velocity in systole and diastole
Alignment of PR maybe better PR required for measurement 41,45
than TR Modest correlation with mean pulmonary
artery pressure
Alignment of PR maybe better PR required for measurement 41,45
than TR
Can easily be measured in all HR dependent 62,63
patients
Easy to obtain, impaired RV Single dimension, does not take into 64,65
systolic function when the account of the circumferential or radial
TAPSE is <2 SD of age-related function of the RV

value Alignment can be a problem.

Poor correlation with RV function and
survival
 RV TDI MPI Abnormal TDI MPI values indicate RV Can easily be measured in HR dependent 66
dysfunction. patients Angle dependent
 RV FAC (%) Decreased FAC (<35%) correlates with Clinically easy to obtain 2D image with slices of the heart that 66
decreased systolic function. does not take into account of the entire
right ventricle
Difficult to measure with suboptimal
images
 3D RV EF (%) Decreased RV EF (<45%) indicates Full volume data sets to evaluate Required breath holding for adequate 50,51
decreased RV function. for RV volumes and function volumes. Can be difficult even in
Accurate measurements of RV single-beat acquisitions when the
function and can be prognostic pediatric probe is too big.
in PH
 RV strain (%) RV free wall longitudinal strain decrease RV free wall longitudinal strain May not have adequate frame rate when 55,67
indicates decreased systolic RV function. maybe more sensitive in the HR is too high
detecting ventricular function
and is prognostic in PH
 LV EF (%) LV EF may be decreased in severe pulmo- Quantification of LV function Biplane Simpson’s may not be accurate 66
nary hypertension via RV-LV interaction because the LV is distorted in severe PH.
Echocardiographic parameters to assess right heart diastolic function
 RV TDI E’ (cm/s) <8cm/s may indicate increased risk of Can easily be measured in all HR dependent 68
mortality patients Angle dependent
RA function Evaluate RV diastolic function Evaluation of diastolic function Severe tricuspid valve regurgitation 69
εS=reservoir RA εS, RA εA, SRS, and atrial minimum makes the measurements unreliable.
εE=conduit volume predicted adverse clinical Normative pediatric data required
εA=pump outcomes.
DPAP indicates diastolic pulmonary arterial pressure; εA, pump function; εE, conduit function; EF, ejection fraction; εS, reservoir function; FAC, fractional area change;
HR, heart rate; LV, left ventricular; mPAP, mean pulmonary arterial pressure; MPI, myocardial performance index; mRAP, mean right atrial pressure; PAAT, pulmonary arte-
rial acceleration time; PAP, pulmonary arterial pressure; PH, pulmonary hypertension; RA, right atrial; RAP, right atrial pressure; RV, right ventricular; RVSP, right ventricle
systolic pressure; SPAP, systolic pulmonary arterial pressure; SRS, right atrial strain rate filling; TAPSE, tricuspid annular planar systolic excursion; TDI, tissue Doppler
imaging; 3D, 3-dimensional; TR, tricuspid regurgitation; 2D, 2-dimensional; and V, velocity.

Circ Heart Fail. 2023;16:e00080. DOI: 10.1161/HHF.0000000000000080 July 2023 648

 Jone et al Pulmonary Hypertension in Congenital Heart Disease

Table 4. Echocardiographic Views to Obtain Hemodynamic
and Functional Parameters in Patients With PH
Echo view Functional parameters
Doppler Parasternal short Pulmonary acceleration time/ejection time
axis Pulmonary regurgitation early and late
diastolic velocity
Apical 4 chamber TR severity (none, mild, moderate, severe)
TR peak velocity
MPI (tricuspid tissue Doppler)71
Systolic/diastolic duration ratio from TR
Doppler61
Tissue Doppler systolic and diastolic
velocities (tricuspid, septal, mitral)
RA Apical 4 chamber RA area, RA strain61
RV Apical 4 chamber Qualitative RV function (good, mildly/
moderately/severely depressed)
RV end diastolic and end-systolic
dimensions indexed for BSA (2D)
FAC percent
TAPSE with z score (M mode when
available, 2D)
RV strain (global and segmental)51,72,73
3D RV volumes and function50,51
LV Apical 2+4 LV EF (biplane Simpson or 5/6 area-length
chamber method)
LV eccentricity index57
LV strain (global)53
3D LV volumes and function66
Other Presence and severity of pericardial effusion
(none, small, moderate, large)74
EF indicates ejection fraction; FAC, fractional area of change; LV, left ventricle;
MPI, myocardial performance index; RA, right atrium; RV, right ventricle; TAPSE,
tricuspid annular planar systolic excursion; 3D, 3-dimensional; TR, tricuspid regur-
gitation; and 2D, 2-dimensional.
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relationship between surrogate markers and the effect of a
therapy. That is, surrogate markers may be associated with
a disease but not be part of the pathophysiology of the dis-
ease, may not be sensitive to the intervention, or are part
of a pathway that is not affected by the intervention. The
limitations of surrogates compared with clinically meaning-
ful outcomes, including quality of life and survival, must be
understood in order to interpret therapy response.
Pharmacotherapy
Pharmacotherapy is commonly used in the management
of PH–congenital heart disease, and hemodynamic stud-
ies demonstrating elevated PVR are usually performed
before initiation. Therapy requires an exact morphologi-
cal and functional diagnosis. The goals of therapy are to
improve hemodynamics and quality of life. Therapy can
be considered in context of specific treatment paradigms:
(1) treat to close, meaning lowering the PVR to facili-
tate safe repair; (2) treat after repair of the defect(s); (3)
improve quality of life in patients with ES; or (4) further
lower pulmonary artery pressures and PVR in patients
with pulmonary hypertensive vascular disease and Fon-
tan circulations to improve forward pulmonary artery flow.
For targeted PH therapy, 3 classes of drugs are avail-
able: (1) phosphodiesterase-5 inhibitors, (2) endothe-
lin receptor antagonists (ERAs), and (3) prostacyclins.
Phosphodiesterase-5 inhibitors such as sildenafil and
tadalafil are commonly used drugs shown to improve
both hemodynamics and exercise capacity in patients

with PAH–congenital heart disease,91 including those

Treatment
The rarity of death and transplantation in childhood has
necessitated the reliance on surrogate markers such as acute
change in pressure or resistance to understand responses
to therapy. Inherent to this approach is the uncertainty of the
with ES.92 Hemodynamic benefits have also been shown
in patients with univentricular circulation after cavopul-
monary anastomosis.93–95 ERAs are recommended in the
setting of congenital heart disease because endothe-
lin-1 has been shown to be a potent mediator of vascu-
lar constriction.96 Single-center clinical trials of bosentan

Table 5. Advantages and Disadvantages of Cardiac Magnetic Imaging and Cardiac Tomography

MRI CT
Advantages High-resolution imaging of intracardiac and extracardiac vascular anatomy High-resolution imaging of extracardiac vascular anatomy
Reference standard for ventricular size, mass, stroke volume, and EF Short imaging time minimizing sedation needs
High reproducibility for serial monitoring Delineation of pulmonary parenchyma
No exposure to ionizing radiation Multiplanar reconstruction to view structures in 3 dimensions
Multiplanar reconstruction to view structures in 3 dimensions simultaneously simultaneously
Not limited by body habitus or scar tissue Not limited by body habitus or scar tissue
Phase-contrast imaging allows evaluation of flow (antegrade and retrograde) Detection of segmental and subsegmental pulmonary embolism
across vascular structures Dual-energy CT scan quantifies lung perfusion
Detection of myocardial fibrosis Evaluation of pulmonary vasculature
Evaluation of the pericardium Evaluation of the pericardium
Disadvantages Long scan time Exposure to ionizing radiation
Need for breath holding Life-threatening reaction to iodinated contrast
Metallic prosthetic valves and implanted devices may cause
susceptibility artifact, obscuring anatomy
Requires electrocardiographic gating
Gadolinium-based contrast associated with rare nephrogenic systemic fibro-
sis seen with impaired renal function
Concentration-dependent retention of gadolinium in brains after
repeated gadolinium-based contrast
CT indicates computed tomography; EF, ejection fraction; and MRI, magnetic resonance imaging.

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 Jone et al
and ambrisentan but not macitentan have been shown
to be efficacious in improving hemodynamics in patients
with congenital heart disease and ES.97,98 Larger stud-
ies of ERAs are warranted. Patients on medical therapy
warrant interval monitoring with echocardiograms and
repeat hemodynamic evaluations, most often done 6
to 12 months after initiation of therapy and yearly once
established on therapy, although no current recommen-
dations are in place.
Nursing Considerations
Given the complexity of drug delivery, prescription man-
agement, and transition from inpatient to outpatient ther-
apy, a specialized team approach is critical for therapeutic
success. This is particularly true with multidrug therapies
and parenteral prostacyclins. Advanced practice profes-
sionals, nurses, and specialty pharmacies provide a vital
role in supporting patients with prostacyclin infusions.
These teams provide targeted education and expertise in
troubleshooting the challenges that patients often face,
including high-risk situations such as management during
a continuous prostacyclin infusion interruption with poten-
tial for “rebound” PH from line break or occlusion.99,100
Surgical Repair of Patients With PAH–Congenital
Heart Disease and Biventricular Circulations
For patients with PAH–congenital heart disease and
shunts, early repair and elimination of the shunt are para-
mount to reduce the overall burden of pulmonary vascular
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disease.101 Although there are no definitive data demon-
strating specific outcomes at specified PVR thresholds,
most pediatric guidelines suggest relatively safe closure
up to a PVRi <4 WU∙m2 and a PVR/systemic vascular
resistance ratio <0.3 to 0.5 with evidence of reactivity
with acute vasoreactivity testing.2 In patients who have a
PVRi between 4 and 8 WU∙m2 with limited or no reactiv-
ity, management of their pulmonary vascular disease with
pharmacotherapy and subsequent surveillance catheter-
izations demonstrating significant decrease in PVRi may
aid in surgical decision-making for possible partial or com-
plete shunt closure.18,102,103 Consideration of fenestrated
closures of defects to reduce Qp but still allow a decom-
pressive shunt if needed may also be considered in high-
risk populations. In adults in whom therapy is being used in
a treat-to-repair context, evidence is incomplete. In recent
European Respiratory Society/European Society of Car-
diology guidelines, patients with an atrial septal defect, a
PVR >5 WU∙m2, and a fall in PVR to <5 WU∙m2 after ther-
apy may undergo surgery, but an individualized approach is
required for patients with other defects.104 The long-term
outcome of such a strategy requires further investigation.
Surgical Repair/Palliation of PAH–Congenital Heart
Disease and Univentricular Circulations
For patients with univentricular circulations and a
requirement for passive pulmonary blood flow, current
recommendations are for next-stage palliation if the
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Pulmonary Hypertension in Congenital Heart Disease
PVRi is <3 WU∙m2 and the transpulmonary gradient
is <6 mm Hg and use of a fenestration in the Fontan
circuit to act as pop-off, especially in the early postop-
erative period.16 In a recent meta-analysis, both ERAs
and phosphodiesterase-5 inhibitors have been shown
to lower the PVR of patients with Fontan physiology, to
reduce New York Heart Association functional class, to
increase 6-minute walk distance, and to improve peak
oxygen consumption; however, no significant change
was observed in mortality.93,104 Although both ERAs and
phosphodiesterase-5 inhibitors are often used in this
particular cohort to lower PVR, a paucity of data demon-
strating true efficacy remains.
Palliation of PAH–Congenital Heart Disease
Through Pulmonary-to-Systemic (Reversed Potts
Shunt) Shunt Creation
Creation of a pulmonary-to-systemic shunt (reversed
Potts shunt) through either a surgical or an interventional
catheterization approach has been increasingly used in
patients with suprasystemic pulmonary artery pressures
and progressive RV dysfunction despite pharmacother-
apy.105–108 Such a strategy is of value in patients with PAH
after surgical correction of congenital heart disease in
the setting of failure of maximal medical therapy. Recent
results from an international registry published by Grady et
al108 have demonstrated successful palliation of patients
with this approach, with improvement in exercise parame-
ters and World Health Organization functional status and a
decrease in pharmacotherapy burden, which may facilitate
weaning of parenteral prostanoids. Whether lung trans-
plantation is advisable after a Potts shunt and whether a
Potts shunt should precede continuous prostacyclin ther-
apy remain controversial. The presence of a Potts shunt
may complicate a subsequent lung transplantation.
Lung Transplantation
In patients with severe PAH–congenital heart disease
after repair or in those with insignificant shunts, the clini-
cal course is similar to that for IPAH, and transplantation
evaluation is appropriate along with maximal medical
therapy. Expected survival for a patient with ES com-
pared with survival after lung transplantation should
be seriously considered before the patient is listed for
transplantation. In patients with PAH with progressive
right-sided heart failure and associated end-organ injury,
posttransplantation mortality is significantly higher and
often requires extracorporeal membrane oxygenation
support as a bridge to recovery or lung transplantation.
Therefore, eligible patients in World Health Organization
functional class IIIb and IV should have timely discus-
sions of end-stage goals and be referred for transplan-
tation evaluation.
Double-lung transplantation is the most common
consideration for patients with congenital heart disease
and end-stage PH and offers shorter wait-list times
and improved organ use compared with heart-lung
July 2023 650
 Jone et al
transplantation. Patients with ES associated with atrial
or ventricular septal defect or patent ductus arteriosus
can undergo double-lung transplantation combined with
repair of these cardiac defects.109
Heart-Lung Transplantation
Although overall technically easier than double-lung
transplantation, heart-lung transplantation prevalence
among patients with congenital heart disease has
declined significantly worldwide over the past decade
because of the success of double-lung transplantation in
conjunction with aggressive treatment of early RV dys-
function.110,111 Conditions for which heart-lung transplan-
tation is the best option include ES in conjunction with
severely compromised RV or left ventricular function or
complex PH–congenital heart disease and associated
pulmonary vein stenosis.
Transplantation Outcomes
Overall, early survival (eg, perioperative or 3 month)
outcomes for patients with PAH are the lowest among
all lung transplant recipients, with higher posttrans-
plantation mortality after bridging with extracorporeal
membrane oxygenation. However, 5- and 10-year
survival rates are similar to rates for those with trans-
plantation for other pathogeneses.112 However, 1-year
survival for transplant recipients for PAH is significantly
better than survival for transplant recipients with pri-
mary lung disease.
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SOCIAL DETERMINANTS OF HEALTH IN
PH–CONGENITAL HEART DISEASE
An analysis of the PPHNet registry (Pediatric Pulmo-
nary Hypertension Network) found significant racial
variability in the prevalence of PH subtypes and survival
in children with PH.113 Karamlou et al114 elucidated the
interaction between Black race and neonatal age: Black
neonates admitted for congenital heart disease care had
better survival but longer length of hospital stay than
neonates from other ethnicities and races, suggesting
that modification of inpatient processes may mitigate
risk.114–116 Current literature highlights the following
inequalities: (1) People of color and lower socioeco-
nomic status are associated with a higher incidence of
cardiovascular death; (2) 42% of the US population in
2020 belonged to underrepresented races and ethnici-
ties; and (3) survival in PAH is dependent on both early
diagnosis and early institution of therapy.117–119 Despite
these potential precipitants, research to further elucidate
the relationship between health disparities and PAH is
challenged because clinical registries and trials have
not traditionally had adequate representation of racial
and ethnic and socioeconomically fragile populations.
In addition, socioeconomic and geographic barriers and
social determinants of health can disproportionally affect
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Pulmonary Hypertension in Congenital Heart Disease
underrepresented racial and ethnic groups’ access to
and safe provision of medically indicated advanced care,
including heart transplantation and heart-lung transplan-
tation. When possible, these factors must be addressed
to promote equitable delivery of care. Availability of sub-
specialty care will continue to affect patients in parts of
the world where advanced medical, surgical, and trans-
plantation therapies are unavailable.117,120
PROGNOSIS
The prognosis for patients with PH can vary significantly,
both between those with PH with different WSPH
classifications and between those within the same
classification category. Nevertheless, for any subgroup,
prognosis is also greatly influenced by socioeconomic
factors, general medical care, access to PH treatment,
availability of medications, use of combination ther-
apy, and partial or total repair after the PH diagnosis.
Addressing those patients with PH–congenital heart
disease specifically, van Loon and colleagues19 nicely
demonstrated that patients with PH–congenital heart
disease tend to have better outcomes than patients
with idiopathic PH (1-, 3-, and 5-year survival rates
of 73%, 63%, and 60% versus 62%, 50%, and 46%).
Of particular interest within the van Loon et al data
was the demonstration that a subgroup of infants with
posttricuspid shunts had worse survival than those with
IPAH. Children with concurrent genetic syndromes and
congenital heart disease also were at risk for acceler-
ated development of pulmonary vascular disease and
worse outcomes. Current registry studies are ongo-
ing to look at prognosis for pediatric patients with PH.
Patients with ES are known to have better survival than
those with unrepaired congenital heart disease who
do not develop traditional Eisenmenger physiology or
those who undergo shunt closure but have continued
evidence of pulmonary vascular disease.18,19,102,121,122
Prognostic factors for worse outcomes in patients with
ES include complex heart defects,123 increasing age,
pretricuspid shunt, oxygen saturation at rest, presence
of sinus rhythm, elevated NT-proBNP, and presence of
pericardial effusion.
Patients with coincidental shunt have shown out-
comes similar to those of patients with IPAH, whereas
patients with unrestricted, predominant left-to-right
shunt, and high PVR have the best prognosis.124 In this
last group of patients, because there are not enough
data on the long-term impact of defect closure, the bet-
ter prognosis in this subgroup should be kept in mind
when considering the operability of these patients, in
whom outcome may worsen if PH persists or recurs
after defect closure. The patient’s age and comor-
bidities, exercise-induced desaturation, and response
during vasoreactivity testing; the center experience;
the availability of PH therapy after surgery; and the
July 2023 651
 Jone et al Pulmonary Hypertension in Congenital Heart Disease

genetic background all influence outcomes. Although
some published cases and short series have raised the
option of the so-called treat-and-repair strategy,18,102,103
large series with long-term follow-up are still needed to
provide criteria to select the patients who benefit most
from this strategy.
FUTURE DIRECTIONS AND RESEARCH
Multiple opportunities exist to improve the care of patients
with PH–congenital heart disease. From imaging to tai-
lored pharmacotherapy strategies based on anatomical
lesion, the possibilities are limitless. For example, patients
would benefit from the development of an echocardiog-
raphy score that could reduce the number of cardiac
catheterizations needed in a lifetime to guide disease
management. Improvements in cross-sectional cardiac
imaging to refine the evaluation of flow in the pulmo-
nary bed and to assess PVR could serve a similar role.
In addition, targeted application of artificial intelligence
in cardiac imaging could drive the synthesizing of multi-
modality data into meaningful analytics to inform patient
management.
With early diagnosis and management of simple
congenital heart disease and prolonged survival of
individuals with complex congenital heart disease, the
paradigm of PH–congenital heart disease has shifted
toward more complex adult patients whose survival is
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these trials have yet to include patients with complex
congenital heart disease and those with PH after shunt
closure. In patients with PH after shunt closure or those
with smaller incident shunts, the use of a reversed Potts
shunt seems a promising alternative to improve quality
of life and survival.108,128 Last, ambulatory extracorporeal
membrane oxygenation as a bridge to recovery in preg-
nant patients with ES before delivery and other adult
patients with PH–congenital heart disease as a bridge
to recovery or lung transplantation may improve overall
survival.129,130
CONCLUSIONS
PH–congenital heart disease in its various forms car-
ries strikingly different management strategies, is
increasingly recognized as a particularly challenging
type of PH to manage, and requires nuanced, expert
management to improve survival. However, much
remains unknown about these patients, from the incit-
ing pathophysiology to their optimal management. Ulti-
mately, understanding the cause and pathophysiology
of PH in congenital heart disease within the various
subgroups will allow targeted drug development and
effective treatment strategies. Although great strides
have been made in the management of patients with
PH in general, as well as those with PH–congenital
heart disease, significant gaps remain that demand tar-

similar to that of patients with IPAH and worse than
that of patients with ES. New insights from randomized
controlled trials using medications for ES have shown
variable but primarily positive results with improvement
in 6-minute walk distance and PVRi.97,125–127 However,
geted research endeavors. Sustained and committed
multidisciplinary collaboration remains key to reducing
the global medical burden caused by pulmonary vascu-
lar disease associated with congenital heart disease,
the most preventable cause of PH.

Disclosures
Writing Group Disclosures
Writing Other Speakers’ Consultant/
group research bureau/ Expert Ownership advisory
member Employment Research grant support honoraria witness interest board Other
Pei-Ni Jone Lurie Children’s None None None None None None None
Hospital
Usha S. Columbia University Janssen-Actelion None None None None None None
Krishnan Medical Center/New (CUIMC receives
York Presbyterian funding; she has no
Hospital financial benefit. PI for
sponsored research)*;
United Therapeutics
(CUIMC receives fund-
ing; she has no finan-
cial benefit. PI for the
sponsored research)*
Ryan D. Texas Children’s Hos- None None None None None None None
Coleman pital, Baylor College
of Medicine
María Hospital Universita- None None Janssen* None None Ferrer* None
Jesús del rio Ramon y Cajal
Cerro Marín (Spain)

(Continued )

Circ Heart Fail. 2023;16:e00080. DOI: 10.1161/HHF.0000000000000080 July 2023 652

 Jone et al Pulmonary Hypertension in Congenital Heart Disease

Writing Group Disclosures Continued

Writing Other Speakers’ Consultant/
group research bureau/ Expert Ownership advisory
member Employment Research grant support honoraria witness interest board Other
Pirooz Washington Uni- None None None None None None None
Eghtesady versity School of
Medicine
Amanda Ann & Robert Lurie None None None None None None None
Hauck Children’s Hospital of
Chicago, Northwestern
University
D. Dunbar University of Colo- Janssen†; Bayer*; None None None None Janssen (un- None
Ivy rado Health Sciences FDA† (all funds go to paid)*; Merck-
Center institution) Acceleron
(unpaid)*; Gos-
samer Bio
(unpaid)*; GSK
(unpaid)*; Alta-
vant (unpaid)*;
Association
of Pediatric
Pulmonary Hy-
pertension*
Tara Karam- Cleveland Clinic None None None None None Edwards Life- None
lou Foundation sciences*
Juan Pablo Ignacio Chavez None None None None None None None
Sandoval National Institute of
Cardiology (Mexico)
Kathryn Till- Medical College None None None None None None None
man of Wisconsin-
Children's Wisconsin
Uyen Truong Children's National None None None None None None None
Hospital Washington
D.C.
Downloaded from http://ahajournals.org by on December 1, 2023

This table represents the relationships of writing group members that may be perceived as actual or reasonably perceived conflicts of interest as reported on the
Disclosure Questionnaire, which all members of the writing group are required to complete and submit. A relationship is considered to be “significant” if (a) the person
receives $5000 or more during any 12-month period, or 5% or more of the person’s gross income; or (b) the person owns 5% or more of the voting stock or share of the
entity, or owns $5000 or more of the fair market value of the entity. A relationship is considered to be “modest” if it is less than “significant” under the preceding definition.
*Modest.
†Significant.

Reviewer Disclosures
Other Speakers’ Consultant/
Research research bureau/ Expert Ownership advisory
Reviewer Employment grant support honoraria witness interest board Other
Catherine Children’s Hospital of Philadelphia/ None None None None None None None
Avitabile University of Pennsylvania
Martin Division of Pediatric Cardiology, None None None None None None None
Koesten- Department of Pediatrics, Grown-
berger Up Congenital Heart Disease Unit,
Medical University Graz (Austria)
Shahin Great Ormond Street Hospital for None None None None None None None
Moledina Children NHS Foundation Trust
(United Kingdom)
Rohit Rao UCSD None None None None None None None
Dietmar Pediatric Heart Center, None None None None None None None
Schranz Johann-Wolfgang-Goethe
University Clinic (Germany)
This table represents the relationships of reviewers that may be perceived as actual or reasonably perceived conflicts of interest as reported on the Disclosure Ques-
tionnaire, which all reviewers are required to complete and submit. A relationship is considered to be “significant” if (a) the person receives $5000 or more during any
12-month period, or 5% or more of the person’s gross income; or (b) the person owns 5% or more of the voting stock or share of the entity, or owns $5000 or more of
the fair market value of the entity. A relationship is considered to be “modest” if it is less than “significant” under the preceding definition.

Circ Heart Fail. 2023;16:e00080. DOI: 10.1161/HHF.0000000000000080 July 2023 653

 Jone et al
ARTICLE INFORMATION
The American Heart Association makes every effort to avoid any actual or poten-
tial conflicts of interest that may arise as a result of an outside relationship or a
personal, professional, or business interest of a member of the writing panel. Spe-
cifically, all members of the writing group are required to complete and submit a
Disclosure Questionnaire showing all such relationships that might be perceived
as real or potential conflicts of interest.
This statement was approved by the American Heart Association Science Ad-
visory and Coordinating Committee on March 14, 2023, and the American Heart
Association Executive Committee on April 4, 2023. A copy of the document is
available at https://professional.heart.org/statements by using either “Search for
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reprints, call 215-356-2721 or email Meredith.Edelman@wolterskluwer.com.
The American Heart Association requests that this document be cited as follows:
Jone P-N, Ivy DD, Hauck A, Karamlou T, Truong U, Coleman RD, Sandoval JP, del
Cerro Marín MJ, Eghtesady P, Tillman K, Krishnan US; on behalf of the American
Heart Association Congenital Cardiac Defect Committee of the Council on Lifelong
Congenital Heart Disease and Heart Health in the Young; Council on Cardiopulmo-
nary, Critical Care, Perioperative and Resuscitation; Council on Cardiovascular and
Stroke Nursing; Council on Cardiovascular Surgery and Anesthesia; Council on Clini-
cal Cardiology; and Council on Peripheral Vascular Disease. Pulmonary hypertension
in congenital heart disease: a scientific statement from the American Heart Asso-
ciation. Circ Heart Fail. 2023;16:e00080. doi: 10.1161/HHF.0000000000000080
The expert peer review of AHA-commissioned documents (eg, scientific
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