Anatomy of Congenital Heart Disease LesionsAssociated With Pulmonary ArterialHypertensionTodd L. Kiefer, MDAssistant ProfessorDivision of CardiologyDuke University Medical CenterDurham, NC

Thomas Bashore, MDProfessor of MedicineSenior Vice Chief, Division of CardiologyDuke University Medical CenterDurham, NC

Adult congenital heart disease represents a growing population of patients.Many patients survive to adulthood and lead functional, productive lives. Infact, there are more adults living with congenital heart disease than pediatricpatients. Many adult patients will have had prior surgical repair as children.However, some patients present in adulthood with a new diagnosis of congen-ital heart disease. Furthermore, there are a variety of complications associatedwith each individual congenital lesion and specific surgical repair procedure.

Pulmonary arterial hypertension (PAH) isone of the well-characterized sequelae. Itis particularly common with unrepairedlarge left to right shunt lesions that occurdistal to the tricuspid valve. Despite priorcardiac surgery, some patients have resid-ual defects that contribute to the develop-ment of PAH. The diagnosis of PAH re-quires right heart catheterization and isdefined as a mean pulmonary artery (PA)pressure greater than 25 mm Hg, with apulmonary capillary wedge pressure, leftatrial pressure, or left ventricular end-diastolic pressure less than 15 mm Hg,and a pulmonary vascular resistance(PVR) greater than 3 Wood units.1

It is estimated that overall 5%-10% ofpatients with congenital heart disease andas many as 30% of unrepaired patientshave PAH.2 When PAH does occur inconjunction with congenital heart disease,it is associated with increased morbidityand mortality.2,3 However, the outcomeand response to vasodilator therapies ismuch better for the cohort with congenitalheart disease than for all other etiologiesof PAH.1

The pathophysiology leading to the de-velopment of PAH in congenital heart dis-ease patients is related to increased pres-sure and blood flow in association with aleft to right shunt lesion. This scenario iscommon in a large, uncorrected ventricu-lar septal defect (VSD) or patent ductusarteriosus (PDA), and in surgically con-structed shunts where the pulmonary vas-culature is exposed to aortic systolic pres-sure. Alternatively, pre-tricuspid valve

shunts, which are low-pressure lesions as-sociated with increased volume circulat-ing through the right ventricle (RV) andpulmonary circulation, such as atrial sep-tal defects (ASD) and partial anomalouspulmonary venous return (PAPVR), leadto PAH much less often (Table).

Over time these shunt lesions lead todistinct changes in the pulmonary arteri-oles with the development of plexiformlesions and subsequent increases in PApressures and PVR. This often results inright ventricular dysfunction, and in somecases as the PA pressures increase, rever-sal of shunting from net left to right to netright to left occurs with notable cyanosisand the onset of Eisenmenger syndrome.One rationale for early surgical or percu-taneous repair of congenital cardiac dis-ease is to prevent the onset or avoid theprogression of PAH.

In this review, we will focus on theanatomy of the various congenital cardiaclesions that are associated with PAH.There are several congenital lesions thatproduce pulmonary venous hypertension,such as pulmonary veno-occlusive dis-ease, cor triatriatum sinister, mitral valveabnormalities, and other left-sided ob-structive lesions (coarctation of the aortaand supra-, sub-, and valvular aortic ste-nosis), but these lesions produce a differ-ent pathophysiology and will not be thefocus of this discussion.

A VSD is a common form of congenitalheart disease with an estimated preva-lence of 3 per 1000 in children and 0.3 per1000 adults, as some VSDs close sponta-

neously during childhood into adult-hood.4,5 It is also the most common con-genital cardiac lesion associated withPAH in a Dutch registry.6 There are mul-tiple types of VSDs depending on theirlocation: membranous or perimembra-nous, muscular, inlet and outlet varieties(doubly committed or infundibular) (Fig-ure 1). Often more than 1 defect in theventricular septum is present. Anatomi-cally, a membranous VSD is bordered bythe membranous portion of the ventricularseptum, the aortic valve, and the tricuspidvalve. In some cases, the septal leaflet ofthe tricuspid valve will cover this defectand form a “windsock” deformity withventricular systole. Often the windsock isfenestrated with left to right shunting ofblood from the left ventricle (LV) to theRV. At times, the septal tricuspid leafletcan fuse with the membranous ventricularseptum, leading to closure of the defectand obliteration of shunting.5 MuscularVSD, as the name suggests, is surroundedby myocardium and can be located any-where in the ventricular septum. There areoften multiple VSD sites in a given pa-tient. An inlet VSD is bordered by themitral valve, the tricuspid valve, and themuscular septum. Given this location, it isa part of the spectrum of the atrioventric-ular (AV) canal or AV septal defect, pre-viously referred to as endocardial cushiondefects, and is often associated with tri-somy 21 (Down syndrome). The inletVSD is most commonly associated withPAH, with nearly 40% of such patientsdeveloping PAH.6 Finally, an outlet VSD,also referred to as an infindibular, doublycommitted, or supracristal VSD with itlocation superior to the crista supraven-tricularis, is surrounded by ventricular

Key Words—atrial septal defects, congenital heart disease, Eisenmenger syndrome, patent ductusarteriosus, ventricular septal defectCorrespondence: thomas.bashore@duke.edu

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septum, aortic valve, and pulmonic valve.It is important to recognize that any typeof VSD may occur either in isolation orwith other congenital abnormalities.

The size of a VSD (small vs large) isclinically often estimated, especially inchildren, by the ratio of the diameter ofthe VSD to the diameter of the aorticannulus.7 Defects that are less than orequal to 25% of the diameter of the aorticannulus (usually less than 1 cm) are des-ignated as small, restrictive defects. Ingeneral, the smaller size limits flow andleft to right shunt magnitude. In this sce-nario, the development of PAH is muchless likely. Conversely, a large defect isdefined as having a diameter greater than75% of the diameter of the aortic annulus(usually greater than 1 cm). Given thelarger defect and lack of restriction toflow, the pulmonary arterial bed is ex-

posed to a greater degree of systemic LVsystolic pressure, and the subsequent de-velopment of PAH is much more com-mon.

Atrial septal defects are another com-mon form of congenital heart disease.However, PAH develops less commonly(10%) with this lesion than in post-tricuspid valve shunt lesions in which thepulmonary vascular bed is exposed tohigher pressures as well as the increasedshunt volume.8 Five subtypes of ASDhave been described: secundum (75%),primum (15%), and superior sinus veno-sus (10%) are the most common. Lesscommon are the unroofed coronary sinusand the inferior sinus venosus defect (Fig-ure 2).9 A secundum ASD is characterizedby a defect in the fossa ovalis region (gen-erally central region) of the atrial septum.The primum ASD involves the inferior

aspect of the atrial septum near the atrio-ventricular valves. If a concomitant inletVSD is present, then the defect is classi-fied as an AV septal defect (see previoussection on VSD subtypes). In addition, theprimum ASD is often associated with anabnormality in the anterior mitral valveleaflet termed a cleft mitral valve, whichis associated with varying degrees of mi-tral regurgitation. The sinus venosus ASDis divided into 2 anatomic subtypes: asuperior sinus venosus defect and an in-ferior sinus venosus defect. The superiorsinus venosus ASD involves a defect inthe superior aspect of the atrial septum atthe junction of the roof of the atria and theentrance of the superior vena cava into theright atrium (RA). A superior sinus veno-sus ASD is associated with greater than90% of cases with PAPVR of the rightupper pulmonary vein, which aberrantlydrains into the RA instead of the leftatrium. The inferior sinus venosus ASD isdefined by a defect in the interatrial sep-tum inferiorly near the junction with in-ferior vena cava.

Partial anomalous pulmonary venousreturn functions as a low-pressure, pre-tricuspid valve shunt lesion, which servesto volume load the RV and pulmonarycirculation in a similar manner to an ASD.It is also a rare lesion, with autopsy stud-ies demonstrating an incidence of 0.6%-0.8%.17,18 Likewise, in addition to thepreviously discussed association of supe-rior sinus venosus ASD and right upperpulmonary vein anomalous return, there isan association in 5%-10% of cases of se-cundum ASD with PAPVR.19 Anomalouspulmonary venous return also occurs at anincreased frequency in patients withTurner syndrome.

There are multiple variations ofPAPVR in terms of the anatomic locationof the vein and number of veins involvedand location of anomalous venousattachment/drainage. Anomalous veinsmay drain into the right atrium, left in-nominate vein, coronary sinus, superiorvena cava, or the inferior vena cava(Scimitar syndrome) (Figure 3). Giventhat PAPVR is an uncommon lesion, anaccurate population level estimate of as-sociation with PAH is not available. How-ever, multiple case reports have been pub-

Table: Risk for development of PAH with various shunt lesions

Low Risk Intermediate Risk High Risk

• Secundum ASD • Sinus venosus ASD • Large, unrestricted VSDor PDA

• Partial anomalous pulmonaryvenous return

• Cooley-Waterston shunt

• Small, restrictive VSD • Pott’s shunt• Primum ASD• AV septal defect

Figure 1: Anatomic locations of VSD subtypes.

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lished describing PAH due to PAPVR inthe absence of other congenital anomalies.The pathophysiology is similar to an iso-lated ASD, and thus a small percentage ofpatients with this pathology may developPAH.

A PDA is another post-tricuspid valve,high-pressure to low-pressure shunt lesionthat may lead to subsequent PAH. Anessential component of fetal circulationand physiology, the ductus arteriosus usu-ally closes during the first few days afterbirth. However, in some individuals theductus does not close and persists as acongenital PDA. This represents 5%-10%of all congenital abnormalities.10 Froman anatomic perspective, the fetal duc-tus arteriosus and persistent PDA are afunnel-like connection from the thoracicaorta to the main pulmonary artery. Thedevelopment of PAH is related to thesize of the PDA and the amount ofshunt. In some series, the PDA accountsfor 20% of cases of congenital heartdisease-related PAH.11

An aortopulmonary (AP) window is arare congenital abnormality that is similarto a PDA, but differs in anatomic location.It is an anatomic connection between theascending aorta and the main PA, and is

usually large and unrestricted in terms ofallowing high-pressure systemic flow intothe pulmonary vasculature. This facili-tates and accelerates the development ofPAH and often progression to Eisen-menger syndrome if not surgically cor-rected at an early age.

Truncus arteriosus is a rare type of con-

genital heart disease characterized by acommon great vessel originating from theheart and the PAs and coronaries arisingfrom the ascending vessel. There are 2classification systems, the system of Col-lett and Edwards12 and the Van Praaghand Van Praagh13 system used to describethe relationship between the aorta and thePA. A VSD is essentially universal. Thisform of congenital heart disease is alwaysdiagnosed shortly after birth and unre-paired leads to severe PAH and Eisen-menger physiology. In adults with priorsurgical repair for truncus arteriosus, re-sidual shunt may exist and lead to PAH.

Double-outlet right ventricle (DORV)is another rare expression of congenitalheart disease characterized by the originof both great vessels from the morpho-logic RV, along with a VSD to allowoxygenated systemic blood from the LV,albeit mixed with venous return in mostcases, to reach the aorta. Double-outletright ventricle represents a broad spec-trum of anatomy and pathophysiology de-pending on the location of the VSD inrelation to the great vessels (subaortic,subpulmonic, doubly committed, or re-mote).14 Furthermore, the clinical presen-tation may vary from that of an isolatedVSD, to transposition with a VSD, to te-tralogy of Fallot-like, to single-ventriclephysiology in the case of a remote VSD.

Figure 2: Anatomic locations of ASD subtypes.

Figure 3: Anatomic variants of partial anomalous pulmonary venous return.

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The subaortic subtype of DORV is mostcommon, accounting for approximately50% of cases.14 The subaortic DORVsubtype also has the strongest associationwith development of PAH given patho-physiology similar to a large VSD. Pul-monary arterial hypertension may also oc-cur in the unrepaired subpulmonic DORVsubtype if there is not RV outflow orpulmonary valve level obstruction to min-imize pulmonary blood flow. In one re-cent series from a database of patientswith adult congenital heart disease, 17%of patients with the diagnosis of DORVwere noted to have PAH.6

Some patients with congenital heartdisease have had a surgical shunt to in-crease flow into the pulmonary circuitwhen the congenital abnormality pre-vented adequate pulmonary perfusion.These are generally palliative shunts as abridge to complete surgical repair. Assuch, surgical shunts would often be li-gated or taken down at the time of subse-quent cardiac surgery. However, it is notuncommon to encounter an adult patientwith a patent surgical shunt. Through the1960s and 1970s, as surgical experiencewith congenital heart defects grew, it wasdiscovered that these palliative high-flow,high-pressure shunts that delivered sys-temic blood flow to the lungs commonlyresulted in PAH.

The first surgical shunt, referred to as aBlalock-Taussig (BT) shunt, was per-formed in 1944.20 The BT shunt was con-structed from connection of the right sub-clavian artery to the right PA (Figure 4).The original BT shunt evolved throughseveral modifications, including use of theleft side and a synthetic conduit (modifiedBlalock shunt) to connect the subclavianartery to the PA, which preserved the sub-clavian artery and circulation to the upperextremity along with control over flow tothe lung via diameter of the conduit.

Subsequently, Dr Willis Potts per-formed a surgical procedure connectingthe descending thoracic aorta to the leftPA, which became known as a Potts shunt(Figure 4).20 In a similar manner, Dr Da-vid Waterston devised a surgery wherebyan anastomosis between the posterior as-pect of the ascending aorta and the rightPA was created (Figure 4).20 This is com-

monly known as a Cooley-Waterston shunt.Less frequently used as a palliative shuntwas the central shunt, or a surgically createdequivalent of the congenital AP window, inwhich an anastomosis was made betweenthe ascending aorta and the main PA. ThePotts and Waterston surgical shunts have amuch stronger propensity to produce PAHthan the Blalock shunts due to less restric-tive flow into the PA from the aorta. For thatreason, they were abandoned in favor of theBlalock approach.

Eisenmenger syndrome is the end-stageresult of long-standing PAH. It has a prev-alence of approximately 8%-10% in pa-tients with congenital heart disease.21 Thepathophysiology involves the progressionof irreversible PVR to the point at whichPA pressures are greater than systemicaortic pressures and a shunt lesion thatwas originally left to right reverses indirection of blood flow right to left. Withthe onset of right to left shunting, cyanosisis apparent. In cases of a PDA, differentialcyanosis may be observed due to the an-atomic location of the shunt with cyanoticlower extremities and normal appearingupper extremities. Moreover, Eisen-menger syndrome is associated with a va-riety of other end-organ system complica-tions. Once PA systolic pressure and/orPVR is greater than two thirds of systemicvalues, and certainly when Eisenmengersyndrome with right to left shunting ispresent, surgical intervention to correctthe underlying cardiac pathology is gen-erally contraindicated.

In conclusion, several anatomic formsof congenital heart disease can lead toPAH. In particular, pressure and volumeloading left to right shunt lesions (post-tricuspid valve) in contradistinction toonly volume loading left to right shuntlesion (pre-tricuspid valve) are muchmore likely to cause PAH. From an epi-demiologic perspective, unrepaired VSDand PDA are 2 of the more common le-sions that will be complicated by pulmo-nary hypertension. The management ofpatients with congenital heart disease iscomplex, and pulmonary hypertension ex-perts should work closely with cardiolo-gists who have specialized training inadult congenital heart disease in order tooptimize outcomes for patients with PAHrelated to congenital heart disease.

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Figure 4: Anatomic locations of surgical palliative shunts.

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