cc no adulto ii

Pathophysiology of Congenital Heart Disease in theAdult, Part II

Simple Obstructive Lesions

John F. Rhodes, MD; Ziyad M. Hijazi, MD, MPH; Robert J. Sommer, MD

With the successes in cardiothoracic surgery over thepast 3 decades, adults with congenital heart disease

(CHD) outnumber, for the first time, their pediatric counter-parts.1,2 As a result, adult patients with CHD are beginning toappear more frequently in the practices of adult cardiologists.This series is designed to provide a review of the pathophys-iology and natural history of common congenital heartproblems that are now being seen by adult cardiologists. Inthe first part, simple shunt lesions were reviewed. Thissection will examine the physiology and natural history ofsome of the more common congenital obstructive lesions thatmay be seen by adult cardiologists, as well as indications forintervention. Principally, these lesions will include ventricu-lar outflow obstructions that may or may not have undergoneprior intervention. Congenital obstructions of systemic andpulmonary venous return, congenital intra-atrial obstructions,and congenital atrioventricular valve stenosis will not beincluded in this review because they are far less common andpresent clinically predominantly in childhood.

Congenital Obstructive LesionsIn the normal circulation, the ventricular outflow tracts,semilunar valves, and great arteries present no obstruction toflow. Congenital narrowing of any of these pathways in-creases ventricular afterload and in more distal lesions causesmaldistribution of flow (see individual defects below). Inresponse to the increased afterload, physiological ventricularhypertrophy occurs, which results in thicker chamber walls,reduced chamber compliance, and higher filling pressures inthe atrium. With severe noncompliance (diastolic dysfunc-tion) venous congestion may occur, with exertion or even atrest, which limits cardiac output and physical activity in thispopulation. A reduced stroke volume may also be a directconsequence of increased afterload and may be particularlyimportant in the face of increased demands.

All patients with hemodynamically significant obstructionsof large ventriculoarterial pathways will present with a heartmurmur, the result of the turbulent flow created as blood

passes, under pressure, through the stenosis. For lesions of theoutflow tracts, valves, and proximal great arteries, echocar-diography generally remains the diagnostic modality of choiceto establish both the site and the severity of the obstruction.Magnetic resonance imaging (MRI) and computed tomogra-phy are superior for imaging the more distal anatomy of theaortic arch and the branch pulmonary arteries (PAs).

Symptoms, in general, are related to the severity ofobstruction. The pressure gradient across the lesion reflectsthe degree of obstruction, as estimated either by Doppler orby MRI techniques or as measured directly in the catheter-ization laboratory; however, this value cannot be used inisolation. The pressure drop is a reflection of both the degreeof pathway narrowing and the amount of flow across thenarrowed portion (Ohm’s law: pressure�flow�resistance).The degree of obstruction could be underestimated signifi-cantly by the pressure gradient alone, for example, in a patientwith low cardiac output or in a patient with a shunt lesion thatremoves blood from a chamber proximal to the obstruction.Similarly, small resting gradients may increase substantiallywith exercise or any other state that produces a physiologicalincrease in flow across the lesion.

Conditions With Increased RightVentricular Afterload

Congenital obstruction may occur in the outlet portion of theright ventricle (RV) proximal to the pulmonary valve (sub-valvar stenosis), at the valve itself (valvar pulmonary steno-sis), distal to the valve in the main pulmonary artery (MPA;supravalvar stenosis), or more peripherally in the branch PAs.In the absence of left-sided disease, PA pressure is normaldistal to the obstructive lesion. With increased afterload, theRV hypertrophies, and right atrial filling pressures rise. Mildproximal obstructions and isolated distal lesions are toleratedeasily without symptoms. In more severe cases in which thereis RV noncompliance but normal systolic performance, pa-tients are well at rest but may experience substantial increasesin right atrial filling pressures with transient venous conges-

From the Department of Pediatrics, Division of Pediatric Cardiology, Duke University Medical Center, Durham, NC (J.F.R.); Department of Pediatricsand Medicine, Rush Center for Congenital and Structural Heart Disease, Rush University Medical Center, Chicago, Ill (Z.M.H.); and Center forInterventional Vascular Therapy, Cardiovascular Research Foundation, Columbia University Medical Center, New York, NY (R.J.S.).

This article is Part II in a 3-part series. Part I appeared in the February 26, 2008, issue and part III will appear in the March 11, 2008, issue ofCirculation.

Correspondence to Robert J. Sommer, MD, Director, Invasive Adult Congenital Heart Disease, Assistant Professor of Clinical Medicine and Pediatrics,Cardiovascular Research Foundation, Columbia University Medical Center, 161 Fort Washington Ave, HIP 522, New York, NY 10032.

(Circulation. 2008;117:1228-1237.)© 2008 American Heart Association, Inc.

Circulation is available at http://circ.ahajournals.org DOI: 10.1161/CIRCULATIONAHA.107.742072

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Special Report

tion as flow through the right heart increases with exertion. Atthat point, pulmonary blood flow can be increased no further,the left ventricle (LV) will become relatively preload re-duced, and systemic cardiac output will be limited. In caseswith even more severe obstruction, critical afterload eleva-tions may lead to RV myocardial systolic dysfunction, whichcreates the usual picture of “right heart failure” with hepaticcongestion, jugular venous distension, ascites, and peripheraledema. Ischemia may contribute to exercise intolerance. Withsignificant RV hypertrophy, myocardial oxygen requirementsare increased, whereas high intraventricular diastolic pres-sures may impair perfusion of the RV myocardium. In severecases, ventricular arrhythmia, syncope, and sudden cardiacdeath may be seen.

Subvalvar Pulmonary Stenosis in Adults

Natural History and PhysiologyObstruction within the RV outflow tract is rare in isolation.Most often, isolated subvalvar pulmonary obstruction inadults is a residuum of earlier surgical intervention (ie, fortetralogy of Fallot), but it can be seen in adult patients withCHD who have not undergone surgery.

Severe subvalvar obstruction can present de novo in adultswith a double-chambered RV. In the double-chambered RV,a muscular band obstructs the RV outflow tract, dividing thechamber into a high-pressure inflow portion (proximal tothe obstruction) and a low-pressure outflow chamber (dis-tal). The diagnosis presents most frequently in childhood as acomplex that includes the subvalvar muscular obstruction anda perimembranous ventricular septal defect.3 Membranoussubaortic stenosis will also be present in a small percentage ofpatients. When the subpulmonary obstruction is relativelymild, the child presents with an asymptomatic heart murmur;however, as patients with a double-chambered RV age, thedegree of muscular obstruction tends to progress, whereas theventricular septal defect often closes spontaneously.4 Forpatients with access to regular medical care, the harsh systolicmurmur associated with the outflow obstruction should bringthem to attention long before the increasing afterload reachescritical levels. However, if not diagnosed previously, thesepatients may present with exercise intolerance as youngadults due to RV systolic or diastolic dysfunction. With moresevere obstruction and hypertrophy, ventricular arrhythmia,syncope, and sudden cardiac death may be the first presentingsign.

Indications for InterventionPatients with clinical symptoms, patients with RV systolicpressures approaching that of the aortic pressure, and thosewith global RV hypertrophy, especially with reduced systolicfunction, should be considered for intervention. RV outflowobstruction can be assessed by Doppler (transthoracic echo-cardiography usually gives superior angles of interrogationcompared with transesophageal echocardiography), by MRI,or by diagnostic catheterization. In the catheterization labo-ratory, an end-hole catheter pulled back from the PA acrossthe obstruction yields a typical tracing (Figure 1) that local-izes the obstruction within the ventricle.

Surgical muscle resection with or without patching of theoutflow tract remains the standard of care,5 although medicalmanagement can be useful in alleviating presenting symp-toms. Patients respond both to increasing intravascular vol-ume to dilate the outlet pathway and to a reduction inventricular contractility with �-blockers or calcium channelblockers. Diuretics and afterload-reducing agents are contra-indicated in this population. Although a number of pediatriccase reports involve the use of angioplasty to palliate subval-var pulmonary obstruction,6,7 no evidence exists that such anintervention is beneficial in the adult with severe muscularhypertrophy.

Valvar Pulmonary Stenosis

Natural History and PhysiologyIsolated valvar pulmonary stenosis is present in 8% to 10% ofpatients with CHD.8 In the Second Natural History Study ofcongenital heart defects,9 patients with mild degrees of obstruc-tion (�30 mm Hg peak-to-peak gradient at catheterization)who did not undergo surgery had a course that was indistin-guishable from a control group with respect to survival,symptoms, and need for therapy. More severe obstructivegradients increase RV afterload and lead to chamber hyper-trophy. As noted above, symptomatic patients tend to presentwith symptoms of exercise intolerance. The occurrence ofsymptoms and serious dysrhythmic events is generally relatedto the peak-to-peak gradient across the valve.9 Interestingly,we, and others,10 have observed that moderate valvar gradi-ents, which may be very well tolerated in children, appear to

Figure 1. A, Pullback from MPA to RV inflow in a patient withdouble-chamber RV. On pullback from MPA to RV (second tothird beat), no systolic gradient is present, although the diastolicpressure falls, which indicates entrance into the ventricle. Onfurther catheter withdrawal, a large gradient is present within thebody of the ventricle (fourth to fifth beat). A pullback in a patientwith subvalvar aortic obstruction would have a mirror-imagetracing. B, Angiographic image of the subvalvar obstruction inthe RV (arrows) in a patient with double-chamber RV. RVOTindicates RV outflow tract.

Rhodes et al Pathophysiology of CHD, Part II 1229

become more important clinically with aging in adults. Thismay be due to the normal ventricular myocardial stiffeningfrequently associated with aging. Changes in inherent com-pliance in addition to the long-standing afterload may lead toeven higher RV filling pressures and more readily to venouscongestion.

Indications for InterventionPatients with clinical symptoms, patients with RV systolicpressures approaching that of the aortic pressure, and thosewith global RV hypertrophy, especially with reduced systolicfunction, should be considered for intervention (Figure 2).Balloon valvuloplasty has supplanted surgical valvotomy asthe treatment of choice for valvar pulmonary stenosis sincethe early 1980s. In the Second Natural History Study,9 97%of 210 patients who underwent surgical valvotomy for pul-monary valve stenosis were in New York Heart Associationclass I at 25 years of follow-up, but 85% had some degree ofpulmonary valve incompetence by echocardiography. Theimportance of pulmonary valve incompetence in adults hasbecome increasingly clear, not just in isolated valvar stenosisbut in all right-heart obstructive surgery. It is now acceptedthat significant, long-standing pulmonary regurgitation willlead to progressive RV dilatation and myocardial injury/dysfunction and is an important determinant in the develop-ment of later symptoms in adults with CHD.11–13 Extensivestudy is ongoing in this population with respect to timing ofintervention for pulmonary regurgitation to avoid RV systolicfailure14,15 and to the potential use of the new transcathetervalve-replacement therapies.16,17

In adults with long-standing pulmonary stenosis and RVhypertrophy, secondary subvalvar obstruction may occur withacute removal of the RV afterload. The contractility of thesuddenly unloaded RV outflow musculature may lead to nearobliteration of the outflow tract immediately after interven-tion. As with double-chambered RV patients, fluid bolusadministration and �-blockers can be very useful in thissetting. Careful pullbacks, with end-hole catheters, will beable to distinguish a residual valvar obstruction from anew-onset reactive subvalvar obstruction (Figures 1 and 2).With elimination of the valvar obstruction, RV hypertrophywill regress during the first few weeks of follow-up.18 Thisresults in a diminishing systolic gradient across the subvalvarRV outflow tract but may also result in increasing pulmonaryinsufficiency during follow-up as the RV chamber becomesmore compliant. Surgical valvotomy or valve replacement isreserved for patients who do not respond to balloon interven-tions or who have already developed significant valvarinsufficiency in addition to valve obstruction.

Supravalvar Pulmonary Stenosis

Natural HistoryNative supravalvar pulmonary stenosis can occur as anisolated abnormality or in association with complex cardiacmalformations such as tetralogy of Fallot, with fetal terato-genic exposure such as rubella or toxoplasmosis, or withgenetic syndromes such as Williams or Noonan syndromes.Stenosis of the MPA, above the valve annulus, may also bethe result of surgical scarring from operations such as a PAband or the arterial switch operation for transposition of thegreat arteries. The hemodynamic burden of this lesion isidentical to that of valvar pulmonary stenosis. In some cases,it may be quite difficult for the echocardiographer to distin-guish a doming, stenotic valve from a normal valve thatcannot open fully owing to its abutment against a muscularsupravalvar ridge. MRI and computed tomographic angiog-raphy can be very useful in this setting. In the catheterizationlaboratory, careful pressure measurements with an end-holecatheter can also help distinguish between valvar and supra-valvar obstruction (Figure 3).

Indications for Intervention and ManagementAs in patients with valvar pulmonary stenosis, patients withexercise intolerance and those with significant resting gradi-ents should be considered for intervention. Few data exist oncatheter intervention for this patient population.19,20 Congen-ital supravalvar obstructions occur typically at the sinotubularjunction of the MPA. Because of the elasticity of the MPA,which makes it resistant to balloon dilation, and the proximityto the pulmonary valve, which makes stent implantationundesirable, these patients are most often referred for surgerywhen obstruction is severe and they are symptomatic.21

Significant potential exists in this population for the use ofexperimental transcatheter, stent-based valve implants, asmentioned above.

Postoperative Conduit ObstructionSurgical repairs for congenital atresia or hypoplasia of the RVoutflow tract (pulmonary atresia and tetralogy of Fallot) or

Figure 2. A, Pullback from MPA to RV in an adult with valvarpulmonic stenosis. The PA tracing is normal, with moderate pul-monary hypertension (patient with high LV end-diastolic pres-sures). On pullback across the valve, both systolic and diastolicpressures change simultaneously, which indicates obstruction atthe valvar level. The peak-to-peak gradient is �50 mm Hg. Inaortic valve stenosis, the same pressure tracing morphologiesare seen. B, Echocardiographic images of a patient with valvarpulmonary stenosis. Thickened doming valves are shown inboth systole and diastole.

1230 Circulation March 4, 2008

for complex lesions in which the native pulmonary valve isused as a systemic valve to the aorta (truncus arteriosus,double-outlet RV, and the Ross procedure) often involveplacement of a homograft or bioprosthetic conduit from theRV to the PA. When these grafts are placed during childhoodoperations, with rare exceptions, they will eventually becomeobstructed. The obstruction may simply be due to growth ofthe patient, which results in a pathway that cannot accommo-date increasing flow. It may occur, with scarring, at either theproximal or distal anastomosis site. It may result fromexternal compression of the conduit by the sternum or by theaorta, from graft calcification, from excessive intimal prolif-eration of tissue within the lumen of the conduit, or fromkinking of the conduit itself (with scarring or patient growth).Regardless of the mechanism, the result is pathway obstruc-tion between the RV and MPA, which creates a hemodynam-ic burden for the RV identical to that of the patient with asupravalvar obstruction in the native MPA.

Indications for Intervention and ManagementAs in other RV outflow obstructions, patients who aresymptomatic or who have significant resting gradients thatresult in RV hypertrophy with or without systolic dysfunctionshould be considered for intervention. Most often, adultpatients have outgrown the conduit placed previously inchildhood, and surgical conduit replacement is required. Insome cases, intraconduit balloon or stent angioplasty may be

useful in treating discreet stenoses within an RV-to-PAconduit.22

Although stent angioplasty may be successful in reducingobstruction in adult patients in the short term, particularlywith noncalcified conduits, it does not address the issue of theinsufficient conduit valve, a nearly universal finding late afterimplantation.23 As such, stent angioplasty alone is not anideal long-term solution, even in patients with otherwiseacceptable conduits. As a surgical alternative, this group ofpatients is currently the main focus of investigators workingon stent-based transcatheter pulmonary valve implantation.This patient population is particularly attractive for thisstent-based technology, because the size of the pathwayreceiving the implantable valve is known and fixed, incontrast to the many patients with marked dilatation (oftendynamic in nature) of the native RV outflow tract related toprior obstruction and surgical intervention.

Branch PA Stenosis

Natural HistoryBranch PA obstructions may be isolated or multiple innumber, or they may occur diffusely throughout the pulmo-nary tree. Postmortem studies in children have revealed theselesions to consist of primarily fibrous intimal proliferation,with medial hypoplasia and loss of elastic fibers in affectedvascular segments.24,25 Isolated congenital obstruction of theproximal PA is rare, but when it occurs is more often theresult of prior surgical interventions (ie, Blalock-Taussigshunt or PA banding).26 Multiple or diffuse narrowings of thebranch PAs, especially in conjunction with other cardiac orsystemic malformations, is a marker for congenitally acquiredgenetic or infectious diseases. Williams syndrome, Noonansyndrome, congenital rubella, and Alagille syndrome allcommonly present with branch PA stenosis, hypoplasia, orboth. It is rare that these systemic diseases remain undiag-nosed into adulthood.

Pathophysiology and Natural HistoryBecause of the innumerable parallel pathways available in thepulmonary tree, an isolated branch PA stenosis may notimpose a significant afterload on the ventricle. Rather, thehigher resistance of that pathway will result in blood beingredistributed among the unobstructed (or less affected) seg-ments in a proportion that is inversely related to the resistanceof each branch pathway. Patients may be remarkably symp-tom free, even with severe maldistribution of flow, unlesspulmonary parenchymal disease (ie, pneumonia) affects thewell-perfused segments. In that setting, with the majority ofventilation occurring in the poorly perfused lung, the V̇/Q̇mismatch is maximized, and patients may become seriouslycompromised.

With more diffuse branch PA disease, affecting segmentsof both lungs, RV afterload and systolic pressure may beincreased significantly. In this setting, as with other obstruc-tive lesions, the PA pressure past the most distal obstructionwill be normal (Figure 3); however, unaffected lung segmentsin such a patient will be exposed to both high pressure andhigh flow (redistributed from obstructed areas). These pa-

Figure 3. A, Pullback through MPA to RV in patient with branchor supravalvar PA stenosis. Pullback from the distal MPA (first 3beats) to MPA shows jump in systolic pressure without changein diastolic pressure, which indicates that the catheter is still inthe arterial tree distal to the pulmonic valve. Further pullback(from beat 5 to beat 6) shows no obstruction at the valve as thecatheter is withdrawn into the ventricle, where diastolic pressurefalls. The tracing could be identical in branch PA stenosis,where the obstruction is also distal to the valve. B, Angiographicimage of a patient with Williams syndrome, with multiple levelsof branch PA stenosis.


tients are uniquely at risk of developing segmental pulmonaryvascular disease.

Although uncommon, the diagnosis of branch PA stenosisshould always be considered in patients with a history ofCHD who present with symptoms of pulmonary embolism:dyspnea, fatigability, and segmental lung ventilation-perfusionmismatches. In patients with symptoms or severe maldistribu-tion of flow, intervention is indicated both to redistribute flowmore appropriately and to reduce RV afterload.

Echocardiography cannot readily identify the level ofobstruction in the PAs past the first branch point in childrenor past the bifurcation of the MPA in most adults. MRIincreasingly has become used to assess PA anatomy and flow,particularly because it allows simultaneous assessment of RVejection fraction and regurgitant volumes of the right-sidedvalves, when needed.27 Angiography, however, remains the“gold standard” for defining PA anatomy, whereas quantita-tive lung perfusion scans (technetium-99m) have been invalu-able in identifying discrepancies in segmental or lobar pul-monary flow.28 Of course, without invasive hemodynamicdata, neither a lung scan nor an MRI can distinguish asignificant segmental obstructive lesion from an unobstructedlung segment with pulmonary vascular disease and highresistance.

Indications for InterventionIndications for catheter intervention include symptoms, asignificant decrease in pulmonary blood flow to the left orright lung (or a specific lobe), or elevated RV afterload asdetermined by the ratio of RV systolic to systemic systolicpressures.29,30 Although most proximal stenoses of the pre-hilar area can be repaired surgically, more distal branch PAobstructions are difficult for the surgeon to reach without thepotential for extensive pulmonary parenchymal injury. As aresult, the management of branch PA stenosis has beenpredominantly the domain of the interventionalist since1983.29 Current techniques have been best applied to isolatedlesions and involve balloon angioplasty, stent angioplasty,and the use of cutting balloons when standard balloons havefailed.31–34

Outcomes in patients with diffuse pulmonary obstructions(Williams, Noonan, and Alagille syndromes and rubella)have been generally poor.35 This can be attributed to 2factors. First, given the large number of vessels typicallyinvolved, successful dilation of even a few significant lesionswill not result in an immediate decrease in RV afterload.Second, when angioplasty is successful, the newly unob-structed lung segment will suddenly face high flow, as bloodis redirected from unobstructed segments, as well as highpressure. This may result acutely in a “reperfusion injury”with significant segmental pulmonary edema that may requireventilatory support.36 This does not occur when the proximalPA pressures are normal after intervention, such as in valvarpulmonary stenosis.

Conditions With Increased LV AfterloadSimilar to congenital obstructions on the right side of theheart, left-sided congenital obstructive disease may occur atthe subvalvar, valvar, or supravalvar levels and peripherally

in the aorta (coarctation of the aorta). Although LV obstruc-tive lesions may occur in isolation, they may also be a part ofa number of genetic syndromes. For example, hypertrophiccardiomyopathy (subaortic stenosis) is associated with Noon-an’s syndrome, supravalvar aortic stenosis is virtually alwaysassociated with William’s syndrome, and coarctation of theaorta is part of Turner’s syndrome.37 Left-sided obstructivelesions may not occur in isolation. Shone’s complex presentswith multiple left-sided obstructive lesions and may include asupravalvar mitral ring, parachute mitral valve deformity,subaortic stenosis, valvar obstruction (typically bicommis-sural or unicommissural valves), and distal aortic archobstructions.38

As on the right side, with significant obstruction of the LVoutflow, chamber hypertrophy leads to reduced complianceand higher atrial filling pressures. On the left side, highervenous pressure and congestion may result in pulmonaryedema, particularly in higher-output states. Thus, dyspnea onexertion is the most frequent presenting sign of clinicallyimportant left-heart obstructive disease. Ventricular arrhyth-mia and sudden cardiac death may also occur. Rarely,patients may present with angina/coronary insufficiency,when LV myocardial oxygen requirements are increased(with increased wall thickness), and when elevated ventricu-lar diastolic pressures or early atherosclerotic changes maylimit coronary flow.

Subvalvar Aortic Stenosis

Pathophysiology and Natural HistorySubvalvar aortic stenosis comprises a spectrum of obstructiveprocesses in the LV outflow tract that range from a discretesubaortic membranous obstruction to a fibromuscular tunnel-type obstruction to the more familiar hypertrophic cardiomy-opathy. Regardless of the presenting anatomic features, eachof these lesions tends to be progressive during childhood.

In patients with discrete subaortic stenosis, a thin fibrousmembrane stretches across the LV outflow tract from theseptal surface to the anterior leaflet of the mitral valve. Themembrane may be of variable thickness and of variable distancebelow the aortic valve annulus. The membrane typically has acentral lumen that narrows the LV outflow pathway proximalto the aortic valve. In children, the progression of obstructionmay be rapid. They may develop progressive aortic insuffi-ciency, a result of the distortion of the valve anatomy as themembrane extends onto the valve leaflets.39 In adults, ob-struction progression is much slower, with less change in thedegree of aortic regurgitation over time.40

With the tunnel-type obstructive lesion, a thick fibromus-cular tubular narrowing diffusely reduces the diameter of theoutflow tract. At any given time, the degree of obstruction inboth discrete and tunnel LV outflow obstruction is fixed,with the gradient across the outflow increasing proportion-ately to the increase in cardiac output. These lesions willpresent with heart murmurs long before hypertrophy andreduced LV compliance lead to symptoms of pulmonaryvenous congestion.

In contrast to membranous and fibromuscular obstructions,hypertrophic cardiomyopathy features a dynamic muscularobstruction of the outflow tract. In this population, the


gradient may increase dramatically with decreased afterload41

or with an increase in contractility (inotropic state). Thedynamic nature of this obstruction is easily demonstrated inthe catheterization laboratory by the Brockenbrough-Braunwald-Morrow sign (Figure 4), which occurs with thecardiac cycle immediately after a premature ventricularcontraction.

Under normal circumstances, after a premature ventricularbeat, the physiological pause before the next ventricularcontraction allows for increases in both ventricular filling andintracellular calcium transport. With the next ventricularcontraction, stroke volume is increased, the result of in-creased preload and contractility. In the normal heart, bothLV and aortic systolic pressure will have a correspondingincrease. In patients with discrete membranous or fibromus-cular subaortic obstruction, the ventricular contraction afterthe premature beat will increase the outflow gradient slightly,due to the increased stroke volume of the subsequent beat,even as aortic pressure increases or stays the same; however,in the patient with hypertrophic cardiomyopathy, the in-creased inotropy after the pause causes a marked increase inmuscular contraction and a sharp rise in outflow obstructionassociated with a fall in aortic pressure. Unlike the other 2subaortic obstructions, hypertrophic cardiomyopathy maypresent with sudden arrhythmic death in an otherwise healthyand undiagnosed patient and may be unrelated to the degreeof outflow obstruction at rest.42

Indications for InterventionThe principal effect of subaortic obstruction is increasedventricular afterload, with the same potential hypertrophy,arrhythmia, chamber compliance, and pulmonary venouscongestion issues seen in other left-sided obstructive lesions.For fixed subaortic obstructive lesions, for patients whobecome symptomatic, or when significant LV hypertrophy ispresent, especially in the presence of systolic dysfunction,43

intervention is indicated. Surgery remains the definitivetherapy for these lesions, although a number of authors havepublished small series using balloon angioplasty in childrenand in the veterinary literature.44 Balloon angioplasty may beeffective in transiently reducing the level of obstruction inpatients with thin membranes but appears to be palliative onlybecause the obstruction invariably returns.

In patients with hypertrophic cardiomyopathy, the risk ofsudden arrhythmic death appears to be independent of thedegree of outflow obstruction. Underlying myocardial disor-ganization in the affected tissues may be the primary arrhyth-mogenic source.42 Thus, all patients with this diagnosisshould be treated medically. �-Blockers or calcium channelblockers remain first-line therapy in this population. Implant-able defibrillators are being used in the population at risk.45

When obstruction becomes significant, surgical myomectomyimproves symptoms,46 and transcatheter alcohol ablation ofthe septal tissue (by infusion into the feeding coronarybranch) has developed as a promising alternative.47

Congenital Valvar Aortic Stenosis

Pathophysiology and Natural HistoryCongenital aortic valve abnormalities are common in thepopulation. A nonobstructive bicuspid aortic valve occurs in�1% of the population, with aortic valve stenosis presentingclinically in 3% to 8% of all CHD patients.48 Young adultswith unobstructed bicuspid aortic valves are most oftenasymptomatic and undiagnosed. Most patients are discoveredon the basis of a cardiac murmur, in the absence of othersymptoms. With significant obstruction, LV afterload in-creases, the myocardium hypertrophies, and chamber com-pliance is reduced, which results in higher left atrial fillingpressures. Blood pressure distal to the obstruction is normal.Rarely, patients may present with pulmonary venous conges-tion or coronary insufficiency with the increased output andworkload associated with exertion. Children are almost neversymptomatic, even with the most significant obstructions;however, aortic stenosis tends to progress and becomes moreclinically significant as patients age.49,50

When obstructed, the mechanism of aortic stenosis inyoung adults is generally fibrotic rather than calcification.51

But, these valves do tend to calcify and become obstructed orinsufficient at an earlier age than the typical senescenttricommissural aortic valve.52,53 In addition, patients withbicuspid valves have been found to have abnormalities of theconnective tissues of the aorta and are prone to markeddilation of the ascending aorta even in the absence ofsignificant obstruction or insufficiency.54,55 These patientsshould be followed up noninvasively to rule out rapid aorticgrowth, because root replacement may be required to prevent

Figure 4. Brockenbrough-Braunwald-Morrow sign in patient with hypertrophiccardiomyopathy. With the physiologicalpause after a premature ventricular con-traction in a normal heart, both filling ofthe ventricle and myocardial contractilityare augmented, which creates a largerstroke volume on the next contractionand higher aortic pressure. In a patientwith obstructive hypertrophic cardiomy-opathy, although filling is also aug-mented, muscular contractility at thesubvalvar level increases the degree ofobstruction, which leads to a rise in thecalculated gradient and an actual fall inthe aortic pressure on the beat after thepause (the fifth beat in this tracing).


dissection. Currently, no clear consensus exists for thispopulation as to the size at which prophylactic aortic rootreplacement should be performed.

Indications for InterventionCurrently accepted indications for intervention include symp-toms of exercise intolerance with LV hypertrophy, with orwithout systolic dysfunction, a persistent decrease in myocardialsystolic performance due to excessive afterload, or progressivedilation of the aortic root and ascending aorta (despite medicaltherapy) in association with an obstructed or regurgitant valve.Surgical valve replacement remains the treatment of choice foradult patients. A group from the Toronto General Hospital hasrecommended concurrent ascending aorta and/or root replace-ment for ascending aorta dimensions in excess of 4.5 cm.56

Balloon valvuloplasty in adults with calcific aortic stenosis57 hasbeen largely abandoned as a primary therapy because of therapid rate of restenosis. Balloon valvuloplasty is currentlyreserved as palliative therapy for a few clinical situations in adultpatients, including patients in cardiogenic shock, symptomaticpregnant women, and symptomatic patients who require urgentnoncardiac surgery.58,59 Balloon valvuloplasty may also be usedas a bridge to surgical valve replacement, to assess the LVmyocardial response to afterload reduction. In children,clinically important obstructions may present withoutsymptoms and without calcification. Balloon valvuloplastyhas been shown to have excellent short- and medium-termoutcomes in this population.57–61 In general, peak-to-peakgradients of �50 mm Hg at rest (with normal cardiac output)are accepted as the threshold for intervention in children. Thepatient age at which balloon therapy is not indicated is notwell defined.

A number of percutaneous valve implants have beendeveloped recently and are undergoing initial clinical tri-als.62,63 This holds particular promise for the patient withcombined calcific aortic stenosis and regurgitation. Currenttrials are limited to patients who have been refused surgeryowing to age, cardiomyopathy, or other comorbid conditions.

Supravalvar Aortic Stenosis

Pathophysiology and Natural HistorySupravalvar aortic stenosis is an unusual cardiovascularfinding and is usually a marker for the Williams-Beurensyndrome, an easily recognizable neurodevelopmental disor-der characterized by connective tissue and central nervoussystem abnormalities. Isolated supravalvar aortic stenosisoccurs at the level of the sinotubular junction in �70% ofpatients with cardiovascular manifestations.64,65 Diffuse hyp-oplasia and stenosis of the branch PAs is the most frequentassociated finding, occurring in 41% to 57% of patients withsupravalvar aortic stenosis. Other less frequent associationsinclude coarctation of the aorta, valvar pulmonary stenosis,septal defects, and atrioventricular valve prolapse.

Physiologically, the supravalvar obstruction creates anincreased afterload for the LV, depending on the severity ofthe narrowing, similar to valvar aortic stenosis; however,unlike valvar stenosis, the supravalvar lesion also imposeshigh pressure on the coronary arteries. A pathology seriesreported dilatation and tortuosity, as well as premature

atherosclerotic disease, in this population, similar to patientswith uncontrolled systemic hypertension,66 although the in-cidence of clinically severe coronary disease appears to bevery small in the population with Williams-Beuren syndrome.Congenital stenosis of the coronary, renal, subclavian,splanchnic, and carotid arteries has also been observed.

With a defined elastin-gene heterozygosity identified as thecause of the arteriopathy associated with this syndrome,67 it isinteresting to note the unusual clinical course associated withthese arterial obstructions. Mild supravalvar aortic obstruc-tions (�20 mm Hg gradient) tend to regress or remain stable,as with aortic valve stenosis; however, some patients withmore severe supravalvar obstructions have had regression inthe degree of obstruction during long-term follow-up.68 Onthe pulmonary side, the tendency toward regression is the rulerather than the exception.

Indications for InterventionBecause a documented chance of regression exists, isolatedsupravalvar aortic stenosis without clinical or echocardiographicfindings of LV dysfunction should be monitored noninvasively.In the setting of excessive LV afterload or with clinical symp-toms, surgery is the treatment of choice. Interventional proce-dures are likely to fail. The thickened elastic tissue of the aorticroot will be resistant to balloon angioplasty, like that of thesupravalvar pulmonary stenosis, and stenting has no role so closeto the aortic valve leaflets and the coronaries. In this type ofsystemic syndrome, the patient’s overall condition, includingneurodevelopmental and endocrine status (not just the cardio-vascular component), must be considered in making a recom-mendation to intervene.

Coarctation of the AortaCoarctation of the aorta is a congenital narrowing of the aortathat accounts for 5% to 8% of all CHD.48 The obstructivelesion occurs just distal to the origin of the left subclavianartery where the fetal ductus arteriosus had previously in-serted into the aorta. The obstruction is usually a discrete,tubular narrowing, but common anatomic variations includelong-segment stenosis and transverse aortic arch hypoplasiaproximal to the coarctation. Histological abnormalities of themedial layer can be seen in the affected area.69 Between 50%and 85% of patients with coarctation also have a bicuspidaortic valve.70

Obstruction of the aorta distal to the takeoff of the subclavianand carotid arteries creates not only an afterload for the LV butalso a maldistribution of flow, similar to the branch PA obstruc-tions. Although the proximal/upper segment of the aorta receivesblood flow normally from the LV, there will be a diminishedpressure head reaching the lower portions of the body distal tothe obstruction (Figure 5). The juxtaglomerular apparatus in thekidneys, perceiving a low-flow condition, modulates vasculartone and intravascular volume through the secretion of vasocon-strictive substances to attempt to restore perfusion pressure in thedistal aorta. With the fixed obstruction at the coarctation andmaintenance of flow (cardiac output), the result is a significantblood pressure elevation proximal to the coarctation. Over time,the body will develop alternate pathways from the ascending tothe descending aorta in the form of collateral arterial vessels.


Small branches from the mammary and intercostal arteries willgrow substantially as flow increases. This results in the typicalrib-notching pattern seen on chest radiographs in a patient withcoarctation as the enlarged and dynamic intercostal arterieserode/remodel the lower margins of the ribs. Significant collat-eral flow may “mask” the severity of the obstruction, asmeasured by the pressure gradient from the upper to the lowersegments (either by echocardiography, by MRI, or by directpressure measurement in the catheterization laboratory), becauseonly a percentage of the cardiac output actually traverses theobstruction. In the most extreme cases, teenagers and youngadults may present with an actual interruption of the aorta. Thesepatients are dependent entirely on the collateral flow to the distalaorta but are physiologically no different from patients withsevere coarctation.

Natural HistoryAlthough the disorder is most frequently diagnosed in thechild who presents with hypertension, diminished pulsevolume in the lower extremities, or a heart murmur (eitherfrom the coarctation itself or from the associated bicuspidaortic valve), coarctation may go undetected well into adult-hood. Because of systemic hypertension in the upper body,these individuals are predisposed to premature coronaryartery disease and cerebral berry aneurysm (3% to 5%).71,72

Adults typically present with refractory hypertension but mayalso complain of headaches, nosebleeds, cool extremities,fatigue, and leg weakness/claudication with exertion. Theymay also develop iatrogenic problems related to antihyper-tensive therapy (claudication or prerenal azotemia). Lesscommon clinical manifestations include angina, exertional

dyspnea, and heart failure from chronically increased LVafterload. For the adult with unrepaired, isolated coarctation,the average survival is �35 years of age, with a 25% survivalrate beyond 50 years of age.71

Patients may have undergone prior surgical or interven-tional procedures for coarctation. Surgical scarring or poorgrowth of the repaired segment after a childhood repair mayresult in restenosis. Older surgical repairs, in which Dacronconduits were used to bypass the obstructed segment, maybecome obstructed themselves. This may occur when a childoutgrows the conduit placed, when neoendothelialization ofthe prosthesis narrows the lumen significantly, or as the resultof “kinking” of the conduit from scarring or patient growth.In some patients, congenital hypoplasia of the proximal aorticarch may be unmasked as obstructive when the discreetcoarctation site is opened successfully. In any of theserecurrent coarctation situations, the clinical presentation andthe underlying physiology are the same.

Indications for InterventionCurrent indications for intervention in an adult patient includeclinical symptoms, hypertension at rest, or severe hyperten-sion with exertion. Because the hypertension associated withcoarctation is due to a mechanical obstruction in the circula-tion, patients cannot be treated with any pharmacologicaltherapy that reduces vascular tone, diminishes intravascularvolume, or lessens cardiac output. The blood pressure, asmeasured in the arms, may be “corrected” with such medicaltherapy, but the result will be substantial reduction in theperfusion pressure of the lower part of the body. Coarctationof the aorta requires a mechanical solution to eliminate thepressure difference between upper and lower segments.

Surgical reconstruction of the aorta was the treatment from194573 until the 1980s, when balloon angioplasty became acompetitive option.74,75 More recently, endovascular stentsfor both native and recurrent coarctation of the aorta havegained acceptance as the procedure of choice in teenagers andyoung adults who have achieved full growth.76–84 Althoughearly and mid-term follow-up data appear to favor stentangioplasty over balloon dilation in adults, stenting the aortamay still be associated with serious adverse events.85–88

Long-term outcomes remain unknown.Covered stents89 may become the primary therapy in the

future in an effort to avoid the potential complications ofarterial dissection, tear, or rupture, but they are not yetavailable in the United States in sizes large enough for atypical aorta. No comparative studies have yet appeared thatcompare covered stents with other options.

ConclusionsObstructive disease is relatively common in the adult popu-lation with CHD and may affect ventricular function signif-icantly. Although most adult cardiologists are experiencedand comfortable with the pathophysiology of isolated valvarand subvalvar aortic valve stenosis, right-sided outflow andarterial obstructions are less common. More distal obstruc-tions in either the right or left sides of the circulation produceredistribution of blood flow to lower-resistance pathways,which creates more complicated physiologies. Comfort with

Figure 5. A, Pullback from ascending to descending aorta inpatient with severe coarctation of the aorta. Pullback throughthe aortic obstruction reveals a dampening of the tracing with asignificant drop in peak systolic pressures. B, Aortic angiogramin a patient with coarctation of the aorta. Arrow indicatesobstructed segment.


the physiology of the simple obstructions is critical inunderstanding the more complex congenital malformationsthat will be presented in the next article in this series.

DisclosuresNone.

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KEY WORDS: coarctation � heart defects, congenital � physiology


cc no adulto ii

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