This chapter discusses pulmonary stenosis as an isolated finding. When pulmonary stenosis exists as part of a more complex anomaly, such as tetralogy of Fallot, the reader is directed to the complete descriptions found in the relevant chapters.
Incidence and Associated Anomalies
Pulmonary stenosis is the third most common congenital cardiac malformation. In a large prospective study of all live-born infants that also included data from the autopsies of stillborn infants, the total incidence of congenitally malformed hearts was 6.6 per 1000 live births. Of these, pulmonary stenosis accounted for 5.8%. Half of all congenitally malformed hearts include pulmonary stenosis as a component of the defect.
Morphology and Embryology
Obstruction at the valvar level is by far the most common lesion producing stenosis within the pulmonary outflow tract. An understanding of the mechanisms responsible for stenosis requires a proper appreciation of normal valvar anatomy. At present such understanding is constrained by varying use of the term annulus in accounting for the structure of the normal valve. Paradoxically, it is only when the valve is stenotic that the attachments of the leaflets approximate to an annular arrangement. The essence of normal valvar anatomy is the suspension of the valvar leaflets in semilunar fashion within the sinuses of the pulmonary trunk. Proper understanding then requires appreciation that the hinges of the leaflets cross the anatomic ventriculoarterial junction. The arrangement is best seen when the normal outflow tract is spread open, having already removed the valvar leaflets ( Fig. 42.1 ).
In the normal heart, each valvar leaflet is attached by its two extremities at the sinutubular junction, with the basal attachment supported by the musculature of the subpulmonary infundibulum. True anatomic rings can then be identified at the level of the sinutubular junction and also at the anatomic ventriculoarterial junction. The latter structure is the locus over which the fibroelastic walls of the pulmonary trunk are supported by the muscular subpulmonary infundibulum. A third ring can then be constructed by joining together the basal attachments of the leaflets. This third ring, however, is a geometric construction rather than an anatomic reality. The semilunar line of attachment of each of the leaflets marking the hemodynamic ventriculoarterial junction crosses twice the anatomic ventriculoarterial junction. By virtue of this geometry, crescents of muscular infundibulum are incorporated at the base of each pulmonary valvar sinus, while three tapering triangles of fibrous pulmonary truncal wall extend beyond the anatomic ventriculoarterial junction as parts of the ventricular outflow tract, reaching to the level of the sinutubular junction ( Fig. 42.2 ).
In the normal arrangement, the free edge of each valvar leaflet is appreciably longer than the cord of the sinus that supports it, thus permitting the three leaflets to fit snugly together when closed so as to produce a competent valvar orifice. It is the semilunar nature of suspension of the leaflets, therefore, that permits competent closure and unobstructed opening of the valve. When seen in closed position, the zones of apposition between the adjacent leaflets extend in triradiate fashion from the centroid of the valvar orifice to their peripheral attachments at the sinutubular junction ( Fig. 42.3 ).
Fusion of the adjacent leaflets along their zones of apposition is the essence of valvar stenosis. The fusion is typically uniform, so that the valvar orifice is narrowed to a central opening. The more the fusion extends toward the center of the valve, the narrower will be the central opening and the more severe will be the valvar stenosis. When the stenosis is mild to moderate, the opening will have a triangular configuration ( Fig. 42.4 ).
In contrast, in the most severe forms of stenosis, which produce the typical critical arrangement seen in neonates, the extent of fusion is sufficient to leave only a central pin-sized opening. In this so-called domed stenosis, the central part of the cupola tends to be smooth, with evidence of the fused zones of apposition seen to varying degrees as peripheral raphes, with tethering at the sinutubular junction ( Fig. 42.5 ).
Opening the critically stenotic valve shows that, because of the obliteration of the zones of apposition between the leaflets, the extent of their semilunar hinging is reduced. Because of this, their line of attachment within the pulmonary root has a more circular configuration ( Fig. 42.6 ).
This feature, in which ring-like attachments of the leaflets become evident only when the valve is malformed, can be considered to represent an annular paradox. Thus, although the orifice of the normal pulmonary valve is often described in terms of the “annulus,” the measurement taken at this level by the echocardiographer is a virtual diameter at the level of the basal ring ( Fig. 42.7 ).
In some instances it is possible to identify four raphes, suggesting that the valve itself initially had four leaflets. Commissural fusion can also produce pulmonary stenosis in the setting of a bifoliate valve ( Fig. 42.8A ), whereas in other instances the pulmonary valve can be not only bifoliate but also bisinuate (see Fig. 42.8B ).
Nonetheless, the typical lesion producing pulmonary valvar stenosis is uniform fusion of the peripheral zones of apposition of a trifoliate valve, leaving a central aperture. Usually this arrangement is associated with some degree of thickening at the union of the zones of apposition with the sinutubular junction. This is described surgically as tethering (see Fig. 42.4 ). Accentuation of such tethering can produce marked narrowing at the sinutubular junction, often described as being supravalvar. In reality the sinutubular junction is an integral part of the valvar complex. In some instances valvar stenosis is the consequence of dysplasia of the leaflets, making them thick and mucoid. Such thickening is sufficient to produce obstruction of the valvar orifice, even when the leaflets themselves are not fused along their zones of apposition ( Fig. 42.9A ). Most of the patients with Ullrich-Noonan syndrome have this type of stenosis. Dysplasia can also be found when either the trifiliate or bifoliate valve is already itself stenotic, thus exacerbating the extent of the narrowing at the valvar orifice (see Fig. 42.9B ).
Although pulmonary valvar stenosis may be considered a simple lesion, it is rare for the lesion to be totally isolated. There is almost always hypertrophy of the right ventricular walls. In the neonate with critical valvar stenosis, such hypertrophy may be severe, with accompanying fibrosis of the endocardium and thickening of the tension apparatus of the tricuspid valve. The right ventricle then resembles the situation seen at the functionally biventricular end of the spectrum of pulmonary atresia with intact septum (see Chapter 43 ). The findings of areas of subendocardial right ventricular infarction in the absence of coronary artery disease, coupled with extensive areas of disarray in the myocardial and arterial walls, point to the disease being more generalized than would be expected from a simple valvar lesion producing direct hemodynamic effects. In a good proportion of cases with pulmonary valvar stenosis of whatever type, there is an associated deficiency of the atrial septum. In days gone by, so-called cardiac cirrhosis was noted in adults dying with pulmonary stenosis, but such hepatic changes are unlikely to be encountered now.
Infundibular Stenosis
Pure narrowing of the muscular subpulmonary infundibulum is rare in the setting of an intact ventricular septum. Probably many of the cases described as having isolated infundibular stenosis also had a ventricular septal defect, which then closed spontaneously.
Combined Valvar and Infundibular Stenosis
Hypertrophy of the subpulmonary infundibulum occurs along with hypertrophy of the rest of the right ventricle in response to valvar stenosis. This reduces the infundibular diameter. Endocardial fibroelastosis may also be seen along with the hypertrophy. Such reactive stenosis is an important component to be noted when the results of balloon valvoplasty are judged, since time is needed for its regression.
Other Types of Stenosis Occurring Within the Right Ventricle
Other types of stenosis within the right ventricle are rare when the ventricular septum is intact. Hypertrophy of the body of the septomarginal trabeculation, which in its severest form produces the typical two-chambered right ventricle, is usually found with a ventricular septal defect. It can occur with an intact septum. In other patients the valves of the embryonic venous sinus can persist and become so expanded and aneurysmal that they pass through the tricuspid valve and obstruct the pulmonary outflow tract. This is called spinnaker syndrome . Aneurysmal dilation of the membranous septum can also produce subpulmonary stenosis, as can cardiac tumors or aneurysm of the right coronary sinus of the aorta. Hypertrophic cardiomyopathy can also afflict the right ventricle, particularly in the setting of lentiginosis, although left ventricular obstruction usually dominates.
Pulmonary Arterial Stenoses
Stenoses of the pulmonary arterial tree are frequent in association with complex malformations such as tetralogy of Fallot or transposition. They can also complicate more simple lesions, such as pulmonary valvar stenosis or ventricular septal defect. Stenoses in the pulmonary arteries can also occur in isolation and can be found in various parts of the pulmonary arterial tree. Thus the stenosis may be localized and central within the pulmonary trunk, involve the intrapericardial part of the right and left pulmonary arteries, or be localized and peripheral at the sites of branching of major intrapulmonary arteries. It can also be more extensive, producing hypoplastic arterial segments commencing either at the end of the right or left pulmonary artery or at a major intrapulmonary branch point. When found, the changes are often not limited to the pulmonary arteries but also involve the systemic vessels.
Developmental Considerations
As described in Chapter 3 , the heart develops as a tubular structure, initially with a solitary lumen. Remodeling of the lumen of the outflow tract to produce the aortic and pulmonary channels, each with its own arterial valve, involves tissues derived from several sources. The walls of the outflow tract are derived from the second heart field, with the walls initially being myocardial to the margins of the pericardial cavity. Additional contributions from the second heart field then produce the nonmyocardial walls of the intrapericardial arterial trunks and the arterial valvar sinuses. Septation then involves components developed within the outflow tract itself but also an extrapericardial component growing from the dorsal wall of the aortic sac. Both sources contain tissues initially derived by migration from the neural crest. The protrusion growing from the dorsal wall of the aortic sac divides the distal part of the outflow tract into the intrapericardial components of the arterial trunks. The cushions developing throughout the outflow tract, in contrast, separate the components of the developing arterial roots and, similarly, separate the ventricular outflow tracts. These cushions, packed with cells derived from the neural crest, fuse with each other in a distal-to-proximal direction. However, only the central parts of the distal cushions fuse together. The peripheral parts, which occupy the intermediate part of the overall length of the outflow tract, remain unfused. Together with the intercalated cushions, which are also developed in the intermediate part of the outflow tract, they produce the primordia of the developing aortic and pulmonary valves. At the beginning of these changes, which will eventually lead to formation of the arterial roots, the cushions themselves remain encased in a turret of myocardium. Already, however, the most distal part of the outflow tract has separated into the intrapericardial components of the aorta and the pulmonary trunk, with each trunk developing its own discrete walls ( Fig. 42.10 ). The distal ends of the outflow cushions themselves then excavate to produce the valvar leaflets and their semilunar hinges ( Fig. 42.11 ).
The walls of the sinuses are formed by additional ingrowth of nonmyocardial tissues from the second heart field. The significance of the cells derived from the neural crest was demonstrated by experimental ablation of the neural crest in the chick. This resulted in failure of septation and persistence of a common arterial trunk. The tissues derived from the second heart field were also subsequently shown to be important in differentiation and separation of the ventricular outflow tracts. In terms of maldevelopment of the outflow tract, it is now established that the bicuspid aortic valve can be produced either by exuberant fusion of the peripheral components of the major outflow cushions or by fusion of the end of one of the major cushions with the intercalated cushion, thus producing a conjoined leaflet. It is also feasible that failure of formation of the intercalated cushion could produce a valve with only two leaflets. The same processes must be capable of producing the pulmonary valve with two leaflets. Stenosis of the pulmonary valve, however, develops as an acquired condition during intrauterine life. Interrogation of the developing fetus has now shown how progression of stenosis can produce pulmonary valvar atresia with an intact ventricular septum. The degree of severity of obstruction seen at birth then depends on the extent of the process during gestation. It is also well established that peripheral pulmonary arterial stenosis may be caused by congenital rubella. Comparable changes are also seen in recognizable syndromes of malformation, such as the syndromes of Williams and Alagille.
Clinical Diagnosis
Presentation
The presentation of pulmonary stenosis depends on age and severity. In the neonate, critical pulmonary stenosis presents with life-threatening cyanosis and atrial-level right-to-left shunting. The differential diagnosis would include other forms of neonatal cyanosis, including transposition of the great vessels and the various forms of pulmonary atresia. Such patients are likely to depend on the arterial duct to provide the flow of blood to the lungs. Hence palliation in the short term, by maintaining ductal patency with intravenous infusions of prostaglandin, is lifesaving until a more definitive diagnosis can be made and an appropriate intervention planned.
Outside of the neonatal period, mild or moderate pulmonary stenosis is not likely to cause major symptoms, unless there are associated lesions or other factors. For example, patients with the typical phenotype of Noonan syndrome may have difficulty with feeding and gaining weight, unassociated in most cases with the severity of the pulmonary stenosis.
Discovery of disease of mild or moderate severity is most likely when physical signs are detected during consultations for other matters, most commonly when a cardiac murmur is heard.
Although some patients with mild to moderate pulmonary valve stenosis may present with exertional dyspnea, this may not necessarily be related to inability of the right ventricle to increase the stroke volume across a fixed right ventricular outflow tract obstruction but instead may represent the patient’s physical deconditioning. While De Meester and colleagues found a reduced peak workload and peak oxygen uptake in a study evaluating 19 adults with mild to moderate pulmonary valve stenosis, they also identified a lower baseline heart rate and heart rate reserve as well as a lower threshold of workload reached at anaerobic threshold and peak exercise compared to healthy controls, suggesting that physical deconditioning may play a role in explaining these findings. This is important to keep in mind when patients with mild to moderate pulmonary valve stenosis are being managed so as to avoid inappropriate limitations from physical activities and to encourage them to maintain a healthy lifestyle with regular exercise. The ability to increase cardiac output with exercise beyond increasing the heart rate in patients with mild to moderate pulmonary valve stenosis is supported by a study by Romeih and colleagues, who reported a significantly increased stroke volume and cardiac output during cardiopulmonary exercise and dobutamine stress testing in 11 adults with untreated mild to moderate pulmonary valve stenosis. This is different from patients who were treated late for severe pulmonary valve stenosis, in whom there may be a persistent impairment in the ability to increase right ventricular stroke volume.
In patients with more severe pulmonary stenosis, the onset of symptoms may still be delayed into late childhood or early adult life. In a small proportion of patients with pulmonary stenosis and an atrial communication, central cyanosis can be present, especially with exercise. This is a late physical sign because the atrial-level right-to-left shunting depends on the diastolic properties of the right ventricle. With severe right ventricular hypertrophy and poor right ventricular diastolic compliance, the passage of unoxygenated blood across an interatrial communication into the left atrium is facilitated. In addition to central cyanosis in the presence of a right-to-left shunt across an intraatrial communication, patients with moderate to severe pulmonary stenosis may also develop peripheral cyanosis during exercise, in particular with an intact atrial septum. This is related to a limitation of the right ventricle to increase its stroke volume and cardiac output, resulting in an increased peripheral tissue oxygen extraction. Reported symptoms include exercise intolerance and dyspnea. Chest pain of an ischemic nature―possibly due to subendocardial ischemia of the right ventricle, syncope, and severe dyspnea on minimal exertion―is a late finding and should prompt rapid intervention.
Physical Examination
The physical examination findings are summarized in Table 42.1 . Depending on the degree of stenosis, there may be a thrill at the second left intercostal space. This is not felt over the carotid arteries, thus differentiating the cause of the thrill from aortic stenosis. Palpating for a thrill in the suprasternal notch should be avoided, since thrills here can be due to either aortic or pulmonary stenosis.
| Severity of Pulmonary Stenosis | |||
|---|---|---|---|
| Physical Sign | Mild | Moderate | Severe |
| Cyanosis | Absent | Absent | Possible, if interatrial septal defect |
| Jugular venous pulse | Normal | Normal | Possibly elevated, prominent a-wave |
| Precordial thrill | Absent | Probable | Pronounced |
| Right ventricular heave | Absent | Probable | Pronounced |
| Systolic ejection click | Present | Expiratory | Probably absent |
| Ejection systolic murmur | Midsystolic, ejection | Long ejection systolic | Long, ejection systolic, past aortic closure sound |
| Second heart sound | Normal | Wide, variable | Absent pulmonary closure sound |
Widened splitting of the second heart sound and an ejection systolic murmur is maximally heard here, with radiation into the back. The delayed closure of the valvar leaflets causes the widened splitting. This is not due to electrical prolongation of systole but rather to continued flow through the pulmonary valve even after right ventricular pressures have fallen to levels that would usually have resulted in valvar closure. This is likely to be a ventriculoarterial interaction, favored by normal or increased impedance of the pulmonary vascular bed. It can be termed “pulmonary hangout.” The more severe the degree of stenosis, the wider the splitting of the second heart sound.
As the severity of pulmonary valve stenosis progresses, the mobility of the valvar leaflets is often reduced, thereby also leading to a reduced intensity of P2. Furthermore, the ejection systolic murmur may continue beyond the aortic component of the second heart sound, making it more difficult to appreciate A2. Hence the finding of a single second heart sound is common in patients with more severe pulmonary valve stenosis.
In most cases of valvar pulmonary stenosis, a systolic ejection click precedes the onset of the systolic murmur. The click is usually heard loudest separate from the area of maximal intensity of the cardiac murmur, nearer the apex, or at the left lower sternal edge. The systolic ejection click originates from the rapid deceleration of the pulmonary valvar mechanism, as the fusion along their zones of apposition prevents the valvar leaflets from reaching their intended positions against the walls of the valvar sinuses. Presence of the click also depends on the timing of opening of the pulmonary valve. In mild disease, without right ventricular hypertrophy, the pulmonary valve opens in ventricular systole with the emission of an ejection click. In severe disease, with right ventricular hypertrophy and impaired diastolic compliance, the valve opens in atrial systole, without the rapid deceleration caused by ventricular systole. Thus no click is heard. In moderate pulmonary stenosis, inspiration augments systemic venous flow and atrial filling. The augmented atrial pressure allows atrial systole to open the pulmonary valve. Hence the systolic ejection click is heard only in expiration. In some patients with pulmonary stenosis and tricuspid regurgitation, the right ventricular pressure is high enough to cause a pansystolic murmur at the left lower sternal edge, related more to the degree of tricuspid regurgitation than to the valvar stenosis itself.
The physical findings in patients with supravalvar stenosis are similar except for the absence of the ejection click. Stenosis further out into the pulmonary arterial tree can be heard as long systolic or continuous murmurs in the axillae or over the lung fields at the back. Careful general phenotypic assessment may show the signs or syndromic diagnosis, as seen in Noonan, Alagille, or Williams syndrome.
Basic Investigations
Basic investigations are directed toward assessing the effects and severity of the pulmonary stenosis.
Electrocardiogram
The most pertinent electrocardiographic (ECG) findings are summarized in Table 42.2 . ECG may be normal, it may reveal the degree of right ventricular hypertrophy, or, indeed, it may point to right atrial enlargement, which will be seen only in the more severe cases. There are no features of the ECG that are unique to valvar pulmonary stenosis, although the severity of stenosis is reflected in the degree of right ventricular hypertrophy and strain. A full right bundle-branch-block pattern is rare, but an RSR′ pattern can be seen and reflects a lesser degree of right ventricular hypertrophy than the equivalent exclusive R-wave complex in V 1 .
| Mild | Moderate | Severe | |
|---|---|---|---|
| Electrical axis | Normal | 90–130 | 110–150 |
| R:S ratio | Normal | up to 4 : 1 in V 1 | Also inverted in left leads |
| V 1 R amplitude | Normal | 10–20 mV | >28 mV |
| Right atrial enlargement | Normal | Possible | Present |
The use of ECG findings to estimate the severity of pulmonary valve stenosis has less clinical relevance today, when transthoracic echocardiography is routinely used to follow and evaluate patients with pulmonary valve stenosis. Rudolf proposed that, in children, the voltage of a pure R wave recorded at V 1 correlates with approximately 20% of the right ventricular pressure. It turns out that the QRS axis may be a more reliable indicator of right ventricular pressure. Indeed, the prediction of right ventricular pressure gradient is optimized by use of a number of variables in addition to the measurements of voltage on the ECG, as proposed by Ellison, as follows:
ΔP=RV1+1.5×(SV6)+15×(murmur[grade0−6])+Clinical score−30
The clinical score included presence of cyanosis, worth 25; pulmonary component of the second sound, worth 15 if diminished (or 25 if inaudible); a QRS axis of greater than 90 degrees, worth 10; negative T waves in aVF and V 1 , worth 35; and RV 1 above 10 mm worth 15. This complex formula has been superseded by the quicker, more accurate, and more reliable use of Doppler echocardiography.
Chest Radiograph
The chest radiograph shows the features of right ventricular hypertrophy and, if present, poststenotic dilation of the pulmonary trunk. Right ventricular hypertrophy is seen as an upturned cardiac apex. The dilated pulmonary trunk is seen as a prominence of the left upper heart border, inferior to the aortic knuckle ( Fig. 42.12 ). Right atrial enlargement causes a more pronounced convexity of the right lower heart border. Although it is important to know those findings, a routine chest radiograph is usually not indicated in the evaluation of patients with pulmonary valve stenosis.
Echocardiography
The gold standard investigation for the assessment of the morphology of pulmonary stenosis is cross-sectional echocardiography coupled with Doppler analysis of the flow in the right ventricular outflow tract and pulmonary arteries. Advantages such as widespread availability and lack of adverse side effects have helped make echocardiography the primary imaging modality by which pulmonary stenosis is diagnosed and managed.
Cross-sectional echocardiography will define whether the obstruction is at the level of the valvar leaflets ( Fig. 42.13 ; ) or subvalvar ( Fig. 42.14 ) or supravalvar ( Fig. 42.15 ). The presence and severity of restricted motion of the leaflets as well as dysplasia can readily be assessed, along with any poststenotic dilation of the pulmonary trunk ( Fig. 42.16 ). The diameter of the pulmonary valve at the hemodynamic ventriculoarterial junction can be measured accurately ( Fig. 42.17 ), facilitating the planning of intervention. Attempts have been made to quantify these methods, with recommendations being published on how to measure the pulmonary outflow tracts and semilunar valves in the pediatric population. Specifically, the pulmonary valve annulus should be magnified in the parasternal long- or short-axis view and measured between the inner edges of the hinge points in midsystole. Although routinely done in valvar pulmonary stenosis, echocardiographic measurement of the pulmonary valve annulus does not preclude the need to measure by angiography during intervention, as echocardiographic measurement appears to underestimate annular size.
Distal to the valve, it is possible to identify stenosis within the proximal pulmonary arterial tree, although other forms of imaging are necessary to assess pulmonary arterial pathology distal to the bifurcation. The presence of additional abnormalities, such as atrial septal defects, can be recorded.
Three-dimensional echocardiography is being used more frequently in the imaging of congenital heart defects due to its ability to provide more detailed noninvasive imaging of these anomalies. Specifically, with regard to pulmonic valve stenosis, three-dimensional echocardiography may provide better visualization of the morphology and function of the pulmonic valve. Although it enhances visualization of the morphologic features of the pulmonic valve, it is uncommon that three-dimensional echocardiography yields additional information affecting clinical management in pulmonary valve stenosis over traditional methods, such as color-flow and Doppler gradient assessment.
Previously, ECG was the mainstay of noninvasive assessment of the severity of pulmonary valve stenosis despite ECG correlates of right ventricular hypertrophy being relatively weak. Since the advent of Doppler echocardiography, assessment is greatly simplified. Color-flow Doppler shows turbulent blood originating at the point of stenosis ( Fig. 42.18 ; and ). Both pulsed and continuous-wave interrogations permit measurement of the maximal velocity of the flow across the stenosis ( Fig. 42.19 ). The pressure gradient can be estimated more accurately using the modified and simplified Bernoulli equation, where the valvar pressure gradient, expressed in millimeters of mercury or ΔP, is calculated from the maximal Doppler velocity at meters per second, or V, across the pulmonary valve:
ΔP=4×V2
A study by Hanya and colleagues attempted to validate the specified Bernoulli constant (K), which was 3.9 and therefore very close to the simplified Bernoulli constant (4.0). The authors found that the more severe the pulmonary valve stenosis, the less widely scattered the results were, suggesting that the simplified Bernoulli constant was more suitable for more severe pulmonary valve stenosis.
Calculations of estimated pressure gradients derived from Doppler measurements of velocity are an automatic part of all commercially available systems for cardiac ultrasonic investigation. Although both peak and mean Doppler gradients can easily be calculated using these methods, peak Doppler gradients are typically used in the clinical setting in managing pulmonary stenosis. A study by Aldousany and colleagues found a good correlation between peak-to-peak catheter-derived gradient and peak instantaneous Doppler gradient obtained by echocardiography, even though the peak instantaneous gradient appeared to overestimate the peak-to-peak gradient fairly consistently by 25% to 40%. In terms of absolute numbers, though, the mean Doppler gradient may be more closely related to the peak-to-peak gradient obtained in the catheterization laboratory.
Two settings in which the measured pressure gradient may underestimate the degree of stenosis are in the context of an elevated pulmonary vascular resistance or decreased right ventricular contractility. The pulmonary vascular resistance frequently remains elevated in critical neonatal pulmonary stenosis, causing the pulmonary arterial pressure to be elevated distal to the obstruction as well. When ventricular function is compromised, the contractility may be insufficient to generate a pressure gradient reflective of the degree of stenosis.
Similarly, the right ventricular pressure can also be estimated by the velocity of the jet of tricuspid valvar regurgitation, when present, added to the estimated right atrial pressure ( Fig. 42.20 ). The right ventricular pressure estimate can be compared to the measured systemic blood pressure to provide the clinician with an approximation of the degree of right ventricular hypertension (half-systemic, three-quarters systemic, etc.). Therefore an accurate measurement of the systemic blood pressure at the time of tricuspid regurgitation jet velocity calculation is needed for comparison.
Fetal Echocardiography
Improvements in imaging technology have enhanced the capability of improved prenatal detection of many children with pulmonary stenosis. Color Doppler flow has been credited with improved prenatal detection of defects such as pulmonary stenosis ( Fig. 42.21 ) due to the turbulence of the high-velocity jets it can produce across semilunar valves. Multiple factors affect the prenatal detection rate of congenital heart disease, including pulmonary stenosis. Inclusion of the outflow tract views in obstetric scanning increases the sensitivity of prenatal detection of congenital heart disease. Prenatally, the four-chamber view may be normal in patients with pulmonary stenosis; therefore the inclusion of outflow tract visualization would aid in prenatal detection.
Fetal echocardiography is indicated when congenital heart disease is suspected, which, in the absence of other indications, is often following routine obstetric ultrasound assessment. Fetal echocardiography is frequently performed between 18 and 22 weeks of gestation, but examinations are sometimes performed earlier in selected high-risk cases. Given that image resolution may preclude diagnosis or that certain lesions (such as pulmonary stenosis) can be subtle and/or progress, current recommendations are to repeat the assessment for those undergoing fetal echocardiography in early gestation. Fetal echocardiography is limited in predicting postnatal disease due in part to both postnatal physiologic changes and progression of disease. Therefore a normal fetal echocardiogram should not preclude postnatal assessment when there is clinical suspicion of congenital heart disease.
At present prenatal diagnosis of pulmonary stenosis by fetal echocardiography is limited to parental counseling and monitoring for the progression of disease with serial examinations. In cases where moderate or severe stenosis is suspected, admission to a neonatal intensive care unit for monitoring and prompt cardiology assessment should be considered. Fetal cardiac intervention in pulmonary stenosis is not currently routinely used and is limited to cases of pulmonary atresia/intact ventricular septum with evolving right ventricular hypoplasia.
Magnetic Resonance Imaging and Computed Tomography
For most patients with isolated pulmonary valve stenosis, echocardiography is the main imaging tool to estimate the valvar gradient, and indication for transcatheter therapy is usually based on a combination of echocardiographic and clinical data. Although cross-sectional techniques, such as magnetic resonance angiography ( Fig. 42.22 ) or computed multislice spiral tomography, are considered to be less invasive than cardiac catheterization, these imaging modalities are rarely needed in the evaluation of simple pulmonary valve stenosis. If the baseline gradient by echocardiography suggests the need for (transcatheter) intervention, then adding computed multislice spiral tomography prior to cardiac catheterization would expose the patient to additional radiation without necessarily adding to the medical decision making at the time of cardiac catheterization. Conversely, in a patient who does not meet any indication for valvar intervention based on echocardiographic data, adding computed tomography evaluation is unlikely to change management.
Cardiac magnetic resonance imaging (MRI) and angiography may have a role in selected patients and has an advantage over computed tomography evaluation due to the lack of radiation exposure. These imaging modalities may complement (not supplement) standard imaging in selected patients, such as those with supravalvar pulmonary stenosis. Furthermore, they offer the ability to not only obtain anatomic dimensions but also physiologic data such as right ventricular function and volumes, estimated gradients, and pulmonary regurgitant fraction. However, advantages in small children may still be offset by the need for general anesthesia in some patients, even though advances have allowed the technique to expand to smaller children without general anaesthesia.
Whereas cross-sectional techniques, particularly three-dimensional reconstructions ( Fig. 42.23 ), are helpful when the pulmonary trunk and its branches are being assessed, especially in relation to surrounding structures, they are less helpful in assessment of the pulmonary valve. However, future technologic advances in the speed of acquisition of images, ECG gating, and postprocessing may enhance the utility of MRI in the evaluation of isolated pulmonary valve stenosis. At present, however, it is likely that more information about the morphology of the pulmonary valve will be available with echocardiography (including three-dimensional echo).
Cardiac Catheterization and Angiography
Diagnostic cardiac catheterization has been almost completely superseded by less invasive techniques, such as echocardiography, for the assessment of pulmonary valve stenosis, and is now undertaken only to perform catheter interventions or if additional associated anomalies (such as branch pulmonary artery stenosis) warrant cardiac catheterization. The one advantage of cardiac catheterization over other imaging techniques is the accurate measurement of ventricular and pulmonary arterial pressures. It is important to remember that in contrast to Doppler echocardiography, which estimates peak instantaneous differences in pressure across the stenosis (see Fig. 42.19 ), gradients obtained in the catheterization laboratory through a pullback technique show a peak-to-peak difference in pressure between the sites of measurement, which is usually up to 25% to 40% lower than the peak instantaneous Doppler gradient ( Fig. 42.24 ). Importantly though, hemodynamic evaluation alone does not justify a diagnostic cardiac catheterization unless the patient is considered for possible balloon pulmonary valvuloplasty.
Key Diagnostic Features
The key features are summarized in Box 42.1 .
Physical Examination
- ▪
Physical signs of right ventricular hypertrophy
- ▪
Systolic ejection click (unless severe)
- ▪
Ejection systolic murmur, second left intercostal space and back
- ▪
Wide splitting of the second heart sound (depending on severity)
- ▪
Reduced intensity of P2 (depending on severity)
- ▪
Associated thrill (depending on severity)
Investigations
- ▪
Right ventricular hypertrophy on electrocardiogram
- ▪
Echocardiography
- ▪
Thickened and doming valve
- ▪
Evidence of turbulence and flow acceleration at pulmonary valve
- ▪
Hemodynamics and Physiology
The consequence of obstruction at the right ventricular outflow necessitates an increase in right ventricular pressure to force blood through the stenosed valve. The right ventricular pressure that develops is usually proportional to the degree of obstruction present. If stenosis develops early in fetal or neonatal life, right ventricular mass increases by ventricular myocytic hyperplasia, and there is also hyperplasia of the supporting apparatus, such as the capillaries supplying blood to the myocytes, so that the density of capillaries remains normal. In this way in neonates, the capacity for the right ventricle to generate high pressures and tolerate moderate stenosis is high. Where pulmonary stenosis develops later in life, after the neonatal period, the capacity for hyperplasia is lost, and any increases in ventricular bulk are due to a hypertrophic response. There is a compensatory increase in capillary supply, but this does not compensate for the increase in ventricular myocardial mass, and there is a reduction in capillary density. Thus the capacity of the ventricle to sustain high pressures and tolerate stenosis is less than in the newborn. In the fetus, severe forms of pulmonary stenosis may result in a circulation that resembles pulmonary atresia and right ventricular development may be impaired, resulting in the development of a hypertrophic right ventricle with a hypoplastic cavity.
When right ventricular dilation is severe, interventricular interaction may occur, such that the left ventricle is constrained within the pericardium, impairing its ability to fill and contributing to the compromised circulation. Central cyanosis can occur in neonates when there is a duct-dependent pulmonary circulation or when right ventricular diastolic dysfunction allows right atrial to exceed left atrial pressure, producing a cyanotic shunt across a defect in the atrial septum.
Natural History
Mild pulmonary valve stenosis with a gradient of less than 40 mm Hg that is seen after the first 6 months of life is, in general, a benign condition. The severity of the disease may even improve as the child grows, certainly with a very low incidence of deterioration to the point of requiring an intervention. In children with moderate or even severe pulmonary stenosis, right ventricular function seems to be maintained. When first seen in infancy, however, even mild pulmonary stenosis can progress and deteriorate. Using Doppler echocardiography monitoring, 25% of infants with mild pulmonary stenosis in the neonatal period were shown to develop further significant stenosis, and up to half of these patients require intervention. Not all of these cases can be explained solely by a postnatal drop in pulmonary vascular resistance. Thus it is important to monitor infants carefully, especially when the diagnosis is made in the neonatal period, regardless of their severity of pulmonary stenosis. The appearance of the valve in terms of the thickness and mobility of the leaflets is only weakly predictive of future deterioration.
In patients with deteriorating pulmonary stenosis and intact ventricular septum, right ventricular pressure may, over time, exceed left ventricular pressure. The ventricular pressure waveform changes from a broad-based triangular shape with early peak maximal pressure ( Fig. 42.25 ) to a tall peaked waveform with the point of maximal pressure delayed to close to the end of systole ( Fig. 42.26 ). Compensation for fixed severe stenosis with right ventricular hypertrophy can fail as the patient grows and further demands are made on the ventricle. At this stage, the right ventricle may decompensate by dilating, and there is heart failure. Further compensatory mechanisms for low cardiac output include increased extraction of oxygen. During exercise, even this compensatory mechanism is insufficient, and exercise intolerance is noted, often with the presence of peripheral cyanosis.
