Diagnosis and management of acyanotic heart disease: Part I - obstructive lesions
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《美国医学杂志》
Division of Pediatric Cardiology, University of Texas-Houston Medical School, Medical Director, Childrens Heart Institute, Memorial Hermann Childrens Hospital, Houston, Texas, USA
Abstract
In this review, the clinical features and management of most commonly encountered acyanotic obstructive cardiac lesions are discussed. Mild lesions, especially in children are usually asymptomatic while neonates and infants may present with symptoms. Ejection systolic murmurs in patients with pulmonic and aortic stenosis and decreased femoral pulses and blood pressure difference (>20 mmHg) between arms and leg in patients with aortic coarctation are usually seen. Clinical diagnosis is not difficult and the diagnosis can be confirmed and quantitiated by non-invasive echocardiographic studies. Whereas surgical intervention was used in the past, balloon dilatation appears to be effective in the treatment of these lesions.
Keywords: Pulmonary stenosis; Aortic stenosis; Coarctation of the aorta; Balloon valvuloplasty; Balloon angioplasty
Congenital heart defects (CHDs) may be classified into acyanotic and cyanotic, depending upon whether the patients clinically exhibit cyanosis. The acyanotic defects may further be subdivided into obstructive lesions and left-to-right shunt lesions. The cyanotic defects, by definition, have right-to-left shunt. In this review obstructive cardiac lesions will be discussed. The objective of this review is to describe the important findings in history, physical examination and laboratory studies that are suggestive of the diagnosis of the respective obstructive lesions and to discuss the available options in the management of these defects.
Obstructive lesions
When there is a significant narrowing of a valve or a blood vessel, there is a higher pressure proximal to the obstruction compared to the distal pressure; this pressure gradient is necessary to maintain flow across the stenotic site. Hypertrophy of the cardiac chamber proximal to the obstruction and flow disturbance across the site of' obstruction and their effects will determine the clinical features. More commonly encountered obstructive lesions, namely pulmonary stenosis, aortic stenosis and coarctation of the aorta will be reviewed.
Pulmonary Stenosis
The obstruction can be at valvar, subvalvar or supravalvar sites or in the branch pulmonary arteries. Valvar stenosis is the most common type and will be discussed in this section. Valvar pulmonary stenosis (PS) constitutes 7.5% to 9.0% of all CHDs.[1] The pathologic features of valvar stenosis vary, but the most commonly found pathology is what is described as "dome shaped" pulmonary valve with fusion of the thickened pulmonary valve leaflets. Hypertrophy of the right ventricle (proportional to the degree of obstruction) and dilatation of main pulmonary artery (not related to the severity of obstruction) are also seen.
Symptoms: Children with PS usually present with asymptomatic murmurs, although they can present with signs of systemic venous congestion (usually interpreted as congestive heart failure) due to severe right ventricular dysfunction or cyanosis because of right-to-left shunt across the atrial septum.
Physical Findings: The right ventricular and the right ventricular outflow tract impulses are increased and a heave may be felt at the left lower and upper sternal border. A thrill may be felt at the left upper sternal border and/or in the suprasternal notch. The first heart sound may be normal or loud. The second heart sound is variable, depending upon the degree of obstruction and will be detailed latter in this section. An ejection systolic click is heard in most cases of valvar stenosis. The click is heard best at the left lower, mid and upper sternal borders and varies with respiration (decreases or disappears with inspiration). An ejection systolic Figure1 is heard best at the left upper sternal border and it radiates into infraclavicular regions, axillae and back. The intensity of the murmur may vary between grades II to V/VI; the intensity is not necessarily related to the severity of the stenosis.
Clinical assessment of severity. The timing of the click, the extent of splitting of the second sound, the intensity of the pulmonary component of the second sound, the length (duration) of the murmur, and timing of peaking of the systolic murmur are usually suggestive of the severity of pulmonary valve obstruction Figure1.[2] In mild cases of pulmonary valve narrowing, the click is clearly separated from the first heart sound, almost normal splitting of the second heart sound with normal or slightly increased pulmonary component of the second sound is heard, and an ejection systolic, diamond-shaped murmur that peaks early in systole and ends way before the aortic closure of the second heart sound is appreciated. The findings in moderate PS include an ejection systolic click that is much closer to the first heart sound than in milder forms Figure1, widely split second sound with diminished pulmonary component of the second sound and an ejection systolic murmur that peaks in mid to late systole and ends just before the aortic component of the second sound. The features of severe valvar PS are an ejection systolic click which is either not present or falls so close to the first heart sound that it becomes inseparable from it, markedly increased splitting with a soft or inaudible pulmonary component of the second heart sound, and a long ejection systolic murmur that peaks late in systole and extends beyond the aortic component of the second sound so that the latter cannot be heard. The loudness of the ejection systolic murmur does not indicate the severity of obstruction but rather its duration and time of peaking; the longer the murmur and the later it peaks, the more severe is the PS. Similarly, the shorter the time interval between the first heart sound and ejection click, the wider the splitting of the second heart sound, and softer the pulmonary component, the more severe is the degree of pulmonary valve obstruction.[2]
Noninvasive evaluation: Chest X-ray, in most cases, shows no cardiomegaly, but a characteristically dilated main pulmonary artery segment (post-stenotic dilatation) is visualized Figure2. The magnitude of pulmonary artery dilatation has no bearing on the severity of pulmonary valve stenosis. The electrocardiogram shows right ventricular hypertrophy Figure3; the degree of right ventricular hypertrophy is proportional to the severity of stenosis. Right atrial enlargement may be present. Echocardiogram shows right ventricular enlargement without paradoxical septal motion and thickened and domed pulmonary valve leaflets. The Doppler flow velocity across the site of obstruction is increased and the magnitude of this increase reflects the severity of pulmonary valve stenosis. The peak instantaneous pressure gradient can be calculated by the use of a modified Bernoulli equation:
D P = 4 V2
where D P is instantaneous peak pressure gradient in mmHg and V is the peak velocity across the valve in meters/sec.
It was initially thought that the peak instantaneous gradient is reflective of the peak-to-peak systolic gradient measured during cardiac catheterization; however, the peak instantaneous gradient over-estimates the peak-to-peak gradient, presumably related to pressure recovery phenomenon.[3] In our experience, the catheter peak-to-peak gradient is somewhere in between Doppler peak instantaneous and mean gradients.
Cardiac Catheterization and Selective Cineangiography. Though these procedures are not required for diagnosing valvar PS, they are usually required prior to therapeutic intervention, to be discussed below. The oxygen saturation data usually do not show evidence for left-to-right shunts. A right-to-left shunt across the patent foramen ovale (or an atrial defect) may be present in moderate to severe pulmonary valve obstruction. Right atrial pressure (particularly 'a' wave) may be increased. The right ventricular peak systolic pressure is increased.[4],[5] Transpulmonary valve peak-to-peak gradient is indicative of severity of obstruction. A peak-to-peak gradient in excess of 50 mmHg is usually considered an indication for therapeutic intervention. Right ventricular angiogram usually reveals thickened and domed pulmonary valve leaflets Figure4 with a thin jet of passage of contrast across the pulmonary valve. Enlargement of the right ventricle and dilated main pulmonary artery segment are also seen. In patients with severe or long-standing pulmonary valve obstruction, infundibular constriction may be seen.[6]
Management: Until early 1980s, surgical pulmonary valvotomy was the only treatment available, but at the present time relief of pulmonary valve obstruction can be accomplished by balloon pulmonary valvuloplasty. Indeed, at the present time balloon pulmonary valvuloplasty is treatment of choice. The indications for intervention are similar to those prescribed for surgery: a peak-to-peak systolic pressure gradient > 50 mmHg across the pulmonary valve with a normal cardiac index.[7] Detailed description of the procedure of balloon valvuloplasty and the results of such a procedure are beyond the scope of this presentation. In brief, a balloon catheter (with a deflated balloon) is positioned across the pulmonary valve and the balloon inflated Figure5; the radial forces of balloon inflation produce valve leaflet commissural disruption and thus relief of pulmonary valve obstruction. Although the initial recommendations are use a balloon 1.2 to 14 time the valve annulus,[8],[9] the current recommendations are to use a balloon that is 1.2 to 1.25 times the size of the pulmonary valve annulus.[10],[11] When the pulmonary valve annulus is too large to dilate with a single balloon, valvuloplasty with simultaneous inflation of two balloons across the pulmonary valve annulus is recommended. Both immediate and short-term results of balloon pulmonary valvuloplasty are good; long term results are limited.[12],[13]
Occasionally surgical pulmonary valvotomy under cardiopulmonary bypass may become necessary when there is severe supravalvar stenosis, significant valve annulus hypoplasia or severely dysplastic pulmonary valves. Similarly persistent and severe infundibular narrowing despite successful balloon pulmonary valvuloplasty may also require surgical intervention.
In patients with mild pulmonary valve stenosis, periodic clinical follow-up and antibiotic prophylaxis prior to any bacteremia-producing procedures to prevent subacute bacterial endocarditis are recommended. Routine well-child care, including routine immunizations, as per the primary care physician is indicated. There is no need to limit their exercise or activity level.
Aortic Stenosis
Left ventricular outflow tract obstruction may occur at valvar, subvalvar (fixed subaortic stenosis and idiopathic hypertrophic subaortic stenosis) and supravalvar locations. Valvar stenosis is the most common form and will be discussed in this section. The prevalence of congenital valvar aortic stenosis (AS) is 5% to 6% of patients with CHD.[1] Pathology of the stenotic aortic valve is variable, most commonly it is a bicuspid valve with varying degrees of commissural fusion of thickened, domed, nonpliable valve leaflets. Tricuspid and rarely unicuspid aortic valve leaflets can also cause aortic valve obstruction. Dysplasia of the aortic valve leaflets with or without hypoplasia of the valve ring may be found in neonates and young infants. Calcification of the aortic valve leaflets so frequently seen in the elderly, is uncommon during childhood. Dilatation of ascending aorta, post-stenotic dilatation, is seen in most cases, and the extent of aortic dilatation is independent of the severity of aortic obstruction. Hypertrophy of the left ventricular muscle is concentric in nature and is largely proportional to the degree of obstruction.
Symptoms. The majority of children with valvar AS are asymptomatic and detected because of a cardiac murmur heard on routine auscultation. When symptoms are exhibited, dyspnea, easy fatigability or chest pain are the presenting complaints. Syncope may be a presenting complaint in some children with severe AS. In contradistinction to children, neonates and young infants usually present with dyspnea and signs of heart failure.
Physical Findings: The left ventricular impulse is increased (left ventricular heave) in all but mild cases. A thrill may be felt it the right upper sternal border and/or in the suprasternal notch. The first heart sound is usually normal. The second heart sound is also normal unless the aortic stenosis is extremely severe when there may be a paradoxical splitting of the second heart sound. An ejection systolic click is heard best at the apex and left mid and right upper sternal borders and the click does not vary with respiration. An ejection systolic murmur of grade II-V/VI intensity is usually heard best at the right upper sternal border with radiation into both carotid arteries. The arterial pulses are usually normal.
Noninvasive Evaluation: Chest roentgenogram, in most cases, shows a normal sized heart but may frequently reveal an enlarged ascending aorta, a sign of post-stenotic dilatation. The electrocardiogram may be normal or may show varying degrees of left ventricular hypertrophy. Inverted T waves in the left chest leads indicate that aortic valve obstruction is severe. However, not all severe AS patients show T wave inversion. None of the above described clinical and laboratory data have any predictive value in determining the severity of aortic obstruction; this is in contradistinction to the predictive value of auscultatory findings in valvar pulmonary stenosis described in the preceding section.
Echocardiogram may show thickened and domed aortic valve leaflets Figure6 usually bicuspid Figure7, with eccentric opening. The left ventricular muscle may be thickened and its shortening fraction may be increased, depending upon the severity of AS. Doppler flow velocity across the aortic valve is increased and can be used to quantitate peak instantaneous gradient across the aortic valve in a manner similar to that described for the pulmonary valve. However, Doppler-derived mean systolic gradient appears to reflect peak-to-peak catheter gradient (see below) more accurately than peak instantaneous Doppler gradients; this is presumably related to pressure recovery phenomenon[3] alluded to in the pulmonary stenosis section. Mild degree aortic insufficiency may be seen by color Doppler, even in patients without auscultatory evidence for aortic regurgitation.
Catheterization and Angiography: The data show elevated left ventricular peak systolic pressure with a peak-to-peak pressure gradient across the aortic valve indicative of the severity of obstruction. Angiography will confirm, thickened domed aortic valve leaflets and exclude any other abnormalities.
Management: The indications for intervention in valvar AS is a peak-to-peak gradient >50 mmHg with either symptoms or electrocardiographic ST-T wave changes or a peak gradient >70 mmHg irrespective of symptoms or ECG changes.[14],[15] When pressure gradients are used as criteria for intervention (instead of valve area), it must be assured that the cardiac index is normal during pressure measurement. The available options are surgical aortic valvotomy, percutaneous balloon aortic valvuloplasty and valve replacement.[14] Since the introduction of balloon valvuloplasty for valvar AS in 1983, increasing number of pediatric cardiologists, including the author have been using balloon aortic valvuloplasty as a first therapeutic procedure for relief of aortic valve obstruction. When surgery is chosen, commissurotomy is performed on cardiopulmonary bypass and transverse aortotomy. If the aortic valve is not repairable because of valve dysplasia, severe aortic insufficiency or annular hypoplasia, aortic valve replacement may be necessary. The aortic valve may be replaced with a mechanical valve, allograft or autograft (Ross procedures).[14] When balloon valvuloplasty Figure8 is performed, a balloon diameter size equal to the size of the aortic valve annulus is chosen for valvuloplasty. Immediate results following balloon aortic valvuloplasty are encouraging[15],[16],[17] with immediate reduction of the gradient. At short-term follow-up recurrence requiring reintervention may be necessary in 20% patients. Only limited long-term results are available to-date;[13] but, the existing data suggest development of significant aortic insufficiency in 25% patients.
For milder forms of AS, subacute bacterial endocarditis prophylaxis and periodic follow-up are necessary. Restriction from participation in competitive sports is recommended for all but mildest forms of AS. Issues related to management of the fetus and neonate with critical aortic valve stenosis are beyond the scope of this review and will not be reviewed.
Coarctation of the Aorta
The prevalence of coarctation of the aorta (CoA) was found to vary between 5.1% and 8.1 % of CHDs[1]; however, coarctation may be found more frequently in infants presenting with symptoms prior to one year of age. In the past, CoA was designated as preductal (or infantile) or postductal (or adult) type, depending on whether the coarctation segment was proximal or distal to the ductus arteriosus, respectively. However, a closer examination of the anatomy suggests that all coarctations are juxtaductal.[18] The coarctation may be discrete, or a long segment of the aorta may be narrowed; the former is more common. Classic CoA is located in the thoracic aorta distal to the origin of the left subclavian artery, at about the level of the ductal structure. However, rarely, a coarcted segment may be present in the abdominal aorta. Varying degrees of hypoplasia of the isthmus of the aorta (the portion of the aorta between the origin of the left subclavian artery and the ductus arteriosus) and transverse aortic arch (the arch between the origin of the innominate artery and the left subclavian artery) are present in the majority of patients with CoA; this hypoplasia may be significant in symptomatic CoA of the neonate and infant, whereas in older children there may be only a mild degree of narrowing. The most commonly associated defects are patent ductus arteriosus, ventricular septal defect and AS. The younger the infant presents, the more likely that there is a significant associated defect. Bicuspid aortic valve and abnormal mitral valve are also seen. Sometimes, CoA is a complicating feature of more complex, cyanotic heart defects, such as transposition of the great arteries, Taussig-Bing anomaly More Details, double-inlet left ventricle, tricuspid atresia with transposition of the great arteries, and hypoplastic left heart syndrome.
Symptoms: Children beyond infancy usually are asymptomatic; an occasional child will complain of pain or weakness in the legs. Most often, the coarctation is detected because of a murmur or hypertension found on a routine examination. Neonates and infants are more likely present with symptoms associated with congestive heart failure.
Physical Findings: A clinical diagnosis of CoA is best made by simultaneous palpation of femoral and brachial pulses. The left ventricular impulse may be increased. A thrill is usually felt in the suprasternal notch. The first and second heart sounds are usually normal in isolated aortic coarctation. Since a large percentage (up to 60%) of patients with CoA have associated bicuspid aortic valves, an ejection systolic click may be heard at right upper and left mid sternal borders and apex; this click does not change with respiration. An ejection systolic murmur may be heard at left or right upper sternal borders, but is usually heard best over the back in the interscapular regions. Some times a continuous murmur may be heard in the left interscapular region secondary to continuous flow in the coarcted segment or on the back (secondary to flow in the collateral vessels). Palpation of the brachial and femoral artery pulses simultaneously will reveal decreased and delayed or absent femoral pulses. Blood pressure in both arms and one leg must be determined: a pressure difference of more than 20 mmHg in favor of arms may be considered as evidence for coarctation of the aorta. Involvement of the left subclavian artery in the coarctation or anomalous origin of the right subclavian artery (below the level of coarctation) may produce decreased or absent left or right brachial pulses, respectively, and therefore palpation of both brachial pulses and measurement of blood pressure in both arms are important.
Neonates and infants usually have signs of the associated cardiac defects (for example ventricular septal defect) and other signs of heart failure such as hepatomegaly and tachypnea.
Noninvasive Evaluation: Chest x-ray may show a normal sized heart or the heart may be mildly enlarged. Other roentgenographic features include a "3" sign on a highly penetrated chest x-ray, inverted "3" sign of the barium filled esophagus and rib-notching (secondary to collateral vessels); these latter signs are seen in older children. The electrocardiogram may be normal or may show left ventricular hypertrophy. In neonates and infants, there may be predominant right ventricular hypertrophy. Echocardiographic studies usually reveal the coarctation in suprasternal notch, two-dimensional echocardiographic views of the aortic arch Figure9. Increased Doppler flow velocity in the descending aorta by continuous-wave Doppler Figure9 and demonstrable jump in velocity at the coarcted segment by pulsed-Doppler technique are usually present. Extension of the Doppler flow signal into the diastole is indicative of significant obstruction. Instantaneous peak pressure gradients across the aortic coarctation can be calculated by employing modified Bernoulli equation in manner similar to that described for PS and AS. Because of higher proximal velocity, coarctation gradients may be more accurately estimated by:
D P = 4 (V22 - V12)
where D P is peak instantaneous gradient and V2 and V1 are peak Doppler velocities in the descending aorta distal to the coarctation (continuous wave Doppler) and proximal to the coarctation (pulsed Doppler), respectively.
But the calculated gradient is usually an over-estimation, especially if there is no diastolic extension of the Doppler velocity.[19]
Catheterization and Angiography: In isolated aortic coarctation, elevation of left ventricular and ascending aortic peak systolic pressure with a significant peak-to-peak pressure gradient across the coarctation is found. Selective aortic root or aortic arch angiography is necessary to clearly demonstrate the aortic narrowing [Figure - 10].
Management: Significant hypertension and/or congestive heart failure are indications for intervention. In the presence of congestive heart failure, conventional anticongestive measures including digitalis and diuretics should be promptly instituted. In the presence of hypertension, it is better to relieve the obstruction promptly rather than attempting to "treat" hypertension with antihypertensive drugs. Aortic coarctation may be relieved either by surgery, balloon angioplasty or percutaneous stent deployment. Symptomatic children should undergo relief of coarctation soon after the child is stabilized. Asymptomatic children should undergo the procedure electively. If neither hypertension nor heart failure are present, elective relief of the obstruction between the ages of 2 and 5 years is suggested. Waiting beyond 5 years is not advisable because of evidence for residual hypertension if the aortic obstruction is not relieved by the age of 5 years.
Surgical relief of aortic coarctation is the conventional treatment option. Since the description balloon angioplasty in 1983, increasing number of cardiologists, including our group, have used this technique for relief of aortic coarctation. There is a reasonable consensus that children (> 1 year) are good candidates for balloon angioplasty. While I believe that balloon angioplasty is the treatment option of choice for relief of native aortic coarctations even in the neonate and infant,[20] the overall consensus seems to be in favor of surgical intervention. Stents seem to be emerging as therapeutic procedure of choice in the adolescent and adult with aortic coarctation.[21],[22]
When surgical option is chosen, resection and end-to-end anastomosis, subclavian flap angioplasty or prosthetic patch angioplasty may be used depending upon anatomy of the aortic arch and coarctation as well as surgeon's preference. Prosthetic patch angioplasty is no longer used because of development of aneurysms at long term follow-up. When balloon angioplasty [Figure - 11] is contemplated, the balloon size should be carefully chosen: the diameter of the balloon should be two or more times the size of the coarcted segment, but no larger than the diameter of the descending aorta at the level of diaphragm. Balloon angioplasty is not suitable for treatment of long segment coarctations. The immediate [Figure - 12], [Figure - 13], [Figure - 14] and intermediate-term results of balloon coarctation angioplasty have been good [23],[24] although long-term follow-up is scanty.[13]
More recently stents have been used effectively to treat coarctation in adolescents and adults, particularly if a long segment is involved.
References
1. Fyler DC, ed. Nadas' Pediatric Cardiology, Hanley & Belfus, Inc., Philadelphia, PA, 1992.
2. Rao PS. Evaluation of cardiac murmurs in children. Indian J Pediat 1991; 58: 4 71-489.
3. Singh GK, Balfour IC, Chen S, Ferdman B, Jureidini SB, Fiore AC et al. Lesion specific pressure recovery phenomenon in pediatric patients: a simultaneous Doppler and catheter correlative study (
Abstract). J Am Coll Cardiol 2003; 41: 493A.
4. Rudolph AM: Congenital Disease of the Heart. Year-Book Medical Publishers, Inc., Chicago, IL, 1974.
5. Rao PS. Pulmonary valve disease. In, eds. Alpert JS, Dalen JE, Rahimtoola, eds. Valvular Heart Disease , 3rd edn. Lippencott Raven, Philadelphia, PA, 2000; 339-376.
6. Thapar MK, Rao PS. Significance of infundibular obstruction following balloon valvuloplasty for valvar pulmonic stenosis. Am Heart J 1989; 118: 99-103.
7. Rao PS. Indications for balloon pulmonary valvuloplasty (Editorial). Amer Heart J 1988; 116: 1661-1662.
8. Rao PS. Balloon pulmonary valvuloplasty. J Intervent Cardiol 1998; 11: 303-18.
9. Rao PS. How big a balloon and how many balloons for pulmonary valvuloplasty (Editorial). Am Heart J 1988; 116: 577-580.
10. Rao PS. Late pulmonary insufficiency after balloon dilatation of the pulmonary valve (Letter). Cathet Cardiovasc Intervent 2000; 49: 118-119.
11. Rao PS. Balloon pulmonary valvuloplasty (Editorial). J Saudi Heart Assoc 2003; 15: 1-4.
12. Rao PS, Galal O, Patnana M et al. Results of three-to-ten year follow-up of balloon dilatation of the pulmonary valve. Heart 1998; 80: 591-595.
13. Rao PS. Long-term follow-up results after balloon dilatation of pulmonic stenosis, aortic stenosis and coarctation of the aorta: a review. Progr Cardiovasc Dis 1999; 42: 59-74.
14. Singh GK, Rao PS. Left heart outflow obstructions. In Crawford MH, DiMarco JP, Paulus WJ, eds. Cardiology, 2nd edn. Mosby International, Edinburgh, 2004; 1317-1326.
15. Rao PS. Balloon aortic valvuloplasty. J Intervent Cardiol 1998;11: 319-29.
16. Rao PS, Thapar MK, Wilson AD, Levy JM, Chopra PS. Intermediate-term follow-up results of balloon aortic valvuloplasty in infants and children with special reference to causes of restenosis. Am J Cardiol 1989; 64: 1356-1360.
17. Galal O, Rao PS, Al-Fadley F, Wilson AD. Follow-up results of balloon aortic valvuloplasty in children with special reference to causes of late aortic insufficiency. Am Heart J 1997; 113: 418-427.
18. Rao PS. Coarctation of the aorta. In Ram CVC, ed. Secondary Forms of Hypertension. W.B. Saunders, Philadelphia, PA 1995; 15(2): 81-105.
19. Rao PS, Carey P. Doppler ultrasound in the prediction of pressure gradients across aortic coarctation. Am Heart J 1989; 118: 299-301.
20. Rao PS. Current status of balloon angioplasty for neonatal and infant aortic coarctation. Progress Pediats Cardiol 2001; 14: 35-44.
21. Rao PS. Stents in the treatment of aortic coarctation (Editorial). J Am Coll Cardiol 1997; 30: 1853-1855.
22. Rao PS. Stents in the management of congenital heart disease in the pediatric and adult patients. Indian Heart J 2001; 53: 714-730.
23. Rao PS, Galal O, Smith PA, Wilson AD. Five-to-nine-year follow-up results of balloon angioplasty of native aortic coarctation in infants and children. J Am Coll Cardiol 1996; 27: 462-470.
24. Rao PS. Interventional pediatric cardiology: state of the art and future directions. Pediatric Cardiol 1998; 19: 107-204.(Syamasundar Rao P)
Abstract
In this review, the clinical features and management of most commonly encountered acyanotic obstructive cardiac lesions are discussed. Mild lesions, especially in children are usually asymptomatic while neonates and infants may present with symptoms. Ejection systolic murmurs in patients with pulmonic and aortic stenosis and decreased femoral pulses and blood pressure difference (>20 mmHg) between arms and leg in patients with aortic coarctation are usually seen. Clinical diagnosis is not difficult and the diagnosis can be confirmed and quantitiated by non-invasive echocardiographic studies. Whereas surgical intervention was used in the past, balloon dilatation appears to be effective in the treatment of these lesions.
Keywords: Pulmonary stenosis; Aortic stenosis; Coarctation of the aorta; Balloon valvuloplasty; Balloon angioplasty
Congenital heart defects (CHDs) may be classified into acyanotic and cyanotic, depending upon whether the patients clinically exhibit cyanosis. The acyanotic defects may further be subdivided into obstructive lesions and left-to-right shunt lesions. The cyanotic defects, by definition, have right-to-left shunt. In this review obstructive cardiac lesions will be discussed. The objective of this review is to describe the important findings in history, physical examination and laboratory studies that are suggestive of the diagnosis of the respective obstructive lesions and to discuss the available options in the management of these defects.
Obstructive lesions
When there is a significant narrowing of a valve or a blood vessel, there is a higher pressure proximal to the obstruction compared to the distal pressure; this pressure gradient is necessary to maintain flow across the stenotic site. Hypertrophy of the cardiac chamber proximal to the obstruction and flow disturbance across the site of' obstruction and their effects will determine the clinical features. More commonly encountered obstructive lesions, namely pulmonary stenosis, aortic stenosis and coarctation of the aorta will be reviewed.
Pulmonary Stenosis
The obstruction can be at valvar, subvalvar or supravalvar sites or in the branch pulmonary arteries. Valvar stenosis is the most common type and will be discussed in this section. Valvar pulmonary stenosis (PS) constitutes 7.5% to 9.0% of all CHDs.[1] The pathologic features of valvar stenosis vary, but the most commonly found pathology is what is described as "dome shaped" pulmonary valve with fusion of the thickened pulmonary valve leaflets. Hypertrophy of the right ventricle (proportional to the degree of obstruction) and dilatation of main pulmonary artery (not related to the severity of obstruction) are also seen.
Symptoms: Children with PS usually present with asymptomatic murmurs, although they can present with signs of systemic venous congestion (usually interpreted as congestive heart failure) due to severe right ventricular dysfunction or cyanosis because of right-to-left shunt across the atrial septum.
Physical Findings: The right ventricular and the right ventricular outflow tract impulses are increased and a heave may be felt at the left lower and upper sternal border. A thrill may be felt at the left upper sternal border and/or in the suprasternal notch. The first heart sound may be normal or loud. The second heart sound is variable, depending upon the degree of obstruction and will be detailed latter in this section. An ejection systolic click is heard in most cases of valvar stenosis. The click is heard best at the left lower, mid and upper sternal borders and varies with respiration (decreases or disappears with inspiration). An ejection systolic Figure1 is heard best at the left upper sternal border and it radiates into infraclavicular regions, axillae and back. The intensity of the murmur may vary between grades II to V/VI; the intensity is not necessarily related to the severity of the stenosis.
Clinical assessment of severity. The timing of the click, the extent of splitting of the second sound, the intensity of the pulmonary component of the second sound, the length (duration) of the murmur, and timing of peaking of the systolic murmur are usually suggestive of the severity of pulmonary valve obstruction Figure1.[2] In mild cases of pulmonary valve narrowing, the click is clearly separated from the first heart sound, almost normal splitting of the second heart sound with normal or slightly increased pulmonary component of the second sound is heard, and an ejection systolic, diamond-shaped murmur that peaks early in systole and ends way before the aortic closure of the second heart sound is appreciated. The findings in moderate PS include an ejection systolic click that is much closer to the first heart sound than in milder forms Figure1, widely split second sound with diminished pulmonary component of the second sound and an ejection systolic murmur that peaks in mid to late systole and ends just before the aortic component of the second sound. The features of severe valvar PS are an ejection systolic click which is either not present or falls so close to the first heart sound that it becomes inseparable from it, markedly increased splitting with a soft or inaudible pulmonary component of the second heart sound, and a long ejection systolic murmur that peaks late in systole and extends beyond the aortic component of the second sound so that the latter cannot be heard. The loudness of the ejection systolic murmur does not indicate the severity of obstruction but rather its duration and time of peaking; the longer the murmur and the later it peaks, the more severe is the PS. Similarly, the shorter the time interval between the first heart sound and ejection click, the wider the splitting of the second heart sound, and softer the pulmonary component, the more severe is the degree of pulmonary valve obstruction.[2]
Noninvasive evaluation: Chest X-ray, in most cases, shows no cardiomegaly, but a characteristically dilated main pulmonary artery segment (post-stenotic dilatation) is visualized Figure2. The magnitude of pulmonary artery dilatation has no bearing on the severity of pulmonary valve stenosis. The electrocardiogram shows right ventricular hypertrophy Figure3; the degree of right ventricular hypertrophy is proportional to the severity of stenosis. Right atrial enlargement may be present. Echocardiogram shows right ventricular enlargement without paradoxical septal motion and thickened and domed pulmonary valve leaflets. The Doppler flow velocity across the site of obstruction is increased and the magnitude of this increase reflects the severity of pulmonary valve stenosis. The peak instantaneous pressure gradient can be calculated by the use of a modified Bernoulli equation:
D P = 4 V2
where D P is instantaneous peak pressure gradient in mmHg and V is the peak velocity across the valve in meters/sec.
It was initially thought that the peak instantaneous gradient is reflective of the peak-to-peak systolic gradient measured during cardiac catheterization; however, the peak instantaneous gradient over-estimates the peak-to-peak gradient, presumably related to pressure recovery phenomenon.[3] In our experience, the catheter peak-to-peak gradient is somewhere in between Doppler peak instantaneous and mean gradients.
Cardiac Catheterization and Selective Cineangiography. Though these procedures are not required for diagnosing valvar PS, they are usually required prior to therapeutic intervention, to be discussed below. The oxygen saturation data usually do not show evidence for left-to-right shunts. A right-to-left shunt across the patent foramen ovale (or an atrial defect) may be present in moderate to severe pulmonary valve obstruction. Right atrial pressure (particularly 'a' wave) may be increased. The right ventricular peak systolic pressure is increased.[4],[5] Transpulmonary valve peak-to-peak gradient is indicative of severity of obstruction. A peak-to-peak gradient in excess of 50 mmHg is usually considered an indication for therapeutic intervention. Right ventricular angiogram usually reveals thickened and domed pulmonary valve leaflets Figure4 with a thin jet of passage of contrast across the pulmonary valve. Enlargement of the right ventricle and dilated main pulmonary artery segment are also seen. In patients with severe or long-standing pulmonary valve obstruction, infundibular constriction may be seen.[6]
Management: Until early 1980s, surgical pulmonary valvotomy was the only treatment available, but at the present time relief of pulmonary valve obstruction can be accomplished by balloon pulmonary valvuloplasty. Indeed, at the present time balloon pulmonary valvuloplasty is treatment of choice. The indications for intervention are similar to those prescribed for surgery: a peak-to-peak systolic pressure gradient > 50 mmHg across the pulmonary valve with a normal cardiac index.[7] Detailed description of the procedure of balloon valvuloplasty and the results of such a procedure are beyond the scope of this presentation. In brief, a balloon catheter (with a deflated balloon) is positioned across the pulmonary valve and the balloon inflated Figure5; the radial forces of balloon inflation produce valve leaflet commissural disruption and thus relief of pulmonary valve obstruction. Although the initial recommendations are use a balloon 1.2 to 14 time the valve annulus,[8],[9] the current recommendations are to use a balloon that is 1.2 to 1.25 times the size of the pulmonary valve annulus.[10],[11] When the pulmonary valve annulus is too large to dilate with a single balloon, valvuloplasty with simultaneous inflation of two balloons across the pulmonary valve annulus is recommended. Both immediate and short-term results of balloon pulmonary valvuloplasty are good; long term results are limited.[12],[13]
Occasionally surgical pulmonary valvotomy under cardiopulmonary bypass may become necessary when there is severe supravalvar stenosis, significant valve annulus hypoplasia or severely dysplastic pulmonary valves. Similarly persistent and severe infundibular narrowing despite successful balloon pulmonary valvuloplasty may also require surgical intervention.
In patients with mild pulmonary valve stenosis, periodic clinical follow-up and antibiotic prophylaxis prior to any bacteremia-producing procedures to prevent subacute bacterial endocarditis are recommended. Routine well-child care, including routine immunizations, as per the primary care physician is indicated. There is no need to limit their exercise or activity level.
Aortic Stenosis
Left ventricular outflow tract obstruction may occur at valvar, subvalvar (fixed subaortic stenosis and idiopathic hypertrophic subaortic stenosis) and supravalvar locations. Valvar stenosis is the most common form and will be discussed in this section. The prevalence of congenital valvar aortic stenosis (AS) is 5% to 6% of patients with CHD.[1] Pathology of the stenotic aortic valve is variable, most commonly it is a bicuspid valve with varying degrees of commissural fusion of thickened, domed, nonpliable valve leaflets. Tricuspid and rarely unicuspid aortic valve leaflets can also cause aortic valve obstruction. Dysplasia of the aortic valve leaflets with or without hypoplasia of the valve ring may be found in neonates and young infants. Calcification of the aortic valve leaflets so frequently seen in the elderly, is uncommon during childhood. Dilatation of ascending aorta, post-stenotic dilatation, is seen in most cases, and the extent of aortic dilatation is independent of the severity of aortic obstruction. Hypertrophy of the left ventricular muscle is concentric in nature and is largely proportional to the degree of obstruction.
Symptoms. The majority of children with valvar AS are asymptomatic and detected because of a cardiac murmur heard on routine auscultation. When symptoms are exhibited, dyspnea, easy fatigability or chest pain are the presenting complaints. Syncope may be a presenting complaint in some children with severe AS. In contradistinction to children, neonates and young infants usually present with dyspnea and signs of heart failure.
Physical Findings: The left ventricular impulse is increased (left ventricular heave) in all but mild cases. A thrill may be felt it the right upper sternal border and/or in the suprasternal notch. The first heart sound is usually normal. The second heart sound is also normal unless the aortic stenosis is extremely severe when there may be a paradoxical splitting of the second heart sound. An ejection systolic click is heard best at the apex and left mid and right upper sternal borders and the click does not vary with respiration. An ejection systolic murmur of grade II-V/VI intensity is usually heard best at the right upper sternal border with radiation into both carotid arteries. The arterial pulses are usually normal.
Noninvasive Evaluation: Chest roentgenogram, in most cases, shows a normal sized heart but may frequently reveal an enlarged ascending aorta, a sign of post-stenotic dilatation. The electrocardiogram may be normal or may show varying degrees of left ventricular hypertrophy. Inverted T waves in the left chest leads indicate that aortic valve obstruction is severe. However, not all severe AS patients show T wave inversion. None of the above described clinical and laboratory data have any predictive value in determining the severity of aortic obstruction; this is in contradistinction to the predictive value of auscultatory findings in valvar pulmonary stenosis described in the preceding section.
Echocardiogram may show thickened and domed aortic valve leaflets Figure6 usually bicuspid Figure7, with eccentric opening. The left ventricular muscle may be thickened and its shortening fraction may be increased, depending upon the severity of AS. Doppler flow velocity across the aortic valve is increased and can be used to quantitate peak instantaneous gradient across the aortic valve in a manner similar to that described for the pulmonary valve. However, Doppler-derived mean systolic gradient appears to reflect peak-to-peak catheter gradient (see below) more accurately than peak instantaneous Doppler gradients; this is presumably related to pressure recovery phenomenon[3] alluded to in the pulmonary stenosis section. Mild degree aortic insufficiency may be seen by color Doppler, even in patients without auscultatory evidence for aortic regurgitation.
Catheterization and Angiography: The data show elevated left ventricular peak systolic pressure with a peak-to-peak pressure gradient across the aortic valve indicative of the severity of obstruction. Angiography will confirm, thickened domed aortic valve leaflets and exclude any other abnormalities.
Management: The indications for intervention in valvar AS is a peak-to-peak gradient >50 mmHg with either symptoms or electrocardiographic ST-T wave changes or a peak gradient >70 mmHg irrespective of symptoms or ECG changes.[14],[15] When pressure gradients are used as criteria for intervention (instead of valve area), it must be assured that the cardiac index is normal during pressure measurement. The available options are surgical aortic valvotomy, percutaneous balloon aortic valvuloplasty and valve replacement.[14] Since the introduction of balloon valvuloplasty for valvar AS in 1983, increasing number of pediatric cardiologists, including the author have been using balloon aortic valvuloplasty as a first therapeutic procedure for relief of aortic valve obstruction. When surgery is chosen, commissurotomy is performed on cardiopulmonary bypass and transverse aortotomy. If the aortic valve is not repairable because of valve dysplasia, severe aortic insufficiency or annular hypoplasia, aortic valve replacement may be necessary. The aortic valve may be replaced with a mechanical valve, allograft or autograft (Ross procedures).[14] When balloon valvuloplasty Figure8 is performed, a balloon diameter size equal to the size of the aortic valve annulus is chosen for valvuloplasty. Immediate results following balloon aortic valvuloplasty are encouraging[15],[16],[17] with immediate reduction of the gradient. At short-term follow-up recurrence requiring reintervention may be necessary in 20% patients. Only limited long-term results are available to-date;[13] but, the existing data suggest development of significant aortic insufficiency in 25% patients.
For milder forms of AS, subacute bacterial endocarditis prophylaxis and periodic follow-up are necessary. Restriction from participation in competitive sports is recommended for all but mildest forms of AS. Issues related to management of the fetus and neonate with critical aortic valve stenosis are beyond the scope of this review and will not be reviewed.
Coarctation of the Aorta
The prevalence of coarctation of the aorta (CoA) was found to vary between 5.1% and 8.1 % of CHDs[1]; however, coarctation may be found more frequently in infants presenting with symptoms prior to one year of age. In the past, CoA was designated as preductal (or infantile) or postductal (or adult) type, depending on whether the coarctation segment was proximal or distal to the ductus arteriosus, respectively. However, a closer examination of the anatomy suggests that all coarctations are juxtaductal.[18] The coarctation may be discrete, or a long segment of the aorta may be narrowed; the former is more common. Classic CoA is located in the thoracic aorta distal to the origin of the left subclavian artery, at about the level of the ductal structure. However, rarely, a coarcted segment may be present in the abdominal aorta. Varying degrees of hypoplasia of the isthmus of the aorta (the portion of the aorta between the origin of the left subclavian artery and the ductus arteriosus) and transverse aortic arch (the arch between the origin of the innominate artery and the left subclavian artery) are present in the majority of patients with CoA; this hypoplasia may be significant in symptomatic CoA of the neonate and infant, whereas in older children there may be only a mild degree of narrowing. The most commonly associated defects are patent ductus arteriosus, ventricular septal defect and AS. The younger the infant presents, the more likely that there is a significant associated defect. Bicuspid aortic valve and abnormal mitral valve are also seen. Sometimes, CoA is a complicating feature of more complex, cyanotic heart defects, such as transposition of the great arteries, Taussig-Bing anomaly More Details, double-inlet left ventricle, tricuspid atresia with transposition of the great arteries, and hypoplastic left heart syndrome.
Symptoms: Children beyond infancy usually are asymptomatic; an occasional child will complain of pain or weakness in the legs. Most often, the coarctation is detected because of a murmur or hypertension found on a routine examination. Neonates and infants are more likely present with symptoms associated with congestive heart failure.
Physical Findings: A clinical diagnosis of CoA is best made by simultaneous palpation of femoral and brachial pulses. The left ventricular impulse may be increased. A thrill is usually felt in the suprasternal notch. The first and second heart sounds are usually normal in isolated aortic coarctation. Since a large percentage (up to 60%) of patients with CoA have associated bicuspid aortic valves, an ejection systolic click may be heard at right upper and left mid sternal borders and apex; this click does not change with respiration. An ejection systolic murmur may be heard at left or right upper sternal borders, but is usually heard best over the back in the interscapular regions. Some times a continuous murmur may be heard in the left interscapular region secondary to continuous flow in the coarcted segment or on the back (secondary to flow in the collateral vessels). Palpation of the brachial and femoral artery pulses simultaneously will reveal decreased and delayed or absent femoral pulses. Blood pressure in both arms and one leg must be determined: a pressure difference of more than 20 mmHg in favor of arms may be considered as evidence for coarctation of the aorta. Involvement of the left subclavian artery in the coarctation or anomalous origin of the right subclavian artery (below the level of coarctation) may produce decreased or absent left or right brachial pulses, respectively, and therefore palpation of both brachial pulses and measurement of blood pressure in both arms are important.
Neonates and infants usually have signs of the associated cardiac defects (for example ventricular septal defect) and other signs of heart failure such as hepatomegaly and tachypnea.
Noninvasive Evaluation: Chest x-ray may show a normal sized heart or the heart may be mildly enlarged. Other roentgenographic features include a "3" sign on a highly penetrated chest x-ray, inverted "3" sign of the barium filled esophagus and rib-notching (secondary to collateral vessels); these latter signs are seen in older children. The electrocardiogram may be normal or may show left ventricular hypertrophy. In neonates and infants, there may be predominant right ventricular hypertrophy. Echocardiographic studies usually reveal the coarctation in suprasternal notch, two-dimensional echocardiographic views of the aortic arch Figure9. Increased Doppler flow velocity in the descending aorta by continuous-wave Doppler Figure9 and demonstrable jump in velocity at the coarcted segment by pulsed-Doppler technique are usually present. Extension of the Doppler flow signal into the diastole is indicative of significant obstruction. Instantaneous peak pressure gradients across the aortic coarctation can be calculated by employing modified Bernoulli equation in manner similar to that described for PS and AS. Because of higher proximal velocity, coarctation gradients may be more accurately estimated by:
D P = 4 (V22 - V12)
where D P is peak instantaneous gradient and V2 and V1 are peak Doppler velocities in the descending aorta distal to the coarctation (continuous wave Doppler) and proximal to the coarctation (pulsed Doppler), respectively.
But the calculated gradient is usually an over-estimation, especially if there is no diastolic extension of the Doppler velocity.[19]
Catheterization and Angiography: In isolated aortic coarctation, elevation of left ventricular and ascending aortic peak systolic pressure with a significant peak-to-peak pressure gradient across the coarctation is found. Selective aortic root or aortic arch angiography is necessary to clearly demonstrate the aortic narrowing [Figure - 10].
Management: Significant hypertension and/or congestive heart failure are indications for intervention. In the presence of congestive heart failure, conventional anticongestive measures including digitalis and diuretics should be promptly instituted. In the presence of hypertension, it is better to relieve the obstruction promptly rather than attempting to "treat" hypertension with antihypertensive drugs. Aortic coarctation may be relieved either by surgery, balloon angioplasty or percutaneous stent deployment. Symptomatic children should undergo relief of coarctation soon after the child is stabilized. Asymptomatic children should undergo the procedure electively. If neither hypertension nor heart failure are present, elective relief of the obstruction between the ages of 2 and 5 years is suggested. Waiting beyond 5 years is not advisable because of evidence for residual hypertension if the aortic obstruction is not relieved by the age of 5 years.
Surgical relief of aortic coarctation is the conventional treatment option. Since the description balloon angioplasty in 1983, increasing number of cardiologists, including our group, have used this technique for relief of aortic coarctation. There is a reasonable consensus that children (> 1 year) are good candidates for balloon angioplasty. While I believe that balloon angioplasty is the treatment option of choice for relief of native aortic coarctations even in the neonate and infant,[20] the overall consensus seems to be in favor of surgical intervention. Stents seem to be emerging as therapeutic procedure of choice in the adolescent and adult with aortic coarctation.[21],[22]
When surgical option is chosen, resection and end-to-end anastomosis, subclavian flap angioplasty or prosthetic patch angioplasty may be used depending upon anatomy of the aortic arch and coarctation as well as surgeon's preference. Prosthetic patch angioplasty is no longer used because of development of aneurysms at long term follow-up. When balloon angioplasty [Figure - 11] is contemplated, the balloon size should be carefully chosen: the diameter of the balloon should be two or more times the size of the coarcted segment, but no larger than the diameter of the descending aorta at the level of diaphragm. Balloon angioplasty is not suitable for treatment of long segment coarctations. The immediate [Figure - 12], [Figure - 13], [Figure - 14] and intermediate-term results of balloon coarctation angioplasty have been good [23],[24] although long-term follow-up is scanty.[13]
More recently stents have been used effectively to treat coarctation in adolescents and adults, particularly if a long segment is involved.
References
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2. Rao PS. Evaluation of cardiac murmurs in children. Indian J Pediat 1991; 58: 4 71-489.
3. Singh GK, Balfour IC, Chen S, Ferdman B, Jureidini SB, Fiore AC et al. Lesion specific pressure recovery phenomenon in pediatric patients: a simultaneous Doppler and catheter correlative study (
Abstract). J Am Coll Cardiol 2003; 41: 493A.
4. Rudolph AM: Congenital Disease of the Heart. Year-Book Medical Publishers, Inc., Chicago, IL, 1974.
5. Rao PS. Pulmonary valve disease. In, eds. Alpert JS, Dalen JE, Rahimtoola, eds. Valvular Heart Disease , 3rd edn. Lippencott Raven, Philadelphia, PA, 2000; 339-376.
6. Thapar MK, Rao PS. Significance of infundibular obstruction following balloon valvuloplasty for valvar pulmonic stenosis. Am Heart J 1989; 118: 99-103.
7. Rao PS. Indications for balloon pulmonary valvuloplasty (Editorial). Amer Heart J 1988; 116: 1661-1662.
8. Rao PS. Balloon pulmonary valvuloplasty. J Intervent Cardiol 1998; 11: 303-18.
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13. Rao PS. Long-term follow-up results after balloon dilatation of pulmonic stenosis, aortic stenosis and coarctation of the aorta: a review. Progr Cardiovasc Dis 1999; 42: 59-74.
14. Singh GK, Rao PS. Left heart outflow obstructions. In Crawford MH, DiMarco JP, Paulus WJ, eds. Cardiology, 2nd edn. Mosby International, Edinburgh, 2004; 1317-1326.
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16. Rao PS, Thapar MK, Wilson AD, Levy JM, Chopra PS. Intermediate-term follow-up results of balloon aortic valvuloplasty in infants and children with special reference to causes of restenosis. Am J Cardiol 1989; 64: 1356-1360.
17. Galal O, Rao PS, Al-Fadley F, Wilson AD. Follow-up results of balloon aortic valvuloplasty in children with special reference to causes of late aortic insufficiency. Am Heart J 1997; 113: 418-427.
18. Rao PS. Coarctation of the aorta. In Ram CVC, ed. Secondary Forms of Hypertension. W.B. Saunders, Philadelphia, PA 1995; 15(2): 81-105.
19. Rao PS, Carey P. Doppler ultrasound in the prediction of pressure gradients across aortic coarctation. Am Heart J 1989; 118: 299-301.
20. Rao PS. Current status of balloon angioplasty for neonatal and infant aortic coarctation. Progress Pediats Cardiol 2001; 14: 35-44.
21. Rao PS. Stents in the treatment of aortic coarctation (Editorial). J Am Coll Cardiol 1997; 30: 1853-1855.
22. Rao PS. Stents in the management of congenital heart disease in the pediatric and adult patients. Indian Heart J 2001; 53: 714-730.
23. Rao PS, Galal O, Smith PA, Wilson AD. Five-to-nine-year follow-up results of balloon angioplasty of native aortic coarctation in infants and children. J Am Coll Cardiol 1996; 27: 462-470.
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