Park's Pediatric Cardiology for Practitioners, 6th Ed.

Pathophysiology of Obstructive and Valvular Regurgitation Lesions

This chapter discusses hemodynamic abnormalities of obstructive and valvular regurgitant lesions of congenital and acquired causes. For convenience, they are divided into the following three groups based on their hemodynamic similarities:

1. Ventricular outflow obstructive lesions (e.g., aortic stenosis [AS], pulmonary stenosis [PS], coarctation of the aorta [COA])

2. Stenosis of atrioventricular (AV) valves (e.g., mitral stenosis [MS], tricuspid stenosis [TS])

3. Valvular regurgitant lesions (e.g., mitral regurgitation [MR], tricuspid regurgitation [TR], aortic regurgitation [AR], pulmonary regurgitation [PR])

Obstruction to Ventricular Output

Common congenital obstructive lesions to ventricular output are AS, PS, and COA. All of these obstructive lesions produce the following three pathophysiologic changes (Fig. 10-1):

1. An ejection systolic murmur (as heard on auscultation)

2. Hypertrophy of the respective ventricle (as seen in the electrocardiographic [ECG] or echocardiography study)

3. Poststenotic dilatation (as seen in chest radiographs or echocardiography images) (this is not seen with subvalvular stenosis)

Aortic and Pulmonary Valve Stenoses

An ejection type of systolic murmur can best be heard when the stethoscope is placed over the area distal to the obstruction. Therefore, the murmur of AS is usually loudest over the ascending aorta (i.e., aortic valve area or upper right sternal border), and the murmur of PS is loudest over the pulmonary artery (i.e., pulmonary valve area or upper left sternal border). However, the actual location of the aortic valve is under the sternum at the level of the third left intercostal space; therefore, the murmur of AS may be quite loud at the third left intercostal space.

In isolated stenosis of the pulmonary or aortic valve, the intensity and duration of the ejection systolic murmur are directly proportional to the severity of the stenosis. In mild stenosis of a semilunar valve, the murmur is of low intensity (grade 1 to 2/6) and occurs early in systole, with the apex of the “diamond” in the first half of systole. With increasing severity of the stenosis, the murmur becomes longer and louder (often with a thrill) with the apex of the murmur moving toward the S2.

With mild pulmonary valve stenosis, the S2 is normal or split widely because of prolonged “hangout time” (see Chapter 2). With severe PS, the murmur is long and may continue beyond the A2 and the S2 splits widely, but the intensity of the P2 decreases (Fig. 10-2A). With severe AS, the S2 becomes single or splits paradoxically because of the delayed closure of the aortic valve (A2) in relation to the P2 (Fig. 10-2B). In semilunar valve stenosis, an ejection click may be audible. The click is produced by a sudden checking of the valve motion or possibly by the sudden distention of the dilated great arteries.

If the obstruction is severe, the ventricle that has to pump blood against the obstruction will hypertrophy. The left ventricle (LV) hypertrophies in AS and the right ventricle (RV) in PS, which results in left ventricular hypertrophy (LVH) and right ventricular hypertrophy (RVH), respectively, on the ECG. Cardiac output is maintained unless myocardial failure occurs in severe cases; therefore, the heart size remains normal (on chest radiographic films or echo study).

Poststenotic dilatation is the hallmark of a stenosis at the semilunar valve level. The artery distal to the stenotic semilunar valve dilates circumferentially. Poststenotic dilatation is not seen with subvalvular stenosis; it is only mild or not seen at all with supravalvular stenosis. It was once believed that the jet of blood resulting from the stenosis strikes a localized area of the great artery with weakening of that area causing the dilatation. However, there is a circumferential dilatation of the great artery where the jet does not strike. The current understanding is that sustained vibration of the vessel distal to the narrowing causes generalized fatigue of collagen fibers with resulting dilatation, which may add circumferential dilatation. In pulmonary valve stenosis, a prominent PA segment is visible on chest radiographic film (see Fig. 4-7A). In aortic valve stenosis, the dilated aorta may look like a bulge on the right upper mediastinum or a prominence of the aortic knob on the left upper mediastinum on chest films (see Fig. 4-7C). Mild dilatation of the ascending aorta secondary to aortic valve stenosis is usually not visible on plain chest radiographic films because the ascending aorta does not form the cardiac border.

Coarctation of the Aorta

In older children with COA, an ejection-type systolic murmur is present over the descending aorta distal to the site of coarctation (i.e., in the left interscapular area). Because many of these patients also have abnormal aortic valves (most commonly bicuspid aortic valves), a soft AS murmur, ejection click, and occasional AR murmur may be heard. Depending on the severity of the obstruction, the femoral pulses are either weak and delayed or absent. The weak pulse results primarily from a slow upstroke of the arterial pulse in the lower extremity sites. On chest radiographs, poststenotic dilatation of the descending aorta (distal to the coarctation) often produces the figure-of-3 sign on the plain film or an E-shaped indentation on the barium esophagogram (see Fig. 4-10). The poststenotic dilatation of the descending aorta distal to the coarctation can be easily imaged by echocardiographic study. The ECG shows LVH because of a pressure overload on the LV. In newborns and small infants, RVH or right bundle branch block (RBBB) is commonly seen, but LVH is not (see later section for the reasons).

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FIGURE 10-1 Three secondary changes are seen in aortic valve and pulmonary valve stenosis: an ejection systolic murmur, hypertrophy of the responsible ventricle, and poststenotic dilatation of a great artery. A normal-sized ventricle and a great artery are shown by broken lines. The end results of a semilunar valve stenosis are illustrated by solid lines. A similar change occurs with coarctation of the aorta.

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FIGURE 10-2 Systolic murmurs of pulmonary valve stenosis (PS) (A) and aortic valve stenosis (AS) (B). The duration and intensity of the murmur increase with increasing severity of the stenosis. Note the changes in the splitting of S2 (see text). An ejection click (EC) is present in both conditions. Abnormal heart sounds are shown as black bars.

The coarctation is almost always juxtaductal (i.e., located opposite the entry of the ductus arteriosus). What are the differences in pathology and pathophysiology between symptomatic infants and asymptomatic children with coarctation of the aorta?

1. Symptomatic newborns with COA

Many patients who become symptomatic early in life have an associated defect such as ventricular septal defect (VSD) or left-sided obstructive lesions. The obstructive lesions may be in the left ventricular outflow tract, the aortic valve, or the proximal aorta (see Fig. 10-3A). These associated defects tend to decrease blood flow to the ascending aorta and to the aortic isthmus (i.e., the segment between the left subclavian artery and the ductus arteriosus) during fetal life. As a result, these structures become relatively hypoplastic.

These associated anomalies result in more volume work delegated to the RV, which supplies blood to the descending aorta through a large ductus arteriosus. The RV, which is normally dominant, becomes more dilated and hypertrophied, and the LV becomes smaller than normal. This may explain why infants with COA show RVH, rather than LVH, on the ECG. RVH on the ECG is usually replaced with LVH by 2 years of age.

Decreased flow in the proximal aorta does not produce a pressure gradient between the aortic segments proximal and distal to the coarctation (which is supplied by large PDA). The absence of pressure gradient does not stimulate the development of collateral circulation between the ascending and descending aortas. When the ductus closes after birth, the pressure work imposed on the relatively small LV suddenly increases. This results in a noticeable decrease in the perfusion of the descending aorta (with resulting circulatory shock), renal failure, and signs of left heart failure (i.e., dyspnea and pulmonary venous congestion).

2. Asymptomatic coarctation of the aorta

On the contrary, in the absence of the associated defects, the normal amount of blood reaching the isthmus area produces a pressure gradient between the aortic segments above and below the coarctation, and it stimulates the development of collateral circulation between them. Most of these infants, who do not have associated defects, tolerate the postnatal closure of the ductus well and remain asymptomatic (see Fig. 10-3B), although some infants develop LV failure. The ECG will show LVH as expected.

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FIGURE 10-3 Diagrammatic comparison of the heart and aorta in symptomatic infants and asymptomatic children with coarctation of the aorta. A, In symptomatic infants, associated defects are frequently found, which include ventricular septal defect, aortic and mitral valve abnormalities, and hypoplasia of the ascending and transverse aortas. These abnormalities are shown in heavy lines. B, In asymptomatic children, the coarctation is usually an isolated lesion except for bicuspid aortic valve (not shown). AO, aorta; LA, left atrium; LV, left ventricle; PA, pulmonary artery; RA, right atrium; RV, right ventricle.

Stenosis of Atrioventricular Valves

Stenosis of the AV valves produces obstruction to pulmonary or systemic venous return. Passive congestion in the pulmonary or systemic venous system cause the clinical manifestations associated with these conditions.

Mitral Stenosis

Stenosis of the mitral valve is more often rheumatic than congenital in origin. It produces a pressure gradient in diastole between the left atrium (LA) and the LV, which in turn produce a series of changes in the structures proximal to the mitral valve (e.g., the LA, pulmonary veins, PAs, and RV). When a significant MS is present, the LA becomes dilated and hypertrophied. The pressure in the LA is raised, which in turn raises pressures in the pulmonary veins and capillaries (Fig. 10-4). Pulmonary edema may result if the hydrostatic pressure in the capillaries exceeds the osmotic pressure of the blood. Therefore, chest radiographs may reveal pulmonary venous congestion or pulmonary edema and enlargement of the LA. Dyspnea with or without exertion and orthopnea may manifest. The high pulmonary capillary pressure results in reflex arteriolar constriction, which in turn causes pulmonary arterial hypertension and eventually hypertrophy of the RV. These changes will be seen as RVH on the ECG and as prominence of the PA segment on chest radiographs. Right heart failure may eventually develop.

The pressure gradient during diastole produces a mid-diastolic rumble that is best heard at the apex on auscultation. When the mitral valve is mobile (not severely stenotic), an opening snap precedes the murmur (see Fig. 21-1). During the last part of diastole, if the pressure gradient still exists between the LA and LV, the LA will contract to push blood forward, producing a presystolic murmur. At the time of the onset of ventricular contraction, the mitral valve leaflets are relatively wide apart due to the prolonged atrial contraction, thereby producing a loud S1. If the cardiac output reduces significantly, thready pulses result. The dilated LA contributes to the frequent occurrence of atrial fibrillation, which may result in the loss of the presystolic murmur.

The following conditions all have in common an elevated pulmonary venous pressure, with similar pathophysiology and must be differentiated from mitral stenosis:

1. Total anomalous pulmonary venous return with obstruction (see Chapter 14)

2. Cor triatriatum (see Chapter 15)

3. Pulmonary vein stenosis (see Chapter 15)

4. Hypoplastic left heart syndrome (see Chapter 14)

5. Left atrial myxoma (see Chapter 22)

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FIGURE 10-4 Hemodynamic changes in severe mitral stenosis. Enlargement and hypertrophy of the left atrium (LA), pulmonary venous hypertension, and possible pulmonary edema result. Reflex vasoconstriction of pulmonary arterioles leads to pulmonary arterial hypertension and right ventricular hypertrophy. AO, aorta; LV, left ventricle; PA, pulmonary artery; PV, pulmonary vein; RA, right atrium; RV, right ventricle.

Tricuspid Stenosis

Stenosis of the tricuspid valve is rare and usually congenital. It produces dilatation and hypertrophy of the right atrium (RA) for obvious reasons. Therefore, chest radiographs reveal right atrial enlargement, and the ECG may show right atrial hypertrophy (RAH).

Increased pressure in the systemic veins produces hepatomegaly and distended neck veins. A pressure gradient across this valve during diastole produces a mid-diastolic murmur. A prolonged contraction of the RA to push blood through the narrow valve may produce a presystolic murmur.

Valvular Regurgitant Lesions

Important valvular regurgitant lesions are AR and MR. Severe pulmonary valve regurgitation is relatively rare, except in a postoperative state, such as those seen following surgery for tetralogy of Fallot and other conditions that require conduit placement between the RV and the PA. Significant tricuspid valve regurgitation is also rare.

In general, when regurgitation is severe, the chambers both proximal and distal to a regurgitant valve become dilated, with volume overload of these chambers. Whereas with MR both the LV and LA dilate, with AR the LV enlarges and the aorta enlarges or increases its pulsation. If the regurgitation is minimal, only auscultatory abnormalities indicate its presence.

Mitral Regurgitation

The major problem in MR is volume overload of both the LA and LV, with resulting enlargement of these chambers (Fig. 10-5). Therefore, chest radiographs reveal enlargement of the LA and LV, and the ECG may show LVH and left atrial hypertrophy (LAH).

Regurgitation of blood from the LV to the LA produces a regurgitant systolic murmur that is best heard near the apex. Because of an increased amount of blood flows across the mitral orifice during the rapid filling phase of diastole, the S3 is usually loud. When the regurgitation is severe, a mid-diastolic rumble may be present because of “relative” MS that results from handling an excessive amount of left atrial blood through the normal-sized mitral orifice. The dilated LA chamber tends to dampen the transmission of the pressure from the LV, and the pressure in the LA is usually not notably elevated. Therefore, unlike with mitral stenosis, marked pulmonary hypertension occurs only occasionally with mitral regurgitation.

Tricuspid Regurgitation

In tricuspid regurgitation, hemodynamic changes similar to those described for MR result. The RA and RV enlarge for obvious reasons. The ECG may show RAH and RVH (or RBBB).

A systolic regurgitant murmur, a loud S3, and a diastolic rumble develop, as in MR, but they are audible at the tricuspid area (both sides of the lower sternal border) rather than at the apex. With severe regurgitation, pulsation of the liver and neck veins may occur, reflecting a phasic increase in right atrial pressure by the regurgitation.

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FIGURE 10-5 Diagrammatic representation of hemodynamic changes in mitral regurgitation. Note that the chambers with two arrows (left atrium [LA] and left ventricle [LV]) are enlarged.

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FIGURE 10-6 Diagrammatic representation of hemodynamic changes in aortic regurgitation. Note that the left ventricle (LV) and aorta (AO), with two arrows, are enlarged.

Aortic Regurgitation

There is volume overload of the LV because this chamber must handle normal cardiac output in addition to the amount that leaks back to the LV (Fig. 10-6). This is represented as left ventricular enlargement on radiographs and LVH on the ECG. Because of the increase in stroke volume received by the aorta, the aorta pulsates more than normal and becomes somewhat dilated, although the aorta does not retain all the increased stroke volume.

An increase in systolic pressure results from an increase in stroke volume. The diastolic pressure is lower because of a continuous leak back to the LV during diastole. This results in a wide pulse pressure and bounding peripheral pulse. The regurgitation during diastole produces a high-pitched, decrescendo diastolic murmur immediately after the S2 (see Fig. 21-4). The regurgitant flow is directed toward the apex; therefore, the diastolic decrescendo murmur is well audible at the apex as well as in the third left intercostal space. The AR flow, which coincides with the forward flow of left atrial blood, produces a flutter motion of the mitral valve, producing an Austin-Flint murmur in diastole. With severe AR, a high left ventricular end-diastolic pressure approximates the mitral valve leaflets at the onset of ventricular systole, resulting in reduced intensity of the S1.

Pulmonary Regurgitation

The pathophysiology of PR is similar to that of AR. The RV dilates, and the PA may enlarge. This is represented in radiographs as right ventricular enlargement and prominence of the PA segment. The ECG may show RVH or RBBB.

Because of the low diastolic pressure of the PA, the murmur of PR is low pitched, and the gap between the S2 and the onset of the decrescendo diastolic murmur is wider than that seen in AR. In the presence of pulmonary hypertension, however, the murmur of PR resembles that of AR. The direction of the regurgitation is to the body of the RV; therefore, the PR murmur is audible along the left sternal border rather than at the apex (where the AR murmur is loud). The different direction of the radiation of the diastolic murmur is helpful in differentiating PR from AR.