is Professor of Medicine and Director of the Coronary Care Unit and of the Graphic Laboratory in the Department of Medicine WAxxdiology Division) at the University of Rochester !+lchool of Medicine and Dentistry. He received his M.D. degree from Seth G. S. Medical College in Bomhay, India in 1958 and completed his internship and residency in medicine at K. E. M Hospital in Bombay. His cardiology traineeship was at Mount Sinai Hospital and the Chicago Medical School, Postgraduate Medical School of London and Hammersmith Hospital and The Hospital for Sick Children, Toronto, Canada. Prior to his present position he was an Associate Professor in Medicine and Pediatrics at the University of Rochester. Doctor Shah’s chief interest is in clinical research in the pathophysiology of disease. His major contributions are in echocardiography, noninvasive techniques, phonocardiography and hypertrophic cardiomyopathies.

is Assistant Professor of Medicine at the State University of New York, Buffalo and Director of the Coronary Care Unit at the E. J. Meyer Memorial Hospital. Doctor Roberts finished his cardiology fellowship at Strong Memorial Hospital and received his M.D. from the State University of New York at Buffalo. His research interests include coronary blood flow, aortic valve disease and myocardial infarction.

PRO&WI’ AND JUDICIOUS control of streptococcal infection with antibiotic therapy has been responsible for a remarkable decline in the number of cases of acute rheumatic fever over the past three dqca&es. The clinician is likewise encountering a decreased incidence of rheumatic valvular heart disease. Aortic stenosis, however, continues to remain a major clinical problem. The incidence of this disease has changed little over the preced5

ing decades and either a congenital or degenerative etiology now is appreciated in most cases. In this issue of CURRENT ~OBLEMS IN thRDIOL.OGY we would like to focus on the diagnosis and treatment of valvular aortic stenosis in adults, with some considerations of etiology, pathophysiology and its natural history. We hope to emphasize the pitfalls in bedside assessment of its severity and a need for prompt and accurate diagnosis. ETIOPATHOLOGY Valvular aortic stenosis may be congenital, a residual of rheumatic inflammation or secondary to cusp calcifications of unknown cause. Rheumatic fever, which commonly involves the mitral and aortic valves, for many years was thought to be the most common etiology of aortic valve stenosis. Detailed pathologic studies by Roberts and his associates have cast doubt on rheumatic etiology in patients with isolated aortic valve stenosis.1-4 Most, if not all, cases of multivalvular lesions still are considered to be on the rheumatic basis. Isolated aortic valve disease, however, commonly has a congenital origin. Roberts described pathologic criteria that helped in identification of a bicuspid versus a tricuspid calcified stenotic valve (Fig. 1). In a series of autopsied cases with aortic stenosis with or without regurgitation, 4% bicuspid and 14% unicuspid or unicomFig 1.-A pid, bicuspid

6

schematic illustration and unicuspid aortic

to show valves.

the

common

appearances

of tricus-

missural valves were found. A congenital malformation was believed to be responsible for more than 76% of the cases. The remainder were believed to have a tricuspid valve with superimposed calcification and stenosis. Rheumatic involvement may lead to commissural fusion and these patients may present with symptoms earlier than those with calcific valves. Heavy calcification per se of the cusps may irnRair mobility and thus result in obstruction.5 This process occurs later in life and often is superimposed on a congenitally deformed valve. This surprisingly high incidence of a congenital defect producing calcific aortic stenosis in adults may be attributed to a relatively high incidence of bicuspid aortic valve, estimated to occur in more than ‘2% of the population, and would make it the most common congenital malformation2 It is well known that bicuspid valves can function normally throughout life and thin pliable leaflets be an incidental finding at autopsy.6 In other individuals, extensive fibrosis, calcification and commissural fusion result in symptomatic stenosis and/or regurgitation. In patients over 65 years of age, the valve commonly is tricuspid and calcified. These pathologic consequences usually are explained by a wear-and-tear phenomenon on a valve with secondary degeneration, fibrosis and calcification. This process over several decades may result in commiasural fusion and increasing rigidity of the valve apparatus. Thus, what begins as a mild congenital anomaly at birth may end up as a severely dysfunctional valve after the fifth or sixth decade of life. Endocarditis on a bicuspid aortic valve has been proposed as a cause of calciflc aortic stenosis developing as a late sequela.‘j More frequently, however, endocarditis results in valvular regurgitation. ) W. hKNXOR HARVEY: One interesting concept of the progression of disease such as with the congenital bicuspid aortic valve is that of “wear and tear.” Probably the closing of a bicuspid valve prediprposes to pathologic change, subaequentIy ending up with stenosis, whereas with the normal tricuspid valve there apparently is less “wear and tear.” Dr. William Roberts, one ofour Editors ofcvaRe~psoB~~~ IN Cmmy, has amply stressed this in his lectures and writing. It is interesting that this “wear-and-tear” phenomenon also probably explains the p~as~ession of disease in a patient developing sign&ant mitral stenosis rather than having to attribute this to the recurrence of rheumatic fever, &en of a low-grade type, as I used to bebeve. Certainly a recurrence of rheumatic fever can do so, but with knowledge learned from other valves such as the bicuspid valve resulting in 5teenocsia, “wear and tear” is the likely chief culprit in the development of mitral stenosis also.

THE SALIENT

PATHOLOGIC

(a) Thickened, commissures

often calcified,

FEATURES aortic

result in effective reduction

valve cusps with

fused

of the size of the aortic

orifice. In patients with severe outflow obstruction, the aortic valve orifice area is less than 1.0 cme and generally below 0.75 cm*. Heavy calcification may render anatomic identification of unicuspid, bicuspid or tricuspid valves difficult (Fig. 2). The valve structure may appear totally immobile or one cusp may be less severely involved, with preservation of some mobility. (b) TheotosticanrrI~also~beca~insome~.The’ anular calcification may be light or heavy, occasionally extending into the membranous portion of the interventricular septum. extend into the region of the His bundle and proximal left bun&a nally, the cak&cation involves t compromising its orifice and D: The proximal ascending aorta for about aoztic or&e shows postatenotic dilatation. is not directly related to the severity of with intimal thickening and plaquing hypertrophy: In patients with the aortic than 1.0 cm*, the le& ventricular muscle . The degree of hypsrtrophy generaliy depends on the severity of the v&e thmmis. The hypertrophy commonly is concentric, with IMe or no increase in cavity size but considerabb increase in free wall thickness. The cavity size may be enlarged in patients with chronic end-stage cardiac decompensation. Heart weight may be two- or threefold normal and occasionally weight in excess of 1000 gm has been observed. ThickFig 2.-A

pathologic

sp@nen

of a tricuspid

calcific

and stenotic

aortic

ness of the left ventricular free wall exceeds 12 mm and often is in the range of 16-20 mm. F WILLIAM C. ROBERTS: Heart weight in excess.of 1000 gm is exceedingly rare and I have never encountered such a weight in a patient with aor-

tic valve stenosis alone. The most common cause of massive cardiomegaly (> 1000 gm) is pure aortic regurgitation, not stenosis, On rare occasions (2 of 65 cases studied personally at autopsy), however, hypertrophic cardiomyopathy may lead to massive cardiomegaly.

(e) Associated pathology: (1) Mitral valve disease: In most patients with rheumatic etiology, the mitral valve is diseased also. The functional result may be pure stenosis, predominant regurgitation or a combination of the two. Pathologic changes associated with mitral valve disease, i.e., left atria1 enlargement, pulmonary vascular changes and right heart enlargement, may be present. ) WILLIAM C. ROBERTS I would define rheumatic heart disease as a disease of the mitral valve; other valves also may be involved either anatomically or functionally or both, but always the mitral valve. The involvement of the mitral valve may be of 2 types anatomically: (1) diffuse fibrosis of all portions of both leaflets and (2) marginal fibrosis only, but of all margins (distal portions) of both leaflets. The diffuse or marginal fibrosis may or may not lead to functional disturbance; the diffuse scarring may lead to stenosis or to regurgitation, the marginal scarring only to regurgitation. Thus, in a patient with aortic valve disease and an anatomically normal mitral valve, the aortic valve etiology, by definition, would be nonrheumatic. Of course, some patients with severe aortic stenosis terminally may develop mitral regurgitation, but usually the mitral regurgitation in this circumstance is due to malalignment of the left ventricular papillary muscles and not to intrinsic disease of the mitral leaflets or their chordae tendineae.

(2) Coronary artery disease: Independent coronary artery occlusions with arteriosclerotic changes may be present in older patients. Occasionally, the heavy calcification associated with aortic valve stenosis may compromise the coronary ostia and rarely calcium emboli may lodge in the coronary arterial system.’ (3) Asymmetric hypertrophy: Although the pressure overload from aortic stenosis generally results in concentric or symmetric hypertrophy of the left ventricle, some patients with associated asymmetric hypertrophy have been described. The latter resembles the asymmetric hypertrophy seen in hypertrophic obstructive cardiomyopathy or idiopathic hypertrophic subaortic stenosis; whether the asymmetric hypertrophy represents an independent coexistence of the two disorders or a genetically determined response to the increased work load remains speculative. W. PROCTOR HARVEY: It is worthy of reemphasis that patients with a rheumatic etiology of aortic valve stenosis frequently have associated

k

9

mitral valve involvement. When only the aortic valve is involved and the stenosis has been thought to be on a rheumatic basis, it is much more likely that it will be on a congenital basis. Another clinical finding (cardiac pearl) that has stood the test of time is that if a patient has what appears to be evidence of only aortic valve disease, such as aortic stenosis, and atria1 fibrillation is present, there probably is a 90% chance that there is concomitant mitral valve involvement, thereby affording another clue as to the presence of associated mitral valve disease. It is a known clinical point that patients with isolated aortic valve disease, either stenosis or insufficiency, or both generally are in normal sinus rhythm.

PATHOGENESIS An adult with isolated aortic valve stenosis is thought to have had a progressive functional narrowing of the valve orifice over several years, if not decades. The cross-sectional area of the aortic orifice must be reduced by 50% of normal for a significant pressure gradient to develop across it. The ventricular hypertrophy generally is observed when the orifice size is less than 1.0 cm2. When critical stenosis develops with orifice size less than 0.75 cm%, ventricular hypertrophy is pronounced and impairment of the left ventricular function may set in. The latter is facilitated

genation

by myocardial

in aortic

ischemia

resulting

from reduced oxy-

stenosis or from associated

coronary

artery

disease. Progressive left ventricular decompensation results in an increase in end-systolic and end-diastolic volumes. Once overt left ventricular failure sets in, rapid deterioration is the rule, unless prompt relief from obstruction is undertaken.

SYMPTOMS A classic triad of symptoms common to all forms of left ventricular outflow obstruction includes dyspnea, angina and syncope or dizziness (Fig. 3). In addition, palpitations also may be present in some cases. DYBPNEA.-Effort dyspnea is the most common symptom and geuerally is a manifestation of left ventricular decompensation with pulmonary congestion. Other evidences of left ventricular failure, namely, paroxysmal nocturnal dyspnea, orthopnea or frank pulmonary edema, may be the presenting symptoms. Once these symptoms develop, they are rapidly progressive over weeks or months. The left ventricular failure in aortic valve stenosis represents deterioration of function with dilatation and hypertrophy. The progressive development of left ventricular outflow obstruction results

in high intraventricular

trophy and dilatation. 10

pressures

Elevated enddiastolic

and secondary hyper-

pressure associated

SYMPTOMSOF IV OUTFLOWOBSTRUCTION DYSPNEA ANGINA SYNCOPE-DIZZINESS PALPITATIONS

Fig 3.-A left ventricular valvar aortic hypertrophic

schematic outflow stenosis subaortic

to emphasize the common symptoms for all forms of obstruction, i.e., supravalvar aortic stenosis(S.V.A.S.), (V.A.S.), membranous subaortic stenosis (M.S.A.S.) and stenosis (H.S.A.S.).

with a decreased ejection fraction and increased end-systolic volume due to ventricular dysfunction leads to a rise in left atrial pressure. The latter, in turn, is transmitted to pulmonary venous and capillary beds, favoring formation of alveolar and interstitial lung edema. The increase in pulmonary capillary wedge pressure with physical exertion results in effort dyspnea. The supine position favors venous return and may result in increased formation of alveolar and interstitial edema, producing orthopnea and paroxysmal nocturnal dyspnea. Sustained elevations in left atria1 and pulmonary capillary pressures facilitate formation of acute pulmonary edema. If the pathologic state of passive pulmonary congestion goes unrelieved, changes of pulmonary arterial hypertension may set in. ANGINA PECTORIS. -Typical angina pectoris is a frequent symptom of aortic valve stenosis. It almost always is effort related. There are a number of potential mechanisms that might adversely affect myocardial oxygenation (Fig. 4). Oxygen demand increases with the increased work of the left ventricle. Systolic and diastolic tension are increased from elevations in pressures and volumes. Second, myocardial hypertrophy with an increase in muscle mass would increase oxygen needs. Oxygen supply may be reduced in several ways. First, coronary blood flow may be hampered in systole as a result of the Bernoulli effect on the coronary ostia. A high-velocity ejection jet into the aortic root actually may reduce the systolic flow through the ostium in close proximity to the jet. This mecha11

SUPPLY

DEMAND

I.) VENTURI EFFECT----+ FLOW

t LV WALL TENSION /”

2) COMPRESSION + +CBF IN SYSTOLE

9_____., :______ ; +MVO~~ I.________._I

3.) HYPERTROPHY

4

+ 4 INTERCAPILLARY MSTANCE

4 LV MUSCLE MASS

4

+

---

POOR 0, DELIVERY

Fig 4.-This schematic summarizes velopment of angina. (CW = coronary consumption.)

+ 4 WORK

the factors blood flow;

LV HYPERTROPHY

that may contribute MVO, = myocardial

to deoxygen

nism has not been well documented. Second, compression of intramyocardial coronary arteries may completely obstruct flow to the inner layers in systole. This interruption of subendocardial flow is especially facilitated by a higher intraventricular pressure than coronary arterial pressure in aortic stenosis. Third, the intercapillary distances between adjacent intramyocardial capillaries have been shown to be increased in the presence of experimentally induced myocardial hypertrophy.* This may impair diffusion of oxygen across the capillary bed. In a given patient with aortic stenosis, one or more of the above mechanisms may tip the balance unfavorably between oxygen supply and demand. In the absence of obstructive coronary artery disease, the supply to the myocardium can be represented by the area between the aortic and left ventricular pressure curves (Fig. 5). This area has been termed the diastolic pressure time index (DI’TI) by Buckberg and colleagues. 0 Demand can be estimated from the area under the left ventricular pressure tracing in systole. Sarnoff et ~1.‘~ termed this the tension time index and recently it has been more accurately called systolic pressure time index (SBTI). Experimental work using microspheres to measure coronary blood flow has validated the use of these indices. The ratio of DIWSPTI has been shown to be an accurate expression of the supply/demand ratio and thus reflects the adequacy of subendocardial blood flow. It is believed that at a ratio less than 0.7, subendocardial ischemia results, and this has been used to predict the clinical appearance of angina pectoris in aortic valve disease.” In aortic stenosis, demand CSFTI) is increased because of an increased pressure in the left ventricle and a prolonged ejection time. The supply (DPTI) is normal or reduced. Tachycardia, 12

Fig C-Simultaneously obtained left ventricular (L.V.) and aortic (Ao)pressure pulses in a patient with angina and severe aortic valve stenosis to illustrate the concept of systolic pressure time index (SPTI) in cross-hatched area and diastolic pressure time index (DPTI) in lined area. The former is largely an index of oxygen demand and the latter of oxygen delivery. The ratio of DPTVSPTI would be markedly reduced, favoring development of ischemia.

which reduces the diastolic portion of the cardiac cycle, further ieopardizes flow. As maximal dilatation of the subendocardial coronary bed is achieved, a further ischemia results in angina. Some have speculated that the ST and T wave changes seen in the electrocardiogram of patients with severe aortic stenosis reflect an ongoing subendocardial ischemia.12 Adults with aortic stenosis develop symptoms in later life, often at a time when coronary atherosclerosis.has a peak incidence. An earlier impression that the obstruction to left ventricular outflow somehow protects against the development of coronary atheromas is thought to be erroneous, as the two conditions often are known to coexist .I3 A coronary arterial narrowing that may not be sufficient to produce angina could be contributing to ischemia when severe aortic stenosis is superimposed. There are no conclusive clinical or laboratory parameters to differentiate whether angina is due to the aortic stenosis, atherosclerotic disease or both. b W. PROCTOR HARVEY: I recall a patient

who had classic findings of aortic valve stenosis and also had anemia with a hematocrit of 25. Angina pectoris occurred when he walked from his bed across the hall to the bathroom, and it was also associated with dyspnea. However, after one single unit of packed red cells, these symptoms disappeared with the same amount of effort just described. Obviously, he was walking a tight13

rope as far as the oxygen supply to his myocardium was concerned. Still further improvement occurred when his hematocrit was restored to normal levels. ) AIVIONIO C. DE LEON, JR.: To make matters even more difficult, angina may not be present as a symptom in some patients who have both significant aortic stenosis and atherosclerotic coronary artery disease! SYNC~PE-DI~~INJE~~. -Dizziness or presyncope, a sensation of near fainting, is a common symptom in severe left ventricular outflow obstruction. Episodes of syncope may be experienced that typically follow cessation of physical activity and come on with little or no warning. The duration of syncope rarely exceeds a few minutes, and on recovery no after-effects are present. The etiology of this symptom in aortic valve stenosis has been the subject of several studies. 14,I5 Sudden hypotension without a significant alteration in the cardiac rate or rhythm occurs initially. Subsequently, arrhythmias may develop. It is postulated that physical activity that results in increased intraventricular pressure may be associated with acute left ventricular “failure” and subsequent hypotension. This may be accentuated by peripheral vasodilatation accompanying exertion. The most important mechanism contributing to profound hypotension is likely to be a reflex initiated by stretch on the mechanoreceptors in the Fig &-The mechanisms of syncope in aortic stenosis, lows effort. It is possible that a similar course of events ular arrhythmias might also account for sudden death.

4

which generally folwith terminal ventric-

JExERc’sE\ LV PRESSURE

VASODILA STOP

T ATION

EXERCISE’~ PERSISTENT VASODILATATION

LV BAROCEPTORS

1 HYPOTENSION

I,, ACUTE

LV FAILURE JSYNCOPE NO PULSE SINUS RHYTHM

+ CORONARY 14

/{ FLOW

-

1 ARRHYTHMIA

left ventricular wall (Fig. 6). Although as not yet identified anatomically, the evidence for such mechanoreceptors from experimental studies appears convincing.16$ I7 Tachyarrhythmias producing a sudden drop in cardiac output may provide an alternative mechanism for dizziness. This is true of both atria1 and ventricular arrhythmias. The atria1 “booster” mechanism is important for adequate filling of the hypertrophied stiff left ventricle. The ventricular tachycardia is poorly tolerated and may degenerate into catastrophic events. ) ANTONIO C. ns LEON, JR.: In the adult patient with aortie stenosis, it has been our impression that syncope also had some correlation with age. The increased chance of coexisting cerebrovascular arteriosclerotic changes in the older age group may make them more likely to be symptomatic from the limitation

to appropriate cardiac output increase with

exercise imposed by the stenotic aortic valve. PALPITATIONS. -A heaving, forcible left ventricle may be felt by patients with severe aortic stenosis on assuming a left lateral decubitus position and the patient may prefer to sleep on his right side. An ectopic beat, or more often the stronger postectopic beat, may be felt. Sustained tachyarrhythmias generally cause severe palpitations.

PHYSICAL

EXAMINATION

(Fig.

7)

BWD PRESSURE. -The blood pressure usually is normal in adults with aortic stenosis, but a characteristic narrowing of the pulse pressure may be seen with advanced disease. A reduction in systolic arterial pressure due to outflow obstruction and an increase in diastolic pressure from peripheral vasoconstriction induced by low cardiac output account for the narrowed pulse pressure. In practice, however, this “classic” feature is an exception rather than a rule. Indeed, the adult with aortic stenosis in the fifth or sixth decade of life may have systolic hypertension due to structural changes in the aorta and the pulse pressure may be greater than the normal 40- 50 mm Hg. It is clear from the above discussion that absence of a narrow pulse pressure cannot be used as a point against the diagnosis of severe aortic stenosis in the adult. Rarely, an independent systemic arterial hypertension may be present. An arterial systolic pressure in excess of 200 mm Hg is not incompatible with associated severe aortic stenosis, as the left ventricle is capable of generating peak systolic pressures in excess of 300 mm Hg. It can, therefore, be readily appreciated that a clinical assessment of the presence and severity of aortic stenosis culty.

in a hypertensive

subject

may offer considerable

diffi15

Fig 7.-A schematic of the classic physical signs in aortic valve stenosis. The location of maximal site of the murmur with areas of radiation are shown by the arrows. In adults with calcific disease, the S,A generally is absent and is shown by a dotted line. The systolic murmur (SM) may extend beyond S,P. The carotid pulse (CP) often is characteristic, with delayed upstroke. The apex impulse may demonstrate a presystolic impulse with S, and a sustained systolic impulse.

Arterial pulse. -A characteristic slowly rising arterial pulse is considered to be a classic finding in severe aortic stenosiPzO (Fig. 8). The upstroke time is prolonged, with a prominent anaerotic notch.*l This is based on early experimental observations by Wiggers22 on the effects of progressive aortic constriction on the distal aortic pulse. This observation can be readily supported Fig Il.-The characteristics of the arterial pulse are shown in the actual recordings of a normal pulse, of a bisferiens pulse in aortic regurgitation (AR), of a brisk bifid pulse in hypertrophic subaortic stenosis (HOCM, H-KS) and of an anacrotic pulse in aortic valve stenosis (AS).

INDIRECT CAROTID

PULSE HOCM (IHSS)

16

AS

Fig 9.-A, indirect carotid pulse (CP) with upstroke time (UT) of 0.07 set, which is normal in a patient with severe aortic stenosis, demonstrates that this sign is not infallible unless a high-fidelity central aortic pressure pulse is obtained. (4 = S,; 1 = S,; 2 = S,. 6,47-year-old man with severe aortic stenosis and left ventricular failure demonstrating the second heart sound to be closely split in the pulmonic area (upper tracing). The recording over the apex (lower tracing) shows only the later component, which occurs 40 msec before the dierotic notch and is therefore S,A. Cardiac auscultation revealed only single S,, but the timing with the dicrotic notch suggests reversed splitting, since S,A follows S,P. The presence of S, is indicative of LV failure.

in patients with severe aortic stenosis when obtaining highfidelity central aortic pressures. However, the peripheral arterial pulse and the indirect carotid pulse show less consistent findings (Fig. 9). This is not surprising, since other factors, such as caliber of the distal vessels, reflection waves and compliance of the arterial wall, affect peripheral arterial pulse contour. Furthermore, associated aortic regurgitation even of mild to moderate severity will significantly alter the pulse contour. Thus, a slowly rising, low-volume (from narrow pulse pressure) arterial pulse of severe aortic stenosis is not a common feature in adult patients. On the other hand, a brisk arterial, pulse generally will argue against a severe lesion. ) ANTONIO C. DE LEON, JR.: These points are worthy of emphasis. Indeed, the older patient with severe aortic stenosis may present with a peripheral aria1 pulse that feels normal and has a normal or even a slightly increased pulse pressure. Conversely, we have seen patients with mild aortic stenosis, in left ventricular failure secondary to other causes such as coronary artery disease, present with a small arterial 17

pulse suggesting a more severe degree of obstruction. As pointed out, systemic hypertension and significant degrees of aortic stenosis can coexist. JU&CLF venous pulse. -The jugular venous pulse fails to show a striking change in the absence of right ventricular decompensation. However, the “a” wave may be prominent as the hypertrophied interventricular septum bulges into the right ventricle to effectively reduce its volume and compliance.23

Apical impulse. -In the early phases with concentric left ventricular hypertrophy, the apical impulse may not be abnormally displaced. Its contour, however, is strikingly abnormal to the pairing fingers. It may, an occasion, be best elicited in the left lateral deeubltus position. The impulse is well localized and typ ically forcible and sustained throughout systole. In addition, a prominent atria1 impulse may also be felt in presystole (see Fig. 7). A careful palpation of the apical impulse may provide more reliable evidence of left ventricular hypertrophy than some of the laboratory aids and thus provide important clues in the assessment of the severity of aortic stenosis. In more advanced cases, when left ventricular dilatation and failure ensue, the apical impulse is displaced in the left thorax and often down an intercostal space. Systolic thrill. -In aortic stenosis, the turbulence produced by blood flow across a narrowed valve orifice often produces a palpable thrill over the base of the heart. This can best be appreciated during forced expiration with the subject leaning forward. It may radiate to the carotid arteries. This may be absent in the emphysematous or largechested patient but is a helpful diagnostic aid in the child and generally indicates a severe lesion. However, when significant aortic regurgitation is present, a systolic thrill cannot be relied on to aid in diagnosing either presence or severity of valve stenosis. b W. F’IKJCIORHARVEY:The finding of a palpable thrill is very helpful in the diagnosis of aortic stenosis. This is felt at the base of the heart and the direction of the thrill is toward the right side of the neck or the right shoulder. The thrill generally is best felt by placing the plam of the hand lightly over the precordium. The vibrations of a thrill are beat detected by one’s palmar surface of the hand rather than the tips of the fingers, which generally are best to detect impulses, localized precordial movements or arterial pulses. As shown in Figure A, the area of the palm adjacent to the fingers generally is best for detecting thrills. Probably the reason why some physicians are able to detect thrills better than others is because they use this part of the hand. One can easily convince himself as to which area is most sensitive by gently stroking with the tips of the fingers, the palmar surface of the opposite hand, from the tips of the fingers down to the wrist, noting which area is most sensitive. Also do this with the opposite hand; one may note that one hand is more sensitive 18

than the other. Important clues also ~oaa~f&m palpation concerning the diagnosis of aortic stenosis (and the degree of aortic insufficiency, if associated). By placing both hands over the precordium, as shown in Figure B, the right hand palpates the left ventricular impulse indicating left ventricular hypertrophy and the left hand detecta a palpable thrill at the base of the heart, the direction of which is toward the right side of the neck or the right shoulder. This, then, meana that the murmur should be at least a grade 4 (grading on the baais of 1 to 6). The diagnosis of aortic stenosis thereby generally can be made. If one feels the radial pulse or any other arterial pulse and fails to detect any quick rise or “flip” to the Fig B.-Clues by palpation,

concerning

the diagnosis

of aortic stenosis can be obtained

pulse (characterizing the so-called waterhammer pulse) or even slight degrees of this, one can assume that there is no signiticant aortic insufficiency and that the predominant lesion is that of aortic stenosis. Usually in such patients, after a complete work-up, including cardiac catheterization, the final diagnosis substantiates the diagnosis as predominant aortic stenosis, which was first suspected at the bedside.

HEART

SOUNDS

FIRBT HEART SOUND 6,). -The S, generally is normal.

first major or mitral

component

of

AORTICEJECTION SOUND. -The presence of a prominent highpitched ejection sound denotes at least one mobile cusp. In the elderly, when the valve cusps are heavily calcified and immobile, the ejection sound is conspicuously absent. The ejection sound of aortic valve stenosis has been correlated with angiographic demonstration of valve doming.24 Its presence has no hearing on severity of the valve stenosis,25 although diagnosticaily it is useful in distinguishing from membranous or hypertrophic subaortic stenosis. 26 The murmur in hypertrophic aortic stenosis (IHSS) may be ushered in by a somewhat

low-pitched though

sound,

termed

pseudoejection

recognized in the phonocardiogram,

sound, rarely

sublater

which,

al-

is audible.27

b W. PROCTORHARVEY:Speaking of the ejection sound with the congenital bicuspid aortic valve, I remember frequently having heard an ejection sound in patients with coarctation of the aorta. Some years ago, I had the unique opportunity of seeing some of the first patients having surgical repair of coarctation of the aorta, performed by Dr. Robert Gross of Children’s Hospital in Boston. I saw a number of his adult patients who were admitted for this operation and recorded on the phonocardiogram an aortic ejection sound. At that time, I thought that this ejection sound must be related to ejection of blood into the aorta and that the coarctation in some way contributed to this sound, since it was not present in patients without coarctation. Today, however, we know that the finding of an aortic ejection sound in a patient with coarctation of the aorta affords an immediate clue as to the presence of a bicuspid aortic valve, which is the most common congenital defect associated with it. SECOND HEART SOUND (S,).-The aortic component of S, (AJ, normally appreciated over the aortic area, left sternal edge and the apex, may be reduced or absent in cald-fic aortic stenosis. This is largely due to impairment of cusp movement from extensive calcification. In some casea, especially when the ejection sound is present, the A, may be well preserved and similarly indicates cusp mobility. Paradoxic or reversed splitting of S, results from prolongation of the left ventricular ejection due to severe outflow obstruction.** This, however, rarely is appreciated in adults with aortic stenosis, but more oft& suggested in the 20

phonocardiogram, where the timing of P2 can be shown in relation to the the dicrotic notch of the carotid pulse (which identifies aortic valve closure), even when A, is small or absent. This sign should be carefully sought, since a reversed splitting in the absence of conduction defect is virtually diagnostic of critically severe stenosis.5 ) ANTONIO C. DE LEON, JR.: In adults with severe calcific stenosis, the second sound most frequently is judged as single on auscultation and is the pulmonic component of the second sound. In trying to assess second sound splitting in patients with aortic stenosis, it may be of help to deliberately auscultate in areas where the ejection systolic murmur is less intense (3d left interspace1 so that the ear can better appreciate the soft, deIayed aortic closure sound in the cases in which paradoxic splitting is present. FOURTH HEART sou~n (S,). -An audible fourth heart sound (S,) or atria1 gallop and a palpable presystolic impulse over the apex imply a stiff, noncompliant hypertrophied ventricle. This finding was used to indicate severity of the aortic stenosis. In younger patients between 20 and 40 years of age without other evident reasons for left ventricular hypertrophy, the presence of a fourth heart sound is associated with a peak systolic gradient in excess of 50 mm Hg and thus represents a useful sign. In older subjects, it is a less reliable sign, since S, is a common finding in the presence of coronary artery disease. THIRD HEART SOUND.-The presence of a third heart sound in adults over the age of 40 years indicates left ventricular failure (see Fig. 9, B). This occurs late in the disease process and may

have serious prognostic import. It is not of specific diagnostic help in determining the severity of the lesion. Clearly, a patient with a mild valve lesion may have hypertrophy and heart failure from associated conditions, e.g., coronary‘ artery disease, hypertension or cardiomyopathy. SYSTOLIC MURMUR. -The hallmark of aortic stenosis on physical examination is a harsh, medium to high-pitched systolic ejection murmur that usually is loudest in the aortic area in” the second right intercostal space. The intensity of the murmur is variable and offers little help in estimating the severity of the lesion,3O although a loud murmur (grade 4/6 or greater) in isolated aortic stenosis generally favors a severe lesion. However, when the disease is far advanced, with reduced volume and velocity of flow, the murmur may be markedly diminished or inaudible (silent aortic stenosis). Occasionally in emphysematous patients, the base of the neck is a better listening site for this murmur.31 A late peaking of the murmur has been said to indicate a severe stenosis,3e but in our experience this is not a par-

ticularly

useful or reliable

sign. 21

The pathogenesis of the murmur is related to the aortic pressure gradient as well as to flow across it. The velocity profile of aortic flow pulse often is more important than the actual pressure gradient in determining intensity and shape of the murmur. This, in turn, is related to a number of factors, including left ventricular contractility and its ejection dynamics. A failing left ventricle may result in reduced velocity of aortic ejection flow pulse independent of the size of the aortic orifice, and improvement in left ventricular performance often will result in a louder murmur. This phenomenon is especially well demonstrable with p&us alternans33, 34 (Fig. 101. The murmur often radiates to the apex, where it may assume a slightly different pitch (Galhvardin phenomenon1.35 Therefore, it often is confused with murmurs of mitral regurgitation, which can assume a so-called diamond shape.% The interval between the end of the murmur and the second heart sound may be helpful, although, as mentioned earlier, in adults with calcific aortic stenosis the aortic second sound often is absent. Careful attention to the character of the murmur is important. In patients in whom a distinction is difficult between the two murmurs, a response to amyl nitrite inhalation is especially helpful. Following amyl nitrite inhalation, systemic vasodilatation and tachycardia ensue. The degree of mitral regurgitation is reduced, with a striking decrease in the intensity of the murmur. The aortic stenosis murmur, on the other hand, generally is increased, due to tachycardia and increased flow velocity. Fig lO.-An example of alternating intensity of the systolic ejection murmur in a patient with aortic stenosis with pulsus alternans. Note the decreased amplitude of the murmur in the first and third beats as compared to the second and fourth beats. The R-R and P-R intervals are unchanged.

TO

RESPONSE DRUGS

OF MURMURS AND MANEUVERS

“ALVAR AORTIC STENOSlS

Amy1 nitrite Valsalva Vasopressors Post extra beats Squatting

Increase Decrease No change Increase Increase

IEm8

Increase Increase Decrease Increase Decrease

MITRAL

REGURGlTATION

Decrease Decrease Increase No change Increase

Particular attention should be paid to patients with cardiac arrhythmia. The murmur of aortic stenosis is markedly accentuated in the postectopic beat and varies in intensity with varying cycle lengths in atria1 fibrillation. In contrast, the murmur of mitral regurgitation varies but little.3s The mechanism for this possibly is related to decreased arterial resistance and peripheral runoff with the prolonged cycle length and augmentation of the end-diastolic volume in the left ventricle. The subsequent beat in aortic stenosis is associated with higher pressure gradient, a bigger stroke volume and a louder murmur. In contrast, the forward aortic flow is facilitated in patients with mitral regurgitation, the degree of regurgitation not especially accentuated, and the murmur is unaltered. The accompanying table lists the response of the murmurs of aortic valve stenosis, of IHSS and of mitral regurgitation to various drugs and maneuvers. DIASTOLIC MURMUR. -Coexistence of mild aortic regurgitation with an early diastolic murmur is not infrequent.

LABORATORY

EVALUATION

ELECTROCARDIOGRAM AND VECTORCARDIOGRAM.-When

a significant hemodynamic gradient exists across the aortic valve, the majority of patients have evidence of left ventricular hypertrophy on the 12-lead electrocardiogram. The axis usually is normal, the QRS voltage is increased and associated ST depression and T inversions are common (Fig. 11). These signs may precede the development of symptoms. In rare instances, the ECG will remain normal despite serious left ventricular obstruction. Hence, the absence of left ventricular hypertrophy on the ECG should not provide a false sense of security as regards the severity of the lesion. The anterior precordial leads (V, - V,) frequently do not show the normal R wave progression with aortic stenosis. These mimic anterior wall scarring but may be simply due to the posterior displacement of the Q&3 forces from the left ventricular hypertrophy.“’ Left bundle-branch block may be present in some indi23

vi!

V4

Fig Il.-A representative 1%lead ECG to show evidence of left ventricular hypertrophy (LVH) and “strain” pattern. Poor R wave progression from V,V, is consistent with LVH. The QRS axis in the frontal plane is normal (W), as is the case in most patients without complicating conduction disturbance.

viduals due to infiltration of the conducting tissue by the calcific process. However, severe hypertrophy may be sufficient to prolong the QRS duration with notching and simulate left bundlebranch block. Advanced AV conduction defects, including complete heart block, are not rare in severe calcific aortic stenosis.38~ 39 Atria1 fibrillation generally is a late feature and occurs when the course is complicated by left ventricular failure. An early development of this rhythm should raise a suspicion of associated mitral valve involvement.*B, 4o The vectorcardiogram is of little help in adults with aortic stenosis, despite earlier claims. 41 Posterior displacement of the 20 msec QRS vector in the transverse plane had been proposed to discriminate between anteroseptal infarction and left ventricular hypertrophy. The accuracy of this parameter is questionable. However, excellent correlations between the vectorcardiographic parameters and the degree of obstruction have been observed in children with aortic stenosis .a In adults, it has not provided more useful information than the B-lead EGG. 24

CHEST X-RAY. -Figure 12 shows the location of a calcified aortic valve in PA and lateral views of the heart. This often is present but not detected on a routine roentgenogram and shows up on image-intensified fluoroscopy. The presence of valvular calcification is a helpful clue in diagnosing aortic stenosis in the individual over 40 years of age It is extremely rare for significant aortic stenosis to exist without valve calcification in this age group. However, calcification may be present in older males without significant disease. On the other hand, a calcified valve in a woman below 60 years of age almost invariably indicates severe stenosis.4” The heart size usually is normal except in advanced cases, but Fig 112.- Lateral chest x-ray to Typica carina to the lower sternal edge hind it

show aortic valvq calcification .in &ant !A. wherees the mltrat catcilt~

bebw the ar I‘OW. .line joir iing is krcated be-

the appearance of a normal cardiothoracic ratio may be deceptive, as a thick-walled chamber may not give rise to a significant abnormality, even on four views of the chest. Gross cardiomegaly implies a far-advanced stage and generally is a poor prognostic sign. Poststenotic dilatation of the ascending aorta is present but unhelpful in assessing severity of the lesion. Left atria1 enlargement is a late feature and represents left ventricular failure.21 NONINVASIVE

TECHNIQUES

PHONOMRDIOGRAM AND INDIRECT PULSES. -The phonocardiogram is a valuable laboratory aid not only to confirm the physical signs on auscultation but also to provide measurements of acoustic events in reference to ECG and the pulse waves.

Atria1 gallop or S,: -This low-frequency sound is best recorded over the apical impulse, often in the left lateral decubitus position. When the P-R interval is normal, the separation of S, from the subsequent S, (first heart sound) is indicative of the severity of left ventricular dysfunction. As the hypertrophy gets more advanced and compliance is reduced, S, moves farther away from the succeeding 5,. 44 Acute changes in arterial blood pressure or in venous return also may alter this relationship. Ejection sound. -An aortic ejection sound may be recorded at high-frequency settings, although in the adult with calcific disease it is an uncommon finding. When present, it occurs after the initial upstroke of the carotid pulse, often near the anacrotic notch, and represents preserved cusp mobility. It does not provide any clue to the quantitation of the valve stenosis. Second heart sound. -As stated earlier, although paradoxic splitting of S, (second heart sound) rarely is appreciated owing to absence of the aortic component (A& its presence virtually always means severe aortic stenosis. Phonocardiography is of additional help in demonstrating reversed splitting of S,, when P? (pulmonic component) occurs more than 50 msec before the dicrotic notch of the indirect carotid pulse. The relationship between 4 and the dicrotic notch generally is predictable, such that A, precedes it by 30-40 msec. This observation can be utilized to assume the expected timing of A, even when the latter cannot be discretely identified. )

ANWNIO C. DE LEON, JR.: Demonstration that the recorded S, moves away from S, on inspiration helps to identify it as the pulmonic compo-

nent and is especially helpful when A, or the dicrotic notch of the carotid pulse trace is not discretely 26

present.

---

Systolic murmur. - The systolic murmur is ejection type with its onset after onset of the carotid pulse. It may go through Pz and with absent A, it may be mistaken for a regurgitant murmur. When present over the apex, it may be distinguished by its late onset, characteristic envelope and frequency content. The eject&n murm~s generaIIy have more medium-frequency components whereas the mitral regurgitant murmur generally is of higher frequency. Simultaneous recordings over the aortic area and the apex generally help in determining if two separate murmurs are present. Systolic time interuakWeissler and associates have proposed the use of systolic time intervals to assess ventricular function.45, 46 These are derived from simultaneous recordings of the phonocardiogram, the ECG and the indirect carotid pulse. The essential intervals are: Q-S, (from onset of QRS to AJ, LVET (left ventricular ejection time from onset to the dicrotic notch of the carotid impulse) and PEP (pre-ejection period estimated as Q-S, minus LVET). A correction for heart rate is proposed in order to interpret independent changes. Typically, in severe aortic stenosis, the PEP is shortened and LVET prolonged, and the PEP/LVET ratio is markedly abnorma1.47 In an individual with mild symptoms and signs of aortic stenosis, the abnormal systolic time intervals may provide a clue to a severe underlying lesion. However, when left ventricular failure complicates aortic stenosis, the PEP lengthens and the LVET shortens, as in other forms of heart failure, and this makes assessment of severity of the obstruction difficult. ECHOCARDIOGRAPHY. - Standard M-mode echocardiography permits evaluation of structural and functional changes in the aortic and mitral valves in most patients. In addition, the left ventricle can be examined generally with a caudal transducer angulation. Significant useful information may be derived by this technique.

Aortic root and value. -Calcification of the aortic valve can be readily appreciated as heavy multilayered echo reflections within the aortic root. This abnormal appearance replaces the normal box-like opening of the aortic cusps in systole.48 Generally, little or no motion of the calcified cusps is evident, although some opening movement may be discerned. A study in adults with aortic valve disease demonstrated a more frequent finding of heavily calcified immobile cusps when the stenosis was more severe and predominant than regurgitation.48 Since this technique is extremely sensitive in demonstration of calcification, it can replace fluoroscopy (Fig. 13). A structurally normal aortic valve virtually excludes significant aortic stenosis in patients 27

PHON EC

PCG ECG

Fig 13.-A, normal aortic valve echogram (AoV) shows the characteristic boxlike appearance as the right coronary cusp opens anteriorly and the noncoronary cusp posteriorly in systole. The left cusp, being at a plane perpendicular to the ultrasound beam, generally is not seen in the echo. 0, examples of diseased aortic valves with various degrees of calcification. Panel A shows a heavily calcified valve without discernible motion in systole. Panel 6 shows a thickened and calcified valve with retained motion of the two leaflets. Panel C shows a thickened valve with only restricted motion of the noncoronary arsp. Typically, the echographic appearance as in panel A is consistent with severe calcific aortic stenosis, in panel B with a calcified valve without significant obstruction and in panel C with a thickened, minimally calcified and only mildly obstructive valve. Exceptions to these findings do occur but are infrequent.

over 40 years of age. Calcification in females between 40 and 60 years is much more indicative of severe disease than in males. In children with aortic valve stenosis, the valve cusps appear normal and retain the normal box-like opening. The extent of the opening cannot be used to assess the severity of stenosis, probably because the midportion of the cusps may open fully despite restriction of the distal opening. A bicuspid aortic valve often may be present and can be recognized by this technique from its eccentric position in diastole and its multilayered appearance.4s Left ventricle. -An assessment of the left ventricle includes measurement of the thickness of the interventricular septum and of the left ventricular posterior wall along its minor axis. In addition, enddiastolic diameter and end-systolic diameter of the minor axis provide valuable information as regards size and function of the chamber. Thus, end-diastolic diameter may progressively enlarge50 and indicate worsening failure. The diameter shortening correlates extremely well with ejection fraction in 28

symmetrically contracting ventricles, as in valvular heart disease. Therefore, it can be a useful noninvasive indicator of overall left ventricular function and for follow-up evaluation. In some patients with aortic valve stenosis, unsuspected asymmetric septal hypertrophy with features of hypertrophic cardiomyopathy have been uncovered by the echo examination.51 When asymmetric septal hypertrophy is identified as septal to posterior wall ratio in excess of 1.5, it would therapeutically be relevant to ascertain the presence of dynamic muscular subaortic stenosis, which may be masked by sustained afterload induced by the valve stenosis. CARDIAC CATHETERIZATION AND ANGIOGRAPHY. - Patients with severe advanced aortic valve stenosis constitute a high-risk group for cardiac catheterization. They tend to tolerate atria1 arrhythmias poorly, with a striking drop in cardiac output. Catheter-induced ventricular premature beats may degenerate into ventricular tachycardia and fibrillation, partly due to the hypertrophied and often ischemic or scarred left ventricle. Vasovagal episodes with hypotension, bradycardia and drop in cardiac output may also have deleterious consequences. When transseptal catheterization is attempted, an inadvertent entry into the pericardial cavity with small effusion is poorly tolerated. Furthermore, patients with coexisting coronary artery disease offer an additional risk of electrical instability. For these reasons, it has been suggested that when a clinical diagnosis is made of severe aortic stenosis supported by noninvasive techniques, the patient may be sent to surgery without cardiac catheterization studies. Since very few of the so-called characteristic features of severe aortic stenosis are truly diagnostic and since we have come across frequent “surprises,” particularly when hypertension or coronary artery disease coexist, we strongly favor catheterization and angiography in virtually all suspected cases prior to surgery. The knowledge of potential risks does give one reason for special caution and the cardiac surgical team should be alerted. In some instances, the patient may best be taken to the operating room following catheterization once the diagnosis is confirmed.

) ANTONIO C. DE LEON, JR.: Our experience is similar. Although good, careful clinical assessment often is correct, there are enough instances when the severity of aortic stenosis may be overestimated or underestimated to make us believe that all patients should have cardiac catheterization assessment prior to surgery.

The primary objectives of cardiac catheterization are (1) to confirm the severity of valve stenosis, (2) to assess left ventricular function, (3) to ascertain the coronary artery anatomy, espe29

cially in patients with angina, and (4) to exclude the presence of clinically unsuspected disease, e.g., mitral valve disease, cardiomyopathy. Flowdirected balloon catheterization is safe and provides important information as regards pulmonary arterial and pulmonary wedge pressures. Retrograde left heart catheterization requires passage of a catheter across the stenotic valve, a procedure that is generally successful in more than 80% of patients. This approach also permits aortic root angiography and selective coronary arteriography when indicated. In some patients, when the all-important information of transvalvar gradient is not forthcoming from the above approach, a transseptal catheterization may be necessary. Typical simultaneous left ventricular and aortic pressure tracings are shown in Figure 5. The hallmark of this condition is the systolic gradient at the level of the aortic valve, which can be demonstrated on pullback recordings. w ANTONIO C. DE LEON, JR.: An alternative to the transseptal approach would be a transthoracic (apical or subxiphoid approach) left ventricular puncture.

Pulsus alternans, which frequently goes undetected clinically, is observed commonly in the left ventricular and aortic pressure tracings. It often is initiated following an extrasystole. The left atria1 and the right heart pressures are normal if the disease is not far advanced. A prominent ‘“a” wave in the left atrial or pulmonary “wedge” pressure pulse reflecting a stiff, noncompliant ventricle usually is found. This “a” kick serves to augment left ventricular volume and pressure and improves ventricular function by the Starling mechanism. This sometimes is referred to as the “booster pump” and is a reason why sinoatrial rhythm is important to the patient with aortic stenosis.52 The pressure gradient from the aorta to the left ventricle may be misleading when this alone is used to make a decision about the degree of obstruction. The systolic gradient is dependent on flow and the duration of ejection. These variables can be considered together by using the Gorlin formu1a,53 if simultaneous cardiac output is also measured (Fig. 14). This expresses a figure for valve area based on the blood flow in systole and the mean systolic pressure gradient. In the absence of significant aortic regurgitation, an area of 0.75 cm2 or less represents a critical lesion. Besides calculation of the valve area and exclusion of associated lesions, it is also important to assess left ventricular function by angiography. Diffuse subendocardial fibrosis and scarring leads to impaired contractility. The presence of an extremely dilated chamber with poor global contractility adds to the risk of 30

Fig 14.-A schematic illustration of the hemodynamic relationships between pressures and flows in aortic stenosis. The shaded area demonstrates the aortic pressure gradient (P) and the aortic flow (0) pulse follows the general contour of the pressure gradient. The pressure gradient is dependent on the flow per unit time and inversely related to the aortic orifice size (AVO). The estimation of the AVO from cardiac catheterization data based on the Gorlin formula Cardiac output/Systolic ejection period (sec/min) is deAortic valve area = 44.5viiia - FA. rived from these hemodynamic interrelations. 1 =

valve replacement. 54 The ejection fraction is an important determinant, therefore, in any surgical decision. Associated coronary artery disease, as mentioned earlier, is common in patients with aortic stenosis and particularly those with symptomatic angina. Review of the patients in our institution who underwent aortic valve replacement over a 6-year period from 1964 to 1970 shows that coronary artery disease was a leading cause of hospital and short-term morbidity.55 Angina was the leading symptom in long-term morbidity following valve replacement. It is our current policy to perform selective coronary arteriography in patients with aortic stenosis having chest pain. Some centers recommend a routine preoperative study of the coronary arteries in all adults with aortic valve disease. Such information may be useful, for example, at the time of coronary perfusion during surgery. A recent study, however, demonstrated significant coronary artery lesions only in patients with angina.56 If severe coronary narrowings are found, concomitant coronary artery bypass and valve replacement may improve the longterm results.j7, jH 31

DIFFERENTIAL

DIAGNOSIS

A. OTHER FORMS OF LEFT VENTRICULAR OBSTRUCTION

OUTFLOW

The symptoms in all forms of left ventricular outflow obstruction tend to be similar. They all have a prominent systolic murmur over the left ventricular outflow. The site of obstruction may be subvalvar (either discrete membranous, muscular or musculomembranous) or supravalvar (Fig. 15). I. SUBVALVAR MEMBRANOUS AORTIC STENOSIS. -This is a congenital condition with a discrete membrane just below the aortic leaflets, which may be deformed and rendered incompetent.59-fi2 The condition, when severe, generally is recognized in childhood, but may be seen first in adult life. The distinguishing clinical features include (1) the site of maximal intensity of the systolic murmur being to the left of the sternum, with poor transmission to the aortic area and the carotid, (2) absence of ejection click and (3) associated diastolic murmur of aortic regurgitation from deformation of the valve cusp. Echocardiography occasionally may demonstrate abnormal echoes in the outflow space originating from the membrane,63 but more commonly a distinctive feature is early systolic preclosure of the aortic valve cusp (Fig. 16). This latter movement is thought to result from the Bernoulli effect of a high-velocity iet beyond the obstruction. Its Fig 15-A schematic to illustrate the variety of physical signs commonly used to differentiate between different forms of LV outflow obstruction. Note that the supravalvar, valvar and subvalvar fixed forms of obstruction are associated with a slowly rising anacrotic pulse. The hypertrophic subaortic stenosis with functional outflow obstruction has the typical rapid upstroke bifid pulse. The aortic ejection sound (X) is a feature of the valve stenosis, especially in younger patients. The early diastolic murmur is typically most frequent with a discrete subaortic diaphragm, although it may also be associated in valve stenosis.

32

Fig 16.-A, the phonocardiogram in a patient with discrete subvalvar aortic stenosis obtained over the pulmonic area (PA) and lower left sternal edge (LX). Note that the second sound (S,) shows a well-preserved aortic component and is normally split. The soft diastolic murmur, although audible, is only faintly recorded. The carotid pulse shows a delayed upstroke. B, the echocardiogram of the aortic valve in the same patient shows systolic preclosure of the right coronary cusp as shown by the arrow. (AV = aortic valve, LA = left atrium, PCG = phonocardiogram, SM = systolic murmur, ECG = electrocardiogram.) C, echocardiogram of the mitral valve in the same patient demonstrates the diastolic flutter as shown by the arrow. (IVS = interventricular septum, PW = posterior wall of the left ventricle.)

presence is helpful in diagnosis but provides only a rough measure of severity. A definitive diagnosis generally can be established at cardiac cathetherization and selective angiocardiography. II. IDIOPATHIC HYPERTROPHIC SUBAORTIC STENOSIS (IHSS) OR HYPERTROPHIC OBSTRUCTIVE CARDIOMYOPATHY (HOCM).-This condition is associated with a dynamic and variable left ventricular outflow obstruction from asymmetric hypertrophy of the heart. It should be clinically distinguishable by (1) a characteristic brisk, almost jerky, arterial pu1se,“4 (2) site of maximal in33

tensity of the murmur being to the left of the sternum and with poor radiation to the aortic area and the carotids, (3) a harsher, more blowing, systolic murmur over the apex, suggestive of mitral regurgitation, (4) accentuation of the murmur with the Valsalva maneuver and (5) bifid apical impulse in systole. An echocardiogram provides a characteristic constellation of findings (Fig. 171, which include (a) disproportionate hypertrophy of the septum in relation to the left ventricular posterior wall, (b) narrowed left ventricular outflow space and (cl systolic anterior motion of the mitral valve, resulting in the outflow obstruction.65 Cardiac catheterization is not needed to distinguish the two conditions, although coexistence of valve stenosis with IHSS may be inferred from abnormal postectopic response with narrowed arterial pulse pressure and an increase in pressure gradient during the Valsalva strain. III. SUPRAVALVAR AORTIC STENOSIS. -A congenital narrowing of the aortic root just above the level of the valve is an uncommon cause of outflow obstruction beyond early childhood. The Fig 17.-The salient echocardiographic features of idiopathic hypertrophic subaortic stenosis (IHSS) are shown. The lower left-hand echocardiogram shows a disproportionately thicker interventricular septum (/KS) in relation to the posterior wall (PW) and anterior mitral leaflet (AM) with systolic anterior motion, as shown by the arrow. The latter is better demonstrated in the enlarged image of the mitral valve echo in the lower right-hand figure. The upper righthand echo of the aortic valve shows midsystolic closure of the two cusps. The schematic shows an asymmetrically hypertrophied heart and the dashed lines of mitral and aortic cusps show their midsystolic positions during the outflow obstruction.

RV ivs AM1 PM1 PW

characteristic high location of the systolic murmur, peculiar faties, unequal pulses in the two upper extremities and signs of coexisting peripheral pulmonary artery branch stenosis may help distinguish this entity.‘j6, 67 B. MITRAL REGURGITATION

The aortic stenosis murmur may be most intense over the apex and have some higher-frequency harsh sound simulating mitral regurgitation. Associated features such as radiation of the murmur to the axilla and its response to amyl nitrite, enlarged left atria1 size and signs of pulmonary hypertension generally will help in the differentiation. Coexistence of severe aortic stenosis and mitral regurgitation is poorly tolerated and may require a selective left ventriculogram for a definitive evaluation. C. CORONARY ARTERY DISEASE Many of the symptoms of aortic valve stenosis may point to arteriosclerotic disease with involvement of coronary arteries to account for angina and either arrhythmia or involvement of cerebral circulation to explain dizziness or syncope. The aortic ejection murmur may be interpreted as flow murmur due to aortic valve sclerosis or aortic dilatation (Fig. 18). Rarely, the carotid bruits may be mistaken for bilateral occlusive arterial disease. Left ventricular hypertrophy and the S, (atria11 gallop may be due to coronary disease or hypertension. A routine chest xFig 18.-A schematic to emphasize the difficulties encountered in the diagnosis of end-stage aortic stenosis with heart failure. Coronary artery disease with congestive heart failure may closely simulate the clinical picture. AS in CHF

CAD in CHF

Aorti; Ejection M. or Papillary Dysfunction

M. 35

ray may not distinguish aortic calcification from hilar markings. The 12-lead ECG with ST and T changes or left ventricular strain may be mistaken for subendocardial ischemia due to coronary artery disease. The differential diagnosis may be extremely difficult in some cases unless one thinks of the possibility of valve stenosis, and fluoroscopy or echocardiography is obtained to look for calcification. There is some urgency in making a conrect diagnosis owing to the risk of sudden death and of progredsive ventricular dysfunction. The problem is further compounded by the fact that the two conditions may coexist. NATURAL

HISTORY

Several studies have analyzed the natural history of symptomatic aortic stenosis in adults prior to the advent of corrective surgery.6R-7n Although hemodynamically severe aortic valve disease is well tolerated for a number of years without symptoms, once the clinical deterioration sets in, the course is progressively downhill. In contrast to severe mitral valve disease, which has a long, slowly progressive, symptomatic phase spanning over one or two decades, the course in symptomatic patients with aortic stenosis is measured in months rather than in years. Clinical studies have demonstrated an average life expectancy of 3- 4 years from the onset of syncope, 2-3 years from the onset of angina and 18 months to 2 years after the onset of dyspnea and heart failure68 (Fig. 19). Another important statistic showed that Fig 19.-Characterization of the natural history of aortic stenosis through development of heart failure in adults. Progressive outflow obstruction with ventricular hypertrophy from the systolic overload results in reduced compliance. Progressive dysfunction and dilatation results in atrial hypertension and pulmonary congestion. Subsequent deterioration generally is rapid, ending in death over months. HEART FAILURE Time Course o-n years

Outflow Obstruction + Ventricular

(Prcgressivel

Hypertension

+ Hypertrophy (Compliance)-Atrlal 4 Dysfunction Between 40-M) Years

1 1 IAvg. 1 62.5 years

36

G

& Dilatation

+ Atrial &Venous Hypertension-

Ventricular

4 Dyspnea C. H. F.

Pulmonary Congestion

+ Death

G

80% of patients dying of aortic stenosis had been symptomatic for less than 4 years. Sudden death is well recognized in aortic stenosis and is observed in all forms of left ventricular outflow obstruction. The mechanism is not known. It has been estimated to account for 20% of all deaths from aortic valve stenosis.68 This mode of termination is observed rarely, if ever, in totally asymptomatic patients. The obvious implication is that in symptomatic patients with suspected severe aortic stenosis, further investigations and appropriate treatment should not be delayed. SURGERY Since the natural history of symptomatic patients with aortic stenosis treated medically is poor, a number of attempts at surgical correction has been made. Initially, debridement and valvotomy were attempted with virtually no significant improvement of obstruction except in the occasional young patient. The next phase has been the development of prosthetic valves and almost simultaneously the use of aortic valve homografts.71r 72 The, present experience is turning away from the homografts because of an increased rate of late complications. The valve may undergo degenerative or sclerotic changes, often with considerable aortic regurgitation. The prosthetic valves are also not free from complications. One has to balance the immediate and longterm risks of the operation against the natural history of the condition (Fig. 20). The ultimate goal of surgery is to improve the quality of life as well as to prolong life. One of the primary considerations in the estimation of operative risks is the status of left ventricular function. Most studies have shown that the operative mortality (inclusive of inhospital stay of 3-4 weeks) is influenced by the cardiac index, the clinical classification and the left ventricular function. The changes in left ventricular thickness, volume and contractility often’l, 73 are irreversible, especially in patients with advanced heart failure. It is our current practice to recommend cardiac catheterization for the symptomatic patient with the clinical features of aortic stenosis. If the calculated aortic valve area is shown to be 0.75 cm2 or less, an early valve replacement is recommended at the time of hospitalization. A difficult problem is the occasional asymptomatic patient with aortic valve disease who has clinical or ECG evidence of marked left ventricular hypertrophy. The possibility of sudden death or irreversible myocardial dysfunction has to be considered in the plans for management. Our current practice is to ascertain if the patient is truly asymptomatic, by talking with the spouse and by objective assessment on treadmill testing. We 37

t EMBOLIZATION 1 1HEMOLYSIS 1 1SHORT AND 1 LONtG TERM SURVIVAL Of’ERATIVE MORTALITY

NATURAL HtSTORY OF AORTtC STENOSIS Fig 20.-A in any given replacement.

schematic patient

to illustrate with aortic

CoMpLICATt~S Of WUVE REPLACEMENT

the considerations valve stenosis prior

that have to be balanced to recommending valve

prefer not to operate on completely symptom-free patients but rather follow them closely for the earliest development of symptoms. The surgical technique, in essence, involves placing the patient on cardiopulmonary bypass and cooling the heart to decrease oxygen requirements. Some surgeons prefer to cannulate the left coronary artery during the aortic cross clamp, especially if extreme cooling is not used. The valve is excised through an aortic incision, with due care to avoid calcium emboli. Heavy calcification extending into the aortic ring may render seating of the valve prosthesis difficult (Fig. 21). The operative mortality reported in most recent series of patients varies from 4% to 10% .74175 Aside from left ventricular function as judged by ejection fraction, coexisting coronary artery disease influences mortality adversely. Several centers prefer to combine coronary artery bypass surgery with the valve replacement in order to reduce mortality and long-term morbidity. A variety of prosthetic valves currently are in use (Fig. 22). The major complications of the aortic valve prosthesis include (a) embolism, (b) infection, (c) hemolysis, Cd) prosthetic dysfunction and (e) paravalvar aortic regurgitation. A) E&inoLIsM.-The incidence of systemic emboli in the early Starr-Edwards series was as high as 31% over a B-year period. The newer cloth-covered valves and the disk valves are associated with a much lower incidence of embolism, such that several centers have discontinued the routine use of anticoagulants. 38

Fig 21.-Pathologic appearance of a heavily valve at surgery. In such cases, the differentiation tricqspid valve may be nearly impossible.

calcified and distorted between a bicuspid

aortic and a

They surmise that the danger from the medications outweighs the risk of embolism. Our current practice is to place all patients on oral anticoagulants unless a contraindication exists. B) INFECTION. -Bacterial endocarditis on the prosthetic valve fortunately is rare. The common offenders are staphylococci.76 Such an infection carries a high mortality. The infection may develop at any time after the operation. Fig 22.-Different types of aortic Starr-Edwards valve with a Silastic with a metal ball and to the extreme

valve prostheses. At the extreme ball, in the middle is a cloth-covered right is a Bjork-Shiley disk valve.

left

is a strut

c) HEMOLYSIS. -Mild hemolysis from mechanical trauma to the red cells resulting in fragmentation is common in virtually all patients with a valve prosthesis. This mild degree of hemolysis generally is well compensated but may require supplementation with iron and folic acid in order to replace urinary loss. More severe and symptomatic hemolysis may complicate a malfunctioning prosthetic valve, generally associated with regurgi: tation. If the condition is not controlled and the hemafocrit continues to drop, it may constitute an indication for reoperation. D) PJUNT~TIC VALVE DYSFUNCTION. -The valve dysfunction can result from a clot preventing proper functioning. This results in obstruction to flow and may prevent effective valve closure as weI1. The prosthetic valve sounds may become soft or inaudible, intermittently. An echocardiogram may reveal the presence of the clot. A cause of late valve dysfunction with a Starr-Edwards prosthesis was ball variance (Fig. 23). This resulted from deformation of the ball, and on occasion the ball was extruded out of the cage, with development of acute catastrophic aortic regurgitation.” This generally was a fatal event. This complication has been almost completely prevented by the use of metal-coated balls in place of the silastic. E) PARAVALVAR AORTIC REGURGITATION. -In some cases when the sutures around the aortic ring do not hold, paravalvar regurgitation develops. This generally is in the setting of heavy calcification in the ring, with technically difficult seating of the valve.76 The regurgitation becomes evident in the first few days after surgery. It may become progressively more severe with time. A volume load is likely to be poorly tolerated by the hyperFig 23.-B ;alI variance with cracking and distortion of the ball, wh tich permits ous extrlraisn from the cage, with d&a&mm m&xxne. ^

its sp bontane

40

1

MO1

1

I

I

I

I

NATURAL f-fISTOTTY CIF AORTK VALM DISEASE I I 1 I

2

3 4 YEAl6

5

6

7

0

9

Fig 24.-Isolated aortic valve replacement, 19641970. Cumulative survival rate estimated for patients with symptomatic aortic valve disease without surgery (triangles), for similar patients following aortic valve replacement (closed circles), and for a general population of comparable age (open circles). It is obvious that survival is significantly improved following valve replacement such that a 10% survival at 6 years without surgery is improved to a W%survival. Following the intraoperative and early postoperative mortality, the survival rate tends to parallel the rate in the general population.

trophied left ventricle and may require reoperation if cardiac decompensation results. Despite the above listing of complications, the reports of longterm follow-up in patients with severe aortic stenosis are generally encouraging. It is clear that the symptoms are relieved and life is prolonged (Fig. 24). There is, however, a significant incidence of sudden death even following the aortic surgery.55 Whether the actual risk is significantly lower after surgery as compared to before is not known. SPECIAL

CONSIDERATIONS

I. AORTIC STENOSIS

IN THE ELDERLY

As pointed out in an earlier section, the underlying etiopathology appears to be different in this age group. The majority of the patients have a heavily calcified tricuspid aortic valve and this is thought to be the end result of degenerative changes and subsequent calcification. The symptomatology often is mixed due to the frequency of associated vascular occlusions. Thus, coronary artery disease, cerebrovascular disease or peripheral vascular disease commonly is present singly or in combination. The presenting symp41

toms, therefore, may be intermittent claudication, transient ischemit attacks or myocardial infarction or unstable angina. Discovery of associated aortic valve stenosis then may uncover the other symptoms of outflow obstruction. On physical examination, the presence of systolic hypertension is far more common and the pulse pressure rarely is narrowed.78 Unequal extremity pulses may be felt. Carotid bruits may be more prominent on one side than the other. With unfolding of the aortic arch, a SW

prasternal thrill is common. The cardiac findings include a high incidence of cardiomegaly and an associated murmur of mitral regurgitation due to papillary muscle dysfunction. Indeed, the aortic murmur is also heard much more frequently over the apex, where it may be the loudest, giving some difficulty in diagnosis. An S, gallop is too common in this age group to have any diagnostic relevance. The ECG may be conspicuous by the absence of increased voltage of LVH and the presence of features of myocardial ischemia in addition to ST and T changes of left ventricular “strain” pattern. Chest x-ray and fluoroscopy demonstrate extensive calcifica-

tions, which may involve, besides the aortic root, the mitral anulus as well as the coronary arteries. Angiographic assessment must include, depending on symptoms, evaluation of coronary arterial, extracranial, cerebral arterial or other arterial systems. Several reports have demonstrated a feasibility of successful surgery over age 65 years with an acceptable mortality and morbidity.7sp 8o The oldest patient operated on at this center for aortic valve replacement was 78 years of age. There is a more frequent need for implantation of permanent epicardial pacemaker wires, since conduction defects are more frequent and often involve the distal branches. An awareness of the likely presence of severe aortic stenosis in the elderly

tion of a potential oversight

in making

“cure” for this condition the appropriate

and the recogni-

will prevent serious

diagnosis.

b WILLIAM C. ROBEE~TS: Aortic stenosis in persons >65 years of age differs in several respects from that in persons aged 15-65 years: (1) the structure of the aortic valve in 90% of the older patients is tricuspid whereas the structure most commonly is bicuspid in the younger group; (2) commissural fusion is infrequent in the older group but not in the younger group; (3) the sex ratio in the older group is equal whereas 76% of the patients in the younger group are males; (4) mitral anular calcification occurs in about 75% of the patients with aortic stenosis > age 65 whereas it occurs in probably only about 10% of the patients under age 65; (5) diagnosis during life of aortic stenosis in the older population was established in only 56% of the patients > age 65 studied personally at autopsy whereas this diagnosis was made antemortum in nearly all of the younger patients studied personally at autopsy; (6) associated calcific deposits in the coronary arteries is common in the elder patients whereas 42

it is not nearly as common in the younger patients; (7) associated complete heart block or complete left bundle-branch block probably is less common in the older patients compared to the younger ones. The cause of aortic stenosis in the elderly is not certain but presumably it results from wear-and-tear through the years. I suspect that it is related to atherosclerosis because, to my knowledge, it occurs, for practical purposes, only in populations in whom blood cholesterol levels are >200 mg per 100 ml. Thus, in the undeveloped countries, calcific deposits in the coronary arteries, aortic valve cusps and mitral anuli are exceedingly uncommon. In contrast, nearly 100% of persons in high lipid environments over the age of 90 years have calcific deposits in their aortic valves by radiography of the heart specimen at autopsy. If these calcific deposits are large enough, they impart an immobility to the cusps, with resulting stenosis despite the lack of commissural fusion. II. AORTIC STENOSIS IN INFANCY Congenital aortic stenosis associated with symptoms in the newborn almost always is accompanied by underdevelopment of the aorta and the left ventricle .*’ It constitutes the hypoplastic left heart syndrome. During the later months of infancy and early childhood, severe aortic stenosis with left ventricular failure may simulate endocardial fibroelastosis. The left ventricle is dilated and poorly contracting and the systolic murmur is soft. Prognosis of a severe lesion at this stage generally is poor. Fig 25.-Auscultatory features by the presence of a high-pitched

of congenital aortic valve disease ejection click (X) and well-preserved

characterized S,A.

43

III. AORTIC STENOSIS

IN CHILDHOOD

Congenital aortic stenosis producing symptoms commonly between 5 and 15 years and extending into early adulthood is associated with characteristic physical findings. An aortic ejection click invariably is heard as a prominent high-pitched sound and the aortic component of the second sound is also well pre-’ served (Fig. 25). The typical aortic ejection murmur often is loud and radiates into the carotid vessels. Although a murmur of aortic regurgitation may be present, it is distinctly a less common finding. The ECG shows high voltage and, in advanced cases, ST and T wave changes. Risk of sudden death exists in symptomatic patients and provides a sufficient reason to make an early accurate assessment of the severity mandatory. COEXISTENT

MITRAL

STENOSIS

Coexistent stenosis of mitral and aortic valves on a rheumatic basis results in the clinical syndrome that provides a diagnostic and a therapeutic challenge. Generally, the signs of aortic valve stenosis are obscured.R2 The left ventricle is partially underfilled with critical mitral stenosis, and the resulting low cardiac output may be respons&b for less prominent signs of aortic stenosis. Occasionally, the signs of mitral stenosis may be suppressed. The presence of atria1 fibrillation, especially in a woman with aortic stenosis, or associated advanced pulmonary hypertension or a history of systemic emboli may draw attention to this combination. With the advent of echocardiography, it should be possible to diagnose involvement of both valves with confidence. However, an assessment of the severity of each valve lesion can be made only with cardiac catheterization. The operative risk of double valve replacements is significantly increased in this clinical setting and mitral commissurotomy is preferred whenever the anatomy permits it. COEXISTENT

HYPERTROPHIC

SURAORTIC

STENOSIS

A marked asymmetric hypertrophy of the left ventricle may coexist with aortic valve stenosis.51 The clinical picture is clearly that of severe aortic stenosis. The echocardiographic evaluation generally provides the diagnostic clue with asymmetric septal hypertrophy (ASH), such that thickness of interventricular septum/posterior wall ratio is 1.5. The systolic anterior motion (SAM) of the mitral valve generally is absent, since the fixed afterload provided by valve stenosis tends to attenuate the dynamic obstruction of IHSS. Similarly, the cardiac catheterization generally reveals a gradient only across the valve; however, an abnormal postectopic response with a narrow arterial pulse 44

pressure and abnormal increase in gradient with the Valsalva maneuver should alert one to the coexistence of aortic valve stenosis and IHSS. Infusion of isoproterenol or amyl nitrite inhalation generally is not helpful. The therapeutic implication is obvious, since relief from valve obstruction may unmask severe subaortic stenosis. A combined valve replacement and ventriculomyectomy should provide effective relief from outflow obstruction. However, the eventual prognosis may be altered by the underlying cardiomyopathy. SUMMARY The present review has attempted to summarize the classic symptoms and signs of aortic valve stenosis, especially in an adult. It is emphasized that all the classic signs rarely are present and their absence may mislead an unwary clinician. The diagnostic help provided by noninvasive tests, including echocardiography and phonocardiography, has been emphasized. A need for cardiac catheterization and angiography in most patients prior to corrective surgery is stressed. The natural history of tbe disease without operative intervention is dim and a significant risk of sudden death exists. The current surgical approach with immediate and long-term results is summarized. Finally, attention has been drawn to the special clinical circumstances when the aortic valve stenosis provides a strikingly different clinical picture. We cannot find a better way to end this review than by quoting a warning note given by Thomas Lewis in 1920: “It is the faint cry of an anguished and fast failing muscle, which, when it comes, all should strain to hear, for it is not long repeated. A few months, a few years at most, and the end comes.” REFERENCES 1. Roberts, W. C.: The structure of the aortic valve in clinically isolated aortic stenosis: An autopsy study of 162 patients over 15 years of age, Circulation 42:91, 1970. 2. Roberts, W. C.: The congenitally bicuspid aortic valve: A study of 85 autopsy cases, Am. J. Cardiol. 26:72,1970. 3. Roberts, W. C.: Anatomically isolated aortic valve disease: The case against its being of rheumatic etiology, Am. J. Med. 49:151,1970. 4. Morrow, A. G., Roberts, W. C., Ross, J., Jr., Fisher, R. D., Behrendt, D. M., Mason, D. T., and Braunwald, E.: Obstruction to left ventricular outflow: Current concepts of management and operative treatment, Ann. Intern. Med. 69 1257,1968. 5. Braunwald, E., Roberts, W. C., Goldblatt, A., Aygen, M. M., Rockoff, S. D., and Gilbert, J. W.: Aortic stenosis: Physiologic, pathological and clinical concepts, Ann. Intern. Med. 58:494,1963. 6. Fenoglio, J. J., Jr., McAllister, H. A., Jr., DeCastro, C. M., Dania, T. E., and Cheitlin, M. D.: Congenital bicuspid valve after age 20, Am. J. Cardiol. 39: 164,1977. 7. Holley, K. E., Bahn, R. C., McGoon, D. C., and Mankin, H. T.. Spontaneous 45

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