ANNALS 0 THE N W Y RK A AD MY
`
`EN ES
`
`VOLUME 147, ART. 1 8
`
`PAGES 687 -7 52
`
`October 30, 1969
`
`Editorial Director
`pETER D. ALBERTSON
`
`Editor-in-Chief
`MARC KRAUSS
`
`Managing Editor
`MARJORIE A. MUSIL
`
`AORTIC VALVE DISEASE:
`
`CHANGING CONCEPTS IN ASSESSMENT AND MANAGEMENT*
`
`CONTENTS
`. . . . . . . . . . . . . . . . . . . . 689
`Introduction. By GEORGE H. HUMPHREYS II, M.D.
`Contour Spectral Phonocardiography in the Assessment of Aortic Valve Disease. By
`WILLIAM M. ROGERS, Ph.D., JAMES S. HARRISON, M.D., AND STANLEY
`. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 690
`BLANCHARD, B.E.E.
`Pathophysiological Considerations in Aortic Valve Disease. By JOHN 0. BURRIS,
`M.D., FREDERICK L. MAZER, M.D., AND GERARD M. TURINO, M.D ..... . 716
`Obstruction of the Left Ventricular Outflow Tract: Roentgenographic and Angiocar-
`diographic Features. By KENT ELLIS , M.D . .. . ... ... .... . ....... .. .. 725
`Results of Aortic Valve Replacement Utilizing Irradiated Valve Homografts. By
`JAMES R. MALM, M.D., FREDERICK 0. BOWMAN, JR., M.D., PAUL D.
`HARRIS, M.D ., GERARD A. KAISER, M.D., AND A.T.W. KOVAL! K, M.D .. .. 740
`Postoperative Management of Arrhythmias and Low Cardiac Output in Patients
`Undergoing Aortic Valve Surgery. By P.D. HARRIS, M.D., F.O. BOWMAN, M.D.,
`B.F. HOFFMAN, M.D ., G.A. KAISER, M.D., J.R. MALM, M.D ., AND D.
`. ....... .. ..... . ............................ 748
`SINGER, M.D.
`
`*These papers are the result of a symposium entitled Aortic Val11e Disease: Changing
`Concepts in Assessment and Management, held by the Section of Biological and Medical
`Sciences of The New York Academy of Sciences on January 15, 1968.
`NEW YORK
`PUBLISHED BY THE ACADEMY
`
`STJUDE1028
`IPR of Patent No. 6,821,297
`
`

`

`Copyright, 1969, by Tile New Ym·k Academy of Sciences. All rigllts reserved. Except for
`brief q11otations by reviewers, reprocl11ction of tllis p11blicatio11 in whole or in part by any
`means whatever is strictly prohibited witllo11 t written pemzission from the publisller.
`
`STJUDE1028
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`PATHOPHYSIOLOGICAL CONSIDERATIONS IN AORTIC
`VALVE DISEASE*
`
`JOHN 0. BURRIS, M.D. , FREDERICK L. MAZER, M.D.,t AND
`GERARD M. TURINO ,_M.D.:~
`
`Cardiovasculm· LaboratOJy of The Presbyterian Hospital,
`Department of Medicine, College of Physicians and Surgeons,
`Columbia University, New York, N. Y.
`
`The aortic valve, situated as it is, between the outflow tract of the left
`ventricle and the aorta, plays a vital role in cardiovascular function. By holding
`tl1e head of pressure generated by left ventricular contraction, it maintains high
`aortic pressure with relatively small fluctuations favoring continuous perfusion
`of the peripheral tissues. With the head of pressure in the aorta maintained, the
`left ventricle can operate in short bursts of activity (systole) with relatively long
`periods of rest between bursts (diastole). During diastole the left ventricular
`pressure can fall to low levels, the tension in the myocardium is reduced, and
`coronary flow is favored; also ventricular filling occurs with the maintenance of
`a low pressure pulmonary circulation. Diseases which affect tl1e aortic valve
`restrict its opening (stenosis) or cause it to leak during diastole (insufficiency) or
`a combination of tl1ese two.
`The design of the aortic valve with tluee nearly hemi~pheric cusps is uniquely
`suited to its function. The concavity of the cusps, as seen from the aortic side,
`distlibutes the pressure in such a way that lateral pressure along the free
`opposing edges provides mutual support and a tight seal. The tluee cusps oppose
`each other along three radial lines of contact which trisect the aortic lumen in a
`plane perpendicular to the long axis of the aorta. The total free edge of any
`single cusp is tlms equal to twice the radius of the aortic orifice. The three cusps
`provide a total free edge equal in length to six times the radius of the aortic
`orifice which is, in turn, approximately equal to the circumference of the aortic
`orifice. When the valve is open, tl1ere is just enough length of free edge of tl1e
`cusps to fit snugly against the aortic wall. No otl1er number of cusps would allow
`such a perfect accommodation to the aortic lumen during both opening and
`closing. The majority of cases of congenital valvular aortic stenosis are associated
`with an abnormal number of cusps, most frequently two (Edwards, 1965). In
`aortic stenosis in the adult population, it is becoming recognized tl1at bicuspid
`valves occur most frequently as a predisposing abnormality. Even in rheumatic
`disease of the aortic valve, it is likely that fusion of one of the commissures by
`the inflammatory process produces a bicuspid valve which leads to progressive
`obstruction of the valve. Since a biscuspid valve cannot open fully, the free edges
`will be stretched across the aortic orifice during systolic ejection and set into
`rapid vibration. This trauma can lead to fibrosis, thickening, fusion, and eventual
`calcification of tjle leaflets.
`The progressive nature of aortic stenosis can be seen in FIGURE 1, which
`shows a positive correlation between patients' age and tl1e severity of the valve
`
`*Supported in part by U.S.P.H.S. Grant HE-0574-1.
`tTrainee in Cardiology of the National Institute of Health under Grant HE-05443.
`:):Career Investigator at the Health l<.esearch Council of the City of New York under
`Grant 1-182.
`
`716
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`Burris et al.: Pathologi al Considera tiDns
`200 -
`
`•
`
`717
`
`PEAK
`SYSTOLIC
`GRADIENT
`mmt-IQ
`
`150
`
`100
`
`50
`
`ct
`
`r=+0.68
`P=<.OI
`
`10
`
`20
`
`50
`40
`30
`AGE IN YEARS
`
`60
`
`70
`
`80
`
`PIGURE 1. The relationship between patient's age and severity of aortic stenosis as
`reflected by the peak systolic pressure gradient.
`
`their deleterious effects by
`
`obstruction, as measured by the pressure gradient across the valve during systolic
`ejection.
`insufficiency produce
`Aortic stenosis and
`overloading the left ventricle.
`As can be seen in FIGURE 2, aortic stenosis, .by causing obstruction of left
`ventricular emptying, results in an increase in ventricular pressure. A pressure
`difference is developed across the aortic valve which is proportional to the
`severity of the obstruction and the rate of blood flow during systole. The total
`left ventricular work* is proportional to the area under the left ventricular
`pressure curve. The effective work (the actual aortic mean pressure times the
`volume ejected) is roughly propmtional to the area under the aortic curve. The
`shaded area is therefore proportional to the pathological work load imposed by
`the resistance to flow.
`In the case of aortic insufficiency (FIGURE 3) an increased work load is also
`present. During diastole a certain fraction of the ejected stroke volume leaks
`back into the left ventricle. In order to maintain a normal forward flow, each
`stroke volume must be increased by whatever amount returns by diastolic
`leakage to the left ventricle. The amount of blood which regurgitates during
`diastole is the critical index of the severity of the aortic valve abnormality. The
`actual regurgitant volume may be very great, approaching 75-85% of the total
`
`*The calculation here includes that work clone on the left ventricle by th e righ l ventricle
`and left atrium in filling the left ventricle.
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`71 8
`
`Annals New York Aca demy of Sciences
`
`GH61 yrs. d1
`
`TOTAL LV WO I< 11. 5Kg- M/ Min
`EFFECTIVE LV WO K 5.2 KrM/Min
`%TOTAL LV WORK WAS
`055°1.
`
`PRESSURE
`mmHg
`
`200
`
`160
`
`120
`
`eo
`
`40
`
`0
`
`i.l~
`
`TIME
`
`I
`I ·
`
`FIGURE 2. Distribution of cardiac pressure work in a patient with severe aortic stenosis.
`Left ventricle (LV) and left brachial artery (LBA) pressures are recorded. The electro-
`cardiogram (EKG) is standard lead II. Work is calculated as total LV pressure work.
`Effective work is work resulting in forward blood flow. The shaded area under the LV
`pressure pulse is proportional to the work wasted in overcoming the obstruction to outflow.
`
`left ventricular output (Frank eta/., 1967; Brawley & Morrow, 1967). The
`ventricle mus-t dilate to acconm10date such greatly increased stroke volumes.
`With an increase in ventricular volume, and therefore diameter, the myocardial
`tension required to develop a given systolic pressure increases directly according
`to the Law of La Place (Katz, 1965). The ventricle in aortic insufficiency must
`meet an immense volume overload and, in addition , deliver it at the expense of
`increased myocardial wall tension.
`It is apparent from the preceding that aortic valve abnormalities chronically
`stress the left ventricle and cause it to hypertrophy. The mechanisms by which
`the myocardium is able to adjust to its work ·load have been recently and
`concisely summarized (Braunwald et a!., 1967). After years of overwork,
`eventually, the heart relies more heavily on its ability to increase work when its
`filling pressure , i.e., its end-diastolic pressure is increased (the Frank-Starling
`mechanism). The left atrium (FIGURE 4) provides an effective increase in
`end-diastolic pressure by its contraction immediately before ventricular systole.
`This timing of a trial con traction allows an increase in ventricular end-diastolic
`pressure which may far exceed the left atrial and pulmonary venous mean
`pressure. This mechanism allows ventricular filling while protecting the
`pulmonary capillary bed from reaching levels of mean pressure which could
`result in the transudation of fluid into the interstitium and alveoli. Unfortu- ·
`na tely , this compensation by the left atrium is Hmited; during exercise or other
`stresses, further increases in filling pressure induce higher levels of pulmonary
`
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`Burris eta/.: Pathological Considerations
`
`719
`
`MM 44yrs.J
`
`EFFECTIVE EXTERNAL WORI<(LV)=I0.7 1<g- M/ Min
`TOTAL EXTERNAL WORK(LV)=I6.5Kg- I\1/Min
`ASSU~11NG 35% REGURGITATION
`
`L.V.----7AORTA
`
`200
`
`180
`
`160
`
`140
`
`120
`
`100
`80
`60
`
`PRESSURE
`mmH9
`
`o~!t­
`O.I Gee
`
`TIME
`
`FIGURE 3. Distribution of cardiac work in a patient with moderate aortic insufficiency.
`The pressure curve was recorded as a cardiac catheter was withdrawn from the left ventricle
`(LV) to the aorta. Effective work is that work resulting in forward blood flow. Total work is
`work perfonned in ejecting that blood which flows to the peripheral tissues (forward blood
`flow) plus the blood which regurgitates back into the ventricle with each diastole. The small
`arrow indicates the level of left ventricular filling pressure. The degree of aortic insufficiency
`was estimated from angiocardiography.
`
`l.O. 47yrs.d'
`
`110
`
`100
`90
`80
`70
`PRESSURE 60
`mmHo
`50
`
`40
`30
`20
`
`10
`0
`
`~f+-
`O.lsec
`
`TIME
`
`FIGURE 4. Left atrial tnmsport function in a patient with aortic stenosis. Left
`·ventricular filling pressure is high relative to left atrial mean pressure because of vigorous left
`atrial cmitraction immediately prior to left ventricular contraction.
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`720
`
`Annals New York Academy of Sciences
`
`40
`
`30
`
`LEFT VENTRICULAR
`END DIASTOLIC 20
`PflESSURE
`rnmHg
`
`•
`
`20
`
`40
`
`140
`120
`100
`80
`60
`PEAK SYSTOLIC PRESSURE GRADIENT
`mmHg
`
`160
`
`reo
`
`200
`
`FIGURE 5. The relationship between left ventricular end-diastolic pressure and the
`severity of aortic stenosis as reflected by the peak systolic gradient across the aortic valve in
`37 patients with aortic stenosis.
`
`PEA K
`SYSTOLIC
`GRADIENT
`mmHg
`
`200
`
`180
`
`160
`
`140
`
`120
`
`100
`
`80
`
`60
`
`4 0
`
`20
`
`0
`
`•
`
`•
`
`•
`• •
`
`•
`•
`
`• •
`
`•
`
`r=-0.23
`p=>.05
`
`•
`•
`
`2
`
`4
`3
`CARDIAC INDEX
`L/Min/M2
`
`•
`
`5
`
`6
`
`7
`
`FIG URE 6. The relationship between cardiac index and severity of aortic stenosis as
`reflected by the peak systolic pressure gradient.
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`Burris eta/.: Pathological Considerations
`72 1
`capillary pressure, and the patient, characteristically, complafns of dyspnea as his
`lungs become congested and edematous.
`In addition, patients with aortic valve disease frequently complain of angina
`pectoris. While this has usually been thought to occur from an hypertrophied
`left ventricular muscle mass without a concomitant capillary growth, this
`concept has been challenged (Linzbach, 1960) by the demonstration of an
`increase in coronary capillary density proportional to the increase in number and
`size of myocardial cells. While some .of the patients with angina may have
`coexisting coronary arteriosclerosis, many, as shown recently by FaUen eta!.
`(1967), do not, and these authors therefore suggested some abnormality in the
`autoregulation of coronary blood Oow.
`From the foregoing it is suggested that, whereas the structural abnormality of
`the aortic valve induces the hemodynamic stress, the clinical condition of a
`particular patient depends on the competence of his left ventricle. The decision
`to surgically correct the diseased valve is approached by defining the severity of
`the hemodynamic abnormality of the aortic valve by catheterization of the left
`heart which can also provide some assessment of left ventricular function. To
`illustrate
`this problem in hemodynamics, the authors have chosen to use
`catheterization data from 37 randomly selected cases of isolated aortic stenosis
`from the files of the Cardiovascular Laboratory of the Columbia-Presbyterian
`Medical Center. Of the standard measurement made at the time of cardiac
`
`•
`• •
`
`8
`
`7
`
`6
`
`5
`
`CARDIAC
`INDEX
`4
`L/Min/M2
`
`3
`
`2
`
`r=-0.42
`p= <.01
`
`30
`20
`10
`LEFT VENTRICULAR END DIASTOLIC PRESSURE
`mmHQ
`
`40
`
`FIGURE 7. The relationship between left ventricular end-diastolic pressure (a rough
`index of ventricular function) and cardiac output in 37 patients with aortic stenosis.
`
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`722
`
`Annals New York Academy of Sciences
`
`B~J
`
`500
`
`400
`
`PULMONARY
`VASCULAR
`RESISTANCE INDEX 300
`Oyou Sec cm-5/~
`
`200
`
`100
`
`. . . .
`
`/
`/.
`
`r=+0.47
`P=<.OI
`
`o~----~------~------~------~---
`10
`20
`30
`40
`LEFT VENTRICULAR END DIASTOLIC PRESSURE
`mmH~
`
`FIGURE 8. The relationship between pulmonary vascular resistance and left ventricular
`filling pressure (left ventricular end-diastolic pressure) in patients with aortic stenosis.
`
`cathetedzation, the level of left ventricular end-diastolic pressure (LYEDP) may
`be a helpful reflection of left ventricular functional capacity. However, care
`must be taken in the interpretation of LVEDP (Braunwald & Ross, 1963) as it is
`a function of the pressure volume characteristic of a given ventricle which may
`itself be influenced by a number of humoral and intrinsic myocardial factors.
`But the level of LVEDP in a patient with significant aortic valve disease does
`correlate well with
`the severity of his symptoms and is, in fact,
`the
`hemodynamic abnormality responsible for his dyspnea. When LVEDP is plotted
`against peak systolic gradient (FIGURE 5 ), a significant. positive correlation is
`seen. A few cases with marked pressure gradients have a low LVEDP, suggesting
`their left ventricle is tolerating its load reasonably well. In these cases, exercise
`or some other added stress, such as systemic hypertension induced by
`angiotension infusion (Perloff et al., 1967), might reveal a degree of functional
`compromise. Cardiac output is a less reliable measure of ventricular function
`partly because so many factors other than myocardial performance are involved
`in its regulation. When cardiac output, as cardiac index (Cl), is plotted against
`peak systolic gradient (FIGURE 6) and LVEDP (FIGURE 7), a greater scatter of
`results is seen. There is no significant correlation between CI and LVEDP, and a
`poor correlation between aortic pressure gradient and Cl.
`
`f ..,
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`

`Burris eta/. : Pathological Considerations
`723
`Pulmonary artery pressure is usually normal in patients with isolated aortic
`stenosis as can be seen when LVEDP is plotted against the pulmonary vascular
`resistance index (PVRJ) (FIGURE 8). Most of the patients' resistan ces lie in the
`normal range , which is· rather surprising in view of the frequently marked
`elevation of left atrial pressure (which follows relatively closely LVEDP).
`Published resistances in patients with mitral stenosis with comparable elevations
`of left atrial pressure have higher PVRl's (Curti eta/., 1953 · Araujo & Lukas,
`1952; Yu eta!., 1954).
`·
`The level of systolic pressure gradient is most meaningful if the rate of blood
`flow is also determined. Hence cardiac output, although a poor measure of
`ventricular function , must also be known to assess adequately the severity of
`valve obstruction. Aortic valve orifice area can be calculated (Gorlin & Gorlin ,
`1951) and is valuable since it takes into account gradient, flow, and heart rate,
`even though its accuracy has been questioned.
`In summary, the aortic valve is an important structure masterfuUy designed.
`When the structure is disturbed by an ernbryological Inisadventure or by an
`acquired disease , a heavy burden is placed on the left ventricle. The ventricle has
`surprising ability to adjust to the burden, and symptoms appear only when the
`pressure volume characteristics of the left ventricle become substantially at tered
`and maintenance of ventricular function depends on higher and higher levels of
`filling pressure, which may not occur until the sixth or seventh decade. To
`understand where a.given patient is in this continuum requires that the severity
`of the valve abnormality , whether obstruction or leakage be measured and that
`the functional capacity of the left ventricle be studied. The nee d for better
`means
`to study the
`latter points
`the way for future work and clearer
`understanding of the pathophysiology of heart disease.
`
`References
`ARAUJO , J. & D.S. LUKAS. 1952.
`Interrelationships among pulmonary "capillary"
`pressure, blood flow and valve size in mitral stenosis. The Umitecl regulatory effects
`of the pulmonary vascular resistance. J. Clin. Invest. 31: 1082.
`·
`BRAUNWALD, E. & J. ROSS, JR. 1963. Editorial. The ventricular end-diastolic pressure.
`An appraisal of its value in the recognition of ventricular failure in man. Am. J. ivied.
`34: 137.
`BRAUNWALD, E., J. ROSS, JR. & E.H. SONNENJ3LICK. 1967. Mechanisms of contraction
`of the normal and failing heart. New Eng. J. Med. 277: 794 ,853,910,962.
`BRAWLEY , R.K. & A.G. MORROW. 1965. Direct determination of aortic blood flow in
`patients With aortic ref,'ltrgitation. Circulation 32: 871.
`CURTI, P.C., G. COHEN , B. CASTLEMAN , J.G. SCANNELL, A.L. rRIEDLICH & G.S.
`MEYERS. 1953. Respiratory and circulatory studies of patients with mitral stenosis.
`Circulation 8: 893.
`EDWARDS, J.E. 1965. Pathology of left ventricular outflow tract obstn1ction . Circulation
`31:586.
`FALLEN, E.L., W.C. ELLIOTT & R. GORLIN. 1967. Mechanisms of angina in aortic
`stenosis. Circulation 36: 480.
`FRANK, M.J., P. CASANEGRA, M. NADINI, A.J. MIGLIORI & G.E. LEVINSON. 1967.
`Measurement of aortic regurgitation by upstream sampling with continuous ii1fusion
`of indicator. Circulation 33: 545.
`GORLIN, R. & S.G. GORLIN. 1951. Hydraulic formula for calculation of the area of the
`stenotic mitral valve, other cardiac valves and central circulatory shunts. Am. Heart J.
`41: 1.
`KATZ, A.M. 1965. Editorial. The descending limb of U1e Starling curve and th?e Tailing
`heart. Circulation 32: 871.
`
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`724
`
`Annals New York Academy of Sciences
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`LINZI3ACH A.J . 1960. He;ul failure from the point of view of quantitative n.nato my. Am.
`J. Cru-d iology 5: 370.
`PERLOrf<', J. K., P.F. I3INNION , \V.H. AULriELD & A.C. DeLEON, JR. 1967. T he use of
`angiotension in the assessment of left vcntricuJ;u function in fix ed orifice aortic
`. s te~1 osis. Circulation 35 : 34 7.
`YU, P.N., J.I-1. SIMPSON, F.\V. LOVEJOY, JR. , H.S. JOOS & R.E. NYE, JR. 1954. Studies
`or pulmonary hypertension IV. Pu lmon ary circulatory dynamics in patient with
`mit ral stenosis at rest. Am. Heart J. 47: 330.
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