Quantitative angiographic evaluation and pathophysiologic mechanisms in valvular heart disease

Progress in

Cardiovascular Diseases VOL. XV, NO. 5

MARCH/APRIL 1973

Quantitative Angiographic Evaluation and P a t h o p h y s i o l o g i c M e c h a n i s m s in V a l v u l a r Heart Disease Charles E. Rackley and W i l l i a m P. Hood, Jr.

ECHNICAL ADVANCES in clinical methods for the study of the intact circulation now permit us to define precisely the mechanical abnormalities in valvular heart disease. Cardiac catheterization techniques have been developed for the measurement of pressure in the heart chambers and great vessels and for the measurement of pulmonary and systemic blood flow. In addition, radiographic methods have been developed for visualization of the cardiac chambers and for recognition of valvular regurgitation and obstruction. Recent refinements have made these radiographic methods quantitative as well as qualitative, allowing determination of left ventricular volume, mass, geometry, and wall forces. Such information has been useful clinically in quantitating the magnitude of the mechanical burden, in defining pump function, and in evaluating results of corrective surgery. Such data have also provided considerable insight into the mechanisms of cardiac adaptation to a chronic mechanical burden in terms of hypertrophy, dilatation, and function. The purpose of the present report is to describe quantitative angiographic evaluation of valvular heart disease, to explore its clinical applications, and to review its contributions to the understanding of the pathophysiology of valvular disease.

T

ANGIOGRAPHIC METHODS

Basic Filming Technique Right and left heart catheterization are performed with standard techniques, and forward cardiac output is measured by the Fick principle or the indicator

From the Division of Cardiology, Cardiovascular Research and Training Center, University of Alabama School of Medicine, Birmingham, A la. Supported by NIH Program Project Grant HE, 11,310. Charles E. Rackley, M.D,: Professor of Medicine, University of Alabama School of Medicine, Birmingham, Ala. William P. Hood, Jr., M.D.: Associate Professor of Medicine, University of Alabama School of Medicine, Birmingham, A la. Reprint requests should be addressed to Charles E. Rackley, M.D., University of Alabama School of Medicine, 1919 Seventh Avenue South, Birmingham, Ala. 35233. 9 by Grune & Stratton, Inc. Progress in Cardiovascular Diseases, Vol. XV, No, 5 (March/April), 1973

427

428

RACKLEY AND HOOD

dilution method. Quantitative angiocardiography may be performed with either large film or cine techniques and as either biplane (AP and lateral) or single plane (AP or RAO). Power injection of contrast material, usually 50 60 ml over 2 3 sec, may be accomplished at various sites. Injection directly into the left ventricle is frequently complicated by extrasystoles, but is usually mandatory if the ventricle is significantly dilated. Sufficient ventricular opacification from aortic root injection is possible in the presence of severe aortic regurgitation. Left atrial injection is advantageous in that the likelihood of arrhythmias is lessened, but is disadvantageous in that aortic valve landmarks may be obliterated in the AP plane. Injection into the pulmonary artery with delayed filming is practical only if the subject's chest is thin and if there is no significant obstruction to left ventricular filling. With large film changers, filming is performed at speeds of 6 12/sec for 3 5 sec. With cine units, filming speeds of 30 or 60 frames/sec are generally employed. The electrocardiogram, systemic a n d / o r left ventricular pressure and a film timing signal are recorded during the filming sequence. Extrasystoles and the first postextrasystolic beat are excluded from volume analysis.

Basic Biplane Volume Methods A number of basic biplane methods and modifications thereof have been developed to quantitate volume of the ventricle, l-5 All of the methods cited assume that the left ventricle can be represented by an ellipsoidal geometric reference figure, in which case: volume (cm 3) = 4/31r 9 L DAp 2--" 2

Dlat 2 '

(Eq. 1)

where L = long axis (cm), and D = AP or lateral diameter (cm). The Dodge area-length method i is probably in widest use and will be the one outlined here. In equation 1, above, the long axis (L) actually represents the spatial length from mid-aortic valve to apex. This true spatial length can be calculated by several systems, but these procedures are somewhat cumbersome for routine clinical use. 1,2,4 Since the spatial long axis does not lie parallel to either the frontal or sagittal plane, its projection on both AP and lateral films is foreshortened. Therefore, apex to mid-aortic valve length as directly measured on x-ray films underestimates true spatial length. Empirically it has been found that the longest measurable length within the left ventricular silhouette (on either AP or lateral projection, whichever length is longer) closely approximates the true spatial length. 1,6 Hence, this is the measurement used by Dodge for L in equation 1. There are no landmarks by which the short chamber axes can be precisely identified. Some authors have measured short axis directly on the film at the widest portion of the silhouette (perpendicular to the long axis). 2 Others have measured short axis at the midpoint of the long axis.3 Volumes calculated using directly measured diameters are usually considerably larger than those obtained with the area-length method. 5,7,8 Dodge et al., assuming that the ventricle is ellipsoidal in shape and that its projection onto either plane is an ellipse, calculated the theoretical short axis in each plane as follows.

QUANTITATIVE ANGIOGRAPHIC EVALUATION

429 L

Given: area (A) of an ellipse = ~r . . . . 2 then D -

D

2

4A 7rL'

(Eq. 2)

where A = chamber area (determined by hand planimetry, by an electronic planimeter, or an electronic digitizer), and L -- the longest measured length on a given film.

Correction for X-ray Magnification Regardless of the method employed to derive the various chamber dimensions, before volume can be calculated, each dimension must be corrected for x-ray magnification (since the x-ray source is closer to the " o b j e c t " than 6 ft). Figure 1 illustrates principles of correction for x-ray magnification. As shown, true length (at) can be obtained from the length projected (ap) on the x-ray film by multiplying the projected length by the factor (h - p ) / h , where h = tube-to-film distance (fixed by the apparatus and easily measured) and p = object-to-film distance (cannot be directly measured for h u m a n hearts). Nevertheless, the estimated center of heart mass-to-film distance can be calculated from biplane films if the central x-ray beam is marked by a lead marker. ~ The center of mass (CM) can be considered to lie midway between vertical lines drawn at the right and left margins of the opacified c h a m b e r silhouette (Fig. 2). The distance from CM to central x-ray beam (ap in Fig. 1) is directly measured on the film. The undistorted CM-to-central beam distance (a t in Fig. 1) is then calculated in each plane using equations 4 and 5 of Dodge et al. ~ For incorporation into these equations, the distances from reader's CM-to-center of x-ray beam (lead marker) are taken as: positive if C M is to right, or negative if to left, of the lead marker in the AP film; positive if posterior, or negative if anterior, to the lead marker on the lateral film. Adding or subtracting, as appropriate, the derived undistorted CM-to-central beam distance to directly measured central beam-to-opposite film distance yields object-to-film distance (p). Knowing tube-to-film distance (h), the correction factor may be calculated as (h - p)/h. FOCAL SPOT -"

Fig.1. Principles of correction for x-ray magnification in angiocardiography. Due to the proximity of the x-ray source (focal spot) and the film, a dimension in the heart, a t , will be projected as a p . True length can be found from measurements of h, the tube-to-film distance, and p, the object-tofilm distance. Lead marker denotes the center of the x-ray beam ; C M indicates estimated center of heart mass (see text). (Modified after Dodge et al. 1 )

By similar triangles, at ap

o!\ ap LEAD

MARKER

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h-p h

430

RACKLEY AND HOOD

i

Center of mass

Fig. 2. The line m a r k i n g estimated center of mass is s h o w n in an AP projection of the left ventricle. Center of mass can be related to central x-ray beam to derive a m e a n x-ray correction f a c t o r (see text),

Or, perhaps more simply, its mathematical equivalent may be derived from the ratio ofat/ap (Fig. 1). To avoid going through the calculations each time, in our laboratory x-ray correction factors have been calculated in advance and tabulated for each CM-to-central beam measurement from 0.5-10.0 cm. It should be noted that a correction factor so derived is a mean factor in the sense that one is applying to the whole heart a correction factor determined at its estimated center of mass. It is also mean in the sense that an average factor is applied to all films in a series. Theoretically, individual factors should be determined for each film pair in a given set. In practice, however, since correction factors vary little in an individual patient 7 a factor is usually determined only for a selected end-diastolic film pair and a selected end-systolic film pair, the average of the two being applied to all films in the series.

Accuracy Corrections The accuracy of the area-length method has been tested by comparing known versus calculated volumes in p o s t m o r t e m hearts. 1,9 12 There is a consistent slight overestimation of true volume due in part to the volume occupied by trabeculations and papillary muscles. A correction for this inherent error in the method should be made by using a regression equation derived from such a comparison of known and calculated volumes. The equation derived by Dodge, 7 Vtr,~ = 0.928 X Vc~c - 3.8

(Eq. 3)

has been widely applied in other laboratories. It should be emphasized, however, that this particular regression equation should be applied only if the Dodge area-length method is followed exactly, including the Dodge method of estimating center of mass and deriving x-ray correction factors. Otherwise, a regression equation must be derived for each laboratory. The accuracy of the method has also been tested by comparing angiocardiographic and forward stroke volume or cardiac output in patients without valvular regurgitation. A number of such studies have shown good agreement. 13-17

QUANTITATIVE ANGIOGRAPHIC EVALUATION

431

Calculation Shortcuts If one is interested in volume and not in dimensional analysis, rather than going through the volume calculations and corrections step-by-step, as they have been outlined here, one can save considerable time by combining constants, including correction factors and regression equation, and by combining equations. Basic formula: V = 4/3 r where Lmax = LAp o r

Llat,

Lmax OAp 2

2

Olat

2 '

whichever is longer;

multiplying through: V = 7r Lmax " DAp.

6

Dlat;

adding x-ray correction factors (CF):

V = 71"Zmax(CFmax). DAp(CFAp). Olat(CFlat); 6

substituting for D:

(CFAp) V = 71- Zmax(CFmax) 9 4AAp 7rLAp 6

9

4Alat ~ (CFlat);

simplifying: V = 0.849

(CFmax)

9 AAp(CFAt')

"

Alat(CFlat)

Lmin

where Lmin equation:

=

Lap

or

Llat,

whichever is shorter. Adding the Dodge regression

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=

0"788(CFmax)'AAp(CFmp)'Alat(eFlat)

-

3.8

3.8 (Eq.4)

Lmin Other Volume Methods The basic biplane method has been modified for use as single plane, AP or RAO.5,6,18 20 In this case, the assumption is made that the long axis observed in the single plane available is representative of the true spatial length and that the minor axis in the single plane available is the same as in the opposite plane. In most situations, these assumptions are justified. 6 In general, however, single plane methods overestimate volume considerably more than biplane methods, and it is particularly important here to apply an appropriate regression equation to correct for this systematic error. 6'19,2~ When using cine techniques, it may be necessary to correct for nonlinear (pin cushion) distortion as well as for linear x-ray magnification. 2o

432

RACKLEY AND HOOD

Volume Curves If rapid filming speeds have been used, then sequential volume measurements can be plotted to describe volume changes over one or more cardiac cycles. If slow filming speeds have been used, a composite volume curve must be derived. Volumes from several cardiac cycles can be rearranged according to time after onset of the respective preceding Q R S complex to construct such a curve (as if all measurements had been made in a single cycle) (Fig. 3). F r o m these curves end-diastolic volume and end-systolic volume are taken as an average of the largest and smallest volumes, respectively, in a cycle. Left ventricular stroke volume is the difference between these two. The ejection fraction, which is the fraction of end-diastolic volume ejected per beat, is derived by dividing total left ventricular stroke volume by end-diastolic volume. If aortic or mitral regurgitation is present, the regurgitant volume per beat can be quantitated as the difference between total left ventricular stroke volume as obtained from angiography and forward stroke volume as determined by the Fick or indicator dilution techniques. The slope of the ventricular volume curve during the systolic ejection phase and the diastolic filling phase can be measured to estimate the rate of systolic ejection and diastolic filling. The volume measurements can be related to left ventricular pressure t h r o u g h o u t the cardiac cycle to construct a pressure-volume loop (Fig. 3), which delineates the periods of isovolumic contraction, systolic ejection, isovolumic relaxation, and diastolic filling. The area within and beneath the pressure-volume loop represents the total work of the left ventricle, the area beneath the diagram representing work done on the ventricle during diastole and the area within the loop denoting the net systolic work. The chamber long axis and diameters can be utilized in ways other than calculating volume. For example, the geometry of the c h a m b e r can be described by: (1) the ratio between long axis and short axis, L:D, 21 and (2) eccentricity (e): 22 e - (a2 - b2),

(Eq. 5)

a

where a = L/2 and b = D/2, or by (3) the ratio between the m a j o r radii of curvature along the two axes (RI:R2) , where, for an ellipsoid, R~ =aZ/b, R 2 - - b . 23 The percentage shortening along each axis (~o A axis) during systole is found as: ~oA axis = a x i s o d - axis~s axis~d 9 100,

(Eq. 6)

where ed = end-diastolic, and es = end-systolic. The chamber circumference can be calculated as 7r-D, and the circumferential shortening rate can be determined from the slope of a plot of circumference with time. 2a C h a m b e r pressure, short axis, and wall thickness can be related to derive wall force per unit cross-sectional area (wall stress). 21,25,26 The circumferential shortening rate at the time of peak systolic wall stress is a measure of the velocity of contractile element shortening. 27

QUANTITATIVE ANGIOGRAPHIC EVALUATION Fig. 3. On the left, calculations of left ventricular v o l u m e made during a series of cardiac cycles are related to t h e onset of the Q R S complex to construct a composite volu m e curve. E D V , end-diastolic v o l u m e ; E S V , end-systolic volume; EF, ejection fraction; L V W T , left ventricular mass; and L V E D P , left ventricular end-diastolic pressure. On the

433

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right, left ventricular pres0 012 0.4 0.6 0.8 1.0 20 40 ' 60 ' 80 100 ,~ 120 ' sure and volume are related Secondsafter QRS Volume ml throughout the cardiac cycle to describe a pressure-volume loop. Systolic w o r k is t h e total area within and b e l o w t h e loop, diastolic w o r k , the area b e l o w t h e loop, and net w o r k , t h e area contained within the loop.

Left Ventricular Mass Left ventricular wall thickness can best be visualized on AP films. Average thickness is determined from a 4-cm segment of lateral left ventricular wall just below the equator and is corrected for x-ray magnification using the previously derived CFAp. Assuming uniform thickness of wall around the entire chamber, an assumption that is most nearly correct at end-diastole, volume of chamber plus wall shell can be calculated by adding the average end-diastolic wall thickness to chamber axes. Subtraction of chamber volume from combined wall and chamber volume yields volume of the wall shell. Multiplication of this volume by specific gravity of cardiac muscle (1.050) yields mass of the left ventricle in grams. 28 The mass calculations have been validated by comparing angiographic estimations of left ventricular mass made premortem with actual weights at the time of subsequent postmortem examination. Agreement has been close in both adults and pediatric subjects. 29'3~ Computation of volume and derivation of parameters from left ventricular volume is greatly facilitated by the use of a computer. H

Normal Values Quantitative angiographic studies in patients with normal left ventricles have been performed by several investigators. Their normal values for volume, ejection fraction, wall thickness, and mass are summarized in Table 1. Values for pressure-volume work in a normal subject are shown in Fig. 3. Circumferential stress in normals averages 30 • 4 dynes/cm 2. 103 at end-diastole and 327 :~ 24 dynes/cm 2- 103 at peak systole. 3~ Mean circumferential shortening rate (endocardial) in patients without left ventricular disease has been estimated at 1.50 circ/sec. 24 Circumferential shortening rate (midwall) at the time of peak stress has been reported as 1.74 circ/sec. 24 In the normal left ventricle at enddiastole, the long axis is twice as long as the short axis, with a value for eccentricity of 0.85. 22 The short axis normally shortens by about one-third during systole. 5.22,24,32

434

RACKLEY AND HOOD

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QUANTITATIVE ANGIOGRAPHIC EVALUATION

435

PATHOPHYSIOLOGIC FINDINGS IN VALVULAR HEART DISEASE

Application of quantitative angiographic techniques to valvular heart disease has allowed quantitation of the abnormalities present and documentation of the adaptations and compensatory adjustments made in response to these abnormalities. The abnormalities may be primarily mechanical (valvular), either pressure overload as in aortic stenosis, or volume overload as in aortic or mitral regurgitation. There may be a significant degree of myocardial dysfunction as well, either secondary to the mechanical problem or due to some unrelated primary process; for example, ischemia. The adaptations differ substantially in pressure and volume overload, and the significance of the alterations in certain variables also differs substantially in different physiologic states [for example, the significance of an increased end-diastolic volume in aortic stenosis as opposed to aortic regurgitation (q.v.)]. Volume Overload In the face of chronic aortic or mitral regurgitation, if forward stroke volume is to be maintained, the left ventricle theoretically has four choices open to it: (1) increased percentage emptying per beat at a normal end-diastolic volume, (2) increased percentage emptying per beat at a larger end-diastolic volume, (3) normal percentage emptying per beat at a larger than normal end-diastolic volume, and (4) reduced percentage emptying per beat at an even larger enddiastolic volume. Examples of each type of adaptation are shown in Fig. 4. Increased emptying at a normal end-diastolic volume, as in column B, has not been observed in the normal resting state, either experimentally or clinically. In the presence of a volume load, there is, as a rule, enlargement of the chamber and an increase in end-diastolic volume.~5,33 39 Although increased emptying per beat from a slightly larger end-diastolic volume (as in column C) is characteristic of experimental and clinical acute regurgitation, 4~ it is exceptional in clinical chronic regurgitation. In the absence of clinical decompensation, chronic regurgitant lesions are characterized by the maintenance of a normal (column D) or near normal ejection fraction (column E). 34'36-39 In actue experimental regurgitation, increased emptying has been attributed to a diminished

_A

_B

C

D_

s

End-diastolic volume

100

100

]20

200

280

End-systolic volume

40

20

20

80

140

Forward stroke volume Regurgitant volume

60 0

60 20

60 40

60 60

60 80

Ejection fraction

.60

.80

.83

.60

.50

Fig. 4. Potential adaptive mechanisms of the left ventricle to an increasing volume load while maintaining forward stroke volume at 6 0 ml. Data in column A represent a normally functioning left ventricle. In column B are theoretical adaptations to mild aortic or mitral regurgitation with increased emptying at a normal end-diastolic volume. In column C, in response to a larger volume load a larger end-diastolic v o l u m e has developed with increased emptying, such as may be seen in experimental and clinical acute regurgitation. In D, the usual changes in chronic volume overload are shown; ejection fraction is normal. In E, both the end-diastolic and endsystolic volumes have increased and the ejection fraction has decreased.

436

RACKLEY AND HOOD

resistance to ejection. 4~It has been suggested, therefore, that a normal ejection fraction in chronic regurgitation denotes myocardial dysfunction, n~ This concept implies that resistance to ejection is diminished in chronic regurgitation. This question is unresolved; preliminary observations (unpublished) in our laboratory have suggested that afterload in terms of integrated systolic stress is not less in chronic regurgitation than in the normal state, but this problem needs further investigation. In any case, chronic volume overload is characteristically accompanied by an increase in end-diastolic volume. Within limits, the end-diastolic volume is directly proportional to the regurgitant volume, and similarly, total left ventricular stroke volume is directly proportional to the regurgitant v o l u m e . 38'39 In chronic volume overload, end-diastolic volumes as high as 612 ml have been observed. The upper limit of stroke volume possible seems to be about 300 cc/beat, and total left ventricular minute output may reach 25-30 liters. 42 At some point in time, however, end-diastolic volume rises out of proportion to the regurgitant volume, the ejection volume falls, and forward stroke volume fails. This is shown graphically in Fig. 5. Teleologically, a larger end-diastolic volume provides failing sarcomeres a geometric advantage in maintaining stroke volume in the face of diminishing shortening ability. A very low ejection fraction in chronic volume overload is indicative of myocardial dysfunction and is usually accompanied by clinical signs and symptoms of overt heart failure. 43,44 Since a major adaptation to chronic volume overload is chamber enlargement, it has been traditionally held that the Frank-Starling mechanism is chiefly responsible for maintaining stroke volume. This view implies that the increase in end-diastolic volume is necessarily accompanied by an increase in end-diastolic fiber (or more correctly, end-diastolic sarcomere) length due to stretching. 45 Such has not been found to be the case in operative biopsy specimens from chronically enlarged human hearts, 46 although, admittedly, stretching force was not controlled, or in experimental chronic cardiac dilatation, 47 where stretching force w a s controlled at the time of sarcomere fixation. It must

500

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400

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I

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COMP___._.,~ DECOMP VOL VOL

Fig. 5. Alterations that may occur in the left ventricle during the course of chronic volume overload (VOL) are shown. EF, ejection fraction; EDV, end-diastolic volume; ESV, and-systolic volume ; LVSV, a n g i o g r a p h i c left ventricular stroke volume; and FSV, forward stroke volume. During the compensated ( C O M P ) period, forward stroke volume is maintained through appropriate chamber dilatation and a normal ejection fraction. The decompensated (DECOMP) phase is characterized by further inappropriate dilatation and a reduction in ejection fraction and forward stroke volume.

QUANTITATIVE ANGIOGRAPHIC EVALUATION

437

be remembered that the stretching force (preload) at end-diastole is not a function of end-diastolic volume alone or end-diastolic pressure alone, nor simply of wall tension. Tension, which is directly proportional to pressure and chamber radius (i.e., volume), represents stretching force per unit length of an infinitely thin membrane (Fig. 6A). In a chamber of finite wall thickness, as, for example, the left ventricle, stretching force is more appropriately considered in terms of wall stress, which is directly proportional to pressure and radius and inversely proportional to wall thickness, and which represents force per unit cross-sectional area (Fig. 6B). When end-diastolic stress is calculated in patients with chronic volume overload, it is frequently found to be within normal limits as a result of an increase in wall thickness. 48 Furthermore, even when enddiastolic stress is elevated, if compliance is reduced, sarcomeres may not be stretched. It is apparent, then, that the Frank-Starling mechanism need not be a major compensatory mechanism in chronic volume overload. Chamber enlargement in the absence o f fiber stretching can be accounted for on the basis of fiber slippage 47'49 and by replication of sarcomeres in series. 5~ The chamber enlargement seen in chronic volume overload is not merely a process of "dilatation" but involves hypertrophy as well. Wall thickness is characteristically increased, generally in proportion to cavity size, 37 and left ventricular mass is increased a s well. 31'38'39'51 The magnitude of the hypertrophy seems to be determined by wall stress, wall thickness increasing in proportion to the pressure-volume load until stress is normalized. 31'51 The tendency is seen in end-diastole and especially at peak systole. Whereas diastolic stress represents the ventricular preload, systolic stress represents afterload. Thus, the tendency toward normalization of peak systolic stress minimizes increases in afterload in response to valvular lesions and favors shortening rather than the development of force. Other mechanisms helping to maintain stroke volume include (1) the geometric advantage offered by a larger end-diastolic volume as noted above, and (2) other geometric influences. In both experimental and clinical volume overload the ventricle assumes a more spherical shape. 22,23'47This may have a bearing on (1) above. Examples of end-diastolic and end-systolic geometry in a normal subject, a patient with compensated volume overload, and a patient with decompensated volume overload are shown in Fig. 7. There is a definite

Fig. 6. Forces in the left ventricular well. (A) Tension represents the stretching force per unit length of an infinitely thin membrane and is directly proportional to pressure and chamber radius. (B) Stress is the stretching force per unit cross-sectional area in a wall of finite thickness and is directly proportional to pressure and radius and inversely proportional to wall thickness,

A

Force/unit length

B

Force/unit cross-sectional area

438

RACKLEY AND HOOD

ill-Hi,tilL[

P^TIEhI" I . O. EDV =130. WL, : 42, M-, E . F . : 0.~7 -,

RI = 7.34 {~U. Re : 2,77 CM, R2/RI= 0,37

pATIE~rT d. d. EOV =616. ML. ESv : ~ , ML, E, F , : 0.St m

RI :10.11 13~. R2 : 4,79 Cld, R2/RI: 0.47,

PATIE]~T L. C. EDV :533. ML. ESV =467, kl_. E, F.: 0,1 m -

Ri : 7.15 QM. R2 : 4 , ~ CIM, R2/RI: 0.6;7

[ll-$fSTlL[

C

PATIENT I . 0, EI2V =L.qO, ML, ESV : 42, ML. E* F , : 0,~'7

RI = B,73 CM, R2 : 1,75 { ~ , R2,,~,;.: ObL=O

PATIENT J. O. EI2V =61G, ML. ESV : t : ~ . idL. E.F.: 0.$7

R1 =12,90l. R2 : 3 , 9 C~. R2/Ri: 0,~

EV~TI~IT I.. C. ELW =SJ--3. tdL. ESV :ab~ , t~. s F.= C , ! 2

i

R1 = 7.3B O~RR = 4 . ~ ' C}~~'2/RL: 0.61

Fig. 7. Exact scale drawings of chamber size, major radii of curvature and wall thickness are illustrated for (A) a patient w i t h a normal left ventricle, (B) a patient w i t h compensated volume overload, and (C) a patient w i t h decompensated volume overload. Both volume overloaded ventricles have greatly increased end-diastolic volumes and are rounder than normal at end-diastole, but at end-systole only the compensated ventricle (B) assumes a near-normal geometry and maintains a near-normal ejection fraction.

relationship between end-systolic geometry and function, the ventricle tending to assume a normal end-systolic shape provided function (ejection fraction) is normal. 22 Pressure Overload

The characteristic response to a sustained pressure load is that of concentric hypertrophy, that is, hypertrophy without chamber enlargement. 15,17,37,38,52,53 Wall thickness may increase markedly, and left ventricular mass may enlarge severalfold. 3t'38'48,5LAs in eccentric hypertrophy of volume overload, the magni-

QUANTITATIVE ANGIOGRAPHIC EVALUATION

439

tude of concentric hypertrophy appears to be determined by wall stress. There is a remarkable tendency for wall thickness to increase in proportion to the pressure volume load, such that end-diastolic and peak systolic wall stress are maintained within normal limits. 31,5~ Again, presumably normalization of systolic stress is a compensatory mechanism to diminish afterload per unit area in the face of the tremendous increase in total force and favors shortening rather than tension development. In the absence of decompensation, chamber volume is normal or low and ejection fraction is normal or high. 15'17,52,53 Infolding of the hypertrophied trabeculations may contribute to the ejection (or displacement) of blood from the cavity, and may in part account for the characteristically high ejection fraction. 54 End-diastolic volume in pressure overload usually remains normal until clinical failure appears. 43,44 Even though end-diastolic volume is normal, end-diastolic pressure is elevated as a rule. At about the time clinical failure develops, end-diastolic volume increases and ejection fraction falls. Presumably, as in decompensated volume overload, the chamber enlargement and more spherical configuration offer a geometric advantage for failing sarcomeres to maintain stroke volume. Even in the presence of a normal end-diastolic volume and ejection fraction, that is, "compensated" aortic stenosis, contractility may be reduced. In both experimental and clinical pressure overload, force-velocity determinations have demonstrated diminished contractile ability in the absence of overt failure. ~5,56 Presumably, the increase in the total number of contractile units as a consequence of hypertrophy provides sufficient compensation, at least for a while, although the contractile ability per unit is subnormal. CLINICAL APPLICATIONS

Quantitation of Regurgitation Although subjective appraisal of valvular regurgitation has been available for several years through cineangiography, the development of quantitative angiocardiographic techniques has provided the most accurate clinical method for the measurement of regurgitation across the aortic or mitral valve. As described earlier in the section on methodology, the amount of blood regurgitated per beat across the aortic or mitral valve is obtained by subtracting the forward stroke volume, as measured by the Fick or indicator dilution techniques, from the total left ventricular stroke volume (difference between the end-diastolic and end-systolic volume of the left ventricle). The estimate of total left ventricular stroke volume can be used for the calculation of true orifice size when both stenosis and regurgitation of a valve are present. 33 The regurgitant volume per beat can also be expressed as a percentage of total left ventricular stroke volume. The technique of quantitative angiocardiography does not permit separation of mitral and aortic regurgitation when both lesions are present, but provides only the total quantity of blood regurgitated per beat. This method has revealed much larger regurgitant flow during each beat and over the period of a minute than had previously been estimated by the KornerShillingford technique. 57 In extreme examples, when normal myocardial func-

440

RACKLEY AND HOOD

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Fig. 8. Left ventricular pressure and volume curves are illustrated in two patients with volume overload due to aortic regurgitation. Patient on left demonstrated a left ventricular stroke volume of 217 ml, a regurgitant volume of 120 ml, and an ejection fraction of 0.50. Patient on right revealed a left ventricular stroke volume of 101 ml, a regurgitant volume of 34 ml, and an ejection fraction of 0.23. Patient on left was clinically asymptomatic, while patient on right experienced severe clinical heart failure. (By permission.aS }

tion is present, left ventricular output may reach as high as 20-30 liter/min and the total regurgitant volume may be 20-25 liter/min. Obviously, regurgitation and left ventricular output of such magnitude can ultimately result in a form of high output heart failure, but chronic aortic and mitral valvular regurgitation have not generally been appreciated to produce such a pathophysiologic state. In Fig. 8, two patients with aortic regurgitation with similar end-diastolic volumes are illustrated. Although both patients presented with cardiomegaly and typical physical findings of aortic regurgitation, one patient was asymptomatic, whereas the other patient was severely limited with his heart disease. Examination of the volume curves in each patient reveals that the asymptomatic patient ejected a much larger quantity of blood per beat than did the patient with severe symptoms. As a consequence, the regurgitant volume is much larger in the asymptomatic patient. Although qualitative estimation of aortic regurgitation by cineangiography is widely used, Baxley et al. have recently demonstrated that subjective cineangiographic appraisal of aortic regurgitation correlates poorly with actual quantitative measurements. 5s The quantitative studies indicated that modest amounts of aortic regurgitation may be interpreted as mild, moderate, or severe by the qualitative cineangiographic technique. The discrepancy is related in part to the size of the left ventricle. With rapid dilution of contrast material in such a large chamber, the subjective technique may give rise to significant errors.

QUANTITATIVE ANGIOGRAPHIC EVALUATION

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lndices of Left Ventricular Function For several years, left ventricular function in chronic heart disease was measured in terms of cardiac output and left ventricular end-diastolic pressure. That the range of resting cardiac output is considerable in patients with many forms of heart disease limits the usefulness of this measurement in assessing cardiac function. Furthermore, the cardiac output is a function of several factors other than the inherent contractile state of the ventricle. 59 Similarly, left ventricular end-diastolic pressure has not been shown to be a reliable index of failure in various forms o f chronic heart disease, since changes in left ventricular volume, mass, and distensibility characteristics may influence the pressure recorded at end-diastole. Quantitative angiocardiography permits determination of several useful indices of the pump function of the left ventricle. The ejection fraction is somewhat similar to stroke index, except that total left ventricular stroke volume is normalized for end-diastolic volume of the left ventricle rather than body surface area. In several forms of chronic heart disease, a reduced ejection fraction has correlated with signs and symptoms of clinical heart failure, and this parameter has been proposed as a measure of myocardial contractility? 4,6~In acute animal experiments, the ejection fraction may be altered by changes in preload and afterload, and, therefore, it is not an absolute index of contractile state. 61 64 However, in chronic heart disease the ejection fraction tends to reflect myocardial function in general and correlates with other measurements of muscle performance. 26'65 Miller, Kirklin, and Swan, who originally introduced the measurement of ejection fraction, demonstrated a correlation between this parameter and dp/dt in patients with chronic heart disease. 34 In normal subjects as well as in patients with volume or pressure overload, a relationship has been shown between ejection fraction and the rate of ejection normalized for end-diastolic volume, as well as between ejection fraction and circumferential shortening rate at the time of peak systolic wall stress. 66 Mean circumferential shortening rate and circumferential shortening rate at peak stress more directly reflect the muscle performance of the heart, but, like ejection fraction and normalized ejection rate, they are not absolute indices of contractile state. Nevertheless, all of these parameters obtained by quantitative angiography are clinically useful in separating myocardial from valvular components in valvular heart disease. Although normal values do not exclude myocardial dysfunction, very low values do suggest significant muscle disease.

Criteria for Surgery A frequent clinical problem is the selection of the optimal time for valve replacement in the course of chronic valvular heart disease. Since currently available prosthetic heart valves are at best impermanent devices, because valve replacement surgery still carries a significant mortality risk, and since a pressure or volume overload can be sustained for lengthy periods as long as the contractile state of the myocardium is adequate, operation is usually deferred until the patient has developed significant symptoms. Cardiac symptoms, however, depend on the adequacy of the total oxygen delivery system and not just on

442

RACKLEYAND HOOD

ventricular function. The presence or absence of cardiac symptoms has not been found to be a reliable guide to left ventricular performance. 67 It has been recognized clinically that some patients do not improve after valve surgery, presumably as a result of irreversible muscle disease. Recently, failure of myocardial dysfunction to resolve has been documented in post-operative catheterization studies. 6+ These results suggest that perhaps operation should be undertaken sooner in the course of valvular heart disease. Timing of surgery should be based on the type and magnitude of the overload, the appropriateness of the compensatory adaptations, and the adequacy of muscle performance. An ideal index of ventricular performance would be sensitive enough to reveal deterioration of function before the development of clinical symptoms. Although quantitative angiocardiography can supply considerable data on the state of the left ventricle as a pump and as a muscle, before early surgery can be recommended on the basis of the above information, additional studies with correlations of preoperative data and postoperative course are needed. Such correlative studies are now in progress. Hopefully data of this type will permit establishment of more objective criteria for operative intervention in the future.

Postoperative Evaluation Although hemodynamic studies have been performed after valve replacement, 69-73there still exists a need for quantitative angiographic studies for more Volume

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QUANTITATIVE ANGIOGRAPHIC EVALUATION

443

complete delineation of anatomy and function. 74 Fig. 9 portrays quantitative measurements made in a patient with mitral regurgitation before and after insertion of a mitral prosthesis. Although this patient presented with severe mitral regurgitation and moderate limitation of activity, the ejection fraction measured preoperatively was elevated above the normal range. The regurgitant volume per beat was large, yet the high ejection fraction suggested good myocardial performance. The postoperative study documented the absence of regurgitation, the marked reduction in end-diastolic volume and the regression of hypertrophy. The ejection fraction was reduced following surgery but remained within the normal range. Similarly, in those patients failing to improve after open heart surgery or those developing difficulties after initial improvement, quantitative measurements can identify the mechanical as well as the myocardial components that contribute to the clinical situation. Such combined preoperative and postoperative studies should provide an answer to the important question as to what extent, if any, myocardial dysfunction may be expected to regress or progress after valve surgery. To provide serial or long-term data, yet avoiding repeated catheterizations, ultrasound offers a promising method of following volume and derived parameters of function over a chronic course. 75,76

Prognosis The ultimate prognosis in valvular disease with measured depression in the pump or myocardial performance of the heart remains to be delineated. A recent study by Porter et al. suggested that patients with valvular heart disease and a history of heart failure had a more favorable prognosis with surgery or medical management if the ejection fractions were greater than 0 . 4 0 . 77 Other studies have also suggested that a low ejection fraction carries an unfavorable long-term prognosis. 78'79 With accumulation of sufficient quantitative angiographic data, it may be possible to identify a critical stage of disease beyond which myocardial damage is irreparable or even progressive, and a critical level of function below which corrective valve surgery is likely to be of no benefit. SUMMARY

The development and application of quantitative angiocardiography has contributed to the understanding and clinical management of patients with valvular heart disease. The method of quantitative angiocardiography is reviewed with particular emphasis on filming techniques, calculations of ventricular volume and principles of x-ray magnification. The information available from the ventricular volume curve is described in quantitative mechanical terms. The usefulness of left ventricular chamber dimensions for study of chamber geometry, wall forces, and ventricular function are also delineated. The pathophysiologic mechanisms operative in chronic valvular heart disease are analyzed in response to a volume or pressure overload. The adaptive mechanisms of dilatation and hypertrophy are examined in terms of diastolic wall stress or preload and peak systolic wall stress or afterload. Angiocardiography can be clinically applied to quantitate regurgitation in valvular heart disease, to define

444

RACKLEY AND HOOD

indices of ventricular function, to facilitate selection of patients for surgical repair, to evaluate cardiac performance after surgery, and to describe prognosis of patients with valvular disease. REFERENCES

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QUANTITATIVE ANGIOGRAPHIC EVALUATION

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445

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diastolic pressure in chronic heart disease. Am. J. Meal. 48:310, 1970. 49. Linzbach, A. J.: Heart failure from the point of view of quantitative anatomy. Am. J. Cardiol. 5:370, 1960. 50. Laks, M. M., Morady, F., and Swan, H. J. C.: Canine right and left ventricular cell and sarcomere lengths after banding the pulmonary artery. Circ. Res. 24:705, 1969. 51. Hood, W. P., Jr.: Dynamics of hypertrophy in the left ventricular wall of man. In Alpert, N. R. (Ed.): Cardiac Hypertrophy. New York, Academic Press, 1971, p. 445. 52. Bunnell, I. L., Ikkos, D., Rudhe, J. G., and Swan, H. J. C.: Left heart volumes in coarctation of the aorta. Am. Heart J. 61:165, 1961. 53. Grant, C., Raphael, M. J., Steiner, R. E., and Goodwin, J. F.: Left ventricular volume and hypertrophy in outflow obstruction. Cardiovasc. Res. 4:346, 1968. 54. Katz, A. M., Ellis, K., and Jameson, A. G.: Systolic obliteration of the left ventricular cavity in man. Circulation 33(Suppl. III):IIt 140, 1966. 55. Spann, J. F., Jr., Buccino, R. A., Sonnenblick, E. H., and Braunwald, E.: Contractile state of cardiac muscle obtained from cats with experimentally produced ventricular hypertrophy and heart failure. Circ. Res. 21:341, 1967. 56. Simon, H., Krayenbuehl, H. P., Rutishauser, W., and Preter, B. O.: The contractile state of the hypertrophied left ventricular myocardium in aortic stenosis. Am. Heart J. 79:587, 1970. 57. Korner, P. I. and Shillingford, J. P.: Further observations on the estimation of valvular incompetence from indicator dilution curves. Clin. Sci. 15:417, 1956. 58. Baxley, W. A., Hunt, D., Kennedy, J. W., Judge, T. P., Barcia, A., and Dodge, H. T.: A quantitative evaluation of aortography in aortic insufficiency. Am. J. Cardiol. 26:624, 1970. 59. Braunwald, E.: On the difference between the heart's output and its contractile state. Circulation 43:171,1971. 60. Bartle, S. H., Sanmarco, M. E., and Dammann, J. F., Jr.: Ejected fraction: An index of myocardial function. Am. J. Cardiol. 15:125, 1965. 61. Tsakiris, A. G., Donald, D. E., Sturm, R. E., and Wood, E. H.: Volume, ejection fraction, and internal dimensions of left ventricle determined by biplane videometry. Fed. Proc. 28:1358, 1960.

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62. Taylor, R. R., Cingolani, H. E., and McDonald, R. H., Jr.: Relationships between left ventricular volume, ejected fraction, and wall stress. Am. J. Physiol. 211:674, 1966. 63. KrahenbUhl, H. P., Bussmann, W. D., Turina, M., and Luthy, E.: Is the ejection fraction an index of myocardial contractility? Cardiologia 53:1, 1968. 64. Tsakiris, A. G., Vandenberg, R. A., Banchero, N., Sturm, R. E., and Wood, E. H.: Variations of left ventricular end-diastolic pressure, volume, and ejection fraction with changes in outflow resistance in anesthetized intact dogs. Circ. Res. 23:213, 1968. 65. Hugenholtz, P. G., Ellison, R. C., Urschel, C. W., Mirsky, I., and Sonnenblick, E. H.: Myocardial force-velocity relationships in clinical heart disease. Circulation 41:191, 1970. 66. Hood, W. P., Jr., Rackley, C. E., and Rolett, E. L.: Ejection velocity and ejection fraction as indices of ventricular contractility in man. Circulation 38(Suppl. VI):VI-101, 1968. 67. Rolett, E. L., Hood, W. P., Jr., Vollm, K. R., Young, D. T., and Rackley, C. E.: Relationship of severity of symptoms to cardiac performance during rest and exercise. Circulation 38(Suppl. VI):VI-166, 1968. 68. Gault, J. H., Covell, J. W., Braunwald, E., and Ross, J., Jr.: Left ventricular performance following correction of free aortic regurgitation. Circulation 42:773, 1970. 69. Bristow, J. D., McCord, C. W., Starr, A., Ritzmann, L. W., and Griswold, H. E.: Clinical and hemodynamic results of aortic valvular replacement with a ball-valve prosthesis. Circulation 29(Suppl. l):I 36, 1964. 70. Ross, J., Jr., Morrow, A. G., Mason, D. T., and Braunwald, E.: Left ventricular function following replacement of the aortic valve: Hemodynamic responses to muscular exercise. Circulation 33:507, 1966. 71. Hultgren, H. N., Hubis, H., and Shumway, N.: Cardiac function following prosthetic aortic valve replacement. Am. Heart J. 77:585, 1969. 72. Mason, D. T., Fisher, R. D., Ross, J., Jr., Braunwald, E., and Morrow, A. G." Left ventricular performance following isolated and combined replacement of the aortic and mitral valves. In Brewer, L. A. (Ed.): Prosthetic Heart Valves, Springfield, Ill., Thomas, 1969, p. 352. 73. Lee, S. J. K., Haraphongse, M., Callagban, J. C., Rossall, R. E., and Fraser, R. S.: Hemodynamic changes following correction

QUANTITATIVE ANGIOGRAPHIC EVALUATION

of severe aortic stenosis using the CutterSmeloff prosthesis. Circulation 42:719, 1970. 74. Rackley, C. E., Hood, W. P., Jr., Wilcox, B. R., and Peters, R. M.: Quantitation of myocardial function in valvular heart disease. In Brewer, L. A., (Ed.): Prosthetic Heart Valves. Springfield, I11. Thomas, 1969, p. 342. 75. Pombo, J. F., Troy, B. L., and Russell, R. O., Jr.: Left ventricular volumes and ejection fraction by echocardiography. Circulation 43:480, 1971. 76. Fortuin, N. J., Hood, W. P., Jr., Sherman, M. E., and Craige, E.: Determination of left ventricular volumes by ultrasound. Circulation 44:575, 1971. 77. Porter, C. McG., Baxley, W. A., Eddieman, E. E., Jr., Frimer, M., and Rackley, C. E.: Left ventricular dimensions and dynamics of filling in patients with gallop heart sounds. Am. J. Med. 50:721, 1971.

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78. Tyrell, M. J., Ellison, R. C., Hugenholtz, P. G., and Nadas, A. S.: Correlation of degree of left ventricular volume overload with clinical course in aortic and mitral regurgitation. Br. Heart J. 32:683, 1970. 79. Hugenholtz, P. G., and Wagner, H. R.: Assessment of myocardial function in congenital heart disease. In Adams, F. H., Swan, H. J. C., and Hall, V. E., (Eds.): Pathophysiology of Congenital Heart Disease. Berkeley, University of California Press, 1970, p. 201. 80. Kennedy, J. W., Baxley, W. A., Figley, M. M., Dodge, H. T., and Blackmon, J. R.: Quantitative angiocardiography. I. The normal left ventricle in man. Circulation 34:272, 1966. 81. Falsetti, H. L., Mates, R. E., Greene, D. G., and Bunnell, 1. L.: Vmax a s an index of contractile state in man. Circulation 43:467, 1971.