Biplane cineangiographic determinations of left ventricular function: Pressure-volume relationships

Experimental and laboratory

reports

Biplane cineangiographic determinations of left ventricular function: Pressure-volume relationships Charles E. Xackley, M.D.’ Victor S. Behar, M.D.** Robert E. Whalen, M.D. Henry D. McIntosh, M.D. Durham, N. C.

A

rvidsson,r in 1958, described a method for determining the volume changes of both the opacified left atrium and ventricle with a biplane radiographic technique. The x-ray equipment had the capability of 6 film pairs per second. Therefore, in order to construct. a volume curve, it was necessary to integrate the volume measurements obtained over several cardiac cycles. Dodge, Hay, and Sandier,’ using a similar biplane radiographic technique, studied the pressure and volume relationship of the left ventricle in both the normal and diseased state. Chapman and associates,3 recognized the desirability of faster filming speeds and developed a cinefluorographic unit whereby the image projected on 3.5 mm. cameras at speeds of 15 or 30 frames per second. Since image intensification was not used in this system, the radiation levels necessary to obtain adequate detail were excessive. This POtential hazard restricted the use of the unit to studies of animals and selected

patients. These studies and those of Bunnell, Grant, and Greene4 and Miller, Kirklin, and Swan5 have emphasized the usefulness of the technique for studying cardiac dynamics. With image intensification it is possible to obtain high quality films of the opacified ventricle at a speed of 60 frames per second without serious radiation hazards. A biplane image intensifier cinefluorographic unit therefore was specially constructed so that volume measurements could be made at this speed. Sixty such measurements per second, embracing several cardiac cycles, permit accurate construction not only of a volume curve for a given cardiac cycle but curves of consecutive cycles. This report describes in detail this unit; the technique for calculating ventricular volumes from such radiographic observations; and the integration of the volume data with simultaneous pressure measurements for the construction of pressurevolume loops.

From the Cardiovascular Laboratory, Department of Medicine, Uuke University Medical Center, Durham, N. C. Supported in part by Research Grants H6960, HE-07563, and H-4807 from The National Institutes of Health, United States Public Health Service, a grant from The American Heart Association, and Grants-in-aid from the Council for Tobacco Research and the Life Insurance Medical Re~search Fund. Received for publication Feb. 23. 1967. *.4ddress: Department of Medicine Assistant Professor of Medicine. ITniversity of Nortll Carolina Schor~l nf Mrdicine, North Carolina Memorial Hospital, Chapel Hill, N. C. **Postdoctoral Frllow. Ilnitrd States Public Health Srrviw.

766

Methods

/. when the film travel had Iwen completed and the shutter of the (‘;unera \I as open. In addition, an electronic sliuttering device for each image intensifier tube was added to decrease scatter radiation and fogging of the alternate right angle film. This resulted in the tilm pairs I)eing out of phase 11578.3 milliseconds. The exposed 35 mm. film was developed using ethol Single hlix/90 developer$ and subsequently reduced and copied as a 16 mm. print II): a modified IJhler copier and reducer.8 The films were then analyzed \\-ith a modified Kodak Analyst 16 mnl. projector. LAn electronic device, with moveable lead-tipped plastic rods, was constructed to permit synchronization of the individual frames of hot11 planes \vith the recorded physiologic- data. X moveal)le lead-tipped rod 112s positioned in front of each image 1ulw so as to Iw visible on the biplane film.

‘l‘]le R l\-ave of each QRS (.onl~~lex triggered a square-wave impulse from it triggerchannel in the Electronics for \ledicinc T)R 8 Recorder. This impulse initiated nlovement of the lead tipped plastic rods and inscription of a square \\a~ 011 the photographic record. The onset of will inlcters of Ikum sulfate paste wee-c irijcck4 tlirou~ll the needle into the left vwltricli~. A short strip of filnl nas exposed in 1101]I planes ;kt 60 frames per second. Five OI- 10 C.C. inc-rements of barium paste \I tw injected into the cllaml~er and iilmccl in I lot Ii planes until leakage occurred at. t Iif% nlit r-211or sort ic valve. This procetlurc \\ repeated for eacll of tlic 13 Itearts. .4 iot;il of 07 different film pairs over Skriiiig:t~ of 30 to I.50 c.c. were ol)tained from tilt 13 Iicai-ts. After conipletion of tilmin:;2 ;ilr(l \\-itlrolit nioving tile image tulm. wc.11 llt~nrt. \\ as replacet] l)y an alumiilitlli Ibar- liieasul-iii!4 sx 2x 2 cm. whicll \\;is ;ilso tilnlet] in IGplaiie. ‘I’lie projected itllag’c” t)t’ the 1);~ was sulwqueritl\~ t~sef] to 4~wI-c~~~C’V magnification. it5

screen and tile screen-to-projector distance ~vasadjusted to restore the projected image of the aluminum bar to tile original size, X X 2 cm. This maneuver also served to restore tile projected image of the opacified left ventricle to its original size. As the x-w>- source-object-image tube distances \vere different in the ttvo planes, it was necessary to adjust tile screen-to-projector distance for both tile horizontal and vertical

I) =

whew: area of the ventricular chamber A = planimetered II = longest measured length of the chamber 7r = 3.11.

After calculatiorl of the diameters for both the anteroposterior (AI’) and lateral (Lat) images, left ventricular volume (V) \\-a~ calculated from the volume formula for an ellipsoid :

films.

The image of tile opacified left ventricle uxs traced onto paper from the I)iplane film pairs for each kno\\rn volume. The clamp w+icll had been approximated at the sinuses of \yalsalva ~vas considered to l)e the base of the aorta. Ta-o measurements were obtained from each traced image: (1) the longest lengtll of the chaml)er; (2) the area as determined by planiInetr\-. The diameter, II, of the image \vas calculated from the formula for an ellipse:

Table I. The hemodvwlmic

\ where: I,

longest measured length from either the anteroposterior or lateral image I> AF = calculated diameter of the anteroposterior chamber image diameter of the later chamber 1)1.:&t = calculated image. =

In this manner the left ventricular volulne of tile Ileart for eacll knob1.n amount

cwzd(tngioctrrdiogrtrph,ic

datct

CUldiUG (L./min.)

No valvular

disease

white

female

l%year-old

white

female

1). Ii. 16-year-old

white

female

J. H. 31 -year-old

white

male

r\ortic insufficiency aortic stenosis

female

Hypertrophic and mitral

male

Constrictive pericarditis effusion with mitral insufficient>

c. E.

\v. R. 32-year-old

Patent ductus ventricular

Aortic

M. C. 32-year-old-white

white

Heart

1

Stroke

Meen

aortic

output

Yurient

I,. I,. 49-year-old

1.1 *I.

arteriosus and septal defect

insufficiency

and

subaortic insufficienq

stenosis

and

,

4 7Of

90

4.38f (systemic) 7.00$ (pulmonary)

8.5

52.2

51.5 (systemic) 82.3 (pulmonnr)-)

136

92

1.02f

108

37.0

81

4.53

80

57.0

95

s.ooj:

96

52.0

92

108

29.6

96

3 2:):

sdiat~p;d \I;LS

01 I b;wiulil c;kulated. :I U.;LS determined for regression equation the relationsl~ip I)et\veen the calculated and each of ihe 07 kno\vn volumes as sl~o\\ 11 in IYg. 1. The standard error of estimate 14’:~si 5.6 c.c., and the correlation mcfficient K\S 0.086. l’c~fimt .st~(tZ~.s. The 6 patients in this report (‘l‘al)le I ) had right and left heart catheterizations I)\- previouslqdescril>ed twllniques.‘; (‘ardiac outputs were measured I))- tile d>wdilution technique in I’atieuts I,. I,. and NT. B., and 1)~~ the l*yic.k nietliod in I’atients C‘. E., I ). Ii., 1. I I., and .\I. C‘. The t\vo methods have Iwen demonstrated to agree closely in this l;tl~orator~~.~ I’rior to 0l)taining the ventriculograms, the Ilorizontal and vertical x-m). units wre positioned al)out the supine patient so that the left ventricle \vas at the center of the held for I)otll image tubes. The elect I-oc-;lrctioRt-;lIll, tllc radial art-m!’ ;tnd left

r 160

Y=lO227X SEE

140

0’

+ 731

=56cc

r=0986

I 20

I 40

I I I 60 80 100 Known Volume, cc

L---i-i 120 I40

160

ii0

Rnckley et (11.

ventricular pressure, and tile square-wave of the trigger channel were recorded by the Electronics for LIedicine recorder at a paper speed of 100 mm. per second. The power injector and pressure transducer were connected to the left ventricular catheter (8 F. Gensini) by a three-way stopcock with a Luer connector, permitting left ventricular pressure to be recorded by a Statham P23Db strain gauge, until immediately prior to the injection of contrast medium. The ventriculograms were obtained with the patient at full inspiration. Biplane filming was performed at 30 frames per second in Patient L. L. and 60 frames per second in the remaining 5 patients. Immediately after the appearance of the anteroposterior and lateral images on the television monitors, the circuit of the electronic marker was activated. The occurrence of the R wave of the next and subsequent QRS complexes was therefore indicated on both the biplane film and the photographic record as described above. After visualizing the movement of the rods on the television monitors, 35 to 50 C.C. of Angio-Conray* (sodium iothalamate, 80 per cent) contrast medium were injected into the left ventricle by a Talle, power injector-7 at a pressure of 400 pounds per square inch. Filming was continued until the left ventricle was cleared of contrast medium. Upon completion of the catheterization and removal of the patient from the laboratory the image tubes were repositioned precisely as in the patient study. The aluminum bar was placed on a pillow, centered for both image tubes, and filmed in biplane. VOLUME CUKVES LOOPS. The films

AND

PRESSURE-VOLUME

of each biplane pair were traced with particular attention to identify the base of the aorta by the position of the sinuses of Valsalva. The volumes were calculated as described for the postmortem heart studies and corrected by the regression equation derived from the postmortem ventricular volume data: where: vc = Vc = v eo~ =

0.978 V,,I - 7.15 C.C. corrected ventricular volume calculated volume from pair.

*Mallinckrodt Pharmaceuticnls, tTalley Anaesthetic Equipment,

biplane

St. Louis. MO. Ltd., London. England

‘I‘hesc individual volu~i~c ItleasureItients were plotted sequentially, and connected by a line of best-fit. At a film speed of 30 frames per second a volume observation was made every 33.3 msec. and at 60 frames per second, every 16.7 msec. The initial movement of the lead tipped marker was identified on the biplane film and, after correction for the inherent delay of the system, related to the onset of the QRS complex. Left ventricular volume changes could then be related to left ventricular pressure changes with time common to both. The systemic arterial pressure and heart rate did not change during the injection of contrast medium and biplane filming in these patients. Therefore, the left ventricular pressure was assumed to be unchanged from control pressure. This was confirmed in Patients W. B. and D. R., in whom the left ventricular pressure was recorded during the filming. As the patients selected for this report maintained normal sinus rhythm with similar R-R intervals, the left ventricular pressure contour prior to injection was related to the volume curve by the onset of the QRS complex. A pressure-volume loop, beginning with the onset of the QRS complex, was then constructed by plotting each volume observation, corrected to the line of best fit, and the corresponding pressure coordinate. STROKE WORK.

WOKK

AND

PRESSURE-VOLUME

RIechanical work is the result of moving a given mass through a given distance. When pressure moves a fluid, work may be defined as the integral of pressure and change in volume. Conventionally, external work of the left ventricle has been determined from stroke volume and mean aortic systolic pressure: Sk\: = SV X I’X 1.36 where: SW = stroke work, Gm.M. SV = stroke volume, C.C. from cardiac output I’ = mean aortic systolic 1 .36 X IO-2-factor for Hg to Gm.M. 1.055-specific gravity of

X 10-*X

1.055

per beat per beat, determined and heart rate pressure, mm. Hg conversion from mm. blood

film

Since the pressure-volume loop of the left ventricle represents pressure and volume changes for a single cardiac cycle,

t lit’ loop is ,I ttlt‘;tsure ot left ventricular pressure-voluliic \vork. ‘l‘lie ;tre;~ I)eneatli the ejection portion of the loop indicates tlic I\-ork of the left ventricle in ejecting I)lOOd : IT-\\ w hrw

=

I’\‘

X

1.36 X 1W’ X 1.055

:

I’V\V = I’\. =

pressure-vol~ltlle area beneath pressure-volrlme by the scale vol\lmc.

work, Gm.M per beat the ejection portion of the loop in cm.% multiplied factors for pressure and

ln tllis study, only potential \vork is included in the calculation of stroke nork. In tile resting state kinetic jvork Ilas been shown to range froin 0.9 to 3.5 per cent of the total \vork of the left ventricle.* Snell and Luchsinger” demonstrated tliat the kinetic- or accelerative work can l,e ignored as it represents less than 2 per cent of the total work.

Fig. (left)

2. Biplane

film

pairs.

Illustrated

are

representative

Results IA:/‘I vcx/ric.lrlclr slrokc aol~~rtw. ( )IWTV;Ltions from 6 patients with ;I v;tr-iet!, 01 ~~;tthoph~~siologic ;~l)normaliti~s IVIIO ninint;lined stal)le heart rates and pressures during tile cinefluorognuns xere selected for discussion (Tal,le I ). Iieprest~ntativc and end diastolic I )iplanc end systolic franles front the stud>- of I’atienl L. 1,. are slio~n in Fig. 2. This patient livid no valvular disease or intracardiacsliunt. Continuous volume curves ironi four conrllydlm secutive cardiac c!x-les in regular are displa!-ed in Fig. 3. The left ventricular stroke volume calculated as t Iic tlicffrrencc Ijet \\-een the end diastolic and t lit% end s>xtolic volunle \\.a~ 55, 60. 51, ;tnd 30 c.c. (average of 54.7 c.c. per i,cat; Tai IIC I I J. The forward stroke volunle, c;ll~~ul;lted froni tlie cardiac output arid lic..117 rate \vas

52.2

l’atient.

frames

from

c.c.

('l‘al~le (‘.

the

I<.

biplane

and lateral projections (right) during diastole (upper) and q-stole (lower). the manner in which the opacified chamber was traced onto paper.

I). Il;ltl

;i

tilm

Slllilll

in the

vc:Il!

ric~illar

anteropcwtcrior

‘The dotted lines

demorlstrate

100 L L XG47592 90

:

0070 :: 60 E 50 2 8 40 30 20 -#Urn IO 0

I IO

20

30

I 40 Frames

I 50 (30/set.)

I 60

I 80

70

Fig. 3. Sequential volume determinations. The ventricular volume measurements during diac cycles in a patient without valvular heart disease are illustrated. The left ventricular these four cycles are 55, 60, 54, and 50 c.c., respectively, average 54.7 c.c. per beat. The frames per second.

TuOle I I. The angiographic

90

four consecutive carstroke volumes for filming speed was 30

volume data in 2 patients without vulvulnr heart disease I

End Patient

I,. I,.

c. E.

Cycle

diustolic volume (CL)

End

systolic volume (cd-.)

Left ventriculai stroke volume (C.C.)

1 2 3 4 Mean

74.5 79.0 72.5 69.5 73.8

19.5 19.0 18.5 19.5 19.1

55.0 60.0 54.0 50.0

1 2 Mean

125.0 126.0 125.5

46.0 44.0 45.0

79.0 82.0 80.5

septal defect and a patent ductus arteriosus. There was no arterial unsaturation, indicating the absence of significant rightto-left shunt. In the presence of a left-toright shunt at or beyond the ventricular level, the total volume of blood ejected from the left ventricle is the sum of the systemic stroke volume and the shunt flow per beat. Consequently, the left ventricular stroke volume should equal the pulmonary blood flow per beat as determined by the Fick method. The left ventricular stroke volume determined by angiocardiography for two consecutive beats was 79 and 82 c.c., respectively (Table I I) ; the pulmonary blood flow was X2 c.c. per beat (Table I).

51.7

The remaining four patients in this study had varying degrees of valvular insufficiency (Table I). As described -by Sandler and associateslO the regurgitant volume per beat was calculated as the difference in left ventricular stroke volume determined by the angiographic method, and the forward stroke volume, determined from the cardiac output (Table I). Regurgitant flow per beat ranged from 13 C.C. in the patient with pericardial disease to 109 c.c. in the patient with severe aortic insufficiency. The left ventricular outputs per minute, calculated as the product of angiographic stroke volume and the heart rate, varied from 4.29 liters per minute in the patient

140130120IIO-

ESV =19.5cc LVSV =%Occ

loo-

-Ill0 ,oo

IIOIOO-

90-

-90

go807a60504O3020-

IO0

I

IOI 0.1

I I I I I 0.2 0.3 0.4 0.5 0.6 Seconds

I II 0.7 0.6 ’

OVolume, cc

ITig. 4. The pressure and volume data (left) and pressure-volume loop (right) heart disease. As seen in the panel on the left, the end diastolic volume, El? V, the diastolic pressure is ele\xted. The end systolic volume, ESV, is 19.5 C.C. \.olume, 1: V.YL’, is 5.5 c.c. The pressure-volume loop is seen in the p;tnel on rhc sllrc~-lmlllmc~ u-d<. P if work, is indicated by the lined area.

without ill a patient is normal at 74.5 c.c,, and the left ventricular right. The left vcntriwlar

valvular although stroke pres-

l5Or

40

40

40

30

30

30

2

20

20

IO u ’

IO

IO

Pressure

0.1 0.2 0.3 04 05 06 0.7 Seconds

0 Volume, cc

l;ig. 5. The pressure and volume data (left) and pressure-\-olume loop (right) in a patient with a \.entriculx septal defect and a patent ductus arteriosus. Sate in the panel on the left, that the end diastolic x~olume and pressure are normal. In the pressure-volume loop in the right, the period of isovolumir contraction, represented by the ascending limb, demonstrates a loss of ventricular volume prior to the opening of the aortic. \ ~lve. DII~ing isovolumic relaxation, represented b>, the descending limb, there is a c~ontinued loss of I III~IIW aftrr cltrsnrc of the aorCc. v:~lvc.

\~itliout anatomical disease of the kit ventride to 14.89 liters per minute in the patient with aortic insufficiency. Z.efl ventricn~lw- work. Left ventricular pressure ;lncl volrlrne wrves of the 6 sc-

lected patients ;ire sho\vn ill lhe lefl panel of Figs. 4 through Y. The pressure and volume coordinates are plotted sequentiall~~ on the right side of eacl~ illustration to tlcscrilw 1I)(, I~r(‘s~“r~-v(~l111Ilt’ loq), ‘T’lrc~

300. 300, 280260

-I50 DR #G46196

140

260

-130

240

- 120

Ix,

220

-110

I IO

200

-100

160

-90

t . 160

-80

3= 140

-70

120. 120 looloo

ESV. 128cc LVSV . 146 cc

-60

i IOOp E u’ ; x B

90so7060-

-50

50-

SO60

-40

40.

60

-30

30-

40

-20

20-

20

- IO

IOr

‘0

0 I 02

0.3 04

0.5 Q6 0.7 09

Fig. 6. The pressure and volume data (left) and pressure-volume loop (right) in a patient with massive aortic insufficiency. As seen in the panel on the left, the end diastolic volume is 274 C.C. and the end diastolic pressure is within normal limits. The pressure-volume loop on the right demonstrates that ventricular filling begins at the time of aortic valve closure and continues throughout isovolumic relaxation, as well as during the period of diastolic filling. The ventricle continues to fill during ventricular systoleas demonstrated by the early rightward deviation of isovolumic contraction.

150 JH.#G51792

I50 - I40

Volume.cc

Fig. 7. The pressure and volume data (left) and pressure-volume loop (right) in a patient with moderate aortic insufficiency and mild aortic stenosis. The pressure-volume loop as seen in the panel on the right demonstrates an increase in volume during isovolumic relaxation, indicating aortic insufficiency. The gradual loss of volume during isovolumic contraction indicates mild mitral insufficiency, although it is not clinically evident.

shaded area beneath of each loop indicates volume work of the tient L. L., in whom abnormality of the work calculated from and pressure-volunlc

the ejection portion the systolic pressureleft ventricle. In Pathere was no valvular left ventricle, stroke the dye-dilution data work calculated from

the angiographic data were 101.8 and 99.8 Gm.M. per beat, respectively (Table I). In Patient, C. E., with the ventricular septal defect and a patent ductus arteriosus, stroke work, calculated from the forward Fick output of 4.38 liters per minute was 6X Gm. R I. per beat ; pressure-volume work

- 180 - 160 - 140 - 120 - loo -SO

loo so

i

-60 -40

40

-20

20

i OOL IO 20

Fig. 8. The pressure and volume data (leftj and pressure-volume loop (right) in a patient with hypertrophic subaortic stenosis and mitral insufficiency. The loss in ventricular volume during the early phase of isovolumic contraction, as represented by the doubling back of the pressure-volume loop, suggests abnormal closure of the mitral valve resulting in mitral insufficiency. The rate of systolic ejection into the aorta is extremely rapid in the early phase of the period of systolic ejection. The area beneath the diastolic filling limb of the pressurevolume loop is a measure of the diastolic work or the work done on the ventricle during filling. I30 120

%

WE # G39761

01

02

0.3 04 0.5 Seconds

06 07

0.8

0

1 a

102030405060io80901~ Valumc, cc

I;ig. 9. The pressure and volume data (left) and pressure-volume loop (right) in a patient with constrictive pericarditis, pericardial effusion, and mild mitral insufficiency. The mitral insufficiency occurs during the period of systolic ejection and is due to the transseptal catheter lying across the mitral valve (see text). The area beneath the diastolic filling limb of the pressure-volume loop again indicates the increased work necessary to fill the ventricular chamber.

calculated from the angiographic data was 94.7 Grn.M. per beat. The difference in stroke work and pressure-volume work, 26.7 C;m.M., indicates the work of left ventricle in shunting blood across the defects during each cardiac cycle. In the remaining 4 patients, with varying amounts of vnlvlllar insllfficienc~~

and, or stenosis, stroke work ranged from 40.8 to 77.7 Gm.XI. per beat. It is assumed that in each of these patients the difference between pressure-volume work and stroke work represents the work expended because of the valvular insufficiency and/or stenosis and varied from 16.9 Cm.AI. per Irwt

to

1X3.2

Grrl.Il.

Iwi-1w:rt.

Discussion

The clinical studies described in this report add further support to the accuraq of the radiographic method for determining ventricular volume.11s12 A comparison of the stroke output calculated both by the angiographic and the conventional methods demonstrated excellent correlation in the two patients without valvular insufficiency. The advantages of analyzing cardiac dynamics by means of the construction of a pressure-volume loop have been demonstrated by Arvidsson,’ Dodge, Hay, and Sandler,2 and Bunnell, Grant, and Greene.” These investigators constructed pressurevolume loops by integrating the data from several successive cardiac cycles. Chapman, Baker, and Rlitchel113 employed cinefluorography to describe the pressure volume relationships of a single cardiac cycle in animals during rest and exercise, but only limited studies were performed in man. The pressure-volume characteristics of individual cardiac cycles in various heart diseases are described and analyzed in this report. Pressure-volume loops not only graphically describe the pressure and volume relationships throughout the cardiac cycle but also illustrate disturbances in left ventricular function. The contour of a normal pressure-volume loop is demonstrated in Fig. 4. The right side, or ascending limb, represents the period of isovolumic contraction which describes that interval of the cardiac cycle between closure of the mitral valve and opening of the aortic valve. Although undergoing a rapid rise in pressure, the left ventricle is a closed chamber during this period. When the left ventricular pressure exceeds the diastolic pressure in the aorta, the aortic valve opens initiating the period of systolic ejection. This phase of the cardiac cycle is represented by the superior aspect of the pressure-volume loop. As the rate of the left ventricular ejection slows, the pressure falls and the direction of the loop turns downward. When the left ventricular pressure falls below the aortic pressure the aortic valve closes. lsovolumic relaxation follows represented by the continuation of the descending limb on the left side of the figure. The aortic and mitral valves are both closed during this phase

of the cardiac q.cle. Althougli pressure is falling there is no change in volume. This period is terminated by the opening of the mitral valve. The loop is completed by the inferior limb which represents the diastolic filling period. The period of isovolumic contraction can be altered by a ventricular septal defect or by mitral incompetence as illustrated in the pressure-volume loops in Figs. 5 and 8. Since the left ventricle is undergoing a volume change during this period, it is not truly isovolumic. Although Patient J. H. (Fig. 7) had no clinical evidence of mitral insufficiency, the early loss in volume during the period of isovolumic contraction suggests a small amount. :\finimal mitral regurgitation, apparently due to the catheter crossing the mitral valve, was demonstrated cinefluorographitally in Patient W. B. Nevertheless, the period of isovolumic contraction of the pressure-volume loop appears normal (Fig. 9). It is suggested that the mitral valve was anatomically normal. Therefore, the regurgitation did not occur during this period, but later in systole at a time when the valve, distorted by the catheter, was stressed by the high pressure of left ventricular ejection. On the other hand, Patient, R,l. C. (Fig. a), with hypertrophic subaortic stenosis, demonstrated mitral regurgitation coincident with the onset of ventricular contraction followed by a relatively normal completion of the period of isovolumic contraction. This finding suggests abnormal closure of the mitral valve, possible on the basis of papillary muscle dysfunction. The filming speed of 60 frames per second supplies a sufficient number of volume observations to permit one to make this speculation. The duration of isovolumic contraction, as indicated by the number of volume observations included in this limb of the loop, may also provide information concerning the dynamics of cardiac function. For example, the period of isovolumic contraction is prolonged in patients with systemic hypertension and shortened as iI result of aortic insufficiency. The ejection portion of the pressurevolume loop is abnormal in patients with 0l)struction to left ventricular outflow (l;igs. 7 ant1 X). lri ;Itldition, flo\\, tlirougll

inconll)ctellt Initral valve or tlirougll a ventricular septal defect may continue during this phase of the cardiac cycle M.ithOut appreciable altering the contour of the loop. The period of isovolumic relaxation is altered by aortic insufficiency. It can be seen in Figs. 6 and 7 that significant filling of the left ventricle occurred after the time of aortic valve closure during the early part of this period. On the other hand, there is a continued loss of volume during this period in the patient with the interventricular septal defect (Fig. 5) due to continued left-to-right flow through the defect. This phase of the cardiac cycle ~nay be shortened I)y the presence of an elevated left atria1 pressure, causing an earlier opening of the mitral valve. The diastolic filling period describes Iwth the volume accepted bp the chamber and the pressure changes resulting from this increase in volume. This relationship may be altered by changes in the distensibility of the myocardium or pericardium. The ratio of changing volume to changing pressure is an expression of the compliance of the ventricle.lS Patient I). R. with severe aortic insufficient), had a large end diastolic volume n-ithout an increase in filling pressure (Fig. 6). Patient W. H. n-it11 pericardititis and effusion (Fig. 9) and Patient M. (1. \vitli left ventricular hypertrophy (Fig. 8) had smaller end diastolic volumes but higher filling pressures. The slope of the diastolic limb in the latter 2 patients indicates an increased resistance to left ventricular filling. Patient L. L. had no detectable heart disease and a normal left ventricular end diastolic pressure early in the cardiac catheterization, However, the diastolic pressure rose progressively during coronary arteriograph! bvhic-11required a total of 200 C.C. of Hypaque AI* (sodium and methylglucamine diatrizoates, 73 per cent). The ventricular volume stud)- \~as then carried out after the elevation in diastolic pressure had developed as is evident in the diastolic limb of the pressure-volume loop (Fig. 4). The injection of large volumes of contrast medium is known to increase the circulating I)lood volume.‘” \Vhetlier the elevated

,111

(]iasto]i(, l)rckssure \I;Ih dtlc It, 11115OI Ot IlCI’ factors is unknown. \Tentricular filling in Patient 0. R. (Fig. 6) was particularly interesting. The ventricle filled not only by inflow from the left atrium but also by retrograde flou froni the aorta. The latter began at the time of closure of the incompetent aortic valve and continued throughout the periods and diastolic of isovolumic relaxation filling. In addition, the vent-ricle continued to fill during the period of isovolumic contraction of the ensuing cardiac cycle. This filling, as demonstrated by the ascending limb of the pressure-volume loop, \vas observed to continue until the aorticoventricular gradient \\‘a~ abolished at 55 mm. I-lg. This was in fact the aortic diastolic pressure. I)ressler and Rubin’” reported 2 cases of aortic insufficiency, in \\,Iiich this overlapping 0i ventricular tilling and ventricular systole u as demonst rated l+- ~~l~onocardiograph~ end apexcardiography. The area beneath the ejection portion of tlie pressure-volume loop is an expression of the left ventricular pressrtre-volume IYork for ejection.17,18 In I’atient I,. I,. (Fig. 4), 3 patient. Ivitliout valvular heart disease or shunts, the left ventricular pressure-volume Jvork is c:omparal~le to stroke \vork, calculated I )y conventional methods as descrilled previously. Ho\vever, in the presence of valvular stenosis and,/or insufficient>, and certain left-to-.right cardiac shunts, such as a ventricular septal defect or patent ductus arteriosus, the left ventricular pressure-volume \vork twcomes more informative than stroke \vork. These conditions increase tile pressurevolume work of the left ventricle, although this cannot be measured 11~ the conventional laboratory techniques for ~~lculal itig stroke \vork. The area beneath the diastolic limb of the pressure-volume loop is the work performed on the left ventricle for filling.‘7~‘8 IXastolic pressure-volume work may be increased 1)~ a large volume filling the chamber as in severe aortic insufficiency (Fig. 6)) by pericardial disease (Fig. 9)) myocardial hypertrophy (Fig. x), or possil)lv by an increase in blood volume (Fig. 4). ‘I’hese studies indicate the value of Iwessure-volume loops in analyAng cardiac-

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function. Left ventricular stroke volume can be accurately measured in the presence of valvular insufficiency and left-to-right shunts. The alterations of the systolic and diastolic isovolumic periods in mitral and aortic valvular insufficiency can be illustrated by the rapid cinefluorographic filming technique. The pressure volume loops provide a more accurate estimate of left ventricular systolic work in patients with valvular heart disease or left-to-right shunts than do conventional methods, The measurement of ventricular volume in patients with heart disease will permit additional understanding of the hemodynamic abnormalities. Summary

A biplane cineangiocardiographic technique with filming speeds of 30 or 60 frames per second is described to estimate the instant-to-instant changes of left ventricular volume in man. The results of postmortem studies in 13 human hearts and in 6 patients with various forms of heart disease are presented. Ninety-seven volume observations were made in the 13 postmortem hearts over a volume range of 30 to 150 C.C. The volume calculations were based upon the assumption that the chamber could be mathematically represented by the formula for an ellipsoid. The standard error of estimate was f 5.6 C.C. and the correlation coefficient was 0.986. The angiographic left ventricular stroke volumes in a patient without anatomic left ventricular disease were 55, 60, 54, and 50 c.c., an average of 54.7 C.C. per beat. This compared favorably with the dyedilution stroke volume of 52.2 C.C. per beat. A second patient with a ventricular septal defect and patent ductus arteriosus had consecutive angiographic stroke volumes of 79 and 82 c.c., an average of 80.5 C.C. per beat. This compared favorably to the pulmonary blood flow of 82 C.C. per beat determined by the Fick method. The remaining 4 patients had valvular insufficiency and/or stenosis. The regurgitant flow per beat ranged from 13 to 109 CC. Pressure and volume were related for the construction of pressure volume loops and the determination of the left ventricular pressure-volume work for ejection.

The hemod~~namic significance and changes in the contour of the loops in the various pathophysiologic states are described, The pressure-volume work was determined from the loops and compared to the stroke work calculated from conventional laboratory techniques. The determination of the pressure-volume work was demonstrated to be more informative than the conventional calculation of stroke work. The clinical application of ventricular volume measurements will provide additional information concerning the left ventricular hemodynamics of the normal and diseased state. REFERENCES 1.

Arvidsson, H. : Angiocardiographic observations in mitral disease, Acta radiol. (Suppl.) 158:11,

2.

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Dodge, H. T., Hay, R. E., and Sandler, H.: Pressurevolume characteristics of the diastolic

left ventricle of man with heart disease, Ax HEART J. 64:503, 1962. <3 . Chapman, C. B., Baker, O., Reynolds, J., and Bonte, F. J.: Use of biplane cinefluorography for measurement of ventricular volume,Circulation 18:llOS. 1958. 4. Bunnell, I. L.; Grant, C., and Greene, D. G.: Left ventricular function derived from the pressure-volume diagram, Am. J. Med. 39:881, 1965. 5. Miller, G. A. H., Kirklin, J. W., and Swan, H. J. C.: Myocardial function and left ventricular volumes in acquired valvular insufficiency, Circulation 31:374, 1965. 6. McIntosh, H. D., Sleeper, J. C., Thompson, H. K., Jr., and Whalen, R. E.: Simplification percutaneous of left heart catheterization techniques for catheter insertions, J. A. M. A. 177:600, 1961. 7. Miller, D. E., Gleason, W. I,., and McIntosh, H. D.: A comparison of the cardiac output determined by the direct Fick method and the dye-dilution method using indocyanine green dye and a cuvette densitometer, J. Lab. & Clin. Med. 59:345, 1962. 8. Remington, J. W., and Hamilton, W. F.: The evaluation of the work of the heart, Am. J. Physiol. 150:292, 1947. 9. Snell, R. E., and Luchsinger, I’. C.: Determination of the external work and power of the left ventricle in intact man, AM. Heart J. 69:529, 1965. HI., Dodge, H. T., Hay, R. E., and 10. Sandler, Racklev. , , C. E.: Ouantitation of valvular insufficiency. in man by angiocardiography, A&r. HEART J:65:501, 1983. 11. Arvidsson. H. : Aneiocardiozraohic determination of ieft ventricular vol;m& Acta radiol. 56:321, 1961. 12. Dodge, H. T., Hay, R. E., and Sandler, H.: An angiographic method for directly deter-

mining left ventricular stroke volume in man, Circulation Res. 11:'739, 1962. 13. Chapman, C. B., Baker, O., and Mitchell, J. H.: Left ventricular function at rest and during exercise, J, Clin. Invest. 38:1202, 1959. 11. Corson, LIT. R., Dodge, H. T., Kackley, C. E., and Sandier, 1-l.: Compliance of the diastolic left ventricle in man, Clin. lies. 11:73, 1963. 15. Rahimtoola, S. H., Duffy, J. P., and Swan, H. J. C.: Hemodynamic changes associated with injection of angiocardiographic contrast medium in assessment of valvular lesions, Circulation 3352, 1966.

16. Dressier, W., and Rubin, Ii.: Overlapping of ventricular filling and contraction, AX. HEAIU J. 69599, 1965. 17. Burton, A. C.: Physiology and Biophysics of the Circulation. Chicago. 196.5. Year Book Medical Publishers, p. 1<7: 18. Dodge, H. T., Sandier, H., Haxley-, A’. A., and Hawley, K. Ii.: Usefulness and limitations of radiographic methods for determining left ventricular volume, Am. J. Cardiol. 18:10, 1966.