Left ventricular systolic and diastolic function after total correction of tetralogy of Fallot

CONGENITAL HEART DISEASE

left VentricularSystolic and DiastolicFunction After Total Correctionof Tetralogyof Fallot GEORGE G.S. SANDOR, MB, FRCP, MICHAEL W.H. PATTERSON, MB, FRCP, MARION TIPPLE, MB, FRCP, PHILLIP G. ASHMORE, MD, and RUBY POPOV, RN

Left ventricular (LV) systolic and diastolic function was assessed in 12 patients after total correction of tetralogy of Fallot (age range 5 to 18 years, mean 10) and compared with 10 control patients. Only 1 patient had a shunt before total correction that was performed at a mean age of 3.5 years, (range 0.3 to 8). At cardiac catheterization the following indexed LV parameters were measured: end-diastolic and end-systolic volumes, wall mass, ejection fraction, stroke volume and end-diastolic and end-systolic pressures and stresses. The rate-corrected mean velocity of fiber shortening was calculated. LV diastolic operant chamber stiffness and myocardial stiffness were calculated from simultaneous diastolic pressures and volumes in mid- and late diastole

P

revious angiographic studies of left ventricular (LV) function in patients with postoperative tetralogy of Fallot have reported conflicting results regarding LV systolic dysfunction. 1-7 These were mainly load-dependent and to date there have been no studies examining load-independent systolic indexes or diastolic function after total correction of tetralogy of Fallot. The Sagawa Index and its derivatives8-l1 appear to be the best current methods of assessing load-independent indexes of systolic function. LV diastolic function has been described in terms of operant chamber stiffness, describing the diastolic function of the ventricle as a whole, and myocardial stiffness, which refers to the state of the myocardium.lz-19 This study was thereFrom the Division of Cardiology, Department of Paediatrics and Department of Cardiovascular Surgery, U.B.C., B.C. Children’s Hospital, 4480 Oak Street, Vancouver, British Columbia V6H 3V4. Manuscript received March 16, 1987; revised manuscript received and accepted July 13,1987. Address for reprints: George G.S. Sandor, MB, FRCP, Children’s Hospital, 4480 Oak Street, Room lC47, Vancouver, British Columbia V6H 3V4. 1148

using monoexponential formulas. The 2 groups were compared by unpaired t tests. The tetralogy group had higher mean end-diastolic (93 vs 74 ml/m*), end-systolic (29 vs 19 ml/m*) and stroke (84 vs 55 ml/m*) volumes than controls. Rate-corrected mean velocity of fiber shortening was lower in the tetralogy group (1.07 vs 1.24). fvlyocardial stiffness was higher in the tetralagy group (18 vs 11). Other indexes were not significantly different. Thus, LV function after total correction of tetralogy of Fallot may be abnormal with larger than normal LV size, decreased contractile function and increased myocardial stiffness. (Am J Cardiol 1987;80:1148-1151)

fore performed to assessthese parameters of LV function in a group of patients who had total correction of tetralogy of Fallot.

Methods The catheterization data of 12 patients who had total correction of tetralogy of Fallot are shown in Table I. The patients were not specifically selected, but all except 1 had right ventricular pressures less than 50 mm Hg, and no patient had a significant left to right shunt (i.e., Qp/Qs less than 1.5/l] and most had no shunt at all. Mean age at total correction was 3.5 years (range 0.3 to 8) and at catheterization, 10 years (range 5 to 181.The only selective criteria for the study were that the septal motion on M-mode echocardiography be reasonably normal, and at catheterization the LV angiographic shape be only minimally or not distorted at all‘on biplane angiography. Standard right- and left-sided cardiac catheterization was performed and the cardiac index was measured by thermodilution, oxygen consumption or dyedilution techniques. A Millar microtip high-fidelity

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TABLE I

Pt 1 2 3 4 5 6 7 a 9 10 11 12 Mean &SD P Normal Mean &SD

Results of Patients with Tetralogy EDV, (ml/m*)

ESV, (ml/m*)

EF (%)

SV, (ml/m*)

115 84 106 99 61 109 78 a2 111 88 101 a4 93 16 0.005

30 20 34 29 12 41 26 31 37 29 33 28 29 a 0.002

74 76 68 71 81 62 66 63 67 67 67 67 69 6 NS

a5 64 72 71 50 68 52 51 i4 59 68 56 64 11 0.048

74 11

19.4 5

74 6

55 9

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of Fallot

EDP (mm Hg)

PSP (mm Hg)

Ml (g/m*)

MVCF,

7 12 11 IO IO

86

8 a 11 7 9 2 NS

95 88 100 a5 a5 107 100 90 85 136 95 15 NS

75 57 70 93 54 aa 76 55 69 68 73 a1 70 12 NS

1.08 1.43 1.05 0.85 I.38 1.09 0.96 1.02 1.11 0.76 1.25 0.89 1.07 0.20 0.029

9 3

106 13

62 10

1.24 0.13

a 9

a

80

ESS (g/cm,)

b

K,

215 162 144 283 168 46 NS

0.027 0.054 0.027 0.028 0.033 0.035 0.096 0.040 0.038 0.013 0.016 0.054 0.038 0.022 NS

24 23 14 12 9 16 34 11 16 7 a 21 16 a 0.045

166 29

0.034 0.005

11 2

156 135 176 118 119 179 153

180

b = index of operant chamber stiffness; EDP = end-diastolic pressure; EDV, = end-diastolic volume indexed; EF = ejection fraction; ESS = end-systolic stress; ESV, = end-systolic volume indexed; KE = myocardial stiffness: M, = mass indexed; MVCF, = rate-corrected mean velocity of fiber shortening: NS = not significant: PSP = peak systolic pressure: SD = standard deviation; SV, = stroke volume indexed.

catheter was then passed in retrograde manner and the venous catheter was placed in the pulmonary artery or in the right ventricle. With the high-fidelity catheter recording the LV pressure, a biplane angiogram was recorded in both the anteroposterior and lateral planes to include the levophase. The onset of the injection was marked to give simultaneous pressures and volumes. After catheterization, a l-cm grid was filmed at the measured midthoracic level and used to obtain the magnification factor. Full details of this technique have been given previously.18Jg The measurements for LV volumes were obtained during the first 2 to 4 cycles after satisfactory opacification of the left heart chambers; extra- and postextrasystolic cycles were excluded. With the marking device, 6 to 8 pressure points in the mid-, late- and end-diastolic portions of 1 cycle were matched with the corresponding angiographic frames and the outlines traced for diastolic volumes. The subsequent end-systolic frame tvas also traced and the ejection time and the RR interval for that cycle were both measured. The ventricular volumes were calculated for the anteroposterior plane using the formula of Dodge and Sandle+ and modified by Graham et a1.21The enddiastolic thickness was measured and wall mass was calculated by the method of Rackley et alez2Because wall thickness was difficult to estimate in mid-diastole and end-systole, values for wall thickness were “back calculated” once the wall mass was known.17 As stated previously, only those patients whose LV shapes were normal and were not flattened by an enlarged right ventricle were used for this study. Systolic function: Stroke volume index was calculated from the difference between end-diastolic volume (EDV] and end-systolic volume (ESV) indexes calculated angiographically and LV ejection fraction calculated from LVEDVI - LVESVi/LVEDV1. End-

systole was timed from the onset of the rapid negative phase of the dP/dt tracing. Peak systolic and end-systolic pressures were measured and stress at peak systole and end-systolic stress were calculated using the formula of Mirsky .23Mean velocity of fiber shortening24 (VCF) was calculated by the formula VCF = [(EDD - ESD)/EDD] X ET and the rate-corrected mean VCF calculated by dividing the ET by the square root of the RR interval, where EDD = end-diastolic dimension, &3D = end-systolic dimension, and ET = ejection time in seconds. Diastolic indexes: Pressure-volume data: As reported previously, l8 the formula for instantaneous diastolic pressure-volume relation was assumed to be: dP/dv = bP + d, where p = pressure in mm Hg, v = volume, and 6 and d = constants; dP/dv = LV operant stiffness and derived from P = C1 + aebv(e = base of the natural logarithm, a and C1 = constants) Stress strain data: Instantaneous stress was calculated from p (R/h] (1 - h/2R - r2/2AZ) where u = stress in g/cm2, P = pressure in gJcm2, h = wall thickness, R = midwall minor semiaxis, and A = midwall major semiaxis. The relation of u and R was assumed to be monoexponential, i.e., u = y + aePR(ac,p and y are constants); de = dR/R and E = da/de, where E = elastic stiffness and c = strain; and da/de = GE+ KEU-+ u, where KE = muscle stiffness constant, and CE and u are constants). More complex formulas exist but our previous studylg showed no advantage over the simpler formulas used here. Controls: Ten patients who had trivial hemodynamic lesions and were catheterized with the same protocol used for the patients comprised the control group. Only 8 of these patients had hemodynamic data points suitable for performing diastolic measurements. These patients are controls for this laboratory.

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LV FUNCTION

AFTER CORRECTION

OF TETRALOGY

OF FALLOT

Statistical analysis: Mean f standard deviations were obtained and the 2 groups were compared by unpaired t tests. The mean regression line and 2 standard errors of the estimate were computed for the normal range for the rate-corrected velocity of fiber shortening end-systolic stress relation.

Results The individual results and mean f standard deviations of the patients and controls are listed in Table I. The patients with tetralogy of Fallot had significantly larger mean end-diastolic (93 f 16 vs 74 f 11 ml/m2), mean end-systolic [29 f 8 vs 19 f 5 ml/m21 and mean stroke volume indexes (64 to 11 vs 55 f 9 ml/m21 than control subjects. Ejection fraction, end-diastolic pressure and wall mass indexes were not significantly different in the 2 groups. The rate-corrected mean velocity of fiber shortening for tetralogy of Fallot was lower (1.07 f 0.2 vs 1.24 f 1.3) despite similar values for endsystolic wall stress (168 f 46 vs 166 f 29). Figure 1 illustrates the ratio of mean rate-corrected velocity of fiber shortening vs end-systolic stress for normals, and shows the individual patients with tetralogy of Fallot. The mean operant chamber stiffness was not different between the groups; however, myocardial stiffness with tetralogy of Fallot (16 f 8 vs 11 & 2) was significantly different.

Discussion This study confirms results of other studies showing that the mean LV end-diastolic and end-systolic volumes are enlarged in postoperative tetralogy of Fallot. However, mean stroke volume index and ejection fraction remained normal. These measures of LV systolic function are, however, load-dependent and may explain why there are contradictory results in previous reports. Jarmakani,l Lange,6 De Lorgeri17 and their associates showed either enlarged LV diastolic or systol-

I:$ 1.6

1 6 2

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A

A

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--..

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A

A

71

:

-5.: 4 --5.

I

MVCF‘

-.0026

q

--.

ESo + 1.666

R q -.5619 SEE

q

.I15 t

I

I

I

I

120

160

200

240

280

End-Systolic

Stress (ESd) - gm/cmz

FIGURE 1. The ratio of mean rate-corrected velocity of fiber shortening vs end-systolic stress in normal subjects, showing the individual patients with tetralogy of Fall&.

ic dimensions, decreased ejection fraction or velocity of fiber shortening. In contrast, Sunderland et a12 found normal LV ejection fraction in patients with tetralogy of Fallot repaired in infancy, although values for the indexed LV end-diastolic volume were not given Rocchini et al3 found increased indexes of LV enddiastolic volume and decreased ejection fraction only with an unsatisfactory hemodynamic result. Borow et a14z5 confirmed normal LV work function curves when studied with afterload stress at cardiac catheterization in patients undergoing operation before age 2 years. The development of load-independent indexes of LV contractility should permit greater sensitivity in detecting myocardial dysfunction8-lo Colan et alI1 found that the rate-corrected mean velocity of fiber shortening end-systolic stress relation was load-independent, linear and sensitive for myocardial dysfunction. The advantage of this technique is that only 1 measurement of stress and velocity of fiber shortening may be obtained, and prolonging catheterization procedures by altering preload or afterload is not necessary. In our study, the mean value for this relation was abnormal but a number of the patients were within the normal range. The normal operant chamber stiffness in the tetralogy group indicates normal chamber compliance and would be expected in the absence of massive hypertrophy. The finding that myocardial stiffness is increased indicates that myocardial changes, possibly fibrosis, have developed. However, a number of patients did have normal values for myocardial stiffness. Because only 1 patient had an unsatisfactory hemodynamic result, the abnormal indexes of function cannot be attributed to that cause. There did not appear to be any relation between either the age at surgery or the duration between surgery and time of catheterization and increased myocardial stiffness and decreased LV function; however, the number of infants undergoing repair was small. There are many possible factors involved in the etiology of LV dysfunction in these patients. Experimental models and clinical examples of right ventricular hypertension have shown a detrimental affect on LV function25,26 and myocardial properties.27,28The pathologic changes in tetralogy of Fallot consist of myocardial hypertrophy, fibrosis, altered vascular suppIy to the left ventricle in addition to right ventricular changes that would be expected with pressure load.2gOther studies have suggested that the degree of cyanosis and hypoxia are more important factors in residual dysfunction than age at operation.7 However, other investigators suggest that total correction in infancy results in normal function measured by loaddependent indexes. 2-5Other factors such as myocardial protection, or lack of it, during cardiopulmonary bypass, the duration of bypass and residual lesions contribute to the development of myocardial fibrosis and dysfunction. Seven of these patients had normal diastolic indexes, whereas those in most patients in a previous study with postoperative severe pressure or volume load were abnormal,lg suggesting that the hyperfunction involved with severe LV pressure or vol-

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ume load itself or response to bypass and surgery contribute more to postoperative myocardial fibrosis. There are several possible limitations that should be considered in this study. It would have been preferable to have had larger cohorts of patients who underwent operation at different ages, with different durations and severity of hypoxic symptoms to be certain of the independent effects of these factors on systolic and diastolic function. There are potential technical problems in the performance of these studies, especially with the distortion of the ellipsoid shape of the left ventricle after tetralogy correction. However, patients with anything but minimal LV distortion were excluded from this study. Finally, there are many assumptions and conceptual differences concerning diastolic function that have been discussed previously.30-32 Acknowledgment: We thank Karen Buetow and Debbie Judas for typing the manuscript.

References 1. Jarmakani JMM, Graham TP Jr, Canent RV Jr, Jewett PH. Left heart function in children with tetrology of Follot before and after palliative or corrective surgery. Circulation 1972;46:478-490. 2. Sunderland CO, Matarazzo RG, Lees MH, Menashe VD, Boncheck LI, Rosenberg JA, Starr A. Total correction of tetralogy of Fallot in infancy. Circulation 1973;48:398-405. 3. Rocchini AP, Keane JF, Freed MD, Castaneda AR, Nadas AS. Left ventricular function following attempted surgical repair of tetralogy of Fallot. Circulation 1978;57:798-802. 4. Borow KM, Green LH, Castaneda AR, Keane JF. Left ventricular function after repair of tetralogy of Faflot and its relationship to age at surgery. Circulation 1980;61:1150-1158. 5. Borow KM, Keane IF, Castaneda AR, Freed MD. Systemic ventricular function in patients with tetralogy of Falfot, ventricular septal defect and transpositioli of the great arteries repaired during infancy. Circulation 1981;64:878-885, 6. Lange PE, Onnasch DGW, Bernhard A, Heintzen PH. Left and right ventricular adaptation to right ventricular overload before and after surgical repair of tetrafogy of FafJot. Am 1 Cardiol 1982;50:786-794. 7. De Lorgeril M, Friedli B, Assimacopoulos A. Factors affecting left ventricular function after correction of tetralogy of Falfot. Br Heart J 1984;52:536-541. 8. Sagawa K. The ventricular pressure-volume diagram revisited. Circ Res 1978;43:677-687. 9. Grossman W, Braunwald E, Mann T, McLaurin WP, Green LH. Contractile state of the left ventricle in man as evaluated from end-systolic pressurevolume reJations. Circulation 1977;56:845-852, 10. Borow KM, Green LH, Grossman W, Braunwald E. Left ventricular endsystolic stress-shortening and stress-length relations in humans. Am J Cardiol 1982;50:1301-1308. 11. Golan SD. Borow KM, Neumann A. Left ventricular end-systolic wall

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stress-velocity of fiber shortening reiation: a Joad-independent index of myocordial confractility. [ACC 1984;4:715-724. 12. B&tow JD, Van Zee BE, Judkins MP. Systolic and diastolic abnormalities of the left ventricle in coronary artery disease. Studies in patients with little or no enlargement of ventricular volume. Circulation 1970;42:219-228. 13. Gaasch WH, Battle WE, Oboler AA, Banas JSJr, Levine HJ. Left ventricular stress and compliance in man. With special reference to normalized ventricular function curves. Circulation 1972;45:746-762. 14. Mirsky I, Parmley WW. Assessment of passive elastic stiffness for isolated heart muscle and the intact heart. Circ Res 1973:33:2X-243. 15. Mirsky I, Cohn PF, Levine ]A, Garlin R, Herman MV, Kreulen TH, Sonnenblick EH. Assessment of left ventricular stiffness in primary myocardial disease and coronary artery disease. Circulation 1974;50:128-136. 16. Grossman W, McLaurin LP, Moos SP, Stefadouros M, Young DT. Wall thickness and diastolic properties of the left ventricle. Circulation 1974; 49:129-135. 17. Peterson KL, Tsuju J. Johnson A, DiDonna J, LeWinter M. Diastolic left ventricular pressure-volume and stress-stroin relations in patients with valvular oortic stenosis and left ventricular hypertrophy. Circulation 1978;58:7789. 18. Sandor GGS, Olley PM. Determination of left ventricular diastolic chamber stiffness ond myocordial stiffness in patients with congenital heart disease. Am J Cardiol 1982;49:771-779. 19. Sandor GGS, Puterman ML, Patterson MWH, Tipple MA, Vince DJ. Effect of pressure loading, volume loading and surgery on left ventricular chamber and myocardial stiffness in congenital heart disease, with a reevaluation of normal pediatric values. rACC 1986;8:371-378. 20. Dodge HT, Sandier H, Ballew DW, Lord JD Jr. The use of biplane angiocardiography for the measurement of left ventricular volume in man. Am Heart J 1960;60:762-776. 21. Graham TP Jr, Jarmakani JM, Canent RV, Morrow M J. Left heart volume estimation in infancy and childhood. Reevaluation of methodology and normal values. Circulation 1971;43:895-904. 22. Rackley CE, Dodge HT, Cable JD Jr, Hay Re. A method for determining Jeft ventricular mass in man. Circulation 1964;29:666-671. 23. Mirsky I. Left ventricular stress in the intact human heart. Biophys [ 1969;9:189-208. 24. Karliner JS,Gault JH, Eckberg D, Mullins CB, Ross J Jr. Mean velocity of fiber shortening. A simplified measure of left ventricular myocardial contractility. Circulation 1971;44:323-333. 25. Krayenbuehl HP, Turina JJ,Hess 0. Left ventricular function in chronic pulmonary hypertension. Am r Cardiol 1978;41:1150-1158. 26. Badke FR. Left ventricular dimensions and function during right ventricular pressure overload. Am [ Physiology 1982;242:H611-H618. 27. Visner MS, Arentzen CE, O’Connor MJ, Larson EV, Anderson RW. AJterations in left ventricular three-dimensionai dynamic geometry and systolic function during acute right ventricular hypertension in the conscious dog. Circulation 1983:67:353-365. 28. Visner MS, Arentzen CE, Crumbley AJ III, Larson EV, O’Connor MJ, Anderson RW. The effects of pressure-induced right ventricular hypertrophy on left ventricular diastolic properties and dynamic geometry in the conscious dog. Circulation 1986:74:410-419. 29. Krymsky LD. Pathologic anatomy of congenital heart disease. Circulation 1965;32:814-827. 30. Mirsky I, Pasipoularides A. Elastic properties of normal and hypertrophied cardiac muscle. Fed Proc 1980;39:162-168. 31. Glantz SA. Computing indices of diastolic stiffness hos been counterproductive. Fed Proc 1980;39:162-168. 32. Mirsky I. Assessment of diastolic function: suggested methods and future considerations. Circulation 1984;69:836-841.