Comparison of exercise and catheterization results following total surgical correction of tetralogy of Fallot

Comparison of exercise and catheterization results following total surgical correction of tetralogy of Fallot Although surgery may correct the hemodynamic abnormalities of tetralogy of Fallot (TOF), the long-term effects on exercise tolerance are uncertain. Twenty-eight patients, aged 7 to 30 years, had cardiac catheterization and maximal graded exercise testing to evaluate the adequacy of the hemodynamic repair and its relation to exercise performance. Patients were tested 2 to 9 years after operation, and I3 previously had had palliative shunt procedures. At catheterization, 23 of the 28 patients had good surgical results. Despite the satisfactory hemodynamics, maximal working capacity (MWC), maximum heart rate, and exercise blood pressure were diminished when compared to normal values. In 10 patients who had exercise studies at catheterization, right ventricular systolic pressure (RVSP) and residual gradients were magnified by exercise. Abnormalities were independent of age at time of correction, time elapsed since surgery, use of patch in the outflow tract, or any antecedent procedures.

Stephen Hirschfeld, M.D., Albert J. Tuboku-Metzger, M.D., Gordon Borkat, M.D., Jay Ankeney, M.D., Julie Clayman, M.D., and Jerome Liebman, M.D., Cleveland, Ohio With technical assistance of Louise Muth

Although a successful operation in children with tetralogy of Fallot (TOF) leads to improvement in subjective symptoms, patients may have persistent murmurs, cardiomegaly, and abnormalities of the electrocardiogram.":" Postoperative cardiac catheterization has demonstrated residual hemodynamic abnormalities, but there is little information concerning the long-term effects of surgery on exercise tolerance. Such information is essential to evaluate the benefifits of surgery, to determine the most appropriate age for correction, and to predict a safe level of recreational activities and work. This study was undertaken to compare the exercise performance of patients who had had complete repair of TOF to normal children and relate the maximal workFrom Case Western Reserve University School of Medicine, Department of Pediatrics, Rainbow Babies and Children's HospiIal, Cleveland, Ohio 44106. Supported by National Institutes of Health Grant HL-05803. Received for publication June 28, 1977. Accepted for publication Nov. 15, 1977. Address for reprints: Stephen Hirschfeld, M.D., 2101 Adelbert Rd., Cleveland, Ohio 44106.

446

ing capacity (MWC), exercise heart rate, and systolic blood pressure response to the adequacy of hemodynamic repair. Selected patients were exercised during cardiac catheterization to evaluate hemodynamic changes that occurred with exercise. Patients

Twenty-eight patients, 19 males and nine females, were evaluated. Ages ranged from 7 to 30 years (mean 12.4) and patients were studied 2 to 9.5 years (mean 4.4) after the operation. Mean age at operation was 7.9 years. Thirteen patients previously had had palliative shunt procedures. Corrective surgery consisted of closure of the ventricular septal defect (YSD) and infundibulectomy alone (six patients), infundibulectomy and pulmonary valvotomy (10 patients), and infundibulectomy and insertion of a patch on the outflow tract (12 patients). All subjects were undergoing cardiac catheterization and exercise testing to assess their surgical repair. No one had symptoms at rest or clinical evidence of congestive heart failure. Informed consent was obtained prior to catheterization and the maximal exercise test.

0022-5223/78/0375-0446$00.60/0 © 1978 The C. V. Mosby Co.

Volume75 Number3 March,1978

Methods One day prior to catheterization, each patient had a maximal graded exercise test on a variable-resistance bicycle ergometer (Quinton Instrument Ergometer 848). We used the method initially described by Goldberg? and modified by James." One difference in our protocol from that of James was that our patients decelerated in an upright position on the bicycle, whereas the patients of James were placed in a supine position in the immediate postexercise period. Frank orthogonal Leads X, Y, and Z were continuously monitored on a Hewlett-Packard Sanborn 789-6A visoscope. Electrocardiograms were taken prior to exercise, at the end of each work load increment, and 5 and 10 minutes after exercise. Tracings were analyzed for heart rate, arrhythmia, and ST segment abnormalities. Work load increments depended on surface area (Table I). MCW, defined as maximum work performed at exhaustion, was determined and compared to that of the normal control subjects by James and associates.vThe MCW was calculated from the work loads (kilogram-meters per minute) and the exercise time. The ratio of MCW to surface area was calculated for each subject. The final exercise units were kilogrammeters per minute per square meter. Blood pressure was obtained every 2 minutes with a cuff and sphygmomanometer. Ten patients had supine exercise during cardiac catheterization with a Quinton Instrument Ergometer 848, while the venous catheter was in the pulmonary artery. Resting and exercise measurements were made of cardiac output and cardiac index calculated from indocyanine green dye-dilution curves. Right ventricular systolic pressure (RVSP), right ventricular enddiastolic pressure (RVEDP), and right ventricularto-main pulmonary arterial (RV-PA) peak systolic pressure gradients were obtained by withdrawing the catheter from the pulmonary artery to the right ventricle at the end of the exercise period. Data analysis was accomplished in the following manner. Patients were divided into three groups based on normalcy of postoperative hemodynamics (Table II). Group I comprised patients with an R VSP of 40 mm. Hg or less, an RV-PA systolic pressure gradient of less than 20 mm. Hg, and no residual VSD. Group II had an RVSP of 40 to 60 mm. Hg, an RV-PA systolic gradient of 20 to 40 mm. Hg, and a small VSD, with a pulmonary-to-systemic flow ratio of less than 1.5: I. Group III had an RVSP of greater than 60 mm. Hg, with or without a residual VSD. This separation into groups permitted the use of the t test statistic to evaluate differences of all patients from normal subjects and

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Table I. Exercise protocol* Surface area

I---w-or-k-/-oa-d-(-kg-.-.M-./ -m-in-.)----


200,300,500; then increments of 100 200, 400, 600; then increments of 100 200, 500, 800; then increments of 200

*Three exercise programs were used for three ranges of body surface area. The pedal speed was 60 to 70 r.p.m. Duration of exercise at each level was 3 minutes.

differences within each hemodynamic group. Linear regression analysis was employed to evaluate the relationship of exercise heart rate, blood pressure, cardiac index, and age since operation to MCW. To conform to the format of previous publications, we also divided our patients on the basis of surface area, with children with a surface area of less than 1.2 sq. M. forming one group and those with a surface area of 1.2 sq. M. or more forming another. Normal control data were obtained from the publication of James and associates." The MCW and blood pressure response were refined by use of regression equations derived by James, taking into account the exact age, height, and weight of each child. These data were based on 103 normal children and allow the prediction of the expected MCW/sq. M. and blood pressure for each patient. Results Patients. There were 28 patients whose mean age was 12.4 years and who were tested a mean of 4.4 years after operation. The mean surface area was 1.27 sq. M. There were 13 patients in Group I, IO in Group II, and five in Group III. Thirteen patients had right ventricular outflow patches inserted at operation. There were no significant differences between the hemodynamic groups in age, surface area, or postoperative years. Ten patients had a surface area of less than 1.2 sq. M. and 18, a surface area of 1.2 sq. M. or more. There were 11 male and eight female patients larger than 1.2 sq. M. There was no difference in postoperative age. The average age at operation was 7.9 years. Exercise results. MCWIIsq. M. (Tables II and III, Figs. I and 2). The mean MWC/sq. M. ± I standard error was lower than that predicted on the basis of regression equations for age, height, weight (1,691 ± 151 versus 3,526 ± 164, P < 0.001). There were no statistically significant differences in the MCW of Groups I, II, and III. Although the groups with the better hemodynamic results had greater MCW/sq. M., the broad range of

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Table II. Summary of patient data by surgical result

Patients Age (yr.) Surface area Postop. (yr.) MWC/sq. M. Control Patient Resting BP (mm. Hg) Control Patient Exercise BP (mm. Hg) Control Patient Resting HR/(beats/min.) Exercise HR/ (beats/ min.)

I

I

Total

Group I

Group II

Group III

28 12.4 ± 0.8 1.27 ± 0.05 4.4 ± 0.4

13 12.3 ± 0.8 1.27 ± 0.06 5.2 ± 0.6

10 12.7 ± 2.1 1.27 ± 0.11 3.9 ± 0.66

5 11.8±0.7 1.27 ± 0.19 3.7 ± 0.30

3,526 ± 164 1,691 ± 151

3,502 ± 175 1,864 ± 239

3,507 ± 261 1,678 ± 247

3,622 ± 684 1,266 ± 285

III ± 1.0 104 ± 2.1

110 ± 1.0 101 ± 2.9

110 ± 2.2 107 ± 4.0

III ± 3.0 103 ± 4.9

152 135 87 171

152 ± 126 ± 91 ± 173 ±

± ± ± ±

2.9 3.8 2.8 3.3

2.8 3.8 4.0 5.3

153 ± 147 ± 82.9 ± 173 ±

6.8 7.0 3.8 3.4

153 ± 136 ± 86.2 ± 164 ±

6.3 9.4 9.4 11.7

Legend: All values are the mean :t 1 standard error. MWC, Maximum work capacity. BP, Blood pressure. HR, Heart rate.

Table III. Comparison, by body surface area (SA), of normal subjects and patients who had had repair of tetralogy of Fallot SA

Patients (N = 28) MWC/sq. M. Control Patient Resting systolic BP (mm. Hg) Control Patient Exercise systolic BP (mm. Hg) Control Patient Resting HR (beats/min.) Control Patient Exercise HR (beats/ min.) Control Patient

~/.20

sq. M.

SA <1.20 sq. M.

Male

Female

10

II

7

2,765 ± 280 1,147 ± 209*

5,860 ± 384 1,922 ± 296*

3,857 ± 351 1,757 ± 234*

103 ± 2 101 ± 2t

117 ± I 107 ± 2*

119 ± 2 103 :t 5*

139 ± 5 125 ± 4*

179 ± 4 142 ± 8*

167 ± 4 139 ± 6*

85 ± 3 87 ± 5t

80 ± 2 85 ± 4t

94 ± 3 91 ± 5t

193 ± 4 164 ± 7*

194 ± 2 174 ± 4*

202 ± 2 178 ± 6*

Legend: All values are the mean :t I standard error. For abbreviations see Table II.

*p <0.005. tNot significant.

values did not permit the differences to reach statistical significance. When patients were divided by surface area, the MCW/sq. M. was again reduced from normal. If the surface area was under 1.2 sq. M., MCW/sq. M. was 1,147 as compared to 2,765 for control subjects (p < 0.005). For male subjects with a surface area of 1.2 sq. M. or more, the MCW/sq. M. was 1,922 compared to 5,860 for control subjects (p < 0.005). Female subjects with a surface area of 1.2 sq. M. or more also had reduced MCW: 1,757 versus 3,857 (p < 0.005).

Blood pressure response (Tables II and III, Figs. I and 2). The mean resting blood pressure was diminished in the patients (104 mm. Hg) when compared to that of normal subjects (p < 0.005), and the capacity of the blood pressure to be raised was also diminished, the exercise blood pressure being 135 mm. Hg for patients and 152 mm. Hg for control subjects (p < 0.005). Blood pressure went higher in Group II patients than Group lor III (p < 0.025). The children with a surface area of less than 1.2 sq. M. had a resting blood pressure not significantly different from normal. However, in the larger males and

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females, the blood pressure did not become appropriately elevated during exercise (p < 0.005). Heart rate (Tables II and III, Figs. I and 2). Resting heart rates of normal subjects and patients were not significantly different when evaluated by hemodynamic result or surface area. The heart rate at MWC was significantly reduced from normal in all patient groups (p < 0.005). Electrocardiogram. Unifocal premature ventricular contractions developed in one patient, and premature atrial contractions at rest and during exercise developed in another. No arrhythmias developed during exercise or in the immediate postexercise period in the remaining patients. Catheterization exercise results (Table IV). The resting cardiac index was within normal limits (mean 3.3 liters per minute per square meter). Exercise cardiac index increased to 8.4 with the change secondary to increased heart rate. Mean resting heart rate was 84 beats per minute, which was not different from the heart rate in the exercise laboratory. The exercise heart rate increased to 153, which was lower than the heart rate at MCW and would suggest that their performance during supine catheterization was not maximal. R VSP rose 1.5 to 2.0 times resting value. The mean rise in RV-PA systolic gradient was a result of increased RVSP. The increased R VSP and gradient were not a result of increased stroke volume, as the stroke index increased only 8 c.c. per beat. The capability of the cardiac index to become elevated during exercise correlated well (r = 0.79) with the patient's ability to perform work during the stress test. R VEDP was increased in eight patients but did not change significantly with exercise. Correlations. MCW correlated well with only exercise cardiac index (r = 0.79). MCW was not affected by exercise heart rate (r = 0.36) or blood pressure (r = 0.14). Age at operation and previous palliative procedures did not influence MCW (r = 0.20). Discussion The goal of corrective surgery in patients with TOF is to return them to a functional capacity approaching normal. This study demonstrated significant differences in the response to exercise between normal children and patients who had undergone surgical correction of TOF. The surgical group had decreased MCW and diminished blood pressure and heart rate responses to exercise when compared to normal. The decreased MCW was independent of the hemodynamic success of the operation, as even patients with normal RVSP and no RV-PA gradient had diminished exercise tolerance. The abnormalities of exercise re-

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Fig. 1. There was decreased maximal work capacity/sq. meter (MWC/sq. M.), exercise systolic blood pressure (BP), and heart rate (HR) in the patients who had had repair of tetralogy of Fallot. The differences between the surgical groups were not significant. Values are the mean ± I standard error.

sponse were independent of age at operation, postoperative years, previous palliative procedures, patient surface area, or the insertion of an outflow patch in the right ventricle. Other investigators have noted the diminished exercise performance in patients operated upon for TOF.5, 7-9 James and associates," who studied 43 patients who were asymptomatic after repair of TOF, found results similar to our study for patients with a surface area of 1.2 sq. M. or more. James found that patients with a surface area of less than 1.2 sq. M. performed normally, whereas all of our patients, including IO with a surface area of less than 1.2 sq. M. had diminished exercise performance. Only one of our patients with premature ventricular contractions at rest had them during exercise or in the immediate postexercise period. No patient had ventricular tachycardia. This was in marked contrast to the five patients of James in whom multifocal premature ventricular contractions developed. Investigators-:" have used exercise during cardiac catheterization to evaluate heart function in patients after surgery for TOF. Bristow and associates- reported results of serial hemodynamic measurements during supine exercise. This was similar to our protocol. These authors demonstrated that R VEDP increased abnormally during exercise, this increase suggesting impaired ventricular function. Eight of our 10 patients had

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Fig. 2. When divided by surface area there was decreased maximal work capacity/sq. M. (MWC/sq. M.), exercise blood pressure (BP), and heart rate (HR) in the patients who had had repair of tetralogy of Fallot (TOF) compared to normal control subjects. Values are the mean ± I standard error.

Table IV. Catheterization and exercise hemodynamic measurements

Patient

2 3 4 5 6 7 8 9 10

State

HR (beats/min.)

RVSP (mm. Hg)

MPA (mm. Hg)

Gradient

Rest Exercise Rest Exercise Rest Exercise Rest Exercise Rest Exercise Rest Exercise Rest Exercise Rest Exercise Rest Exercise Rest Exercise

70 158 80 140 98 150 85 170 100 150 78 148 60 130 76 150 100 170 88 160

46 95 70 112 34 50 60 90 60 100 48 75 40 80 36 70 40 75 36 50

35/10 50/9 40/10 50/10 26/15 30/15 24/12 35/10

45 30 62 8 20 36 55

40/15 40/10 36/16 55/30 34/16 45/12 32/8 55/20 30/8 45/20

II

8 35 4 25 2 25 8 20 6 15

RVEDP (mm. Hg)

Brachial artery (mm.Hg)

5 6.5 12

162/84 240/120

7 8 5 6 14 15 8.5 10

120/70

II

12.5 II

15 8 10 10 12

120/70 140/80 100/65 120/80 150/90 170/110 120/70 135/80 110/ 110/80 170/100 110/70 135/80

CI (L./min.)

SI (c.c. tbeai)

3.9 9.0

28 28

4.3

46

3.1 6.3 3.4

25 34 33

3.3 9.0 3.2 10.6 4.5 9.5 4.0 5.7

44 56 27

46 45 56 45 35

Legend: HR, Heart rate. RVSP, Right ventricular systolic pressure. MPA, Main pulmonary artery pressure. RVEDP, Right ventricular end-diastolic pressure. CI, Cardiac index. SI, Stroke index.

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Tetralogy of Failot

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elevated RVEDP at rest, which remained unchanged during exercise. This suggests that elevated RVEDP was not the sole limiting factor in diminished exercise performance. Epstein and associates" and Bjarke'" studied patients during intense upright exercise and found decreased cardiac output in patients when compared to normal subjects. Low cardiac output was attributed to inadequate rise in stroke volume. Our patients likewise had little increase (average 8 c.c.) in stroke index during exercise. In our patients the MWC did correlate best with the capacity of the cardiac output to increase. The diminished heart rate response has been previously noted": 8, 10 in postoperative studies. It has been postulated that the submaximal heart rate and blood pressure could be the result of abnormality in the autonomic nervous system. Since a considerable portion of the increase in cardiac index with exercise is due to a rise in heart rate, the diminished heart rate response may be a large contributor to the diminished MCW. The basis of right ventricular dysfunction and diminished responses of cardiac output and stroke volume, which existed even in our patients with nearnormal resting hemodynamics, may be the result of ultrastructural myocardial changes caused by the stresses of prolonged right ventricular hypertrophy and hypoxia. 11 In conclusion, our study confirms the presence of abnormal exercise performance in a postoperative group of patients with TOF. The diminished work capacity may result from right ventricular dysfunction as indicated by elevated R VEDP, increased RVSP without a marked increase in stroke index, and diminished stroke index during exercise. If prolonged right ventricular hypertrophy and hypoxia are the cause of right ventricular dysfunction postoperatively, we might speculate that corrective surgery earlier than the mean age of our group (7.9 years) may improve the postoperative exercise performance of patients requiring surgical repair of TOF. REFERENCES Ruzzyllo W, Nihill MR, Mullins EE, McNamara DG: Hemodynamic evaluation of 221 patients after intracar-

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diac repair of tetralogy of Fallot. Am J Cardiol 34:565576, 1974 Clayman JA, Ankeney JL, Liebman J: Results of complete repair of tetralogy of Fallot in 156 consecutive patients. Am J Surg 130:601-607, 1975 Gotsman MD, Beck W, Barnard CN, O'Donovan TG, Schrire V: Results of repair of tetralogy of Fallot. Circulation 40:803-821, 1969 John S, Sukuman JP, Cherian G, Gupta RP, Krishnaswamy S: Intracardiac repair in tetralogy of Fallot. Hemodynamic studies following corrective surgery. Circulation 49:958-961, 1974 Bristow JD, Kloster FE, Lees MH, Menashe VD, Griswold HE, Starr A: Correction of tetralogy of Fallot . Circulation 41: 1057-1066, 1970 Sunderland CO, Matarazzo RG, Lees MH, Menashe VD, Bonchek LI, Rosenberg JA, Starr A: Total correction of tetralogy of Fallot in infancy. Circulation 48:398-405, 1973 Goldberg SJ, Weiss R, Adams FH: A comparison of the maximal endurance on normal children and patients with congenital heart disease. J Pediatr 69:46-55, 1966 James FW, Kaplan S, Schwartz DC, Chan TC, Sanker MJ, Naylor V: Response to exercise in patients after total surgical correction of tetralogy of Fallot , Circulation 54:671-679, 1976 Epstein SE, Beiser GO, Goldstein RE, Rosing DR, Redwood DR, Morrow AG: Hemodynamic abnormalities in response to mild and intense upright exercise following operative correction of an atrial septal defect or tetralogy of Fallo!. Circulation 47:1065-1073, 1973 Bjarke B: Oxygen uptake and cardiac output during submaximal and maximal exercise in adult subjects with totally corrected tetralogy of Fallot, Functional Studies in Palliated and Totally Corrected Adult Patients with Tetralogy of Fallot. Scand J Thorac Cardiovasc Surg (Suppl) 16:9-26, 1974 Wessel HU, Stout RL, Guerrero L, Paul MH: Postoperative exercise studies in tetralogy of Fallot , Child With Congenital Heart Disease, BLS Kidd, RD Rowe, eds., Mount Kisco, NY, 1976, Future Publishing Copy, pp. 71-78 Jones M, Ferrans VJ: Myocardial degeneration in congenital heart disease (abstr). Circulation 54:Suppl 2:229, 1976