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J Thorac Cardiovasc Surg 1995;109:1218-1224
© 1995 Mosby, Inc.

SURGERY FOR CONGENITAL HEART DISEASE

Pulmonary vascular resistance during exercise late after repair of large ventricular septal defectsRelation to age at the time of repair

Osaka, Japan

From the First Department of Surgery, Osaka University Medical School, Osaka, Japan.

Received for publication Jan. 11, 1994. Accepted for publication Oct. 10, 1994. Address for reprints: Yasuhisa Shimazaki, MD, First Department of Surgery, Osaka University Medical School, 2-2, Yamadaoka, Suita-city, Osaka, 565, Japan.

Abstract

Postoperative pulmonary artery pressure and resistance were assessed during exercise in 32 patients late after repair of large ventricular septal defect with pulmonary hypertension. Nineteen patients had a preoperative pulmonary-to-systemic resistance ratio of between 0.15 and 0.50 (group 1) and 13 had a ratio between 0.50 and 0.96 (group 2). Age at the time of operation was 0.9 to 13.0 years (4.6 ± 3.6) in group 1 and 0.8 to 15.8 years (4.3 ± 4.2) in group 2. Age at the time of restudy was 9 to 21 years (14.5 ± 3.0) in group 1 and 9 to 22 years (13.5 ± 4.1) in group 2. Pulmonary artery pressure was measured in the supine position at rest and during exercise, as were the measurements underlying the calculations of pulmonary vascular resistance. Mean pulmonary artery pressure was 13 to 21 mm Hg (17 ± 2) and 10 to 26 mm Hg (20 ± 5) in groups 1 and 2, respectively, at rest, and this increased to 17 to 27 mm Hg (22 ± 3) and 14 to 39 mm Hg (27 ± 7) in groups 1 and 2, respectively, during exercise (p < 0.05). Pulmonary vascular resistance was 0.51 to 3.40 U · m²(1.93 ± 0.63) and 0.79 to 3.31 U · m² (2.05 ± 0.65) in groups 1 and 2 at rest. It was 0.58 to 2.24 U m²(1.36 ± 0.57) and 0.81 to 3.85 U m²(2.18 ± 0.97) in groups 1 and 2 during exercise (p < 0.01). Postoperative pulmonary vascular resistance during exercise correlated well with age at the time of repair in both groups (r = 0.65, p < 0.05 in group 1; r = 0.86, p < 0.001 in group 2). These data suggest that 85% of patients with a preoperative pulmonary-to-systemic resistance ratio of between 0.15 and 0.50 would have normal pulmonary vascular resistance during exercise when operated on at younger than 3.8 years old and 85% of those with a preoperative pulmonary-to-systemic resistance ratio of more than 0.50 would have normal pulmonary vascular resistance during exercise when operated on at younger than 1.1 years. (J THORAC CARDIOVASC SURG1995;109:1218-24)

The prognosis of large ventricular septal defect (VSD) with pulmonary hypertension after surgical closure has been documented. Age and pulmonary vascular resistance (PVR) at the time of repair have been shown to be incremental risk factors that relate to outcome and regression of pulmonary hypertension. ^1,2 However, most of the data available were obtained at resting status, and little information is available about late postoperative PVR during the stress of exercise. ^3-5 We therefore assessed pulmonary hemodynamics during exercise, as well as at rest, late after closure of large VSD with pulmonary hypertension and analyzed the relation of age and PVR at the time of repair to postoperative PVR during the stress of exercise.

MATERIAL AND METHODS

Thirty-two patients were studied to evaluate pulmonary hemodynamics at rest and during exercise late after closure of large VSD. Patients with coexisting patent ductus arteriosus or atrial septal defect were included in this study, but those with atrioventricular septal defect were excluded. No patient had a chromosome aberration. All patients had pulmonary hypertension before operation (mean pulmonary artery pressure equal to or greater than 25 mm Hg). Preoperative mean pulmonary artery pressure ranged from 25 to 90 mm Hg (57 ± 16: mean plus or minus standard deviation of the mean) and the pulmonary-to-systemic systolic pressure ratio was 0.27 to 1.10 (0.80 ± 0.21). The pulmonary-to-systemic blood flow ratio was 1.04 to 3.10 (1.65 ± 0.46) and the pulmonary-to-systemic resistance ratio (Rp/Rs) was 0.15 to 0.96 (0.45 ± 0.20). The patients were divided into two groups according to whether they had an Rp/Rs of less than or more than 0.5. ^5,6 Group 1 consisted of 19 patients who had a preoperative Rp/Rs between 0.15 and 0.50 and group 2 of 13 patients with an Rp/Rs between 0.50 and 1.0. Ages at the time of repair (Table I) were 0.9 to 1.3 years (4.6 ± 3.5) in group 1 and 0.8 to 15.8 years (4.3 ± 4.0) in group 2 (not significant).

Postoperative cardiac catheterization
Cardiac catheterization late after operation was done with patients mildly sedated but awake. The catheter was advanced through the right ventricle into the pulmonary artery and into the wedged position. The wedge pressure was measured followed by pressures in the pulmonary artery, the right ventricle, and the right atrium. Then a catheter was inserted into the femoral artery and advanced into the left ventricle. The pressures in the left ventricle and ascending aorta were measured. Oximetry and cineangiography determined that neither intracardiac left-to-right or right-to-left shunts were present. Cardiac output was measured with the indicator-dilution method by injection of indocyanine greens into the pulmonary artery and sampling from the femoral artery. PVR was calculated as unit per meter squared in the usual manner. The same kinds of studies were obtained during exercise. Moderate exercise stress (about 1 watt/kg) was calibrated with bicycle ergometry in the supine position in each patient. The postoperative cardiac catheterization was done 4 to 14 years (9.6 ± 2.7) after the repair. Age at the time of restudy was 9 to 21 years (14.5 ± 3.0) and 9 to 22 years (13.5 ± 4.0) in groups 1 and 2, respectively (not significant). Interval between the operation and restudy was 5 to 14 years (9.9 ± 2.8) and 4 to 13 years (9.2 ± 2.5) in groups 1 and 2, respectively (not significant) (Table II). Normal values of PVR both at rest and during exercise were obtained from seven normal subjects who had undergone catheterization because of functional murmur. Ages of normal subjects were not different from those of patients in groups 1 and 2 at restudy.

Statistics
All data were expressed as mean plus or minus the standard deviation of the mean. Comparison of the data at rest and during exercise was made by the paired t test. Hemodynamic data between two groups were compared with the unpaired t test. Comparison among continuous variables in more than two groups was made by one-way analysis of variance. The relationships between age at the time of repair and pulmonary hemodynamics were evaluated by linear regression analysis as were the associations between preoperative data and postoperative PVR at rest and during exercise. The variables that were significantly related to the postoperative PVR at rest or during exercise in linear regression analysis were then evaluated in stepwise multiple regression analyses. Statistical significance was considered present at p < 0.05. The normal range for PVR was defined as the mean value plus or minus 2 standard deviations obtained from control subjects. Upper limits of the normal PVR were 3.3 units · m² at rest and 1.9 units m² during exercise.

RESULTS

Postoperative hemodynamic profile
Patients in three groups (group 1, group 2, and normal group) had similar hemodynamic data both at rest and during exercise, including heart rate, increasing rate of the heart rate, mixed venous oxygen saturation, and cardiac index (Tables II and III).

View larger version (12K): [in this window] [in a new window]   Fig. 1. Relationship between postoperative PVR during exercise and preoperative Rp/Rs. There was significant correlation between them (r = 0.563, p < 0.005). Ex, Exercise.

PVR
PVR decreased during exercise overall and in patients in group 1, and differences in PVR during exercise between group 1 and normal subjects could have been caused by chance alone. However, during exercise PVR did not decrease in group 2 and was greater than that in normal subjects (p < 0.05) (Table III).

Relationship between postoperative PVR at rest and age at the time of repair
Postoperative PVR at rest correlated well with age at the time of repair overall (Fig. 2, A). It did not correlate with age at the time of repair in group 1 (Fig. 2, B), but correlated well with that in group 2 (Fig. 2, C). These correlations demonstrated that 85% of the patients had normal PVR at rest late after repair even when they had had an Rp/Rs more than 0.5 and had repair before age 10 years.

View larger version (20K): [in this window] [in a new window]   Fig. 2.A, Relationship between postoperative PVR at rest and age at time of repair overall. Dashed lines enclose plus or minus standard error (roughly equivalent to 70%) in this and in C. There was significant correlation between them (r = 0.530, p < 0.005). B, Relationship between postoperative PVR at rest and age at time of repair in group 1. C, Relationship between postoperative PVR at rest and age at time of repair in group 2. There was significant correlation between them as follows: postoperative PVR = 1.532 +1.129 log(age at time of repair = year) (r = 0.583, p < 0.05).

View larger version (41K): [in this window] [in a new window]   Fig. 3.A, Relationship between postoperative PVR during exercise and age at time of repair overall. There was significant correlation between them as follows: postoperative PVR = 0.605 +0.997 log(age at time of repair) (r = 0.607, p < 0.001). B, Relationship between postoperative PVR during exercise and age at time of repair in group 1. There was significant correlation between them as follows: postoperative PVR = 0.827 +1.015 log (age at time of repair) (r = 0.651, p < 0.05). C, Relationship between postoperative PVR during exercise and age at time of repair in group 2. There was significant correlation between them as follows: postoperative PVR = 1.200 +2.134 log (age at time of repair) (r = 0.857, p < 0.001). Ex, Exercise.

Surgical "cure" of patients with large VSD with pulmonary hypertension (defined as surviving the early postoperative period and being alive late after operation with essentially normal pulmonary artery pressure) was reported to be obtained when surgical closure was done within 2 years of age. ^2,7 However, normal pulmonary artery pressure in this definition was pressure measured at rest, not during exercise. The normal response of pulmonary circulation to exercise is a decrease in PVR. ^8,9 Therefore a normal pulmonary hemodynamic response can be said to be present, in a strict sense, only when the response to exercise is normal. However, we do not know that there is a difference in prognosis between patients with normal pulmonary vascular responses only at rest and those having normal responses even during exercise.

Some reports demonstrated an increase in pulmonary artery pressure during exercise in patients who underwent surgical closure of a large VSD at an older age. ^3,4 However, there is still a paucity of this kind of information, especially about pulmonary vascular responses to exercise in patients who underwent closure of a large VSD at a very young age.

This study confirms the results of the previous report that patients with severe pulmonary hypertension caused by a large VSD should be operated on at less than 2 years of life. ² However, our results refine this statement, because they demonstrate that a large VSD with moderately or severely high PVR should be closed when the patient is younger than 1 year old. Patients with a large VSD with mildly elevated PVR appear to have a good response even when the operation is delayed until age 3.8 years, although we would recommend repair at an earlier age.

Mixed venous oxygen saturation during exercise in patients in the present study was 36% to 84% (60% ± 11%) and exercise load would be maximal when mixed venous oxygen saturation was less than 30% ¹⁰; therefore, the exercise stress test used in this study was not maximum but moderate. Cardiac index during exercise in patients in this study significantly increased and was comparable to that of normal subjects. Some patients had pulmonary hypertension during exercise, suggesting good ventricular performance even during exercise.

The PVR rather than the Rp/Rs may be preferable for evaluating pulmonary vascular status. However, the resistance ratio is still clinically useful for assessing the severity of intrinsic PVR when operability is assessed in congenital bidirectional shunts. This ratio takes into account miscellaneous factors (catecholamine level and blood viscosity) that affect both pulmonary and systemic vascular beds. ^6,11 Therefore we still use this resistance ratio at preoperative assessment of pulmonary vascular obstructive disease. On the other hand, the PVR was measured at postoperative study in this study and should be more appropriate when pulmonary vascular responses to exercise are assessed in subjects without shunt.

In conclusion, this study demonstrated that a large VSD with PVR of more than an Rp/Rs of 05 should be closed while the patient is younger than 1 year old. This is also preferable in those with an Rp/Rs less than 0.5, but even when operation is delayed to the age of 4 years normal pulmonary vascular responses to moderate exercise are usually present late after operation.

Acknowledgments

We are deeply indebted to Dr. J. W. Kirklin and Dr. E. H. Blackstone (University of Alabama at Birmingham, School of Medicine) for their advice in analyzing the data.

References

1. Du Shane JW, Kirklin JW. Late results of the repair of ventricular septal defect on pulmonary vascular disease. In: Kirklin JW, ed. Advances in cardiovascular surgery. New York: Grune & Stratton, 1973:9-16.
   
2. Blackstone EH, Kirklin JW, Bradley EL, Du Shane JW, Appelbaum A. Optimal age and results in repair of large ventricular septal defects. J THORAC CARDIOVASC SURG 1976;72:661-79.[Abstract]
   
3. Maron BJ, Redwood DR, Hirshfeld JW Jr, Goldstein RE, Morrow AG, Epstein SE. Postoperative assessment of patients with ventricular septal defect and pulmonary hypertension. Circulation 1973;48:864-74.[Abstract/Free Full Text]
   
4. Hallidie-Smith KA, Wilson SE, Hart A, Zeidfard E. Functional status of patients with large ventricular septal defect and pulmonary vascular disease 6 to 16 years after surgical closure of the defect in childhood. Br Heart J 1977;39:1093-101.[Abstract/Free Full Text]
   
5. Shimazaki Y, Kitamura S, Nakano S, et al. Postoperative hemodynamics in patients with ventricular septal defect and pulmonary hypertension undergoing operation under 10 years of age: response to physical exercise. Nippon Kyobu Geka Gakkai Zasshi 1982;30:1235-41.[Medline]
   
6. Grossman W. Clinical measurement of vascular resistance and assessment of vasodilator drugs. In: Grossman W, ed. Cardiac catheterization and angiography. 3rd ed. Philadelphia: Lea & Febiger, 1986:135-42.
   
7. Kirklin JW, Barratt-Boyes BG. Ventricular septal defect. In: Kirklin JW, Barratt-Boyes BG, eds. Cardiac surgery. New York: John Wiley & Sons, 1986:645-9.
   
8. Dexter L, Dow LW, Haynes FW, et al. Studies of the pulmonary circulation in man at rest: normal variations and the interrelations between increased pulmonary blood flow, elevated pulmonary arterial pressure, and high pulmonary "capillary" pressures. J Clin Invest 1950;29:602-13.
   
9. Lock JE, Einzig S, Moller JH. Hemodynamic responses to exercise in normal children. Am J Cardiol 1978;41:1278-84.[Medline]
   
10. Epstein SE, Beiser GD, Stampfer M, Robinson BF, Braunwald E. Characterization of the circulatory response to maximal upright exercise in normal subjects and patients with heart disease. Circulation 1967;35:1049-62.[Abstract/Free Full Text]
    
11. DiSesa VJ, Cohn LH, Grossman W. Management of adults with congenital bidirectional cardiac shunts, cyanosis, and pulmonary vascular obstruction: successful operative repair in 3 patients. Am J Cardiol 1983;51:1495-7.[Medline]
    

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This Article Abstract Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Yasuhisa Shimazaki Susumu Nakano Hikaru Matsuda Yasunaru Kawashima Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ikawa, S. Articles by Kawashima, Y. Search for Related Content PubMed PubMed Citation Articles by Ikawa, S. Articles by Kawashima, Y.