- Email: [email protected]
Prognostic factors in valvotomy for critical aortic stenosis in infancy
J
THoRAc CARDIOVASC SURG
92:747-754,1986
Prognostic factors in valvotomy for critical aortic stenosis in infancy Aortic valvotomy for critical aortic stenosis in infancy has had a high mortality. To determine the factors that influence survival, we reviewed the cases of 24 infants who underwent aortic valvotomy in the first 6 months of life (mean 41/ 2 weeks) for aortic stenosis from 1978 to 1984. Cardiopulmonary bypass was used in all patients. Operative mortality was 21 % (5/24), four of the five deaths occurring from low cardiac output. Analysis of preoperative factors affecting survival versus nonsurvival revealed that low ejection fraction (60 % ± 17 % in survivors versus 36 % ± 2 % in nonsurvivors), high left ventricular end-diastolic pressure (16 ± 7 mm Hg in survivors versus 30 ± 14 mm Hg in nonsurvivors), and presence of endocardial fibroelastosis (25% in survivors versus 100% in nonsurvivors) aU were predictive of a poor outcome, although the small sample size indicated caution in interpreting results. Factors that did not appear to influence survival included peak systolic gradient (79 ± 30 mm Hg in survivors versus 60 ± 15 mm Hg in nonsurvivors) and left ventricular end-diastolic volume (37 ± 17 cm3/m2 in survivors versus 36 ± 7 cm3/m2 in nonsumvors), Four patients with a left ventricular end-diastolic volume below 26 cm3/m2 survived. Postoperative gradients averaged 25 ± 21 mm Hg at 3.4 ± 2 years' foUow-up in nine recatheterized patients. Ejection fraction of these patients increased from 45 % ± 10% to 70 % ± 11 % and left ventricular end-diastolic volume increased from 37 ± 17 to 58 ± 5 cm3/m2• Two of 17 patients have required apical-aortic conduits; aU other patients are asymptomatic. We conclude that infants with critical aortic stenosis benefit from valvotomy even with impaired left ventricular function and severely reduced left ventricular dimensions and many have nearly normal hemodynamics on late foUow-up.
Steven R. Gundry, M.D., and Douglas M. Behrendt, M.D., Ann Arbor, Mich.
Until recently, operation for congenital valvular aortic stenosis early in infancy has resulted in high mortality rates in most series."? Recent reports from Messina, 10 Sink,II and their colleagues have demonstrated that good results can be achieved with this lesion, and they and others have speculated on the anatomic, physiologic, and operative factors that might contribute to a successful outcome. These recent reports prompted us to review our own experience with operation for critical aortic stenosisin infants under 6 months of age, with particular emphasis on those less than 1 month old.
From the Section of Thoracic Surgery, Department of Surgery, University of Michigan Hospitals, Ann Arbor, Mich. Read at the Eleventh Annual Meeting of The Western Thoracic Surgical Association, Incline Village, Nev., June 16-20, 1985. Address for reprints: Douglas M. Behrendt, M.D., Professor of Surgery, Section of Thoracic Surgery, Room 2110, Box 344, Taubman Health Care Center, Ann Arbor, Mich. 48109.
Patient population and methods
The records of 24 infants (15 boys and nine girls) aged 1 to 180 days (mean 1 month) who underwent aortic valvotomy in the first 6 months of life at the C. S. Mott Children's Hospital, University of Michigan Medical Center, from Jan. 1, 1978, to Oct. 30, 1984, were reviewed. Nineteen infants (80%) were less than 1 month old at operation, and nine (38%) were operated on within the first 3 days of life. All patients had profound congestive heart failure. All underwent emergency cardiac catheterization and, whenever feasible, M-mode and two-dimensional echocardiography. Cardiac catheterization data were available on all patients, and left ventricular cineangiography was available on 18 patients. Ejection fractions and end-diastolic, end-systolic, and stroke volumes were calculated by the Dodge area-length method. Associated intracardiac or extracardiac anomalies as determined by catheterization, physical examination, or operation did not affect inclusion of the patient in this review. 747
The Journal of Thoracic and Cardiovascular
7 4 8 Gundry and Behrendt
Surgery
Table I. Factors potentially affecting survival" (n = 24)
EF(%)
LVEDP (mm Hg)
EFE (%)
SUrvIVOrs 60 ± 17 16 ± 7 25 Nonsurvivors 36 ± 12 30 ± 14 100 Individual] p s O.03t p S 0.04t p s om t test p value
Age (days)
38 ± 52 5± 8 p 2: 0.05t
PSG L VED VI LVESVI (mmHg) (cmJjm2) (cmJjm2)
79 ± 30 60 ± 15 NSt
37 ± 17 I7 ± I3 36 ± 7 19 ± 5 NSt NSt
Valve type
Arterial O2 sat. SVC sat. Clamp time (%) (%) (min)
IOB/9T 89 ± 16 61 ± 16 2B/2T 75 ± 30 45 ± 16 NSt NSt NSt
13 ± 2 15 ± 3 NSt
Legend' EF. Ejection fraction. LVEDP. Left ventricular end-diastolic pressure. EFE. Endocardial fibroelastosis. PSG, Peak dystolic gradient. LVEDVI, Left ventricular end-diastolic volume index. LVESVI, Left ventricular end-systolic volume index. SVC, Superior vena cava. B, Bicuspid. T, Tricuspid. NS, Not significant. • All values are expressed as mean ± standard deviation. tNone of these comparisons is significant at the 5% level using the Bonferroni experimentwise approach because of small sample size. tNone of these comparisons is significant at either the test p value of 5% or the experimentwise 5%.
Operative technique. All patients underwent emergency operation after catheterization. After general endotracheal anesthesia and median sternotomy, cardiopulmonary bypass was instituted via single atrial and ascending aortic cannulas. Surface cooling was used in only five of 24 patients, After systemic cooling to at least 20° C, the aorta was cross-clamped and the ascending aorta opened, The fused aortic valve commissures were incised to, but not into, the anulus. The aorta was then closed with running polypropylene suture and the crossclamp removed after 13 ± 2 minutes. The patients were rewarmed and weaned from cardiopulmonary bypass. Follow-up. Follow-up was available on all patients, Examinations were performed by pediatric cardiologists of the C. S, Mott Children's Hospital. Cardiac catheterization was performed on nine patients for persistent left ventricular hypertrophy by electrocardiogram, a loud murmur and physical signs of aortic insufficiency, or a suspected large residual gradient by Doppler echocardiography. Analysis of data. The data obtained in the survivors were compared to those in nonsurvivors, and the postoperative results were analyzed to determine if prognostic factors could be identified that influenced survival. All directly recorded and derived measurements were compared for statistical significance by either the chi square or Student's paired or unpaired t tests. Results were deemed statistically significant if p was less than 5%. Because of the preliminary nature of these findings (small samples), significances were noted in two ways: Each comparison was assessed as an individual test and, because of the number of comparisons for the same subjects, a more conservative Bonferroni experimentwise a-error was also used. For the eleven comparisons, which assessed factors possibly affecting survival (Table I), the experimentwise a-error was 0.45% (5%/11). Thus an individual comparison would
be significant at the 5% experimentwise level, if its individual test significance attained a p value of 0.0045 or less. Results Two of the 24 patients died in the operating room. One died of a technical error and the second could not be weaned from cardiopulmonary bypass. Three patients died 1 to 14 days postoperatively of the sequelae of preoperative or postoperative low cardiac output; thus the perioperative death rate was 21%. There has been only one death in the last 11 patients operated on since 1982, representing a mortality of 9%. This single death occurred in a newborn infant with severe endocardial fibroelastosis in whom fibrillation developed upon induction of anesthesia. The infant was not weaned from bypass. For the purpose of comparing prognostic factors affecting initial survival, the patient dying as a result of the technical error was excluded from subsequent analysis. Thus 19 survivors were compared with four nonsurvivors. There were two late deaths. One child died of mediastinitis 4 months postoperatively and the second died 3 months after the initial valvotomy after placement of a left ventricular apical-aortic conduit and mitral valve replacement for severe left ventricular outflow tract obstruction and mitral insufficiency. Long-term follow-up is available on 17 patients who have been observed from 6 months to 7 years (mean 3.4 ± 2 years) after valvotomy. No patient has symptoms of congestive heart failure, chest pain, or easy fatigability. Only one other patient has required reoperation, again for placement of an apical-aortic conduit 14 months after the initial valvotomy. That patient has been followed up for 19 additional months postoperatively and is currently asymptomatic.
Volume 92 Number 4 October 1986
Critical aortic stenosis
749
Fig. 1. Preoperative anteroposterior views of cineangiograms during left ventricular end-diastole (A) and end-systole (B) showing small globular ventricular cavity characteristic of endocardial fibrolastosis. This infant did not survive.
Factors affecting survival (Table I) Ejection fraction. The ejection fraction of survivors, 60% ± 17%, was significantly greater than the 36% ± 12% ejection fraction of nonsurvivors (p ::; 0.03*). Nevertheless, more than half of the survivors had depressed ejection fractions of less than 50%. No patient with an ejection fraction of less than 42% survived operation (Figs. 1, 2, 3, and 4, A and C). Left ventricular end-diastolic pressure. The left ventricular end-diastolic pressure (L VEDP) of 16 ± 7 mm Hg in survivors was significantly lower than the LVEDP of 30 ± 14 mm Hg measured in nonsurvivors (p es 0.04*). Indeed, no patient with an LVEDP greater than 26 mm Hg survived the operation. Endocardial fibroelastosis. The presence of echocardial fibroelastosis was determined from preoperative echocardiography in survivors and was also corroborated by autopsy findings in nonsurvivors. Endocardial fibroelastosis was detected in only 25% of survivors but was present in all patients who died (p zs 0.01*). Factors perhaps affecting survival (Table I) Age. The mean age of survivors (38 ± 52 days) was not significantly greater than the much younger age of
A
B
1cm
I
Fig. 2. Anteroposterior (A) and lateral (B) tracings of ejection fraction of patient in Fig. I. Outer tracing represents end-diastolic left ventricular cavity and inner tracing shows end-systolic dimension. Striped area shows ejection fraction.
nonsurvivors (5 ± 8 days) owing to the wide variation in ages of the survivors. Nevertheless, only six of 19 survivors (32%) were less than 2 weeks of age, with four being operated on during the first day of life. Among the nine patients undergoing operation in the first 2 weeks of life, the mortality was 33%; the mortality for operation in the first day of life was 43%. Factors not affecting survival (Table I)
* Although these individual t tests indicate significant differences between survivors and nonsurvivors, the Bonferroni experimentwise comparison does not confirm the significance of these differences. Increasing the sample size through further experience might allow significant differences to be demonstrated with more certainty.
Peak systolic gradient. There was no difference between the peak systolic gradient of 79 ± 30 mm Hg in survivors and 60 ± 15 mm Hg measured in nonsurvivors. Ventricular volumes. Left ventricular volumes were
The Journal of Thoracic and Cardiovascular Surgery
7 5 0 Gundry and Behrendt
Fig. 3. Preoperative anteroposterior views of cineangiograms during left ventricular end-diastole (A) and end-systole (B) showing very poor ventricular ejection fraction and dilated left ventricular cavity in a survivor.
indexed for body surface area and expressed as cubic centimeters per square meter. There was no difference in the calculated end-diastolic volume index (LVEDVI) of 37 ± 17 cm3/m2 in survivors and 36 ± 7 cm3/m2 calculated in nonsurvivors. Moreover, four patients with LVEDIs ofless than 26 cm3/m2 survived, including one patient with an LVEDI of 20 cm3/m2. There was no statistical difference between the ventricular volumes of those patients less than 2 weeks old and those older than 2 weeks (30 ± 8 versus 43 ± 21 cm3/m2, respectively). There was also no difference between the end-systolic volume index (LVESVI) in survivors and nonsurvivors (17 ± 13 versus 19 ± 5 cm3/m2, respectively) or the left ventricular stroke volume index (LVSVI) (20 ± 10 versus 16 ± 3 cm3/m2, respectively). Valve type. Ten bicuspid and nine tricuspid valves were identified in survivors at operation, with six of these valves showing dysplastic changes and three, frank doming of the valve. This ratio was not different from that of the two bicuspid and two tricuspid valves found in the nonsurvivors, although all nonsurvivors had dysplastic valves. Age-weighted analysis
Fig. 3. Cont'd. Anteroposterior viewsof cineangiograms during left ventricular end-diastole (C) and end-systole (D) in same patient as in Fig. 3, A and B, 3 years postoperatively. Note marked increase in ventricular size and ejection fraction.
All nonsurvivors were 3 weeks of age or less. To avoid comparing the results of more healthy children who were operated on later in infancy, we also compared only those children 3 weeks of age or less. There were 13 total patients in this group, including nine survivors and four nonsurvivors (31% mortality). Ejection fraction of survivors was 56% ± 3% versus 36% ± 12% in nonsurvivors (p es 0.06). LVEDP in survivors was 18 ± 6 mm Hg versus 30 ± 14 in nonsurvivors (':::;0.04), similar differences to those for the groups as a whole. No other
Volume 92 Number 4
Critical aortic stenosis
October 1986
Table Il, Follow-up changes (n = 9)
751
A LVSVI (cmJ/nr)
Preop. Postop, p Values
45 ± 10
70 ± 11 p
< 0.05
37 ± 17 58 ± 10
NS
20 ± 10 40 ± 6
NS
Legend: None of these is significantly different by the Bonferroni experimentalwise approach, which for four comparisons must be p < 1.25% to obtain siginficance. For abbreviations see Table I.
significant differences were found between these younger infants. Oxygen saturations. The preoperative aortic oxygen saturation of 89% ± 16% in the survivors did not differ significantly from the 75% ± 30% saturation measured in nonsurvivors. There was no significant difference in the superior vena caval saturation of 61% ± 16% in survivors versus 45% ± 16% in nonsurvivors. Clamp time. There was no difference between the aortic clamp time of 13 ± 2 minutes in survivors and 15 ± 3 minutes in nonsurvivors. Cardioplegia. Cardioplegia was used in 62% of survivors versus only 25% of nonsurvivors; the difference did not reach statistical significance. Associated lesions. Four of 19 survivors had associated mitral regurgitation and an additional four had mitral stenosis (21% each). One patient had mitral regurgitation (25%) and two patients had mitral stenosis (50%) among nonsurvivors. Twenty-five percent of patients in each group had left-to-right shunts at the atrial level. Three surviving patients had an associated coarctation of the aorta, as compared to one nonsurvivor. Two patients who initially survived operation had Shone's complex of aortic stenosis, mitral stenosis, and coarctation." Both died in the late postoperative period, one of mediastinitis and the other after mitral valve replacement and placement of an apical-aortic shunt. Follow-up (Table II) Seventeen patients have been followed up for 3.4 ± 2 years (range 6 months to 7 years). Fifty percent have residual evidence of left ventricular hypertrophy by voltage criteria on electrocardiogram but none has a strain pattern. Four patients have mild to moderate aortic regurgitation as judged by the presence of a diastolic murmur on physical examination. Nine patients have undergone one or more postoperative catheterizations. We compared the preoperative and postoperative catheterization data to determine the efficacy of valvotomy. Peak systolic gradient. The mean postoperative gradient was 25 ± 21 mm Hg with only two patients
9/28/83
Fig. 4. Anteroposterior tracing of ejection fraction of patient in Fig. 3, before (A) and 3 years after operation (B). Outer tracing represents end-diastolic left ventricular cavity contour and inner tracing shows end-systolic dimension. Striped area shows ejection fraction. Note excellent return of ventricular size' and function, Lateral tracings of ejection fraction of patient in Fig 3, before (C) and after operation (D). Outer tracing represents end-diastolic left ventricular cavity and inner tracing shows end-systolic dimension. Striped area shows ejection fraction. Note marked increase in ejection fraction,
having a gradient over 25 mm Hg, both 70 mm Hg. Both of these patients had complex left ventricular outflow tract obstruction and both patients underwent placement of apical-aortic conduits. Ejection fractions. The ejection fractions of the nine patients recatheterized increased from 45% ± 10% preoperatively to 70% ± 11 % (p:s 0.05) postoperatively (Figs. 3 and 4). Ventricular volumes. The LVEDVls of patients increased to 58 ± 5 from 37 ± 17 cm3jm2 and the LVSVls increased to 40 ± 6 from 20 ± 10 cm3jm2, both well within the normal range for age." 13, 14 These results indicate that these hypertrophied, depressed ventricles are capable of returning to normal function after relief of outlet obstruction (Figs. 3 and 4). Discussion The results of operation for congenital aortic stenosis in infancy have been generally dismal, with mortalities ranging from 25% to 79%.1-11,15 The present report and that of Messina and associates 10 demonstrate that congenital aortic stenosis in neonates can be corrected
The Journal of
7 5 2 Gundry and Behrendt
with an acceptable operative mortality and good longterm results. Although all but one of Messina's patients had normal left ventricular volumes, it is generally believed that these patients usually have ventricular volumes below normal. 1,2.5.14 The normal ventricular volumes for children under the age of 2 years are as high as 71 ± 8 cm' Im2.13.14 However, the LVEDVI of our patients was 37 ± 17 cm3/m2, which supports this belief. Hammon and colleagues' have suggested that survival is unlikely in patients with an LVEDVI below 60% of normal, a value that would approximate 25 cm3/m2, and Keane, Norwood, and Bernhard I had no survivors in their patients with LVEDVI below 20 cm 3/m2. We found no relation between ventricular volume and survival. Although no patient in our series had an LVEDVI below 20 cm 3/m2, four survivors and an LVEDVI below 25 cm 3/m2. It would thus appear that within limits a small ventricle does not preclude a successful operation. However, when the ventricular volume is less than 20 cm 3/m2, the patient might better be treated for a hypoplastic left heart syndrome and undergo a Norwood
procedure.i" All authors, including us, have noted a higher mortality in the first month of life, and particularly in the first week of life. Norwood has attributed this to small ventricular volume, but this has not been our observation. Indeed, although three fourths of our deaths occurred in neonates, all three had ventricular volumes above 35 cm3/m2. Others have associated dysplastic valves with the higher mortality of the neonate.v? We could make no such correlation in our series. The young infant is much more likely to have endocardial fibroelastosis than the older patient. This has been attributed to severe intrauterine left ventricular ischemia by some authors and is definitely a major determinate of operative survival.3.4. II In our series endocardial fibroelastosis, while not precluding survival (50% mortality), was a good predictor of a high operative mortality. The role of other associated abnormalities in increasing surgical mortality is not clear. Several groups have reported a high mortality for aortic valvotomy associated with other anomalies. 1·4. 7.10 We found a high incidence of associated anomalies with aortic stenosis, but these did not affect survival. Mitral regurgitation in these patients is often secondary to left ventricular dysfunction and can improve after successful aortic valvotomy. However, patients with Shone's syndrome are particularly troublesome because the serial lesions of coarctation, aortic stenosis, and mitral stenosis may not be ultimately correctable. The influence of operative technique upon survival is
Thoracic and Cardiovascular Surgery
likewise not clear. In the present series, conventional cardiopulmonary bypass was used successfully. The advantage of such a technique is that an unhurried valvotomy can be performed. Regardless of the operative technique used, we consider it essential to provide an adequate aortic valve opening without producing insufficiency, comrnissures being incised to, but not into, the aortic anulus. The good long-term results we have obtained support the logic of this method. Recently, Sink and colleagues I I have reported an operative mortality of 25% with inflow inclusion and open valvotomy in a small series of infants under 7 months of age, and even closed techniques performed with dilators or balloon catheters have been used. NI three techniques are associated with variable oprative mortalities, high postoperative gradients, and aortic regurgitation. I I. 16. 17 Another advantage of techniques involving cardiopulmonary bypass is that the metabolic abnormalities associated with poor perfusion are corrected during the procedure, so that survival is more likely. Messina and colleagues'? have suggested that a cold blood prime and short cross-clamp time are important in this regard. Because our perfusion technique differs somewhat from theirs, it would appear that excellent results can be obtained by several approaches. Our technique has yielded excellent functional postoperative results, with only three patients having aortic valve gradients greater than 25 mm Hg, two of whom have complex left ventricular outflow obstruction below the valve. Particularly gratifying has been the excellent postoperative recovery of ventricular function, even in severely depressed ventricles (Figs. 3 and 4). Ejection fractions and ventricular volumes have returned to normal values after the operation.
Conclusions These results suggest that many critically ill infants with aortic stenosis can survive operation, at least when their ventricular volume exceeds 20 em' 1m2. We have been unable to detect absolute contra indications to operation, although patients with low ejection fractions and high LVEDPs have a lower probability of surviving. A very young age and the presence of endocardial fibroelastosis are unfavorable signs but do not preclude operation. The use of an open technique with cardiopulmonary bypass is recommended because it allows a precise repair to be performed. Only a few patients have significant residual gradients or aortic insufficiency. Long-term results have been excellent, with documented growth in ventricular volume and recovery of ventricular function to normal levels.
Volume 92 Number 4 October 1986
We thank Mr. John Palmisano for his assistance in analyzing the ventriculograms and Dr. Anthony Schork for his assistance in the statistical analysis. REFERENCES Keane JF, Norwood WI, Bernhard WF: Surgery for aortic stenosis in infancy. Circulation 68:Suppl 3:182, 1983 2 Hammon JW, Parrish MD, Graham TP, Boucek RJ, Bender HW: Risk factors for infants undergoing aortic valvotomy for critical aortic valvar stenosis. J Am Coli Cardiol (in press) 3 Sandor GGS, Olley PM, Trusler GA, Williams WG, Rowe RD, Morch JE: Long-term-follow-up of patients after valvotomy for congenital valvular aortic stenosis in children. J THORAC CARDIOVASC SURG 80:171-176, 1980 4 Lakier 18, Lewis AB, Heymann MA, Stanges P, Hoffman JIE, Rudolph AM: Isolated aortic stenoses in the neonate. Natural history and hemodynamic consideration. Circulation 50:801-808, 1974 5 Edmunds LH, Wagner HR, Heymann WA: Aortic valvulotomy in neonates. Circulation 61:421-427, 1980 6 Chiariello L, Agosti J, Vlad P, Subramanian S: Congenital aortic stenosis. Experience with 43 patients. J THoRAc CARDIOVASC SURG 72:182-193, 1976 7 Keane JF, Bernhad WF, Nadas AS: Aortic stenosis surgery in infancy. Circulation 52:1138-1143, 1975 8 Cooley DA, Beall AC, Hallman GL, Bricker DL: Obstructive lesions of the left ventricular outflow tract. Surgical treatment. Circulation 31:612-621, 1965 9 Dobell ARC, Bloss RS, Gibbons JE, Collins GF: Congenital valvular aortic stenosis. Surgical management and long-term results. J THoRAc CARDIOVASC SURG 81:916920, 1981. 10 Messina LM, Turley K, Stanger P, Hoffman JIE, Ebert PA: Successful aortic valvotomy for severe congenital valvular aortic stenosis in the newborn infant. J THORAC CARDIOVASC SURG 88:92-96, 1984 II Sink JD, Smallhorn JF, Macartney FJ, Taylor JFN, Stark J, de Leval MR: Management of critical aortic stenosis in infancy. J THoRAc CARDIOVASC SURG 87:82-86, 1984 12 Shone JD, Sellers RD, Anderson RC: The developmental complex of left atrium and subarotic stenosis and coarctation of the aorta. Am J Cardiol 11:714-725, 1963 13 Silverman NH, Ports TA, Snider AR, Schiller NB, Carlsson E, Heilbron DC: Determination of left ventricular volume in children. Echocardiographic and angiographic comparison. Circulation 62:548-557, 1980 14 Graham TP, Lewis BW, Jarmakani MM, Canent RV, Capp MP: Left heart volume and mass quantification in children with left ventricular pressure overload. Circulation 41:203-212,1970 15 Norwood WI, Lang P, Hansen D: Physiologic repair of aortic atresia-hypoplastic left heart syndrome. N Engl J Med 308:23-26, 1983 16 Trinkle JK, Norton 18, Richardson JD, Grover FL, Noonan JA: Closed aortic valvotomy and simultaneous
Critical aortic stenosis
753
correction of associated anomalies in infants. J THoRAc CARDIOVASC SURG 69:758-762, 1975 . 17 Brown JW, Robinson RJ, Waller BF: Transventricular balloon catheter aortic valvotomy in neonates. Ann Thorac Surg 39:376-378, 1985
Discussion DR. KEVIN TURLEY San Francisco. Calif
I agree with many of the points made by the authors. The points worth stressing are those concerning the use of a precise aortic valvulotomy to maximize the orifice of the aortic valve without producing aortic insufficiency and the use of cardiopulmonary bypass to correct the metabolic abnormalities that are present. Specific to the paper, this lesion had a very high mortality, 50% to 80%, 10 to 15 years ago. However, now this mortality has been reduced significantly and the statistical factors thought to be of importance have concurrently diminished. The multiple factors we used to think were important, such as gradient, ventricular volumes, and the type of valve, have lost significance, as these authors have reported. Now only a few things are noted, such as LVEDP, ejection fraction, and age. This is typical of the successful therapy of any lesion. With a high mortality almost all factors may appear to significantly alter survival in a small patient population, yet as mortality decreases these risk factors "drop out." During the period 1976 to 1985, 92 aortic valvotomies were performed at the University of California, San Francisco. Thirty-two of these patients were less than 6 months of age, the age group discussed in this paper. Thirteen of them were older than I month of age but younger than 6 months of age; seven were older than I week but younger than I month of age; and 12 were younger than I week of age. A number of hemodynamic factors were noted in these patients: mitral regurgitation, pulmonary hypertension, and elevation of the LVEDP and the ejection fraction. Of the 13 patients in the first group, older than I month but less than 6 months, none had mitral regurgitation, none had pulmonary hypertension, only two had an elevation of the LVEDP, and the mean ejection fraction was 62%. Of the seven patients younger than I month but older than I week, two had mitral regurgitation, four pulmonary hypertension, four an elevation of the LVEDP, and the mean ejection fraction was decreased to 46%. Of the 12 patients less than I week, seven had mitral regurgitation, nine had pulmonary hypertension, 10 had an elevation of the LVEDP, and the mean ejection fraction was 38%. Notice that these problems are common in the neonatal group, with a mean ejection fraction of 38% in the 13 patients younger than 7 days of age. These findings suggest that we are really looking at two separate manifestations of a single disease: The older patients, those younger than 6 months but older than I month, have symptoms similar to those of patients older than 6 months of age. In the neonatal group, a high incidence of mitral regurgitation, pulmonary hypertension, and left ventricular failure is evident. The middle groups, those younger than I month but older than 1 week, are a crossover
The Journal of Thoracic and Cardiovascular Surgery
7 5 4 Gundry and Behrendt
group, with individuals having manifestations of each of the other two groups. Further, when associated lesions were reviewed, all were present in the youngest group « 1 week), with coarctation present in three patients. Thus the age at presentation, which the authors note had a significant effect on outcome, may relate to the difference in both the severity of the disease and the associated lesions at presentation. We differ with the authors on one critical factor, that of perfusion technique. Ventricular fibrillation developed at induction in four of the 19 neonates, those younger than I month of age. However, none of these patients died in the immediate postoperative period, one death occurring 3 days postoperatively in a patient who had an unrecognized coarctation of the aorta and the other at 4 days in a patient with hypoplasia of the ascending aorta, left ventricle, and mitral valve. Overall survival rate in this series was 94% (30/32), with none of the patients older than 1 month of age dying. A 91% survival rate was noted in those less than I week of age. We believe that early diagnosis and the diagnosis of associated lesions is obviously critical. Emergency operation with the institution of cardiopulmonary bypass and myocardial protection is likewise critical. Again, an open, precise valvotomy optimizes results. I have several questions for the authors. The first concerns myocardial and total body protection. Do they believe that conventional cardiopulmonary bypass with slow cooling optimally produces such effects and would patients who have ventricular fibrillation during induction of anesthesia or opening of the chest benefit from the cold perfusate prime that we advocate? Second, in the manuscript they discussed low left ventricular volumes and directly addressed this question. A. higher risk may be attenant to patients with less than 20 cm'/m 2 area. I would ask whether the patients with diminutive ventricular volumes also have a diminutive aortic valve and whether they should be considered to have aortic valve stenosis or the hypoplastic left heart syndrome. Finally, there are the questions of distribution of secondary manifestations and associated lesions by age. Have you investigated this factor in your patient group and are your findings consistent with our observation that, in fact, there are two separate presentations of a single pathologic entity? Might those with the neonatal form be considered separately from those with the juvenile form?
DR. ERNST-RAINER
DE
VIVIE
Goettingen, Federal Republic of Germany
I want to discuss two points. In Goettingen in 1984 we began using balloon valvuloplasty instead of commissurotomy in cirtical aortic stenosis in infancy. Our cardiologist, Dr. G. Rupprath, has successfully performed valvuloplasty in four infants (aged from I to 6 weeks) and achieved a reduction of the pressure gradient from the left ventricle to the aorta of more than 50% without major complications. These data were recently published in The American Journal of Cardiology (June, 1985). If the left ventricle cannot be entered in retrograde fashion using the balloon catheter, it is also possible to perform a closed commissurotomy through a left thoracot-
omy. A vascular dilator or a balloon catheter is advanced from the apex of the left ventricle through the stenotic valve. The second point is that I do not agree with the long-term results reported by Dr. Gundry. In our series of patients with critical aortic stenosis, with a long-term follow-upof more than 20 years, the diagnosis was made by heart catheterization in 31 infants. Eight died before operation, and 20 were operated on by commissurotomy with extracorporeal circulation. Twenty percent (n = 4) of these died postoperatively. Three required reoperation after 10 to 13 years, and in these children it was necessary to widen the small aortic anulus and to resect the dysplastic valve. We used the technique of aortoventriculoplasty to enlarge the left ventricular outflow tract and inserted an adult-sized mechanical valve.
DR. GUNDRY (Closing) I would like to thank both of the discussants for their comments. As I mentioned, since 1982 we have only had one death in the last 11 patients, and that occurred in a child who develoepd fibrillation in the operating room and could not be weaned from bypass. That result compares favorably with what Drs. Turley and Ebert reported recently in their last II patients. We do think that conventional cardiopulmonary bypass, while differing somewhat from Dr. Turley's techniques, appears to be giving good results in our hands. We see no indication to change. We have found that when we used a hypothermic perfusate in an attempt to try this method, our core temperatures were not as cold as we would like during the procedure. The heart often fibrillated quite early, even before we were ready to apply the cross-clamp. However, good results can be achieved with either method. We agree with Dr. Turley that cardiopulmonary bypass is the method of choice for aortic valvotomy for several different reasons. First, as Dr. Turley suggested, we believe it is critical to correct the metabolic abnormalities that all these children have when they arrive in the operating room. This allows a leisurely period for the heart to recover from the insult. Second, we also agree that, particularly early in infancy, it is critical to obtain a maximum opening of the aortic valve without producing aortic insufficiency. Although long-term follow-up has shown that many of these children will eventually need reoperation, we believe that by opening the valve wide we can delay that initial reoperation and perhaps lessen the number of subsequent operations these children will have. That is why we and others do not recommend balloon dilatation. There are, of course, advantages to balloon dilatation. It is quick and it is easy. If it is performed through a left thoracotomy, associated lesions such as coarctation of the aorta can also be attacked. However, balloon dilatation does not allow adequate control in opening the aortic valve. Several series have come back with short-term results of fairly severe aortic insufficiency or severe residual gradients that then necessitate an operation with valve replacement early in the child's life. We belive that balloon dilatation is not the best way to go, because of these problems.
THoRAc CARDIOVASC SURG
92:747-754,1986
Prognostic factors in valvotomy for critical aortic stenosis in infancy Aortic valvotomy for critical aortic stenosis in infancy has had a high mortality. To determine the factors that influence survival, we reviewed the cases of 24 infants who underwent aortic valvotomy in the first 6 months of life (mean 41/ 2 weeks) for aortic stenosis from 1978 to 1984. Cardiopulmonary bypass was used in all patients. Operative mortality was 21 % (5/24), four of the five deaths occurring from low cardiac output. Analysis of preoperative factors affecting survival versus nonsurvival revealed that low ejection fraction (60 % ± 17 % in survivors versus 36 % ± 2 % in nonsurvivors), high left ventricular end-diastolic pressure (16 ± 7 mm Hg in survivors versus 30 ± 14 mm Hg in nonsurvivors), and presence of endocardial fibroelastosis (25% in survivors versus 100% in nonsurvivors) aU were predictive of a poor outcome, although the small sample size indicated caution in interpreting results. Factors that did not appear to influence survival included peak systolic gradient (79 ± 30 mm Hg in survivors versus 60 ± 15 mm Hg in nonsurvivors) and left ventricular end-diastolic volume (37 ± 17 cm3/m2 in survivors versus 36 ± 7 cm3/m2 in nonsumvors), Four patients with a left ventricular end-diastolic volume below 26 cm3/m2 survived. Postoperative gradients averaged 25 ± 21 mm Hg at 3.4 ± 2 years' foUow-up in nine recatheterized patients. Ejection fraction of these patients increased from 45 % ± 10% to 70 % ± 11 % and left ventricular end-diastolic volume increased from 37 ± 17 to 58 ± 5 cm3/m2• Two of 17 patients have required apical-aortic conduits; aU other patients are asymptomatic. We conclude that infants with critical aortic stenosis benefit from valvotomy even with impaired left ventricular function and severely reduced left ventricular dimensions and many have nearly normal hemodynamics on late foUow-up.
Steven R. Gundry, M.D., and Douglas M. Behrendt, M.D., Ann Arbor, Mich.
Until recently, operation for congenital valvular aortic stenosis early in infancy has resulted in high mortality rates in most series."? Recent reports from Messina, 10 Sink,II and their colleagues have demonstrated that good results can be achieved with this lesion, and they and others have speculated on the anatomic, physiologic, and operative factors that might contribute to a successful outcome. These recent reports prompted us to review our own experience with operation for critical aortic stenosisin infants under 6 months of age, with particular emphasis on those less than 1 month old.
From the Section of Thoracic Surgery, Department of Surgery, University of Michigan Hospitals, Ann Arbor, Mich. Read at the Eleventh Annual Meeting of The Western Thoracic Surgical Association, Incline Village, Nev., June 16-20, 1985. Address for reprints: Douglas M. Behrendt, M.D., Professor of Surgery, Section of Thoracic Surgery, Room 2110, Box 344, Taubman Health Care Center, Ann Arbor, Mich. 48109.
Patient population and methods
The records of 24 infants (15 boys and nine girls) aged 1 to 180 days (mean 1 month) who underwent aortic valvotomy in the first 6 months of life at the C. S. Mott Children's Hospital, University of Michigan Medical Center, from Jan. 1, 1978, to Oct. 30, 1984, were reviewed. Nineteen infants (80%) were less than 1 month old at operation, and nine (38%) were operated on within the first 3 days of life. All patients had profound congestive heart failure. All underwent emergency cardiac catheterization and, whenever feasible, M-mode and two-dimensional echocardiography. Cardiac catheterization data were available on all patients, and left ventricular cineangiography was available on 18 patients. Ejection fractions and end-diastolic, end-systolic, and stroke volumes were calculated by the Dodge area-length method. Associated intracardiac or extracardiac anomalies as determined by catheterization, physical examination, or operation did not affect inclusion of the patient in this review. 747
The Journal of Thoracic and Cardiovascular
7 4 8 Gundry and Behrendt
Surgery
Table I. Factors potentially affecting survival" (n = 24)
EF(%)
LVEDP (mm Hg)
EFE (%)
SUrvIVOrs 60 ± 17 16 ± 7 25 Nonsurvivors 36 ± 12 30 ± 14 100 Individual] p s O.03t p S 0.04t p s om t test p value
Age (days)
38 ± 52 5± 8 p 2: 0.05t
PSG L VED VI LVESVI (mmHg) (cmJjm2) (cmJjm2)
79 ± 30 60 ± 15 NSt
37 ± 17 I7 ± I3 36 ± 7 19 ± 5 NSt NSt
Valve type
Arterial O2 sat. SVC sat. Clamp time (%) (%) (min)
IOB/9T 89 ± 16 61 ± 16 2B/2T 75 ± 30 45 ± 16 NSt NSt NSt
13 ± 2 15 ± 3 NSt
Legend' EF. Ejection fraction. LVEDP. Left ventricular end-diastolic pressure. EFE. Endocardial fibroelastosis. PSG, Peak dystolic gradient. LVEDVI, Left ventricular end-diastolic volume index. LVESVI, Left ventricular end-systolic volume index. SVC, Superior vena cava. B, Bicuspid. T, Tricuspid. NS, Not significant. • All values are expressed as mean ± standard deviation. tNone of these comparisons is significant at the 5% level using the Bonferroni experimentwise approach because of small sample size. tNone of these comparisons is significant at either the test p value of 5% or the experimentwise 5%.
Operative technique. All patients underwent emergency operation after catheterization. After general endotracheal anesthesia and median sternotomy, cardiopulmonary bypass was instituted via single atrial and ascending aortic cannulas. Surface cooling was used in only five of 24 patients, After systemic cooling to at least 20° C, the aorta was cross-clamped and the ascending aorta opened, The fused aortic valve commissures were incised to, but not into, the anulus. The aorta was then closed with running polypropylene suture and the crossclamp removed after 13 ± 2 minutes. The patients were rewarmed and weaned from cardiopulmonary bypass. Follow-up. Follow-up was available on all patients, Examinations were performed by pediatric cardiologists of the C. S, Mott Children's Hospital. Cardiac catheterization was performed on nine patients for persistent left ventricular hypertrophy by electrocardiogram, a loud murmur and physical signs of aortic insufficiency, or a suspected large residual gradient by Doppler echocardiography. Analysis of data. The data obtained in the survivors were compared to those in nonsurvivors, and the postoperative results were analyzed to determine if prognostic factors could be identified that influenced survival. All directly recorded and derived measurements were compared for statistical significance by either the chi square or Student's paired or unpaired t tests. Results were deemed statistically significant if p was less than 5%. Because of the preliminary nature of these findings (small samples), significances were noted in two ways: Each comparison was assessed as an individual test and, because of the number of comparisons for the same subjects, a more conservative Bonferroni experimentwise a-error was also used. For the eleven comparisons, which assessed factors possibly affecting survival (Table I), the experimentwise a-error was 0.45% (5%/11). Thus an individual comparison would
be significant at the 5% experimentwise level, if its individual test significance attained a p value of 0.0045 or less. Results Two of the 24 patients died in the operating room. One died of a technical error and the second could not be weaned from cardiopulmonary bypass. Three patients died 1 to 14 days postoperatively of the sequelae of preoperative or postoperative low cardiac output; thus the perioperative death rate was 21%. There has been only one death in the last 11 patients operated on since 1982, representing a mortality of 9%. This single death occurred in a newborn infant with severe endocardial fibroelastosis in whom fibrillation developed upon induction of anesthesia. The infant was not weaned from bypass. For the purpose of comparing prognostic factors affecting initial survival, the patient dying as a result of the technical error was excluded from subsequent analysis. Thus 19 survivors were compared with four nonsurvivors. There were two late deaths. One child died of mediastinitis 4 months postoperatively and the second died 3 months after the initial valvotomy after placement of a left ventricular apical-aortic conduit and mitral valve replacement for severe left ventricular outflow tract obstruction and mitral insufficiency. Long-term follow-up is available on 17 patients who have been observed from 6 months to 7 years (mean 3.4 ± 2 years) after valvotomy. No patient has symptoms of congestive heart failure, chest pain, or easy fatigability. Only one other patient has required reoperation, again for placement of an apical-aortic conduit 14 months after the initial valvotomy. That patient has been followed up for 19 additional months postoperatively and is currently asymptomatic.
Volume 92 Number 4 October 1986
Critical aortic stenosis
749
Fig. 1. Preoperative anteroposterior views of cineangiograms during left ventricular end-diastole (A) and end-systole (B) showing small globular ventricular cavity characteristic of endocardial fibrolastosis. This infant did not survive.
Factors affecting survival (Table I) Ejection fraction. The ejection fraction of survivors, 60% ± 17%, was significantly greater than the 36% ± 12% ejection fraction of nonsurvivors (p ::; 0.03*). Nevertheless, more than half of the survivors had depressed ejection fractions of less than 50%. No patient with an ejection fraction of less than 42% survived operation (Figs. 1, 2, 3, and 4, A and C). Left ventricular end-diastolic pressure. The left ventricular end-diastolic pressure (L VEDP) of 16 ± 7 mm Hg in survivors was significantly lower than the LVEDP of 30 ± 14 mm Hg measured in nonsurvivors (p es 0.04*). Indeed, no patient with an LVEDP greater than 26 mm Hg survived the operation. Endocardial fibroelastosis. The presence of echocardial fibroelastosis was determined from preoperative echocardiography in survivors and was also corroborated by autopsy findings in nonsurvivors. Endocardial fibroelastosis was detected in only 25% of survivors but was present in all patients who died (p zs 0.01*). Factors perhaps affecting survival (Table I) Age. The mean age of survivors (38 ± 52 days) was not significantly greater than the much younger age of
A
B
1cm
I
Fig. 2. Anteroposterior (A) and lateral (B) tracings of ejection fraction of patient in Fig. I. Outer tracing represents end-diastolic left ventricular cavity and inner tracing shows end-systolic dimension. Striped area shows ejection fraction.
nonsurvivors (5 ± 8 days) owing to the wide variation in ages of the survivors. Nevertheless, only six of 19 survivors (32%) were less than 2 weeks of age, with four being operated on during the first day of life. Among the nine patients undergoing operation in the first 2 weeks of life, the mortality was 33%; the mortality for operation in the first day of life was 43%. Factors not affecting survival (Table I)
* Although these individual t tests indicate significant differences between survivors and nonsurvivors, the Bonferroni experimentwise comparison does not confirm the significance of these differences. Increasing the sample size through further experience might allow significant differences to be demonstrated with more certainty.
Peak systolic gradient. There was no difference between the peak systolic gradient of 79 ± 30 mm Hg in survivors and 60 ± 15 mm Hg measured in nonsurvivors. Ventricular volumes. Left ventricular volumes were
The Journal of Thoracic and Cardiovascular Surgery
7 5 0 Gundry and Behrendt
Fig. 3. Preoperative anteroposterior views of cineangiograms during left ventricular end-diastole (A) and end-systole (B) showing very poor ventricular ejection fraction and dilated left ventricular cavity in a survivor.
indexed for body surface area and expressed as cubic centimeters per square meter. There was no difference in the calculated end-diastolic volume index (LVEDVI) of 37 ± 17 cm3/m2 in survivors and 36 ± 7 cm3/m2 calculated in nonsurvivors. Moreover, four patients with LVEDIs ofless than 26 cm3/m2 survived, including one patient with an LVEDI of 20 cm3/m2. There was no statistical difference between the ventricular volumes of those patients less than 2 weeks old and those older than 2 weeks (30 ± 8 versus 43 ± 21 cm3/m2, respectively). There was also no difference between the end-systolic volume index (LVESVI) in survivors and nonsurvivors (17 ± 13 versus 19 ± 5 cm3/m2, respectively) or the left ventricular stroke volume index (LVSVI) (20 ± 10 versus 16 ± 3 cm3/m2, respectively). Valve type. Ten bicuspid and nine tricuspid valves were identified in survivors at operation, with six of these valves showing dysplastic changes and three, frank doming of the valve. This ratio was not different from that of the two bicuspid and two tricuspid valves found in the nonsurvivors, although all nonsurvivors had dysplastic valves. Age-weighted analysis
Fig. 3. Cont'd. Anteroposterior viewsof cineangiograms during left ventricular end-diastole (C) and end-systole (D) in same patient as in Fig. 3, A and B, 3 years postoperatively. Note marked increase in ventricular size and ejection fraction.
All nonsurvivors were 3 weeks of age or less. To avoid comparing the results of more healthy children who were operated on later in infancy, we also compared only those children 3 weeks of age or less. There were 13 total patients in this group, including nine survivors and four nonsurvivors (31% mortality). Ejection fraction of survivors was 56% ± 3% versus 36% ± 12% in nonsurvivors (p es 0.06). LVEDP in survivors was 18 ± 6 mm Hg versus 30 ± 14 in nonsurvivors (':::;0.04), similar differences to those for the groups as a whole. No other
Volume 92 Number 4
Critical aortic stenosis
October 1986
Table Il, Follow-up changes (n = 9)
751
A LVSVI (cmJ/nr)
Preop. Postop, p Values
45 ± 10
70 ± 11 p
< 0.05
37 ± 17 58 ± 10
NS
20 ± 10 40 ± 6
NS
Legend: None of these is significantly different by the Bonferroni experimentalwise approach, which for four comparisons must be p < 1.25% to obtain siginficance. For abbreviations see Table I.
significant differences were found between these younger infants. Oxygen saturations. The preoperative aortic oxygen saturation of 89% ± 16% in the survivors did not differ significantly from the 75% ± 30% saturation measured in nonsurvivors. There was no significant difference in the superior vena caval saturation of 61% ± 16% in survivors versus 45% ± 16% in nonsurvivors. Clamp time. There was no difference between the aortic clamp time of 13 ± 2 minutes in survivors and 15 ± 3 minutes in nonsurvivors. Cardioplegia. Cardioplegia was used in 62% of survivors versus only 25% of nonsurvivors; the difference did not reach statistical significance. Associated lesions. Four of 19 survivors had associated mitral regurgitation and an additional four had mitral stenosis (21% each). One patient had mitral regurgitation (25%) and two patients had mitral stenosis (50%) among nonsurvivors. Twenty-five percent of patients in each group had left-to-right shunts at the atrial level. Three surviving patients had an associated coarctation of the aorta, as compared to one nonsurvivor. Two patients who initially survived operation had Shone's complex of aortic stenosis, mitral stenosis, and coarctation." Both died in the late postoperative period, one of mediastinitis and the other after mitral valve replacement and placement of an apical-aortic shunt. Follow-up (Table II) Seventeen patients have been followed up for 3.4 ± 2 years (range 6 months to 7 years). Fifty percent have residual evidence of left ventricular hypertrophy by voltage criteria on electrocardiogram but none has a strain pattern. Four patients have mild to moderate aortic regurgitation as judged by the presence of a diastolic murmur on physical examination. Nine patients have undergone one or more postoperative catheterizations. We compared the preoperative and postoperative catheterization data to determine the efficacy of valvotomy. Peak systolic gradient. The mean postoperative gradient was 25 ± 21 mm Hg with only two patients
9/28/83
Fig. 4. Anteroposterior tracing of ejection fraction of patient in Fig. 3, before (A) and 3 years after operation (B). Outer tracing represents end-diastolic left ventricular cavity contour and inner tracing shows end-systolic dimension. Striped area shows ejection fraction. Note excellent return of ventricular size' and function, Lateral tracings of ejection fraction of patient in Fig 3, before (C) and after operation (D). Outer tracing represents end-diastolic left ventricular cavity and inner tracing shows end-systolic dimension. Striped area shows ejection fraction. Note marked increase in ejection fraction,
having a gradient over 25 mm Hg, both 70 mm Hg. Both of these patients had complex left ventricular outflow tract obstruction and both patients underwent placement of apical-aortic conduits. Ejection fractions. The ejection fractions of the nine patients recatheterized increased from 45% ± 10% preoperatively to 70% ± 11 % (p:s 0.05) postoperatively (Figs. 3 and 4). Ventricular volumes. The LVEDVls of patients increased to 58 ± 5 from 37 ± 17 cm3jm2 and the LVSVls increased to 40 ± 6 from 20 ± 10 cm3jm2, both well within the normal range for age." 13, 14 These results indicate that these hypertrophied, depressed ventricles are capable of returning to normal function after relief of outlet obstruction (Figs. 3 and 4). Discussion The results of operation for congenital aortic stenosis in infancy have been generally dismal, with mortalities ranging from 25% to 79%.1-11,15 The present report and that of Messina and associates 10 demonstrate that congenital aortic stenosis in neonates can be corrected
The Journal of
7 5 2 Gundry and Behrendt
with an acceptable operative mortality and good longterm results. Although all but one of Messina's patients had normal left ventricular volumes, it is generally believed that these patients usually have ventricular volumes below normal. 1,2.5.14 The normal ventricular volumes for children under the age of 2 years are as high as 71 ± 8 cm' Im2.13.14 However, the LVEDVI of our patients was 37 ± 17 cm3/m2, which supports this belief. Hammon and colleagues' have suggested that survival is unlikely in patients with an LVEDVI below 60% of normal, a value that would approximate 25 cm3/m2, and Keane, Norwood, and Bernhard I had no survivors in their patients with LVEDVI below 20 cm 3/m2. We found no relation between ventricular volume and survival. Although no patient in our series had an LVEDVI below 20 cm 3/m2, four survivors and an LVEDVI below 25 cm 3/m2. It would thus appear that within limits a small ventricle does not preclude a successful operation. However, when the ventricular volume is less than 20 cm 3/m2, the patient might better be treated for a hypoplastic left heart syndrome and undergo a Norwood
procedure.i" All authors, including us, have noted a higher mortality in the first month of life, and particularly in the first week of life. Norwood has attributed this to small ventricular volume, but this has not been our observation. Indeed, although three fourths of our deaths occurred in neonates, all three had ventricular volumes above 35 cm3/m2. Others have associated dysplastic valves with the higher mortality of the neonate.v? We could make no such correlation in our series. The young infant is much more likely to have endocardial fibroelastosis than the older patient. This has been attributed to severe intrauterine left ventricular ischemia by some authors and is definitely a major determinate of operative survival.3.4. II In our series endocardial fibroelastosis, while not precluding survival (50% mortality), was a good predictor of a high operative mortality. The role of other associated abnormalities in increasing surgical mortality is not clear. Several groups have reported a high mortality for aortic valvotomy associated with other anomalies. 1·4. 7.10 We found a high incidence of associated anomalies with aortic stenosis, but these did not affect survival. Mitral regurgitation in these patients is often secondary to left ventricular dysfunction and can improve after successful aortic valvotomy. However, patients with Shone's syndrome are particularly troublesome because the serial lesions of coarctation, aortic stenosis, and mitral stenosis may not be ultimately correctable. The influence of operative technique upon survival is
Thoracic and Cardiovascular Surgery
likewise not clear. In the present series, conventional cardiopulmonary bypass was used successfully. The advantage of such a technique is that an unhurried valvotomy can be performed. Regardless of the operative technique used, we consider it essential to provide an adequate aortic valve opening without producing insufficiency, comrnissures being incised to, but not into, the aortic anulus. The good long-term results we have obtained support the logic of this method. Recently, Sink and colleagues I I have reported an operative mortality of 25% with inflow inclusion and open valvotomy in a small series of infants under 7 months of age, and even closed techniques performed with dilators or balloon catheters have been used. NI three techniques are associated with variable oprative mortalities, high postoperative gradients, and aortic regurgitation. I I. 16. 17 Another advantage of techniques involving cardiopulmonary bypass is that the metabolic abnormalities associated with poor perfusion are corrected during the procedure, so that survival is more likely. Messina and colleagues'? have suggested that a cold blood prime and short cross-clamp time are important in this regard. Because our perfusion technique differs somewhat from theirs, it would appear that excellent results can be obtained by several approaches. Our technique has yielded excellent functional postoperative results, with only three patients having aortic valve gradients greater than 25 mm Hg, two of whom have complex left ventricular outflow obstruction below the valve. Particularly gratifying has been the excellent postoperative recovery of ventricular function, even in severely depressed ventricles (Figs. 3 and 4). Ejection fractions and ventricular volumes have returned to normal values after the operation.
Conclusions These results suggest that many critically ill infants with aortic stenosis can survive operation, at least when their ventricular volume exceeds 20 em' 1m2. We have been unable to detect absolute contra indications to operation, although patients with low ejection fractions and high LVEDPs have a lower probability of surviving. A very young age and the presence of endocardial fibroelastosis are unfavorable signs but do not preclude operation. The use of an open technique with cardiopulmonary bypass is recommended because it allows a precise repair to be performed. Only a few patients have significant residual gradients or aortic insufficiency. Long-term results have been excellent, with documented growth in ventricular volume and recovery of ventricular function to normal levels.
Volume 92 Number 4 October 1986
We thank Mr. John Palmisano for his assistance in analyzing the ventriculograms and Dr. Anthony Schork for his assistance in the statistical analysis. REFERENCES Keane JF, Norwood WI, Bernhard WF: Surgery for aortic stenosis in infancy. Circulation 68:Suppl 3:182, 1983 2 Hammon JW, Parrish MD, Graham TP, Boucek RJ, Bender HW: Risk factors for infants undergoing aortic valvotomy for critical aortic valvar stenosis. J Am Coli Cardiol (in press) 3 Sandor GGS, Olley PM, Trusler GA, Williams WG, Rowe RD, Morch JE: Long-term-follow-up of patients after valvotomy for congenital valvular aortic stenosis in children. J THORAC CARDIOVASC SURG 80:171-176, 1980 4 Lakier 18, Lewis AB, Heymann MA, Stanges P, Hoffman JIE, Rudolph AM: Isolated aortic stenoses in the neonate. Natural history and hemodynamic consideration. Circulation 50:801-808, 1974 5 Edmunds LH, Wagner HR, Heymann WA: Aortic valvulotomy in neonates. Circulation 61:421-427, 1980 6 Chiariello L, Agosti J, Vlad P, Subramanian S: Congenital aortic stenosis. Experience with 43 patients. J THoRAc CARDIOVASC SURG 72:182-193, 1976 7 Keane JF, Bernhad WF, Nadas AS: Aortic stenosis surgery in infancy. Circulation 52:1138-1143, 1975 8 Cooley DA, Beall AC, Hallman GL, Bricker DL: Obstructive lesions of the left ventricular outflow tract. Surgical treatment. Circulation 31:612-621, 1965 9 Dobell ARC, Bloss RS, Gibbons JE, Collins GF: Congenital valvular aortic stenosis. Surgical management and long-term results. J THoRAc CARDIOVASC SURG 81:916920, 1981. 10 Messina LM, Turley K, Stanger P, Hoffman JIE, Ebert PA: Successful aortic valvotomy for severe congenital valvular aortic stenosis in the newborn infant. J THORAC CARDIOVASC SURG 88:92-96, 1984 II Sink JD, Smallhorn JF, Macartney FJ, Taylor JFN, Stark J, de Leval MR: Management of critical aortic stenosis in infancy. J THoRAc CARDIOVASC SURG 87:82-86, 1984 12 Shone JD, Sellers RD, Anderson RC: The developmental complex of left atrium and subarotic stenosis and coarctation of the aorta. Am J Cardiol 11:714-725, 1963 13 Silverman NH, Ports TA, Snider AR, Schiller NB, Carlsson E, Heilbron DC: Determination of left ventricular volume in children. Echocardiographic and angiographic comparison. Circulation 62:548-557, 1980 14 Graham TP, Lewis BW, Jarmakani MM, Canent RV, Capp MP: Left heart volume and mass quantification in children with left ventricular pressure overload. Circulation 41:203-212,1970 15 Norwood WI, Lang P, Hansen D: Physiologic repair of aortic atresia-hypoplastic left heart syndrome. N Engl J Med 308:23-26, 1983 16 Trinkle JK, Norton 18, Richardson JD, Grover FL, Noonan JA: Closed aortic valvotomy and simultaneous
Critical aortic stenosis
753
correction of associated anomalies in infants. J THoRAc CARDIOVASC SURG 69:758-762, 1975 . 17 Brown JW, Robinson RJ, Waller BF: Transventricular balloon catheter aortic valvotomy in neonates. Ann Thorac Surg 39:376-378, 1985
Discussion DR. KEVIN TURLEY San Francisco. Calif
I agree with many of the points made by the authors. The points worth stressing are those concerning the use of a precise aortic valvulotomy to maximize the orifice of the aortic valve without producing aortic insufficiency and the use of cardiopulmonary bypass to correct the metabolic abnormalities that are present. Specific to the paper, this lesion had a very high mortality, 50% to 80%, 10 to 15 years ago. However, now this mortality has been reduced significantly and the statistical factors thought to be of importance have concurrently diminished. The multiple factors we used to think were important, such as gradient, ventricular volumes, and the type of valve, have lost significance, as these authors have reported. Now only a few things are noted, such as LVEDP, ejection fraction, and age. This is typical of the successful therapy of any lesion. With a high mortality almost all factors may appear to significantly alter survival in a small patient population, yet as mortality decreases these risk factors "drop out." During the period 1976 to 1985, 92 aortic valvotomies were performed at the University of California, San Francisco. Thirty-two of these patients were less than 6 months of age, the age group discussed in this paper. Thirteen of them were older than I month of age but younger than 6 months of age; seven were older than I week but younger than I month of age; and 12 were younger than I week of age. A number of hemodynamic factors were noted in these patients: mitral regurgitation, pulmonary hypertension, and elevation of the LVEDP and the ejection fraction. Of the 13 patients in the first group, older than I month but less than 6 months, none had mitral regurgitation, none had pulmonary hypertension, only two had an elevation of the LVEDP, and the mean ejection fraction was 62%. Of the seven patients younger than I month but older than I week, two had mitral regurgitation, four pulmonary hypertension, four an elevation of the LVEDP, and the mean ejection fraction was decreased to 46%. Of the 12 patients less than I week, seven had mitral regurgitation, nine had pulmonary hypertension, 10 had an elevation of the LVEDP, and the mean ejection fraction was 38%. Notice that these problems are common in the neonatal group, with a mean ejection fraction of 38% in the 13 patients younger than 7 days of age. These findings suggest that we are really looking at two separate manifestations of a single disease: The older patients, those younger than 6 months but older than I month, have symptoms similar to those of patients older than 6 months of age. In the neonatal group, a high incidence of mitral regurgitation, pulmonary hypertension, and left ventricular failure is evident. The middle groups, those younger than I month but older than 1 week, are a crossover
The Journal of Thoracic and Cardiovascular Surgery
7 5 4 Gundry and Behrendt
group, with individuals having manifestations of each of the other two groups. Further, when associated lesions were reviewed, all were present in the youngest group « 1 week), with coarctation present in three patients. Thus the age at presentation, which the authors note had a significant effect on outcome, may relate to the difference in both the severity of the disease and the associated lesions at presentation. We differ with the authors on one critical factor, that of perfusion technique. Ventricular fibrillation developed at induction in four of the 19 neonates, those younger than I month of age. However, none of these patients died in the immediate postoperative period, one death occurring 3 days postoperatively in a patient who had an unrecognized coarctation of the aorta and the other at 4 days in a patient with hypoplasia of the ascending aorta, left ventricle, and mitral valve. Overall survival rate in this series was 94% (30/32), with none of the patients older than 1 month of age dying. A 91% survival rate was noted in those less than I week of age. We believe that early diagnosis and the diagnosis of associated lesions is obviously critical. Emergency operation with the institution of cardiopulmonary bypass and myocardial protection is likewise critical. Again, an open, precise valvotomy optimizes results. I have several questions for the authors. The first concerns myocardial and total body protection. Do they believe that conventional cardiopulmonary bypass with slow cooling optimally produces such effects and would patients who have ventricular fibrillation during induction of anesthesia or opening of the chest benefit from the cold perfusate prime that we advocate? Second, in the manuscript they discussed low left ventricular volumes and directly addressed this question. A. higher risk may be attenant to patients with less than 20 cm'/m 2 area. I would ask whether the patients with diminutive ventricular volumes also have a diminutive aortic valve and whether they should be considered to have aortic valve stenosis or the hypoplastic left heart syndrome. Finally, there are the questions of distribution of secondary manifestations and associated lesions by age. Have you investigated this factor in your patient group and are your findings consistent with our observation that, in fact, there are two separate presentations of a single pathologic entity? Might those with the neonatal form be considered separately from those with the juvenile form?
DR. ERNST-RAINER
DE
VIVIE
Goettingen, Federal Republic of Germany
I want to discuss two points. In Goettingen in 1984 we began using balloon valvuloplasty instead of commissurotomy in cirtical aortic stenosis in infancy. Our cardiologist, Dr. G. Rupprath, has successfully performed valvuloplasty in four infants (aged from I to 6 weeks) and achieved a reduction of the pressure gradient from the left ventricle to the aorta of more than 50% without major complications. These data were recently published in The American Journal of Cardiology (June, 1985). If the left ventricle cannot be entered in retrograde fashion using the balloon catheter, it is also possible to perform a closed commissurotomy through a left thoracot-
omy. A vascular dilator or a balloon catheter is advanced from the apex of the left ventricle through the stenotic valve. The second point is that I do not agree with the long-term results reported by Dr. Gundry. In our series of patients with critical aortic stenosis, with a long-term follow-upof more than 20 years, the diagnosis was made by heart catheterization in 31 infants. Eight died before operation, and 20 were operated on by commissurotomy with extracorporeal circulation. Twenty percent (n = 4) of these died postoperatively. Three required reoperation after 10 to 13 years, and in these children it was necessary to widen the small aortic anulus and to resect the dysplastic valve. We used the technique of aortoventriculoplasty to enlarge the left ventricular outflow tract and inserted an adult-sized mechanical valve.
DR. GUNDRY (Closing) I would like to thank both of the discussants for their comments. As I mentioned, since 1982 we have only had one death in the last 11 patients, and that occurred in a child who develoepd fibrillation in the operating room and could not be weaned from bypass. That result compares favorably with what Drs. Turley and Ebert reported recently in their last II patients. We do think that conventional cardiopulmonary bypass, while differing somewhat from Dr. Turley's techniques, appears to be giving good results in our hands. We see no indication to change. We have found that when we used a hypothermic perfusate in an attempt to try this method, our core temperatures were not as cold as we would like during the procedure. The heart often fibrillated quite early, even before we were ready to apply the cross-clamp. However, good results can be achieved with either method. We agree with Dr. Turley that cardiopulmonary bypass is the method of choice for aortic valvotomy for several different reasons. First, as Dr. Turley suggested, we believe it is critical to correct the metabolic abnormalities that all these children have when they arrive in the operating room. This allows a leisurely period for the heart to recover from the insult. Second, we also agree that, particularly early in infancy, it is critical to obtain a maximum opening of the aortic valve without producing aortic insufficiency. Although long-term follow-up has shown that many of these children will eventually need reoperation, we believe that by opening the valve wide we can delay that initial reoperation and perhaps lessen the number of subsequent operations these children will have. That is why we and others do not recommend balloon dilatation. There are, of course, advantages to balloon dilatation. It is quick and it is easy. If it is performed through a left thoracotomy, associated lesions such as coarctation of the aorta can also be attacked. However, balloon dilatation does not allow adequate control in opening the aortic valve. Several series have come back with short-term results of fairly severe aortic insufficiency or severe residual gradients that then necessitate an operation with valve replacement early in the child's life. We belive that balloon dilatation is not the best way to go, because of these problems.