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Neonatal aortic stenosis
J THORAC CARDIOV;\SC SURG 1990;99:679-84
Neonatal aortic stenosis Aortic stenosis in the neonate has been associated in the past with a high operative mortality. As a result, in the current era of percutaneous baUoon dilatation, the optimal mode of therapy remains controversial. An approach of stabilization with cardiopulmonary bypass, foUowed by relief of left ventricular outflow tract obstruction, was used at three institutions, and the results are presented. During the period 1983 to 1989,40 neonates with isolated aortic stenosis and patent ductus arteriosus or coarctation of the aorta, or both, underwent operative therapy. Ages ranged from 1 to 30 days, median of 12 days, including 17 patients in the first week of life. There were 30 boys and 10 girls; weights ranged from 2.5 to 5.5 kg with a mean of 3.6 kg. Perioperative conditions included congestive heart failure in 38 and mitral regurgitation in 16; left ventricular-aortic gradients ranged from 15 to 130 mm Hg, with a mean of 67 mm Hg, There were 30 open valvotomies and 10 transventricular dilatations. The hospital survival rate was 87.5% (35/40) with no significant difference between the methods of valvotomy (9/10 in the transventricular dilatation group, 90%; 26/30 in the open valvotomy group, 8.7%). Although multiple methods of perfusion and valvotomy were used, the single unifying factor of cardiopulmonary bypass stabilization was present in aU 40 patients. No significant difference in survival was noted between institutions, methods of cardiopulmonary bypass, cardiopulmonary bypass times, crossclamp times, or method of valvotomy. There have been five reoperations, with one late death in a patient requiring mitral valve replacement and an apical-aortic conduit. One sudden death occurred; autopsy revealed endocardial fibroelastosis. Results demonstrate that in the three institutions using the methods described, a high operative and late survival rate is possible. The results of this' technique, against which percutaneous dilatation should be compared, are standard in the current era.
Kevin Turley, MD, Edward L. Bove, MD, Joseph J. Amato, MD, Mark Iannettoni, MD (by invitation), John Yeh, MD (by invitation), Joseph V. Cotroneo, MD (by invitation), and Ralph J. Galdieri, MD (by invitation),
San Francisco, Calif.. Ann Arbor, Mich., and Newark, N.J.
Critical aortic stenosis in the neonate has been associated in the past with high mortality. 1-3 This has prompted the recommendation in the current era that percutaneous balloon dilatation be performed. The current study explores the results, in a combined series of three institutions, of operative aortic valvuloplasty in neonates with isolated valvular aortic stenosis, candidates for percutaneous valvuloplasty alone. From the University of California, San Francisco, Calif., the University of Michigan, Ann Arbor, Mich., and the University of Medicine and Dentistry, Newark, N.J. Read at the Sixty-ninth Annual Meeting of The American Association for Thoracic Surgery, Boston, Mass., May 8-10, 1989. Address for reprints: Kevin Turley, MD, Department ofCardiothoracic Surgery, M-896, Box 0118, University of California, San Francisco (UCSF), San Francisco, CA 94143-0118. 12/6/18197
Patients and methods During the period 1983 to 1989, 40 critically ill infants with neonatal aortic stenosis were operated on at three institutions. Included in this study were those infants with neonatal aortic stenosis with or without a patent ductus arteriosus or coarctation of the aorta. They were operated on by the technique of valvotomy alone with cardiopulmonary bypass for support. Excluded from the study were those patients with other associated lesions or those in whom other modalities were used. Thus the study group included candidates for percutaneous balloon valvuloplasty, those in whom primary surgical valvuloplasty alone is used. No patients were excluded because of clinical condition or presence of fibroelastosis, and all patients with associated mitral disease, in whom valvotomy alone was used, were included. Ages ranged from I to 30 days (mean I2 days) and weights from 2.5 to 5.5 kg (mean 3.6 kg). There were 30 boys and 10 girls. Congestive heart failure was present in 38 (95%); moderate to severe mitral regurgitation was noted in 16 (40%); and aortic gradients ranged from IS to 130 mm Hg, with a mean of 67 mm Hg. Aortic anulus size ranged from 5 to 9 rnrn, with a mean of 7.2 mm.
679
The Journal of Thoracic and Cardiovascular Surgery
6 8 0 Turley et al.
Table I. Method of support Bypass time (min)
Crosse/amp time (min)
Institution
Valvotomy
No.
Range
Mean
Range
Mean
A B
Open Open Closed Open
15 5 10 10
15-45 42-54 11-22 28-100
24.6 46 15 57
4-12 13-18 0 16-55
7.4 15
C
Severalmethodsof valvotomy and cardiopulmonary support were used. At institutionA, open valvotomy was performed in all 15 patients. Cardiopulmonary bypass techniques included the use of 4 C oxygenator prime with induction of moderate hypothermia and rapid rewarming after valvotomy. At institution B, five patients had an open valvotomy performedduring cardiopulmonary bypassafter induction of deep hypothermia. Ten patients underwentclosed dilatationsduring cardiopulmonary bypassat normothermia, with a short period of cardiopulmonary support. At institution C, all 10 patients underwent open valvotomy duringcardiopulmonary bypass, withdeephypothermia inthree and moderate hypothermia in seven. Hospital survival was examined, both for the entire cohort and for subsets, by analysis of preoperative factors (e.g., congestive heart failure, mitral regurgitation, and aortic gradients) and operativefactors (e.g., institution, duration of perfusion,crossclamp time, degree of hypothermia, and open versus closed valvotomy. Finally, follow-up data were examined, including reoperations and the presence of moderate to severe aortic insufficiency. Statistical analysis was performed by the Fisherexact test becauseof the small n in the subgroups examined. 0
Results Forty critically ill neonates with valvular aortic stenosis underwent aortic valvotomy at three institutions. Cardiopulmonary bypass was used for stabilization during the operative procecure in all 40. Table I demonstrates the length of cardiopulmonary bypass, crossclamp time, and degree of hypothermia used by each institution. Open valvotomy was performed in 30 and closed valvotomy in 10. The distribution of the two techniques is demonstrated in Table I. There were 35 hospital survivors, for an overall survival rate of 87.5%, including 26 of 30 (87%) in the open valvotomy group and nine of 10 (90%) in the closed valvotomy group. The distribution by institution is given in Table II. There were five operative deaths-four caused by low cardiac output or failure to wean from cardiopulmonary support and one caused by a laceration of the right coronary orifice in a patient who likewise could not be weaned from cardiopulmonary support. Among the five
22.5
Mean temperature (C) 26.9 20 37 23.9
early deaths, three patients had a small aortic anulus, 5 to 6 rnm, including the patient with the coronary laceration. Eight of the surviving patients were noted to have a 5 to 6 mm aortic anulus. In four of the five early deaths, postmortem examination showed evidence of endocardial fibroelastosis, and four surviving patients with this condition have been identified. Incomplete data (denominator) precluded statistical analysis of these two factors. Preoperative conditions, including congestive heart failure, presence of mitral regurgitation, and aortic gradients, were examined, and no statistically significant difference in the survivor/nonsurvivor groups were noted. No statistical significant difference in survival was noted between institutions, method of valvotomy (open or closed), duration of perfusion, crossclamp time, or degree of hypothermia. Follow-up assessment from 1 month to 70 months postoperatively (mean 29 months) was achieved through the use of catheterization in 26 patients and echocardiography alone in nine. It revealed moderate to severe aortic insufficiency in five patients and aortic gradients ranging up to 64 mm Hg (mean 23 mm Hg). There were five reoperations, with one late death. The death occurred in a 2-month-old infant who at catheterization had a 55 mm Hg aortic gradient and a 15 mm Hg mitral gradient. A mitral valve replacement (parachute mitral valve) and apical-descending aortic conduit were performed. The patient had a bradycardia arrest 4 days postoperatively. This patient was thus a poor candidate for valvotomy alone, although this treatment modality was used at the original operation. Three successful reoperations were performed for persistent valvular aortic gradients of 50 mm Hg or greater. In each case repeat valvotomy was possible. One patient underwent reoperation for a 64 mm Hg superaortic gradient at the aortotomy site, with successful relief of the obstruction. One sudden death occurred 6 months postoperatively in a symptom-free patient. Severe endocardial fibroelastosis was noted at postmortem examination. Finally, one patient is awaiting transplantation, with a 20 mm Hg aortic gradient but low cardiac output because of severe endocardial fibroelasto-
Volume 99 Number 4
Neonatal aortic stenosis
April 1990
Table III. Late survival (1 month to 6 years)
Table II. Hospital survival Institution A B B
C Total
No. of patients
Survivors No.
15 15 10 5
Institution
%
13
87 93
14
8 35
sis. The late survival rate for the entire series was 82.5%. Late survival by institution and method of valvotomy is demonstrated in Table III. Discussion Surgical treatment of critical neonatal aortic stenosis has been associated in the past with a high operative mortality.'>' In the recent era described in the current study, a number of factors have been identified that increased surgical risk, and both improvements in operative technique and alternate methods of treating complex lesionshave been developed. Yet controversy persists, and the use of percutaneous balloon valvuloplasty has been
advocated." The current study examines the patient group now undergoing surgical valvotomy and the results of such treatment when cardiopulmonary support is used to stabilize the patient's condition during relief of left ventricular outflow tract obstruction. These results differ markedly from many earlier reports, reflecting a number of factors, including the time of the study and the nature of the patient population. Lakier and associates I in 1974 described 10 patients with neonatal aortic stenosis. Of this group, three patients died before operative intervention and five of seven died in the early postoperative period (71%). Sandor and colleagues.' in 1980, reported a 68% mortality rate during the period 1956 to 1975 among 16 neonates. Edmunds, Wagner, and Heymann:' described 14 patients operated on from 1970 to 1977 with a 50% mortality. In each series, although multiple factors were identified with increased risk, small left ventricular volume and annular and aortic size were consistently identified. These findings were corroborated by an analysis by Hammond and associates of 33 patients less than 6 months of age in whom only elevation of mean pulmonary artery pressure and decreased left ventricular end-diastolic volume significantly influenced results. Gundy and Behrendt." in 1986, reported on 24 infants less than 6 months of age,
C Total
No.
9
87 87 90 80
4
10 40
%
13 13
15 15 10 5
80 87.5
Survivors
No. of patients
A B
90 100
9 5 10 40
68 1
7 33
70 82.5
including 19 neona tes, and found no significant difference in survival in patients with small left ventricular volumes. However, none of their patients had a left ventricular end-diastolic volume index below 20 cm 3/m2• They too recommended that an alternate method might be used to treat patients with a small left ventricular volume. Conversely, Messina and colleagues," in 1984, described 11 neonates, 10 of whom had a left ventricular volume within normal limits, with no operative deaths in those patients. Thus it has become increasingly clear that alternate methods of therapy should be applied to patients in whom variants of hypoplastic left heart anatomy are present. The Norwood procedure, pulmonary artery-descending aortic conduits with pulmonary artery banding, and transplantation have increasingly been applied to this group.f'? Thus, in the current era, aortic valvotomy is most commonly performed in infants with root dimensions of 5 mm or greater, as seen in this study. A great risk may exist for patients with small aortic root dimensions, with three of the five deaths in our series occurring in patients with an aortic anulus of 5 to 6 mm, but eight such patients survived operation. Endocardial fibroelastosis likewise may increase risk. It was noted in four of five early deaths in this study and one late death, and one patient awaiting transplantation has evidence of endocardial fibroelastosis. However, the true prevalence of these two factors (denominator) in this series is now known. The population of this study then represents a group in which percutaneous balloon dilatation might currently be applied and the group to whom results should be compared Cardiopulmonary bypass was used to provide stabilization during the relief of left ventricular obstruction in all patients in the current series. Although multiple methods of bypass were used, no significant differences in results were identified. Concern has existed in the past that cardiopulmonary bypass may have deleterious effects in the critically ill neonate. In 1978, Trinkle and associates II reported the technique of closed aortic valvotomy in infants. In 1987, Duncan and colleagues'?
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6 8 2 Turley et al.
described its use in critically ill neonates. Nine patients aged from 1 to 30 days, with aortic valve diameters from 6 to 8 mm, underwent closed valvotomy. There were six operative survivors. Perioperative complications included ventricular in three, acute renal failure in two, and perforation of the heart in one. Pelech and co-workers 13in 1987 compared results of open versus closed valvotomy in 40 neonates: 22 in the open group and 18 in the closed group. There was a significant difference in overall operative survival between the methods. However, the prevalence of early reoperation (less than I year of age) was greater in perioperative survivors undergoing closed valvotomy (7/ 13, 54%) rather than open valvotomy (1/10, 10%) (p < 0.05). The deleterious effects of cardiopulmonary bypass in the critically ill neonate must be questioned as increasing experience with cardiopulmonary bypass in neonates is reported!" and as prolonged cardiopulmonary support is used in neonates during the arterial switch procedure.P Finally, in the case of patients with critical aortic stenosis, Messina and associates? in 1984 reported a 9% mortality rate among 11 patients in whom open valvotomy was performed with hypothermic cardiopulmonary bypass used for support. Of note in that series, four of 11 patients had ventricular fibrillation during induction of anesthesia. Had bypass technique not been used, survival of those patients would have been unlikely. Thus the current series provides us with a three-institution experience with operative valvotomy in which cardiopulmonary bypass is used for support, in an era when bypass techniques have improved and the patient population is well defined. It explores results in patients with valvular aortic stenosis who are currently considered candidates for surgical valvotomy alone, a population comparable to one in which percutaneous balloon dilatation alone might be attempted. Kasten-Sportes and associates" recently reported such a series. Ten neonates with critical aortic valve stenosis underwent percutaneous balloon dilatation during the period August 1975 through December 1987. Ages ranged from 2 to 34 days, with six neonates less than 6 days of age. Anulus size ranged from 6 to 9 mm, as in the current study, and preoperative conditions paralleled those in the current study, with all 10 patients having congestive heart failure when first seen. Dilatation was accomplished in eight patients. There were three early deaths, and one patient required heart transplantation 33 days after dilatation. Two of the surviving patients required surgical valvotomy on the first and fifteenth days, respectively, after dilatation. In one patient, a balloon catheter could not be passed, and the patient died after emergency surgical valvotomy. The second technical failure involved perforation of the right anterior valve cusp (5 mm defect) and severe aortic insufficiency,
Thoracic and Cardiovascular Surgery
with death 2 days after the procedure. Thus, in this group of patients comparable to the present study, successful dilatation was accomplished in four (40%), with three early deaths (30%) and one cardiac transplantation (10%). These results were noted by the authors to compare favorably with surgical treatment, since mortality rates of 50% to 68% exist with surgical valvotomy.s' This three-institution study was initiated in an attempt to define current experience with operative valvotomy in isolated neonatal aortic stenosis. The results reflect a selected series of patients for repair, in that all are neonates in whom valvotomy with cardiopulmonary bypass for support was performed, a group in which percutaneous balloon valvotomy has been advocated because high operative mortality was noted in the past. Multiple methods of valvotomy were used, and no significant difference in results was noted. Cardiopulmonary bypass was used for support during valvotomy in all patients. In the current era, increasing experience with bypass techniques in neonates has resulted in increasing benefits with decreasing risks. In this setting, the question must be raised whether catheterization should be performed in such patients or whether, as suggested by Sink and associates, 16 catheterization is an unwarranted risk. Cardiac catheterization combined with percutaneous balloon dilatation can result in a prolonged period of intervention, during which hemodynamic instability in the unsupported patient is culminated by balloon dilatation of the valve orifice and transient obstruction of the severely impaired left ventricle. In this setting, a high risk of fibrillation might be expected. A protocol of immediate operation, with early institution of cardiopulmonary support after echocardiographic diagnosis alone, is our preferred approach. The current study demonstrates that, with the techniques described, critical aortic stenosis can be treated in neonates with high operative and late survival rates. These results support the concept that these techniques provide the milieu in which the neonatal myocardium can optimally respond to relief of obstruction and are a standard against which results of percutaneous balloon dilatation should be compared. REFERENCES I. Lakier J B, Lewis AB, Heymann MA, Stanger P, Hoffman JIE, Rudolph AM. Isolated aortic stenosis in the neonate. Circulation 1974;50:801-8. 2. 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 1980;80: 171-6. 3. Edmunds LH Jr, Wagner HR, Heymann MA. Aortic valvulotomy in neonates. Circulation 1980;61:421-7. 4. Kasten-Sportes CH, Piechaud J-F, Sidi D, Kachaner J.
Volume 99 Number 4 April 1990
5.
6.
7.
8.
9. 10.
II.
12.
13. 14.
IS.
16.
Percutaneous balloon valvuloplasty in neonates with critical aortic stenosis. J Am Coli Cardiol 1989;13:1101-5. Hammon JW Jr, Lupinetti FM, Maples MD, et al. Predictors of operative mortality in critical aortic stenosis presenting in infancy. Ann Thorac Surg 1988;45:537-40. Gundry SR, Behrendt 0 M. Prognostic factors in valvotomy for critical aortic stenosis in infancy. J THORAC CARDIaVASC SURG 1986;92:747-54. 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 1984;88:92-6. Norwood WI, Lang P, Castaneda AR, Campbell ON. Experience with operations for hypoplastic left heart syndrome. Thorac Cardiovasc Surg 1981;82:511-9. Ilbawi MN, Idriss FS, DeLeon SY, Muster AJ, Benson OW Jr, Paul MH. Ann Thorac Surg 1988;45:174-80. Bailey L, Concepcion W, Shattuck H, Huang L. Method of heart transplantation for treatment of hypoplastic left heart syndrome. J THORAC CARDIOVASC SURG 1986;92: 1-5. Trinkle JK, Grover FL, Grover MD, Arom KV. Closed aortic valvotomy in infants. J THORAC CARDIOVASC SURG 1978;76:198-201. Duncan K, Sullivan I, Robinson P, Horvath P, de Leval M, Stark J. Transventricular aortic valvotomy for critical aortic stenosis in infants. J THORAC CARDIOVASC SURG 1987; 93:546-50. Pelch AN, Dyck JD, Trusler GA, et al. Critical aortic stenosis. J THORAC CARDIOVASC SURG 1987;94:510-7. Turley K, Mavroudis C, Ebert PA. Repair of congenital cardiac lesions during the first week of life. Circulation 1982;66(Pt 2):11214-9. Quaegebeur JM, Rohmer J, Ottenkamp J, et al. The arterial switch operation. J THORAC CARDIOVASC SURG 1986; 92:361-84. SinkJD, Smallhorn JF, Macartney FJ, Taylor JFN, Stark J, de Leval MR. Management of critical aortic stenosis in infancy. J THORAC CARDIOVASC SURG 1984;87:82-6.
Discussion Dr. Gerhard Ziemer (Hannover, Federal Republic ofGermany). The standard set by your results, Dr. Turley, has to be met not only by other surgeons using this or other techniques but also by every cardiologist trying balloon valvuloplasty. For different techniques in neonatal or infant surgery to be compared, however. I think a clear statement must be made whether, during the time frame reported, there have been patients admitted who were not operated on because of poor clinical status. In our experience from 1980 to 1985, we had a 30% mortality rate using cardiopulmonary bypass for valvotomy in infants in the first 3 months of life. Three of 10 patients died. Since 1987 we have used a normothermic caval inflowocclusiontechnique. The mortality rate has not changed significantly: It was 20%,that is, two of 10 patients died. However, during the bypass period six patients were considered unsuitable for operation and died without surgical treatment. The inflow occlusion
Neonatal aortic stenosis
683
group comprises all patients admitted with critical aortic stenosis, including one who had revalvotomy and others after or dur- • ing resuscitation. In up to 2 years of follow-up we have not had to reoperate on any of these patients treated by inflow occlusion. Dr. Turley, are you aware of patients in the participating hospitals who were not operated on because of poor risk, patients who in other series may have contributed to less favorable results? Dr. Turley. We looked into this very closely, and no patient in these three reporting institutions was denied surgical intervention because of clinical state. Eight of the patients were severely acidotic when taken to the operating room after preoperative methods had been unsuccessful in changing their acidotic state. Dr. Bruno J. Messmer (Aachen. Federal Republic of Germany). During the past 8 years, we treated 26 infants below the age of 3 months, 15 being neonates. All underwent open repair. The hospital survival rate was 81%. When looking for operative risk factors, we found severe mitral disease resulting from primary malformation of the valve necessitating simultaneous correction to be the only independent risk factor for the operation. Since this differs from Dr. Turley's findings, I would like to ask him in how many cases he had to approach the mitral valve simultaneously? We had to do so in 20% of our cases. Dr. Turley. In this series there were two patients with concomitant mitral disease. In both, we chose aortic valvotomy alone. Any patient in whom a mitra valvuloplasty or resection of the atrial septum was attempted, for example, because of concern about hypoplastic left heart, was not included in this series. This series specifically comprised aortic valvotomy with coarctation and patent ductus arteriosus. Dr. Messmer. My second point relates more to the pathology and technical aspects. Pathology of congenital aortic stenosis does not consist of fused and rudimentary commissures only, but also of subcommissural fibrosis, protruding myxoid nodules on the ventricular aspect of the cusps, often a bulging valvular ring, and sometimes intrasinusal pillar-like fibrous strings. Single commissurotomy opens only the top level of the valve but may not give satisfactory hemodynamic results. Meticulous resection of additional stenotic elements is mandatory, especially in patients with a small aortic anulus. In my opinion, this can be done only with deep hypothermia and circulatory arrest, as well as cardioplegic arrest, to have an absolutely dry and quiet operative field. I have two final questions: Since the average aortic crossclamp time varied in the three centers between 7 and 22 minutes, has there been a different operative technique and what do you advocate at the moment? Finally, on what basis were the patients in institution B selected for either the open or closed technique? Dr. Turley. The method of valvotomy at each of the centers in the open group was direct opening of the major commissure itself. At my institution resection of valve tissue has been avoided. One patient in the group had a large nodule resected, but we try to avoid that. Regarding your second question, the closed valvotomy has been a recent development at institution B, and it has been used in a consecutive series of balloon dilatations. Dr. John L. Myers (Hershey, Pa.). During the past 4 years we have treated four neonates with critical aortic stenosis by means of transventricular dilation without cardiopulmonary
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6 8 4 Turley et al.
bypass. All patients were maintained on prostaglandin E] preoperatively, as well as endotracheal intubation with mechanical ventilation and inotropic support if needed. All of these patients had adequate perfusion once resuscitated without ongoing acidosis. Our approach was an exposure of the left ventricular apex from a left thoracotomy incision and the passage of calibrated Hegar dilators from an apical stab incision as originally described by Trinkle and associates. The maximal size of Hegar dilators was the same size as the aortic anulus as determined by two-dimensional echocardiography. Coarctation of the aorta was present in two of our patients and was repaired by the subclavian flap technique. Importantly, the ductus arteriosus was left open in one patient because of maredkly impaired left ventricular function. All patients have done well with a follow-up of 6 to 48 months, and only two patients have gradients, both less than 40 mm Hg. The preoperative experience with hypoplastic left heart syndrome has demonstrated the ability of the right ventricle to support the systemic circulation via an unrestrictive patent foramen ovale and maintenance of a patent ductus arteriosus with prostaglandin E j • This pathophysiology can be used to support these infants with aortic stenosis postoperatively. When left ventricular function improves, prostaglandin E] is discontinued and the ductus is allowed to close.
Thoracic and Cardiovascular Surgery
I have two questions for the authors: How was the ductus arteriosus managed in your patients and do you have any intraoperative criteria to determine whether to close the ductus or to leave it open. Dr. Turley. The ductus was maintained patent with prostaglandin E, before the operation in our patients, and at the time of the operation the ductus was snared. It was snared during the bypass run and was ligated as the patient was being weaned from bypass; thus we could evaluate at that point whether the ductus needed to be left open. That was not necessary in any of these patients. All of them had ductus ligation. Dr. Myers. Second, did you find that open valvotomy had any advantage over closed valve dilation? In other words, was your open valvotomy technique a sharp incision of the valve or insertion of a clamp and spreading to dilate the valve? Dr. Turley. In each of the patients treated by open valvotomy, a sharp incision was used. However, over the years I have believed that the initial placement of a suction catheter across the small valves often produces some dilatation along that commissure. The effect of a balloon catheter in doing that is apparent.
Neonatal aortic stenosis Aortic stenosis in the neonate has been associated in the past with a high operative mortality. As a result, in the current era of percutaneous baUoon dilatation, the optimal mode of therapy remains controversial. An approach of stabilization with cardiopulmonary bypass, foUowed by relief of left ventricular outflow tract obstruction, was used at three institutions, and the results are presented. During the period 1983 to 1989,40 neonates with isolated aortic stenosis and patent ductus arteriosus or coarctation of the aorta, or both, underwent operative therapy. Ages ranged from 1 to 30 days, median of 12 days, including 17 patients in the first week of life. There were 30 boys and 10 girls; weights ranged from 2.5 to 5.5 kg with a mean of 3.6 kg. Perioperative conditions included congestive heart failure in 38 and mitral regurgitation in 16; left ventricular-aortic gradients ranged from 15 to 130 mm Hg, with a mean of 67 mm Hg, There were 30 open valvotomies and 10 transventricular dilatations. The hospital survival rate was 87.5% (35/40) with no significant difference between the methods of valvotomy (9/10 in the transventricular dilatation group, 90%; 26/30 in the open valvotomy group, 8.7%). Although multiple methods of perfusion and valvotomy were used, the single unifying factor of cardiopulmonary bypass stabilization was present in aU 40 patients. No significant difference in survival was noted between institutions, methods of cardiopulmonary bypass, cardiopulmonary bypass times, crossclamp times, or method of valvotomy. There have been five reoperations, with one late death in a patient requiring mitral valve replacement and an apical-aortic conduit. One sudden death occurred; autopsy revealed endocardial fibroelastosis. Results demonstrate that in the three institutions using the methods described, a high operative and late survival rate is possible. The results of this' technique, against which percutaneous dilatation should be compared, are standard in the current era.
Kevin Turley, MD, Edward L. Bove, MD, Joseph J. Amato, MD, Mark Iannettoni, MD (by invitation), John Yeh, MD (by invitation), Joseph V. Cotroneo, MD (by invitation), and Ralph J. Galdieri, MD (by invitation),
San Francisco, Calif.. Ann Arbor, Mich., and Newark, N.J.
Critical aortic stenosis in the neonate has been associated in the past with high mortality. 1-3 This has prompted the recommendation in the current era that percutaneous balloon dilatation be performed. The current study explores the results, in a combined series of three institutions, of operative aortic valvuloplasty in neonates with isolated valvular aortic stenosis, candidates for percutaneous valvuloplasty alone. From the University of California, San Francisco, Calif., the University of Michigan, Ann Arbor, Mich., and the University of Medicine and Dentistry, Newark, N.J. Read at the Sixty-ninth Annual Meeting of The American Association for Thoracic Surgery, Boston, Mass., May 8-10, 1989. Address for reprints: Kevin Turley, MD, Department ofCardiothoracic Surgery, M-896, Box 0118, University of California, San Francisco (UCSF), San Francisco, CA 94143-0118. 12/6/18197
Patients and methods During the period 1983 to 1989, 40 critically ill infants with neonatal aortic stenosis were operated on at three institutions. Included in this study were those infants with neonatal aortic stenosis with or without a patent ductus arteriosus or coarctation of the aorta. They were operated on by the technique of valvotomy alone with cardiopulmonary bypass for support. Excluded from the study were those patients with other associated lesions or those in whom other modalities were used. Thus the study group included candidates for percutaneous balloon valvuloplasty, those in whom primary surgical valvuloplasty alone is used. No patients were excluded because of clinical condition or presence of fibroelastosis, and all patients with associated mitral disease, in whom valvotomy alone was used, were included. Ages ranged from I to 30 days (mean I2 days) and weights from 2.5 to 5.5 kg (mean 3.6 kg). There were 30 boys and 10 girls. Congestive heart failure was present in 38 (95%); moderate to severe mitral regurgitation was noted in 16 (40%); and aortic gradients ranged from IS to 130 mm Hg, with a mean of 67 mm Hg. Aortic anulus size ranged from 5 to 9 rnrn, with a mean of 7.2 mm.
679
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6 8 0 Turley et al.
Table I. Method of support Bypass time (min)
Crosse/amp time (min)
Institution
Valvotomy
No.
Range
Mean
Range
Mean
A B
Open Open Closed Open
15 5 10 10
15-45 42-54 11-22 28-100
24.6 46 15 57
4-12 13-18 0 16-55
7.4 15
C
Severalmethodsof valvotomy and cardiopulmonary support were used. At institutionA, open valvotomy was performed in all 15 patients. Cardiopulmonary bypass techniques included the use of 4 C oxygenator prime with induction of moderate hypothermia and rapid rewarming after valvotomy. At institution B, five patients had an open valvotomy performedduring cardiopulmonary bypassafter induction of deep hypothermia. Ten patients underwentclosed dilatationsduring cardiopulmonary bypassat normothermia, with a short period of cardiopulmonary support. At institution C, all 10 patients underwent open valvotomy duringcardiopulmonary bypass, withdeephypothermia inthree and moderate hypothermia in seven. Hospital survival was examined, both for the entire cohort and for subsets, by analysis of preoperative factors (e.g., congestive heart failure, mitral regurgitation, and aortic gradients) and operativefactors (e.g., institution, duration of perfusion,crossclamp time, degree of hypothermia, and open versus closed valvotomy. Finally, follow-up data were examined, including reoperations and the presence of moderate to severe aortic insufficiency. Statistical analysis was performed by the Fisherexact test becauseof the small n in the subgroups examined. 0
Results Forty critically ill neonates with valvular aortic stenosis underwent aortic valvotomy at three institutions. Cardiopulmonary bypass was used for stabilization during the operative procecure in all 40. Table I demonstrates the length of cardiopulmonary bypass, crossclamp time, and degree of hypothermia used by each institution. Open valvotomy was performed in 30 and closed valvotomy in 10. The distribution of the two techniques is demonstrated in Table I. There were 35 hospital survivors, for an overall survival rate of 87.5%, including 26 of 30 (87%) in the open valvotomy group and nine of 10 (90%) in the closed valvotomy group. The distribution by institution is given in Table II. There were five operative deaths-four caused by low cardiac output or failure to wean from cardiopulmonary support and one caused by a laceration of the right coronary orifice in a patient who likewise could not be weaned from cardiopulmonary support. Among the five
22.5
Mean temperature (C) 26.9 20 37 23.9
early deaths, three patients had a small aortic anulus, 5 to 6 rnm, including the patient with the coronary laceration. Eight of the surviving patients were noted to have a 5 to 6 mm aortic anulus. In four of the five early deaths, postmortem examination showed evidence of endocardial fibroelastosis, and four surviving patients with this condition have been identified. Incomplete data (denominator) precluded statistical analysis of these two factors. Preoperative conditions, including congestive heart failure, presence of mitral regurgitation, and aortic gradients, were examined, and no statistically significant difference in the survivor/nonsurvivor groups were noted. No statistical significant difference in survival was noted between institutions, method of valvotomy (open or closed), duration of perfusion, crossclamp time, or degree of hypothermia. Follow-up assessment from 1 month to 70 months postoperatively (mean 29 months) was achieved through the use of catheterization in 26 patients and echocardiography alone in nine. It revealed moderate to severe aortic insufficiency in five patients and aortic gradients ranging up to 64 mm Hg (mean 23 mm Hg). There were five reoperations, with one late death. The death occurred in a 2-month-old infant who at catheterization had a 55 mm Hg aortic gradient and a 15 mm Hg mitral gradient. A mitral valve replacement (parachute mitral valve) and apical-descending aortic conduit were performed. The patient had a bradycardia arrest 4 days postoperatively. This patient was thus a poor candidate for valvotomy alone, although this treatment modality was used at the original operation. Three successful reoperations were performed for persistent valvular aortic gradients of 50 mm Hg or greater. In each case repeat valvotomy was possible. One patient underwent reoperation for a 64 mm Hg superaortic gradient at the aortotomy site, with successful relief of the obstruction. One sudden death occurred 6 months postoperatively in a symptom-free patient. Severe endocardial fibroelastosis was noted at postmortem examination. Finally, one patient is awaiting transplantation, with a 20 mm Hg aortic gradient but low cardiac output because of severe endocardial fibroelasto-
Volume 99 Number 4
Neonatal aortic stenosis
April 1990
Table III. Late survival (1 month to 6 years)
Table II. Hospital survival Institution A B B
C Total
No. of patients
Survivors No.
15 15 10 5
Institution
%
13
87 93
14
8 35
sis. The late survival rate for the entire series was 82.5%. Late survival by institution and method of valvotomy is demonstrated in Table III. Discussion Surgical treatment of critical neonatal aortic stenosis has been associated in the past with a high operative mortality.'>' In the recent era described in the current study, a number of factors have been identified that increased surgical risk, and both improvements in operative technique and alternate methods of treating complex lesionshave been developed. Yet controversy persists, and the use of percutaneous balloon valvuloplasty has been
advocated." The current study examines the patient group now undergoing surgical valvotomy and the results of such treatment when cardiopulmonary support is used to stabilize the patient's condition during relief of left ventricular outflow tract obstruction. These results differ markedly from many earlier reports, reflecting a number of factors, including the time of the study and the nature of the patient population. Lakier and associates I in 1974 described 10 patients with neonatal aortic stenosis. Of this group, three patients died before operative intervention and five of seven died in the early postoperative period (71%). Sandor and colleagues.' in 1980, reported a 68% mortality rate during the period 1956 to 1975 among 16 neonates. Edmunds, Wagner, and Heymann:' described 14 patients operated on from 1970 to 1977 with a 50% mortality. In each series, although multiple factors were identified with increased risk, small left ventricular volume and annular and aortic size were consistently identified. These findings were corroborated by an analysis by Hammond and associates of 33 patients less than 6 months of age in whom only elevation of mean pulmonary artery pressure and decreased left ventricular end-diastolic volume significantly influenced results. Gundy and Behrendt." in 1986, reported on 24 infants less than 6 months of age,
C Total
No.
9
87 87 90 80
4
10 40
%
13 13
15 15 10 5
80 87.5
Survivors
No. of patients
A B
90 100
9 5 10 40
68 1
7 33
70 82.5
including 19 neona tes, and found no significant difference in survival in patients with small left ventricular volumes. However, none of their patients had a left ventricular end-diastolic volume index below 20 cm 3/m2• They too recommended that an alternate method might be used to treat patients with a small left ventricular volume. Conversely, Messina and colleagues," in 1984, described 11 neonates, 10 of whom had a left ventricular volume within normal limits, with no operative deaths in those patients. Thus it has become increasingly clear that alternate methods of therapy should be applied to patients in whom variants of hypoplastic left heart anatomy are present. The Norwood procedure, pulmonary artery-descending aortic conduits with pulmonary artery banding, and transplantation have increasingly been applied to this group.f'? Thus, in the current era, aortic valvotomy is most commonly performed in infants with root dimensions of 5 mm or greater, as seen in this study. A great risk may exist for patients with small aortic root dimensions, with three of the five deaths in our series occurring in patients with an aortic anulus of 5 to 6 mm, but eight such patients survived operation. Endocardial fibroelastosis likewise may increase risk. It was noted in four of five early deaths in this study and one late death, and one patient awaiting transplantation has evidence of endocardial fibroelastosis. However, the true prevalence of these two factors (denominator) in this series is now known. The population of this study then represents a group in which percutaneous balloon dilatation might currently be applied and the group to whom results should be compared Cardiopulmonary bypass was used to provide stabilization during the relief of left ventricular obstruction in all patients in the current series. Although multiple methods of bypass were used, no significant differences in results were identified. Concern has existed in the past that cardiopulmonary bypass may have deleterious effects in the critically ill neonate. In 1978, Trinkle and associates II reported the technique of closed aortic valvotomy in infants. In 1987, Duncan and colleagues'?
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described its use in critically ill neonates. Nine patients aged from 1 to 30 days, with aortic valve diameters from 6 to 8 mm, underwent closed valvotomy. There were six operative survivors. Perioperative complications included ventricular in three, acute renal failure in two, and perforation of the heart in one. Pelech and co-workers 13in 1987 compared results of open versus closed valvotomy in 40 neonates: 22 in the open group and 18 in the closed group. There was a significant difference in overall operative survival between the methods. However, the prevalence of early reoperation (less than I year of age) was greater in perioperative survivors undergoing closed valvotomy (7/ 13, 54%) rather than open valvotomy (1/10, 10%) (p < 0.05). The deleterious effects of cardiopulmonary bypass in the critically ill neonate must be questioned as increasing experience with cardiopulmonary bypass in neonates is reported!" and as prolonged cardiopulmonary support is used in neonates during the arterial switch procedure.P Finally, in the case of patients with critical aortic stenosis, Messina and associates? in 1984 reported a 9% mortality rate among 11 patients in whom open valvotomy was performed with hypothermic cardiopulmonary bypass used for support. Of note in that series, four of 11 patients had ventricular fibrillation during induction of anesthesia. Had bypass technique not been used, survival of those patients would have been unlikely. Thus the current series provides us with a three-institution experience with operative valvotomy in which cardiopulmonary bypass is used for support, in an era when bypass techniques have improved and the patient population is well defined. It explores results in patients with valvular aortic stenosis who are currently considered candidates for surgical valvotomy alone, a population comparable to one in which percutaneous balloon dilatation alone might be attempted. Kasten-Sportes and associates" recently reported such a series. Ten neonates with critical aortic valve stenosis underwent percutaneous balloon dilatation during the period August 1975 through December 1987. Ages ranged from 2 to 34 days, with six neonates less than 6 days of age. Anulus size ranged from 6 to 9 mm, as in the current study, and preoperative conditions paralleled those in the current study, with all 10 patients having congestive heart failure when first seen. Dilatation was accomplished in eight patients. There were three early deaths, and one patient required heart transplantation 33 days after dilatation. Two of the surviving patients required surgical valvotomy on the first and fifteenth days, respectively, after dilatation. In one patient, a balloon catheter could not be passed, and the patient died after emergency surgical valvotomy. The second technical failure involved perforation of the right anterior valve cusp (5 mm defect) and severe aortic insufficiency,
Thoracic and Cardiovascular Surgery
with death 2 days after the procedure. Thus, in this group of patients comparable to the present study, successful dilatation was accomplished in four (40%), with three early deaths (30%) and one cardiac transplantation (10%). These results were noted by the authors to compare favorably with surgical treatment, since mortality rates of 50% to 68% exist with surgical valvotomy.s' This three-institution study was initiated in an attempt to define current experience with operative valvotomy in isolated neonatal aortic stenosis. The results reflect a selected series of patients for repair, in that all are neonates in whom valvotomy with cardiopulmonary bypass for support was performed, a group in which percutaneous balloon valvotomy has been advocated because high operative mortality was noted in the past. Multiple methods of valvotomy were used, and no significant difference in results was noted. Cardiopulmonary bypass was used for support during valvotomy in all patients. In the current era, increasing experience with bypass techniques in neonates has resulted in increasing benefits with decreasing risks. In this setting, the question must be raised whether catheterization should be performed in such patients or whether, as suggested by Sink and associates, 16 catheterization is an unwarranted risk. Cardiac catheterization combined with percutaneous balloon dilatation can result in a prolonged period of intervention, during which hemodynamic instability in the unsupported patient is culminated by balloon dilatation of the valve orifice and transient obstruction of the severely impaired left ventricle. In this setting, a high risk of fibrillation might be expected. A protocol of immediate operation, with early institution of cardiopulmonary support after echocardiographic diagnosis alone, is our preferred approach. The current study demonstrates that, with the techniques described, critical aortic stenosis can be treated in neonates with high operative and late survival rates. These results support the concept that these techniques provide the milieu in which the neonatal myocardium can optimally respond to relief of obstruction and are a standard against which results of percutaneous balloon dilatation should be compared. REFERENCES I. Lakier J B, Lewis AB, Heymann MA, Stanger P, Hoffman JIE, Rudolph AM. Isolated aortic stenosis in the neonate. Circulation 1974;50:801-8. 2. 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 1980;80: 171-6. 3. Edmunds LH Jr, Wagner HR, Heymann MA. Aortic valvulotomy in neonates. Circulation 1980;61:421-7. 4. Kasten-Sportes CH, Piechaud J-F, Sidi D, Kachaner J.
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5.
6.
7.
8.
9. 10.
II.
12.
13. 14.
IS.
16.
Percutaneous balloon valvuloplasty in neonates with critical aortic stenosis. J Am Coli Cardiol 1989;13:1101-5. Hammon JW Jr, Lupinetti FM, Maples MD, et al. Predictors of operative mortality in critical aortic stenosis presenting in infancy. Ann Thorac Surg 1988;45:537-40. Gundry SR, Behrendt 0 M. Prognostic factors in valvotomy for critical aortic stenosis in infancy. J THORAC CARDIaVASC SURG 1986;92:747-54. 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 1984;88:92-6. Norwood WI, Lang P, Castaneda AR, Campbell ON. Experience with operations for hypoplastic left heart syndrome. Thorac Cardiovasc Surg 1981;82:511-9. Ilbawi MN, Idriss FS, DeLeon SY, Muster AJ, Benson OW Jr, Paul MH. Ann Thorac Surg 1988;45:174-80. Bailey L, Concepcion W, Shattuck H, Huang L. Method of heart transplantation for treatment of hypoplastic left heart syndrome. J THORAC CARDIOVASC SURG 1986;92: 1-5. Trinkle JK, Grover FL, Grover MD, Arom KV. Closed aortic valvotomy in infants. J THORAC CARDIOVASC SURG 1978;76:198-201. Duncan K, Sullivan I, Robinson P, Horvath P, de Leval M, Stark J. Transventricular aortic valvotomy for critical aortic stenosis in infants. J THORAC CARDIOVASC SURG 1987; 93:546-50. Pelch AN, Dyck JD, Trusler GA, et al. Critical aortic stenosis. J THORAC CARDIOVASC SURG 1987;94:510-7. Turley K, Mavroudis C, Ebert PA. Repair of congenital cardiac lesions during the first week of life. Circulation 1982;66(Pt 2):11214-9. Quaegebeur JM, Rohmer J, Ottenkamp J, et al. The arterial switch operation. J THORAC CARDIOVASC SURG 1986; 92:361-84. SinkJD, Smallhorn JF, Macartney FJ, Taylor JFN, Stark J, de Leval MR. Management of critical aortic stenosis in infancy. J THORAC CARDIOVASC SURG 1984;87:82-6.
Discussion Dr. Gerhard Ziemer (Hannover, Federal Republic ofGermany). The standard set by your results, Dr. Turley, has to be met not only by other surgeons using this or other techniques but also by every cardiologist trying balloon valvuloplasty. For different techniques in neonatal or infant surgery to be compared, however. I think a clear statement must be made whether, during the time frame reported, there have been patients admitted who were not operated on because of poor clinical status. In our experience from 1980 to 1985, we had a 30% mortality rate using cardiopulmonary bypass for valvotomy in infants in the first 3 months of life. Three of 10 patients died. Since 1987 we have used a normothermic caval inflowocclusiontechnique. The mortality rate has not changed significantly: It was 20%,that is, two of 10 patients died. However, during the bypass period six patients were considered unsuitable for operation and died without surgical treatment. The inflow occlusion
Neonatal aortic stenosis
683
group comprises all patients admitted with critical aortic stenosis, including one who had revalvotomy and others after or dur- • ing resuscitation. In up to 2 years of follow-up we have not had to reoperate on any of these patients treated by inflow occlusion. Dr. Turley, are you aware of patients in the participating hospitals who were not operated on because of poor risk, patients who in other series may have contributed to less favorable results? Dr. Turley. We looked into this very closely, and no patient in these three reporting institutions was denied surgical intervention because of clinical state. Eight of the patients were severely acidotic when taken to the operating room after preoperative methods had been unsuccessful in changing their acidotic state. Dr. Bruno J. Messmer (Aachen. Federal Republic of Germany). During the past 8 years, we treated 26 infants below the age of 3 months, 15 being neonates. All underwent open repair. The hospital survival rate was 81%. When looking for operative risk factors, we found severe mitral disease resulting from primary malformation of the valve necessitating simultaneous correction to be the only independent risk factor for the operation. Since this differs from Dr. Turley's findings, I would like to ask him in how many cases he had to approach the mitral valve simultaneously? We had to do so in 20% of our cases. Dr. Turley. In this series there were two patients with concomitant mitral disease. In both, we chose aortic valvotomy alone. Any patient in whom a mitra valvuloplasty or resection of the atrial septum was attempted, for example, because of concern about hypoplastic left heart, was not included in this series. This series specifically comprised aortic valvotomy with coarctation and patent ductus arteriosus. Dr. Messmer. My second point relates more to the pathology and technical aspects. Pathology of congenital aortic stenosis does not consist of fused and rudimentary commissures only, but also of subcommissural fibrosis, protruding myxoid nodules on the ventricular aspect of the cusps, often a bulging valvular ring, and sometimes intrasinusal pillar-like fibrous strings. Single commissurotomy opens only the top level of the valve but may not give satisfactory hemodynamic results. Meticulous resection of additional stenotic elements is mandatory, especially in patients with a small aortic anulus. In my opinion, this can be done only with deep hypothermia and circulatory arrest, as well as cardioplegic arrest, to have an absolutely dry and quiet operative field. I have two final questions: Since the average aortic crossclamp time varied in the three centers between 7 and 22 minutes, has there been a different operative technique and what do you advocate at the moment? Finally, on what basis were the patients in institution B selected for either the open or closed technique? Dr. Turley. The method of valvotomy at each of the centers in the open group was direct opening of the major commissure itself. At my institution resection of valve tissue has been avoided. One patient in the group had a large nodule resected, but we try to avoid that. Regarding your second question, the closed valvotomy has been a recent development at institution B, and it has been used in a consecutive series of balloon dilatations. Dr. John L. Myers (Hershey, Pa.). During the past 4 years we have treated four neonates with critical aortic stenosis by means of transventricular dilation without cardiopulmonary
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6 8 4 Turley et al.
bypass. All patients were maintained on prostaglandin E] preoperatively, as well as endotracheal intubation with mechanical ventilation and inotropic support if needed. All of these patients had adequate perfusion once resuscitated without ongoing acidosis. Our approach was an exposure of the left ventricular apex from a left thoracotomy incision and the passage of calibrated Hegar dilators from an apical stab incision as originally described by Trinkle and associates. The maximal size of Hegar dilators was the same size as the aortic anulus as determined by two-dimensional echocardiography. Coarctation of the aorta was present in two of our patients and was repaired by the subclavian flap technique. Importantly, the ductus arteriosus was left open in one patient because of maredkly impaired left ventricular function. All patients have done well with a follow-up of 6 to 48 months, and only two patients have gradients, both less than 40 mm Hg. The preoperative experience with hypoplastic left heart syndrome has demonstrated the ability of the right ventricle to support the systemic circulation via an unrestrictive patent foramen ovale and maintenance of a patent ductus arteriosus with prostaglandin E j • This pathophysiology can be used to support these infants with aortic stenosis postoperatively. When left ventricular function improves, prostaglandin E] is discontinued and the ductus is allowed to close.
Thoracic and Cardiovascular Surgery
I have two questions for the authors: How was the ductus arteriosus managed in your patients and do you have any intraoperative criteria to determine whether to close the ductus or to leave it open. Dr. Turley. The ductus was maintained patent with prostaglandin E, before the operation in our patients, and at the time of the operation the ductus was snared. It was snared during the bypass run and was ligated as the patient was being weaned from bypass; thus we could evaluate at that point whether the ductus needed to be left open. That was not necessary in any of these patients. All of them had ductus ligation. Dr. Myers. Second, did you find that open valvotomy had any advantage over closed valve dilation? In other words, was your open valvotomy technique a sharp incision of the valve or insertion of a clamp and spreading to dilate the valve? Dr. Turley. In each of the patients treated by open valvotomy, a sharp incision was used. However, over the years I have believed that the initial placement of a suction catheter across the small valves often produces some dilatation along that commissure. The effect of a balloon catheter in doing that is apparent.