Ann Thorac Surg 1998;66:1565-1570
© 1998 The Society of Thoracic Surgeons
Inoperable pulmonary vascular disease in infants with congenital heart disease
Shigeo Yamaki, MDa,b,
Ai Abe, MDa,b,
Koichi Tabayashi, MDa,b,
Masato Endo, MDa,b,
Hitoshi Mohri, MDa,b,
Tohru Takahashi, MDa,b
a Department of Cardiology, Katta General Hospital, Shiroishi, Japan
b Department of Thoracic and Cardiovascular Surgery, Tohoku University School of Medicine, Sendai, Japan
Accepted for publication May 18, 1998.
Address reprint requests to Dr Yamaki, Department of Thoracic and Cardiovascular Surgery, Tohoku University School of Medicine, 980-8574, Japan
e-mail: (s-heart{at}mail.cc.tohoku.ac.jp)
 |
Abstract
|
|---|
Background. Among 120 infants less than 12 months of age who had lung biopsy and autopsy, 20 were inoperable because of severe irreversible pulmonary vascular disease.
Methods. The infants were classified into three groups. Group 1 comprised 6 patients who showed complete obstruction of the small pulmonary arterial lumen and atrophy of the peripheral arterial media and who were considered to have absolute operative contraindications. Group 2 comprised 6 patients who had no pathologic findings of absolute operative contraindication and had an index of pulmonary vascular disease of more than 2.2. They were isolated as having advanced plexogenic pulmonary arteriopathy. Group 3 comprised 8 patients who had extremely thickened media of small pulmonary arteries, with abnormally thickened media extending into the small peripheral arteries characterized by extremely narrow lumina and medial thickness exceeding luminal diameter.
Results. Six of the 9 patients in whom operative repair was abandoned on the basis of preoperative or intraoperative lung biopsy are still alive. Of the 11 patients who underwent operation without biopsy, none survived.
Conclusions. Preoperative or intraoperative lung biopsy and assessment of arteriopathy based on the above criteria are recommended in all patients in whom fatal pulmonary vascular disease is suspected.
|
Introduction
|
|---|
Pulmonary vascular disease (PVD) develops early in life in patients with congenital heart disease and severe pulmonary hypertension [1, 2]. In the past 10 years, we have treated 20 patients less than 12 months of age who were inoperable because of severe irreversible PVD according to lung biopsy or autopsy. We classified the pulmonary arterial changes in these cases into three types and examined the pathogenesis of the pulmonary arterial changes and prognosis of the patients on the basis of morphometric analysis. We also compared the results of morphometric analysis and hemodynamics in these various types of PVD.
|
Material and methods
|
|---|
We examined lung specimens from biopsy or autopsy in 120 patients less than 12 months of age who had congenital heart disease and severe pulmonary hypertension between 1987 and 1996. In most of these patients, lung biopsy had been performed on the basis of previously reported criteria of cardiac catheterization data [3] or clinical signs of a right-to-left shunt. The diagnoses are listed in Table 1. The material selected from this series for the present study consisted of lung specimens from 20 patients (autopsy in 11 patients and lung biopsy in 9 patients), according to the criteria described below. All autopsy cases had had operative repair without preoperative lung biopsy. In most patients, lung biopsy specimens were taken from the right middle lobe, whereas at autopsy, a specimen was obtained from each lobe of both lungs. The lung sections were prepared according to methods reported previously [4]. The medial thickness of small pulmonary arteries was measured by previously reported histometric methods [4, 5]. The mean medial thickness at a radius of 100 µm was calculated and compared among the patients. The severity of the intimal lesions of small pulmonary arteries in each patient was determined using the index of pulmonary vascular disease (IPVD) we previously reported [5, 6]. The Heath-Edwards classification was also used to assess the arterial changes [7]. The pulmonary arterial changes in these 20 patients were classified into three groups: PVD of absolute operative contraindications [8, 9], plexogenic pulmonary arteriopathy, and extremely thickened media of small pulmonary arteries [4]. Patient inoperability was defined according to the following criteria. When there was complete obstruction of small pulmonary arteries because of acute fibrous proliferation of the intima and medial atrophy in the segments distal to the site of obstruction, the patient was classified as absolute operative contraindication [8, 9]. Patients with plexogenic pulmonary arteriopathy that had no features of the above-defined absolute operative contraindication and had an IPVD value higher than 2.2 were classified as inoperable on the basis of previous study [6, 8, 9]. A classification of extremely thickened media of small pulmonary arteries was given in patients in whom medial hypertrophy of these arteries was so severe as to cause marked luminal stenosis, where the medial thickness was equal to or exceeded the luminal diameter [4]. When such changes were observed in more than 10% of all the pulmonary arteries contained in the microscopic slides, the case was considered inoperable [4].
|
Results
|
|---|
Patients with absolute operative contraindication
All 6 patients with absolute operative contraindication (Fig 1) had complete atrioventricular canal defect with Down syndrome (Table 2). Ages ranged from 3 to 11 months (mean, 8.5 months). Pulmonary arterial systolic pressure was between 63 and 90 mm Hg (mean, 76 mm Hg), and pulmonary vascular resistance was between 7.2 and 34.1 units · m2 (mean, 15.3 units · m2). Medial thickness of small pulmonary arteries was between 9.4 and 12.2 µm (mean 10.8 µm). The IPVD was relatively low, with scores between 1.6 and 1.9 (mean, 1.7); the Heath-Edwards grade was 3 in all patients. Operative repair was performed in 3 of 6 patients, all 3 of whom died shortly after operative repair and had an autopsy (cases 1–3). In contrast, in cases 4–6, who were considered inoperable on the basis of lung biopsy, operative repair was not performed, and the patients have survived and been well for 4 to 5 years since biopsy.
View larger version (144K):
[in this window]
[in a new window]
|
Fig 1. Semiserial sections of a small pulmonary artery from proximal (a) to distal (f) in a patient with absolute operative contraindication (Case 2). Note the complete obstruction (c) and medial atrophy in the periphery (e, f). (a–f, x 100 before 66% reduction.)
|
|
Patients with plexogenic pulmonary arteriopathy
Inoperable plexogenic pulmonary arteriopathy was found in 6 patients (Table 3). In these patients, the lungs had a series of pulmonary arterial changes from intimal cellular proliferation to fibrous proliferation, to plexiform lesions and to necrosis of the media. The age of these patients was between 6 and 11 months (mean, 8.5 months), pulmonary arterial systolic pressure was between 49 and 83 mm Hg (mean, 70 mm Hg), and pulmonary vascular resistance was between 6.0 and 14.5 units · m2 (mean, 9.9 units · m2). The mean medial thickness of the small pulmonary arteries was between 10.5 and 15.2 µm (mean, 13.2 µm). The IPVD was above 2.3 in all patients, with a mean of 2.5, and the Heath-Edwards grade was 3 or greater. Operative death occurred in cases 7 and 8 in which preoperative lung biopsy was not performed. In cases 9–12, lung biopsy resulted in a diagnosis of inoperability, and operative repair was not attempted. Cases 9 and 10 died 4 and 5 months after lung biopsy, respectively. Cases 11 and 12 are still alive, having survived for 6 and 4 years, respectively, since the lung biopsy.
Patients with extremely thickened media of small pulmonary arteries
A total of 8 patients were diagnosed as inoperable because of extremely thickened media of small pulmonary arteries based on morphometric measurement (Fig 2, Table 4). The media of the small pulmonary arteries was extremely hypertrophic at 12.6 to 19.5 µm (mean, 16.7 µm). The IPVD was extremely low, ranging from 1.0 to 1.4, with a mean of 1.2. According to the Heath-Edwards classification, 6 of these patients were classified as having grade 1 and showed few if any intimal lesions. The other 2 patients were classified as having grade 2. Their ages were between 1 and 10 months (mean, 6.3 months), pulmonary arterial systolic pressure was between 60 and 100 mm Hg (mean, 70.0 mm Hg), and pulmonary vascular resistance was between 3.1 and 13.3 units · m2 (mean, 7.8 units · m2). Six of these 8 patients underwent operative repair, and 3 died within 24 hours of the operation (cases 13, 14, and 17) and 2 died within 15 days (cases 15 and 16). Only 1 patient (case 20) is still alive 5 years after the operation, but a significant decrease in pulmonary arterial pressure has not been obtained: preoperative and postoperative pulmonary arterial pressure of 76/30 (49) and 72/25 (46) mm Hg, and ascending aortic pressure of 86/37 (63) and 86/47 (66) mm Hg. In the patient with atrial septal defect (case 19) who had a lung biopsy, operative repair was not done so as to leave a route for right-to-left shunt. This patient died of increased cyanosis 7 years after the lung biopsy.
View larger version (139K):
[in this window]
[in a new window]
|
Fig 2. Small pulmonary arteries from the 8 patients with extremely thickened media of small pulmonary arteries. Note the markedly thickened media equal to or thicker than lumen.
|
|
Differences in pathologic characteristics and hemodynamics among the groups
The values of IPVD and the mean medial thickness at a radius of 100 µm were compared among the groups by using Student’s t test. Highly significant differences in the IPVD scores were found (p < 0.001) (Fig 3). The IPVD value in patients with plexogenic pulmonary arteriopathy was the highest (2.47 ± 0.15), followed by patients with absolute operative contraindication (1.73 ± 0.12) and finally by patients with extremely thickened media of small pulmonary arteries (1.23 ± 0.20). The mean medial thickness at a radius of 100 µm was also significantly different among the three groups (p < 0.02) (Fig 4). The media was the thickest in the patients with extremely thickened media of small pulmonary arteries (16.65 ± 2.21 µm), followed by those with plexogenic pulmonary arteriopathy (13.18 ± 1.79 µm), and then those with absolute operative contraindication (10.80 ± 1.08 µm). The pulmonary arterial systolic pressure and pulmonary vascular resistance values were compared among the groups. Both values were the highest in the patients with absolute operative contraindication and the lowest in the patients with extremely thickened media of the small pulmonary arteries, although the differences were not statistically significant.
View larger version (15K):
[in this window]
[in a new window]
|
Fig 3. Index of pulmonary vascular disease (IPVD) in patients with absolute operative contraindication, plexogenic arteriopathy, and extremely thickened media of small pulmonary arteries (extremely thickened arteries). Significant differences in the IPVD scores were found among the groups.
|
|
View larger version (16K):
[in this window]
[in a new window]
|
Fig 4. The mean medial thickness at a radius of 100 µm in the three groups. Significant differences were found among the three groups.
|
|
|
Comment
|
|---|
In patients with congenital heart disease with severe pulmonary hypertension, plexogenic pulmonary arteriopathy develops in early infancy [1, 2, 10]. Among the 20 patients who were inoperable in the present series, 6 had severe plexogenic arteriopathy. The youngest age of 6 months in this group at the time of lung histopathology indicates that before 6 months, PVD might not have advanced enough to reach a critical level. Although both patients in this group who were treated by surgical intervention died shortly after operation, 2 of the 4 patients who did not undergo surgery are long-term survivors, indicating that surgical intervention should be considered on the basis of lung biopsy results. The results of morphometric measurement in this group of 6 patients with plexogenic arteriopathy demonstrated mild hypertrophy of the media of the small pulmonary arteries, whereas the intimal lesions were shown to have advanced more rapidly, resulting in a high average IPVD score of 2.5. This finding leads us to conclude that in this group, medial hypertrophy of the small pulmonary arteries is insufficient even in the presence of increased pulmonary arterial pressure and that this fact underlies the early progression of intimal lesions [11].
In the six cases of complete artrioventricular canal defect with Down syndrome, complete luminal occlusion caused by fibrous proliferation of the intima and atrophy of the distal media was confirmed in most of the small pulmonary arteries. Thickened media of the distal small pulmonary arteries is considered to regress after the vessels are relieved from the increased pressure load. In this state, the patients cannot survive postoperatively if there is not sufficient recanalization of the occluded portion; therefore, such cases should be classified as absolute operative contraindication. The histopathologic changes of the pulmonary arteries in such patients do not differ from a type of plexogenic pulmonary arteriopathy in that the intimal lesions are extremely severe. However, because the operative criteria in such cases should be quite different from those of usual plexogenic pulmonary arteriopathy in which the IPVD method is quite useful, we distinguished this change. The number of arteries in a certain area of lung section having intimal fibrous proliferation is small because the occlusive lesion occupies only a short segment of the arterial pathway. Therefore, the IPVD score is usually lower than 2.2, the critical upper limit for operability in patients with plexogenic pulmonary arteriopathy. In this group, hypertrophy of the media of small pulmonary arteries was the mildest among the three groups. Thinning of hypertrophied media of small pulmonary arteries appears to be responsible for producing the severe intimal lesions that occur abruptly at about 6 months of age [9], which justifies surgical intervention as early as possible. In this group, all 3 patients who had an operation died postoperatively, whereas the other 3 who did not have an operation have survived. It may be concluded that once a diagnosis of absolute operative contraindication is established by lung biopsy, it is essential not to attempt surgical intervention.
Idiopathic persistent pulmonary hypertension of neonates is defined as an abnormal muscularization of the small pulmonary arteries without pulmonary parenchymal disorder or congenital malformation of the lung and upper airways, which is found in neonates with right-to-left shunt due to patent foramen ovale or patent ductus arteriosus [12, 13]. Because our 8 inoperable cases had no parenchymal disorder or congenital malformation of the lung and upper airways, they justifiably could have idiopathic persistent pulmonary hypertension of neonates. However, the right-to-left shunt in these cases was not only caused by patent foramen ovale or patent ductus arteriosus, but also by other congenital cardiac anomalies. Furthermore, there was no shunt in patient 20 who had neither patent foramen ovale nor patent ductus arteriosus. In this series, all patients were infants, not neonates. For these reasons, we have distinguished them from the usual idiopathic persistent pulmonary hypertension of neonates and introduced the term "extremely thickened media of small pulmonary arteries" [4]. We speculate that the natural history in patients with large cardiac septal defects might be longer than that in patients with idiopathic persistent pulmonary hypertension of neonates, because a large amount of right-to-left shunt protects against pulmonary hypertensive crisis. Therefore, operative repair is hazardous in these patients. The results of operation in this group were poor, with as many as five of six cases that underwent operative repair succumbing within 15 days. Our previous study suggested that in cases of extremely thickened media of small pulmonary arteries, neither radical operation nor pulmonary artery banding relieved medial hypertrophy [4]. We also reported that when these changes were found in less than 7% of the pulmonary arteries in lung sections, operative repair is likely to be effective. However, when such changes are found in more than 10% of the arteries, lung transplantation might be recommended.
In the present study, lung biopsy was done in 9 of the 20 patients (cases 4–6, 9–12, 19, and 20), and all 9 were inoperable. Although 3 of the 9 patients (cases 9, 10, and 19) were late deaths, the remaining 6 have survived. In contrast, the 11 patients in whom lung biopsy was not done all had surgical intervention resulting in death. We conclude that, even among patients less than 1 year of age, when fatal PVD is suspected on the basis of hemodynamic studies, histopathologic diagnosis using the criteria discussed above should be made on the basis of lung biopsy findings.
|
Acknowledgments
|
|---|
We acknowledge the following doctors for supplying us with material: Kiyoshi Nagumo, MD, Hokkaido University School of Medicine, Sapporo; Shigeo Tanaka, MD, Aomori Prefectural Central Hospital, Aomori; Susumu Yonesaka, MD, Hirosaki University School of Medicine, Hirosaki; Tetsuo Sato, MD, Yamagata University School of Medicine, Yamagata; Takeo Sakai, MD, and Takashi Tanaka, MD, Tohoku University School of Medicine, Sendai; Kenji Ouchi, MD, and Hiroyuki Kanno, MD, Katta General Hospital, Shiroishi; Hiroko Wakimoto, MD, Tokyo Medical and Dental University, Tokyo; Toshio Kikuchi, MD, and Katsuhiko Tatsuno, MD, The Sakakibara Heart Institute, Tokyo; Itsuro Takikawa, MD, Otsuka City Hospital, Tokyo; Michio Yokota, MD, Shizuoka Childrens’ Hospital, Shizuoka; Seiichi Watanabe, MD, Tsuchiura Kyoudo Hospital, Tsuchiura; Masaki Aota, MD, Shinichi Nomoto, MD, and Toshihiko Ban, MD, Kyoto University School of Medicine, Kyoto; Hideto Shinpo, MD, Mie University School of Medicine, Mie; and Hisataka Yasui, MD, Kyushu University School of Medicine, Fukuoka. We also wish to express our appreciation to our technical assistants, Mrs Takako Kato, Mr Mitsuru Sasaki, and Miss Junko Kato, Sendai City Medical Center, Sendai.
|
References
|
|---|
- Newfeld E.A., Paul M.H., Idriss F. Pulmonary vascular disease in complete transposition of the great arteries: a study of 200 patients. Am J Cardiol 1974;34:75-82.[Medline]
- Clapp S., Rerry B.L., Farooki Z.Q., et al. Down’s syndrome, complete atrioventricular canal, and pulmonary vascular obstructive disease. J Thorac Cardiovasc Surg 1990;100:115-121.[Abstract]
- Yamaki S., Ogata H., Haneda K., Mohri H. Indication for open lung biopsy in patients with ventricular septal defect and/or patent ductus arteriosus with pulmonary hypertension. Heart Vessels 1990;5:166-171.[Medline]
- Yamaki S., Abe A., Endo M., Tanaka T., Tabayashi K., Takahashi T. Surgical indication for congenital heart disease with extremely thickened media of small pulmonary arteries. Ann Thorac Surg 1998;66:1559-1563.
- Yamaki S., Tezuka F. Quantitative analysis of pulmonary vascular disease in complete transposition of the great arteries. Circulation 1976;54:805-809.[Abstract/Free Full Text]
- Yamaki S., Horiuchi T., Ishizawa E., Mohri H., Fukuda M., Tezuka F. Indication for total correction of complete transposition of the great arteries with pulmonary hypertension. J Thorac Cardiovasc Surg 1980;79:890-895.[Abstract]
- Heath D., Edwards J.E. The pathology of hypertensive pulmonary vascular disease: description of six grades of structural changes in the pulmonary arteries with special reference to congenital cardiac septal defects. Circulation 1958;18:533-548.[Medline]
- Yamaki S., Mohri H., Haneda K., Endo M., Akimoto H. Indication for surgery based on lung biopsy in cases of ventricular septal defect and/or patent ductus arteriosus with severe pulmonary hypertension. Chest 1989;96:31-39.[Abstract/Free Full Text]
- Yamaki S., Yasui H., Kado H., et al. Pulmonary vascular disease and operative indication in complete atrioventricular canal defect in early infancy. J Thorac Cardiovasc Surg 1993;106:398-405.[Abstract]
- Wagenvoort C.A., Nauta J., van der Schaar P.J., Weeda H.W.H., Wagenvoort N. The pulmonary vasculature in complete transposition of the great vessels, judged from lung biopsies. Circulation 1968;38:746-754.[Abstract/Free Full Text]
- Yamaki S., Wagenvoort C.A. Plexogenic pulmonary arteriopathy. Significance of medial thickness with respect to advanced pulmonary vascular lesions. Am J Pathol 1981;105:70-75.[Abstract]
- Moller J.H., Neal W.A. Fetal, neonatal, and infant cardiac disease. In: Emmanouilides G.C., ed. Persistent pulmonary hypertension in the neonate. Norwalk, Connecticut: Appleton & Lange, 1990:777-786.
- Rowe R.D., Hoffman T. Transient myocardial ischemia of the newborn infants. A form of severe cardiorespiratory distress in full-term infants. J Pediatr 1972;81:243-250.[Medline]
This article has been cited by other articles:
|
|
|
|
 
M. Ando, Y. Takahashi, and N. Suzuki
Open Heart Surgery for Small Children Without Homologous Blood Transfusion by Using Remote Pump Head System
Ann. Thorac. Surg.,
November 1, 2004;
78(5):
1717 - 1722.
[Abstract]
[Full Text]
[PDF]
|
|
|
Top
Abstract
Introduction
