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Ann Thorac Surg 1997;64:730-734
© 1997 The Society of Thoracic Surgeons

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Original Article: Cardiovascular

Ventricular Hypertrophy as a Risk Factor in Ventricular Septation for Double-Inlet Left Ventricle

Department of Pediatric Cardiovascular Surgery, Heart Institute of Japan, Tokyo Women's Medical College, Tokyo, Japan

Accepted for publication March 5, 1997.

	Abstract

Top Footnotes Abstract Introduction Material and Methods Results Comment References

 
Background. Ventricular septation is an option for surgical correction of double-inlet or common-inlet left ventricle. However, the surgical risk factors of ventricular septation remain unknown.

Methods. Twenty-three patients with double-inlet or common-inlet left ventricle underwent ventricular septation. Preoperative data were compared between the survivors (n = 18) and the nonsurvivors (n = 5) to assess surgical risk factors.

Results. There were two early deaths (9.5%) and three late deaths (14.3%). Nonsurvivors of ventricular septation were significantly older at the time of operation (14.0 ± 6.0 versus 7.0 ± 5.4 years; p < 0.05) and had greater left ventricular mass (383% ± 100% versus 206% ± 57% of normal predicted value; p < 0.005) and greater left ventricular mass to left ventricular end-diastolic volume ratio (1.84% ± 1.18% versus 0.77% ± 0.17%/% of normal predicted value; p < 0.005). Univariate logistic regression analysis also revealed age at operation (p < 0.05) and mass/end-diastolic volume ratio (p < 0.05) as significant risk factors for death after operation. Multivariate regression analysis revealed that age at operation positively influenced increased mass/end-diastolic volume ratio (p < 0.001). These findings indicated that ventricular hypertrophy was one of the risk factors for ventricular septation, which had a tendency to progress with age.

Conclusions. Early operation before progression of ventricular hypertrophy is recommended in patients with double-inlet or common-inlet left ventricle who have suitable anatomy for the ventricular septation procedure.

	Introduction

Top Footnotes Abstract Introduction Material and Methods Results Comment References

 
Since the first successful report of ventricular septation for double-inlet left ventricle (LV) in 1956 [1], it has been an option for surgical correction of double-inlet or common-inlet LV. However, surgical mortality was relatively high in previous reports [2–5]. One of the reasons for this high mortality is that indications and risk factors for this procedure have not yet been established. A restrictive bulboventricular foramen has been reported to be one of the risk factors [3, 4]. It also has been speculated that ventricular hypertrophy induced by the subaortic obstruction may increase the risk, although the obstruction can be released surgically at the time of ventricular septation. This study estimated the LV mass (LVM) and the ratio of ventricular mass to end-diastolic volume (M/EDV) as indices of ventricular hypertrophy and also evaluated the impact of ventricular hypertrophy on the surgical outcome of ventricular septation in patients with double-inlet or common-inlet LV.

	Material and Methods

Top Footnotes Abstract Introduction Material and Methods Results Comment References

 
Patients
From April 1986 to April 1994, 23 patients underwent ventricular septation for double-inlet or common-inlet LV. The age at operation ranged from 1 to 24 years with an average of 8.6 years. There were 16 male and 7 female patients. One patient had a common-inlet LV and an isolated ventricular inversion with situs solitus, l-loop, D-transposition. The remaining 22 patients had double-inlet LV: 19 patients had situs solitus, L-loop, L-transposition; 1 patient had situs solitus, D-loop, D-transposition with a right anterior subaortic outlet chamber; and 2 patients had situs solitus, D-loop, and normal relation of the great arteries (so-called Holmes heart). Ten patients had restrictive bulboventricular foramen with a pressure gradient of 5 to 85 mm Hg (mean, 36 mm Hg) between the LV and the ascending aorta. Associated anomalies were as follows:

Eighteen patients had undergone one or more previous operations including pulmonary artery banding (PAB) in 16 patients. Three of these 16 patients had simultaneous subclavian flap aortoplasty for associated coarctation of the aorta. Two other patients had previous Blalock-Taussig shunt, 1 had Blalock-Hanlon atrial septectomy, and 1 had a Waterston shunt.

Surgical Techniques
The operations were performed using cardiopulmonary bypass and moderate hypothermia with an average aortic cross-clamp time of 114 ± 44 (standard deviation) minutes. The technical details of ventricular septation have been reported previously [6, 7]. The operation was performed through the right-sided atrioventricular valve in all cases [6–8]. Ten patients with subaortic obstruction required enlargement of the restrictive bulboventricular foramen. The ventricle was separated with a composite patch of glutaraldehyde-treated equine pericardium and Dacron velour, which was placed with pledgeted mattress sutures. One patient with pulmonary atresia underwent a simultaneous extracardiac conduit repair. One patient with a rudimentary right anterior outlet chamber had an additional arterial switch operation. Another patient with common-inlet LV underwent a partition of the atrioventricular valve. Other concomitant procedures at ventricular septation were as follows:

Study Methods
Data were collected retrospectively from medical records, preoperative cardiac catheterizations, and cineangiograms. Preoperative variables included in the analysis were age at operation, systemic oxygen saturation, pulmonary vascular resistance, LV end-diastolic volume, LV ejection fraction, LVM, M/EDV, LV end-diastolic pressure, pulmonary flow index plus systemic flow index [9], and pressure gradient between the LV and the ascending aorta. The LV end-diastolic volume was obtained by the method of Dodge and associates [10] and evaluated as a percentage of normal predicted value, as done by Nakazawa and colleagues [11]. The LVM was calculated according to the method of Rackley and associates [12], substituting the LV posterior wall thickness obtained by short-axis view of echocardiography for the lateral free wall thickness. The LVM was expressed as a percent of normal predicted value, as done by Graham and coworkers [13]. The M/EDV was expressed as a ratio of the LVM and the end-diastolic volume, both in percentage of normal predicted value. The patients were divided into a survivor group and a nonsurvivor group on the basis of the surgical outcome. Preoperative data were compared between the two groups using unpaired t test or Mann-Whitney test as appropriate. Univariate logistic regression analysis was also performed for the variables to detect risk factors of ventricular septation. The relation between the surgical outcome and the presence of previously reported risk factors such as restrictive bulboventricular foramen or previous PAB was analyzed using a contingency table with Fisher's exact test.

	Results

Top Footnotes Abstract Introduction Material and Methods Results Comment References

 
Surgical Results
There were two early deaths (9.5%) and three late deaths (14.3%). The 18 survivors have been followed up for 6 months to 8 years after the ventricular septation, and all were free from reoperation. All but 1 were in New York Heart Association functional class I, and 1 patient was in class II.

A 17-year-old girl who preoperatively had the smallest ventricular volume (168% of normal) and the largest ventricular mass at 533% of the normal value died 2 days after ventricular septation in spite of assisted mechanical circulation. Autopsy of this patient revealed severe concentric ventricular hypertrophy with an LV posterior wall thickness of 29 mm and septal wall thickness of 20 mm. Another 16-year-old male patient died of low cardiac output state 8 days after ventricular septation. Among the 3 patients who died later, 2 patients had severely restrictive bulboventricular foramen preoperatively with pressure gradients of 65 and 85 mm Hg. One of the 2 patients underwent a simultaneous extracardiac conduit repair for pulmonary atresia. They died of low cardiac output state 6 and 7 weeks after operation. The third patient was a 6-year-old boy who had a simultaneous arterial switch operation and later required an aortic valve replacement due to progression of aortic regurgitation at 1 month after ventricular septation. The patient died of congestive heart failure 10 weeks postoperatively.

Assessment of Surgical Risk Factors
Comparisons of the preoperative data of survivors and nonsurvivors revealed statistically significant differences with respect to the age at operation, end-diastolic pressure, LV, LVM, and M/EDV. However, there were no significant differences in preoperative systemic oxygen saturation, pulmonary vascular resistance, end-diastolic volume, and LV ejection fraction (Table 1).

View larger version (18K): [in this window] [in a new window]   Fig 1. . Relation between preoperative left ventricular mass to end-diastolic volume ratio (M/EDV) and probability of death within 6 months determined by univariate logistic regression analysis. The dashed lines depict the 70% confidence intervals.

View larger version (18K): [in this window] [in a new window]   Fig 2. . Relation between age at operation and probability of death within 6 months determined by univariate logistic regression analysis. The dashed lines depict the 70% confidence intervals.

	Comment

Top Footnotes Abstract Introduction Material and Methods Results Comment References

 
The present study has shown that ventricular concentric hypertrophy (increased M/EDV) and older age were significant risk factors for ventricular septation in double-inlet or common-inlet LV and that larger M/EDV was related to older age at operation. McKay and associates [3] reported that obstruction of bulboventricular foramen was an incremental risk factor associated with hospital mortality for ventricular septation procedure. However, the present study demonstrated that restrictive bulboventricular foramen per se was not a risk factor for death after operation. These findings suggest that the left ventricular hypertrophy caused by the obstruction of bulboventricular foramen and older age is likely the factor that is more directly associated with increased mortality. In fact, a multivariate linear regression analysis in the present study demonstrated that larger M/EDV significantly correlated with age. In our series, a 4-year-old boy who had a severe restrictive bulboventricular foramen with a pressure gradient of 65 mm Hg survived, although 2 older patients (10 years and 21 years old) with similar pressure gradients did not.

The mechanisms of ventricular hypertrophy have been extensively studied. During the postnatal period the mitotic activity of cardiac myocytes declines rapidly. It was reported that exposure of the neonatal heart to hypoxia resulted in proliferation of myocytes and fibroblasts [14]. Myocyte mitotic activity and the potential for hyperplasia as a response for a chronic stress may continue from a few weeks to 3 months after birth in mammals [15]. After the capacity for hyperplasia is lost during growth, hypoxia induces ventricular hypertrophy by increasing myocyte size in the mature heart [16]. Hypoxia has been shown to result in increase of LV mass in adult animals [17], suggesting that hypoxia is probably responsible for the mechanisms promoting hypertrophy in the ventricle of the patients with double-inlet LV.

Another important factor related to ventricular hypertrophy is increased afterload. Pressure overload plays a major role in inducing concentric hypertrophy. Generally, the increased afterload of the ventricle is compensated by an increase in wall thickness, thereby reducing the systolic wall stress to a normal level. Increased afterload has been shown to increase the diameter of myocytes and the number of the sarcomeres in parallel [18]. Size of the ventricular cavity does not increase compared with the ventricular wall thickness [19]. Thus, pressure overload due to obstruction of bulboventricular foramen may induce concentric hypertrophy and increase M/EDV ratio of the double-inlet LV. The longer the afterload imposed on the ventricle, the further the ventricular concentric hypertrophy progresses.

Volume overload may also have influence on ventricular hypertrophy. The ventricle of double-inlet LV inherently has to eject both systemic and pulmonary flows, resulting in a long-lasting volume overloading condition. However, this eccentric hypertrophy causes wall thickening to a level that normalizes the wall stress by increasing the LVM proportional to the end-diastolic volume [18]. Thus, it is unlikely that volume overload alone would induce an increase in M/EDV.

The effect of pressure overload on LV functional characteristics is different between neonates and adults. Russell and Robert [20] demonstrated that LV systolic function was preserved in neonatal rats under experimental aortic constriction in contrast to the adult counterparts, which showed LV systolic dysfunction. The capacity for adaptation to pressure load in neonates seems to be greater than that of adults. Therefore, obstruction of bulboventricular foramen or subaortic stenosis associated with double- or common-inlet LV in some patients beyond the neonatal period is likely to cause inadequate adaptation of the ventricle to the pressure overload and may contribute to cardiac dysfunction.

After ventricular septation, the contractile performance of a new LV definitely decreases as a whole because of paradoxical motion of the new prosthetic septum during the systolic phase [21]. Additionally, the hypertrophied ventricle may be less tolerant to ischemia during aortic cross-clamping. This increased susceptibility of the hypertrophied LV to surgical ischemia may lead to postoperative low cardiac output state. Impaired diastolic function in hypertrophied ventricle caused by surgical ischemia may also lead to an elevation of the left atrial pressure, followed by an elevation of the pulmonary arterial pressure. This may contribute to failure of the right ventricle that has a small cavity after ventricular septation [7, 20].

According to previous reports, other surgical risk factors of ventricular septation included small ventricular volume [3, 4, 6] and abnormality of atrioventricular valve [4]. However, these reports did not calculate the ventricular volume. Imai and associates [7] reported that minimal ventricular volume necessary for ventricular septation was approximately 200% of predicted normal LV, and the smallest ventricular volume in the survivors was 172% of normal. Stefanelli and associates [4] and Felt and colleagues [2] also reported that simultaneous atrioventricular valve replacement increased the mortality rate. In our series, among 4 patients who required atrioventricular valve repair, 2 patients died. Both these patients had severe restrictive bulboventricular foramen preoperatively with pressure gradients of more than 65 mm Hg and high LV systolic pressure, which might cause atrioventricular valve regurgitation. We infer that the abnormality of the atrioventricular valve per se is not a risk factor if the atrioventricular valve is repairable. Indeed a patient with a common atrioventricular valve underwent successful ventricular septation. However, we consider that ventricular septation should be done early because restrictive bulboventricular stenosis may cause not only ventricular hypertrophy but also atrioventricular valve regurgitation due to high systolic LV pressure.

Our initial surgical strategy for infants who have double-inlet or common-inlet LV with increased pulmonary blood flow is PAB. Freedom and associates [22] argued that subaortic stenosis in patients with double-inlet LV progressed after PAB because of ventricular hypertrophy. It is not clear whether the PAB would cause ventricular hypertrophy in the absence of primary subaortic stenosis, because the ventricular systolic wall stress will not increase after PAB if the ventricular pressure remains the same as before PAB. On the other hand, a reduction in ventricular cavity volume caused by PAB may disclose a potential narrowing of the LV outflow tract. A loose pulmonary artery banding may be preferable in a sense that it maintains adequate ventricular volume for ventricular septation and wide outflow tract. However, we prefer rather tight banding to leave a Fontan-type procedure as an alternative option and perform early correction (either ventricular septation or Fontan-type procedure) before ventricular hypertrophy progresses.

The methodology for estimation of LV mass, especially that of double-inlet LV, is controversial. Sano and associates [23] calculated LVM of double-inlet LV using Rackley's method. In this report, we also used Rackley's theory, although, we substituted the posterior wall thickness measured in the short-axis view of the echocardiogram for the lateral free wall thickness obtained by cineangiogram. The shadow of the lateral free wall in the cineangiogram was not clear enough for precise measurement of the wall thickness in several cases of double-inlet LV. Moreover, wall thickness from the cineangiogram may be overestimated in a patient with pericardial effusion. Therefore, we believed that the posterior wall thickness measured by echocardiography would be a more accurate estimation of the wall thickness.

We conclude that ventricular hypertrophy, especially concentric hypertrophy, is a risk factor of ventricular septation in patients with double- or common-inlet LV. Although the mechanism of ventricular hypertrophy in double-inlet LV remains unclear, hypoxia, volume overload, and particularly pressure overload may play a role in inducing ventricular hypertrophy. Early ventricular septation is desirable in those patients because the ventricular hypertrophy has a tendency to progress with age and adversely affect the surgical outcome.

	Footnotes

Top Footnotes Abstract Introduction Material and Methods Results Comment References

	References

Top Footnotes Abstract Introduction Material and Methods Results Comment References

 

1. McGoon DC, Danielson GK, Ritter DG, et al. Correction of the univentricular heart having two atrioventricular valves. J Thorac Cardiovasc Surg 1977;74:218–26.[Abstract]
2. Feldt RH, Mair DD, Danielson GK, Wallace RB, McGoon DC. Current status of the septation procedure for univentricular heart. J Thorac Cardiovasc Surg 1981;82:93–7.[Abstract]
3. McKay R, Pacifico AD, Blackstone EH, Kirklin JW, Bargeron LH Jr. Septation of the univentricular heart with left anterior subaortic outlet chamber. J Thorac Cardiovasc Surg 1982;84:77–87.[Abstract]
4. Stefanelli G, Kirklin JW, Naftel DC, et al. Early and intermediate-term (10 year) result of surgery for univentricular atrioventricular connection ("single ventricle"). Am J Cardiol 1984;54:811–21.[Medline]
5. Franklin RCG, Spiegelhalter DJ, Filho RR, et al. Double-inlet ventricle presenting in infancy. III. Outcome and potential for definitive repair. J Thorac Cardiovasc Surg 1991;101:924–34.[Abstract]
6. Kurosawa H, Imai Y, Fukuchi S, et al. Septation and Fontan repair of univentricular atrioventricular connection. J Thorac Cardiovasc Surg 1990;99:314–9.[Abstract]
7. Imai Y, Hoshino S, Koh YS, et al. Ventricular septation procedure for univentricular connection of left ventricular type. Semin Thorac Cardiovasc Surg 1994;6:48–55.[Medline]
8. Doty DB, Schieken RM, Lauer RM. Septation of the univentricular heart. J Thorac Cardiovasc Surg 1979;78:423–30.[Abstract]
9. Mair DD, Hagler DJ, Puga FJ, et al. Fontan operation in 176 patients with tricuspid atresia. Circulation 1990;82(Suppl 4):164–9.[Abstract/Free Full Text]
10. Dodge HT, Sandler H, Ballew DW, Lord JD Jr. The use of biplane angiocardiography for the measurement of left ventricular volume in man. Am Heart J 1960;60:762–76.[Medline]
11. Nakazawa M, Marks RA, Isabel-Jones J, Jarmakani JM. Right and left ventricular volume characteristics in children with pulmonary stenosis and intact ventricular septum. Circulation 1976;53:884–90.[Abstract/Free Full Text]
12. Rackley CE, Dodge HT, Coble YD Jr, Hay RE. A method for determining left ventricular mass in man. Circulation 1964;29:666–71.[Abstract/Free Full Text]
13. Graham TP Jr, Jarmakani JM, Canent RV Jr, Morrow MN. Left heart volume estimation in infancy and childhood. Reevaluation of methodology and normal values. Circulation 1971;43:895–904.[Abstract/Free Full Text]
14. Hollenberg M, Honbo N, Samarodin AJ. Effects of hypoxia on cardiac growth in neonatal rat. Am J Physiol 1976;231:1445–50.[Abstract/Free Full Text]
15. Di Donato RM, Fujii AM, Jonas RA, Castañeda AR. Age-dependent ventricular response to pressure overload. J Thorac Cardiovasc Surg 1992;104:713–22.[Abstract]
16. Perloff JK. Development and regression of increased ventricular mass. Am J Cardiol 1982;50:605–11.[Medline]
17. Genovese A, Chiariello M, Latte S, et al. Bilateral ventricular hypertrophy in rats exposed to acute or chronic hypobaric hypoxia. Respiration 1983;44:289–93.[Medline]
18. Schlant RC, Sonnenblick EH. Pathophysiology of heart failure. In: Schlant EH. The heart, arteries, and veins, 8th ed. New York: McGraw-Hill, 1994:515–55.
19. Sasayama S, Ross J Jr, Franklin D, et al. Adaptation of the left ventricle to chronic pressure overload. Circ Res 1976;38:172–8.[Abstract/Free Full Text]
20. Russell TD, Robert EM III. Pressure-induced cardiac enlargement in neonatal and adult rats. Circ Res 1978;42:303–10.[Free Full Text]
21. Nakazawa M, Aotsuka H, Imai Y, et al. Ventricular volume characteristics in double-inlet left ventricle before and after septation. Circulation 1990;81:1537–43.[Abstract/Free Full Text]
22. Freedom RM, Benson LN, Smallhorn JF, et al. Subaortic stenosis, the univentricular heart, and banding of the pulmonary artery: an analysis of the courses of 43 patients with univentricular heart palliated by pulmonary artery bandings. Circulation 1986;73:758–64.[Abstract/Free Full Text]
23. Sano T, Ogawa M, Yabuuchi H, et al. Quantitative cineangiographic analysis of ventricular volume and mass in patients with single ventricle: relation to ventricular morphologies. Circulation 1988;77:62–9.[Abstract/Free Full Text]

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