The morphologically tricuspid valve in hypoplastic left heart syndrome

European Journal of Cardio-thoracic Surgery 12 (1997) 587 592 The morphologically tricuspid valve in hypoplastic left heart syndrome Christof Stamm, Robert H. Anderson, Siew Yen Ho * Paediatrics, Imperial College School of Medicine, National Heart and Lung Institute, Do ehouse Street, London SW3 6LY, UK Received 3 March 1997; received in revised form 12 May 1997; accepted 21 May 1997 Abstract Objective: Competence of the tricuspid valve is crucial for survival of children with hypoplastic left heart syndrome. We studied the morphology and topology of the valvar and subvalvar structures, trying to identify abnormalities which could impair valvar function. Methods: A total of 82 specimens with hypoplastic left heart syndrome were examined pathologically. Measurements of valvar dimensions were taken, significant dysplasia of the valvar leaflets was noted and the muscular and tendinous supporting structures determined. The findings were correlated to the subgroups of hypoplastic left heart syndrome. Results: Of the hearts, 10 (12%) showed a bileaflet right atrioventricular valve, 27 (33%) a moderately and 2 (2%) a severely dysplastic tricuspid valve. The majority of the abnormalities was found in hearts with a patent mitral valve. In 79% of the hearts with mitral atresia, the septal surface was concave instead of convex to the right ventricular lumen and the direct tendinous attachments of the septal leaflet replaced by a multitude of freestanding papillary muscles. The number of direct septal attachments was significantly higher in hearts with a patent mitral valve. Conclusions: The tricuspid valve in hypoplastic left heart syndrome can differ from the valve seen in normal patients. The subvalvar apparatus is different in hearts with mitral atresia, whereas dysplasia of the leaflets occurs more often together with mitral stenosis. These features should be considered in reconstructive operations as well as during diagnostic procedures. 1997 Elsevier Science B.V. Keywords: Aortic atresia; Aortic stenosis; Hypoplastic left heart syndrome; Mitral atresia; Mitral stenosis 1. Introduction Hypoplastic left heart syndrome represents a spectrum of congenital malformations, which, without surgical intervention, is uniformly fatal within the first weeks of life. Besides the possibility of cardiac transplantation in the newborn or infant, reconstructive surgical techniques have now been in use for over a decade. Norwood and his colleagues established a three-staged concept for treatment, resulting in a modified Fontan-circulation after initial augmentation of the hypoplastic ascending aorta [1,2]. Since mortality of these complex surgical procedures is steadily decreasing, a growing number of children live with the morphologically right ventricle, and the corresponding right * Corresponding author. Tel.: +44 171 3518751; fax: +44 171 3518230; e-mail: yen.ho@ic.ac.uk atrioventricular and ventriculoarterial valves, supporting the systemic circulation. Significant tricuspid regurgitation occurs only rarely, but, if present, can cause severe clinical problems [3 6]. Mild regurgitation, frequently observed, does not represent a risk factor for operative treatment, but its long-term effects are, as yet, not known [7,8]. Although the morphology of the overall hypoplastic left heart syndrome has been extensively reviewed, relatively little attention has been paid to the potentially crucial tricuspid valve [9 13]. Structural abnormalities of the leaflets are rare, but, to the best of our knowledge, the supporting subvalvar structures have been studied only by Bharati and Lev [14]. To add further information, therefore, we studied the morphology and topology of the valvar and subvalvar apparatus of the tricuspid valve in 82 hearts falling in the spectrum of hypoplastic left heart syndrome, focusing on abnormal- 1010-7940/97/$17.00 1997 Elsevier Science B.V. All rights reserved. PII S1010-7940(97)00184-X

588 C. Stamm et al. / European Journal of Cardio-thoracic Surgery 12 (1997) 587 592 Table 1 Measurements of right ventricular and tricuspid valvar dimensions in relation to the subtype of HLHS RV-Inlet length a (mm) Circumference of tricuspid valvar orifice a Septal leaflet Antero-superior leaflet a (mm) (mm) a (mm) Inferior leaflet a (mm) MA/AA 27.5 4.7 45.3 4.5 13 3 (28.7%) b 20.7 3.5 (45.7%) 11.6 3.2 (25.6%) MS/AA 30.6 4.3 45.7 5.7 12.9 2.8 21.1 3.6 (46.2%) 11.7 3.9 (25.6%) (28.2%) MS/AS 31.9 7.6 46.8 7.7 14.8 3.4 23.9 4.3 (51.1%) 11.3 3.4 (24.1%) (31.6%) AA, aortic atresia; AS, aortic stenosis; HLHS, hypoplastic left heart syndrome; MA, mitral atresia; MS, mitral stenosis; S.D., standard deviation. a Mean S.D. b Numbers in parens are % of annulus. ities which might potentially impair long-term valvar function. 2. Material and methods We examined all 82 specimens satisfying inclusion in the category of hypoplastic left heart syndrome which were found in the pathological collection of the National Heart and Lung Institute, London, UK. The criteria for inclusion were: presence of concordant atrioventricular connections, with left ventricular hypoplasia or absent left atrioventricular connection; concordant ventriculoarterial connections with aortic hypoplasia or absent left ventriculoarterial connection; and no significant ventricular septal defect. The inflow and outflow tracts of the morphologically right ventricle were opened carefully. After measuring the length of the inflow tract, we determined the circumference of the tricuspid valvar orifice at the atrioventricular junction, and the width of each leaflet at its hingepoint. The degree of leaflet dysplasia was described as moderate or severe. Moderately dysplastic leaflets were thickened, less mobile, and the free edge often showed nodular malformations. The tendinous chords were often shortened and the interchordal spaces obliterated. Coaptation of the leaflets could be manipulated with forceps. Severely dysplastic leaflets showed thicker and relatively immobile leaflets. The main feature to distinguish severe from moderate forms of dysplasia was that the leaflets could not be coapted in the pathologic specimens, probably representing severe regurgitation in the beating heart. The nature, number, and location of the papillary muscles were noted, together with the arrangement of the zones of apposition (commissures) between adjacent leaflets. Special attention was paid to the supporting structures of the septal leaflet. We also assessed the shape of the ventricular septum, as seen from the right ventricle, as being convex (bulging into the right ventricular cavity as in normal hearts), straight, or concave (giving the right ventricular cavity an almost circular cross-sectional appearance). Of the 82 patients, 42 were male and 40 were female. The age at the time of death ranged between 1 day and 1 year, with a mean of 22 61 days. Of 8 patients who had undergone surgery: 3 died after a first stage Norwood procedure, 2 after implantation of a systemic-topulmonary arterial shunt; 2 after aortic valvar commisurotomy; and 1 after resection of an aortic coarctation. Associated cardiac malformations, other than those belonging to the category of hypoplastic left heart syndrome or concerning the tricuspid valve, were rare. A large defect within the oval fossa was found in one, partially anomalous pulmonary venous connection in another, multiple but diminutive ventricular septal defects in two; and bilateral arterial ducts in a final patient. 3. Results Of the hearts, 38 (46%) showed mitral atresia and aortic atresia, 27 (33%) showed mitral stenosis and aortic atresia, 16 (20%) showed combined mitral and aortic stenosis and 1 heart (1%) showed mitral atresia with aortic stenosis. The dimensions of the right ventricle, the tricuspid valvar orifice, and the width of each leaflet are shown in Table 1. There is no statistically significant difference in those dimensions between the three groups of specimens. A right atrioventricular valve with only two leaflets was found in none of the hearts with combined leftsided atresia, but was seen in 4 (15%) of the hearts with mitral stenosis and aortic atresia, and 6 (38%) of the hearts with combined stenosis, with an overall incidence of 12.2%. We found 2 hearts with a quadricuspid right atrioventricular valve. Accessory orifices were present in 2 hearts, both with mitral stenosis and aortic atresia (Fig. 1 and Fig. 2). Dysplasia of the tricuspid valvar leaflets was distributed with similar frequency throughout the groups (Table 2), but a markedly higher incidence of structural or architectural abnormalities was found in presence of a patent mitral valve (Fig. 1a). Ebstein s malformation

C. Stamm et al. / European Journal of Cardio-thoracic Surgery 12 (1997) 587 592 589 was discovered involving both the tricuspid and mitral valves in one case (Fig. 1b). Interestingly, all 3 hearts from patients who died after the first stage of a Norwood procedure showed abnormalities of the tricuspid valve; in one case the heart had three delicate leaflets but prolapse of the antero-superior leaflet, another heart showed a bileaflet right atrioventricular valve with moderately dysplastic leaflets and the third heart had severely dysplastic leaflets as part of a parachute malformation. Our observations concerning the supporting apparatus of the tricuspid valve reflected the known variability of right ventricular structures. Nevertheless, we noted some features obviously related to the hypoplastic left heart syndrome. In all but two of the hearts with combined mitral and aortic atresia, three distinct Fig. 2. (a) The right side of this heart shows a severely malformed tricuspid valve with a bizzare arrangement of valvar apparatus. The septal leaflet has multiple insertions to papillary muscles located postero-inferiorly, and in the apex instead of direct attachments to the septum. A bridge of valvar tissue between the septal and anterosuperior leaflets results in the formation of an accessory orifice (arrowhead). (b) The left side shows a tiny accessory orifice (arrowhead) in the mitral valve, a short antero-lateral papillary muscle and direct attachments of the mural leaflet to the ventricular wall. The stars indicate the coronary sinus. groups of papillary muscles were identified. They were the prominent anterior papillary muscle, a more variable group of inferior papillary muscles, and a medial Table 2 Frequency of dysplasia of the tricuspid valve in relation to the subtypes of HLHS Fig. 1. (a) A heart with mitral atresia and aortic stenosis displayed to show the right side. The leaflets of the tricuspid valve are thickened with rolled edges (arrowheads). The medial papillary muscle is not evident. A small ventricular septal defect (VSD) is present. (b) This heart with mitral stenosis and aortic atresia had Ebstein s malformation affecting both the tricuspid and mitral valves. The tricuspid valve has been opened through its major orifice. Note the apically displaced hinge of the septal leaflet (small arrows). The regular atrioventricular junction is marked by the broken line. The medial papillary muscle is absent. In its place is an anomalous muscle band (cut through between the stars) attached to the supraventricular crest and the parietal wall. The open arrowheads indicate two accessory orifices. Subtype of HLHS TV-dysplasia Moderate Severe None MA/AA (n=38+1) 6 (15%) 0 (0%) 33 (85%) MS/AA (n=27) 13 (48%) 0 (0%) 14 (52%) MS/AS (n=16) 8 (50%) 2 (12%) 6 (38%) Total (n=82) 27 (33%) 2 (2%) 53 (65%) AA, aortic atresia; AS, aortic stenosis; HLHS, hypoplastic left heart syndrome; MA, mitral atresia; MS, mitral stenosis; TV, tricuspid valve.

590 C. Stamm et al. / European Journal of Cardio-thoracic Surgery 12 (1997) 587 592 Fig. 3. Diagram depicting the three shapes of the ventricular septum as viewed from the apex of the heart in relation to the variations in attachments of the septal leaflet. MA/AA, combined mitral and aortic atresia; MS/AA, mitral stenosis with aortic atresia; MS/AS, combined mitral and aortic stenosis. papillary muscle arising from the supraventricular crest and supporting the zone of apposition between the septal and the antero-superior leaflets. In hearts with a patent mitral valve, the supraventricular crest was markedly shallow, so that in 12 (44.4%) of the hearts with mitral stenosis and aortic atresia, and in 9 (56.3%) of the hearts with combined stenosis, no distinct medial papillary muscle could be identified. The zone of apposition between the septal and antero-superior leaflets was supported mostly by tendinous cords attached to the supraventricular crest. A prominent anterior papillary muscle was present in every heart examined, supporting the antero-superior leaflet itself as well as the zone of apposition between the antero-superior and the inferior leaflets. The inferior papillary muscle showed many variations of size and number of subunits, as is well known for normal hearts. This was the case for all the abnormal hearts examined, irrespective of the patency of the mitral valve. The support of the free edge of the septal leaflet was closely related to the morphology of the ventricular septum. In 30 (79%) of the hearts with combined left-sided atresia, the septal surface was clearly concave to the right ventricular lumen. Very few of these hearts showed the typical direct septal attachments of the septal leaflet. Instead, the leaflet was supported by a multitude of additional muscles arising from the septal part of the ventricular wall. Only in 19 and 25%, respectively, of the hearts with mitral stenosis and aortic atresia, or combined stenosis, was the septal surface concave. In the majority of these hearts, the septum was either straight or convex, as seen in normal hearts (Fig. 3). The number of direct tendinous cords arising from the septum was significantly higher in these hearts (P=0.0002). 4. Discussion The capacity of the morphologically right ventricle to support the systemic circulation has long been debated. In the very particular conditions of the Fontan circulation, as occurs after completion of the Norwood Procedure, this feature becomes even more crucial. Even if the presence of mild tricuspid regurgitation does not necessarily have a negative impact on the operative results of palliative surgery for hypoplastic left heart syndrome [7,8], there can be no question that significant atrioventricular valvar regurgitation reduces long-term hemodynamic performance after the classic or modified Fontan Operation [4,5,15]. After the early morphologic studies on hypoplastic left heart syndrome focused on the deficient structures of the left heart [9,10], the success of the Norwood Procedure drew attention to the now essential right ventricle [12 14]. The overall incidence of moderately or severely dysplastic tricuspid leaflets in our material is similar to that reported by other groups [13,14]. What has not been shown before is the markedly higher incidence of dysplastic changes in hearts with a patent mitral valve. We are unable to offer an explanation for this fact. It is surprising to find a higher degree of abnormal tricuspid leaflets in those hearts with a patent mitral valve which might be considered to be closer to normal.

C. Stamm et al. / European Journal of Cardio-thoracic Surgery 12 (1997) 587 592 591 As in the normal heart [15,16], the tricuspid valve was not perfectly tricuspid in some cases. The bi- or quadricuspid constitition of the valve is unlikely to affect valvar competence. More importantly, accessory orifices, though rare, was observed in two of our cases but none in the 230 specimens examined by Bharati and Lev [14]. In addition, there was 1 heart in our series in which Ebstein s malformation distorted both the tricuspid and mitral valves. These malformations can certainly influence surgical outcome if missed at initial diagnosis. Concerning the subvalvar apparatus, our findings are somewhat easier to explain. Bharati and Lev [14] described in great detail the attachment of the septal leaflet to the septum by accessory papillary muscles in their large series, and emphasised also the abnormal architecture of the other groups of papillary muscles. We were able to correlate these marked changes in intraventricular architecture to the morphology of the ventricular septum. In hearts with a minute left ventricle, the septum becomes functionally part of the free wall of the right ventricle, giving its cavity an almost circular shape with a concave septal surface. Since the tricuspid valve is much more closely related to the septum than is the mitral valve [17,18], this causes fundamental changes in the architecture of the subvalvar apparatus. The typical direct attachments of the septal leaflet are replaced by additional free-standing papillary muscles. We take these changes as an adaptive process; nature might try to prevent incompetence of the valve by giving the septal leaflet a greater degree of mobility. In hearts with a more pronounced ventricular septum, the usual architecture of the septal part of the tricuspid valve is more readily preserved. Overall, therefore, we found markedly dysplastic tricuspid valves almost exclusively in hearts with a patent mitral valve. Since the prognosis of these patients may potentially be limited, we must try to identify them as soon as possible. We also demonstrated that the right atrioventricular valve in patients with hypoplastic left heart syndrome can be very different from the morphologically tricuspid valve in normal patients. The echocardiographer must be aware of this feature while assessing these crucial structures, as must the surgeon when it comes to reconstructive operations. 4.1. Limitations of the study The difficulties of assessing sizes and shapes in formalin-fixed hearts are well known. Because of this, we tried to concentrate on clear morphologic features of the examined structures. The shape of the ventricular septum was so well defined in all specimens we believe that it almost certainly reflects the conditions in the living patient. Since the majority of the examined hearts came from patients only a few days old at the time of death, we could not examine the group of greatest interest, namely patients surviving all the stages of the Norwood Procedure. With a growing morphologically right ventricle, the septal structures are likely to become even more deficient, thus making the right atrioventricular valve in those patients even less a normal tricuspid valve. The long-term anatomic and physiologic changes imposed by a circulation supported by a functionally single right ventricle remain unclear, and surely need further investigation. Acknowledgements During this investigation, CS was a visiting fellow from the Department of Thoracic and Cardiovascular Surgery, University of Göttingen, Germany, supported by a grant from the German Scientific Association (Deutsche Forschungsgemeinschaft). RHA and SYH are supported by the British Heart Foundation together with the Joseph Levy Foundation. References [1] Norwood WI, Lang P, Hansen DD. Physiologic repair of aortic atresia hypoplastic left heart syndrome. N Engl J Med 1983;308:23 6. [2] Norwood WI. Hypoplastic left heart syndrome. Ann Thorac Surg 1991;52:688 95. [3] Helton JG, Aglira BA, Chin AJ, Murphy JD, Pigott JD, Norwood WI. Analysis of potential anatomic or physiologic determinants of outcome of palliative surgery for hypoplastic left heart syndrome. Circulation 1986;74(Suppl I):I70 I76. [4] Barber G, Helton JG, Aglira BA, Chin AJ, Murphy JD, Pigott JD, Norwood WI. The significance of tricuspid regurgitation in hypoplastic left heart syndrome. Am Heart J 1988;116:1563 7. [5] Chang AC, Farrel PE, Murdison KA, Baffa JM, Barber J, Norwood WI, Murphy JD. Hypoplastic left heart syndrome: Hemodynamic and angiographic assessment after reconstructive surgery and relevance to modified Fontan procedure. J Am Coll Cardiol 1991;17:1143 9. [6] Farrel PE, Chang AC, Murdison KA, Baffa JM, Norwood WI, Murphy JD. Outcome and assessment after the modified Fontan Procedure for hypoplastic left heart syndrome. Circulation 1992;85:116 22. [7] Jonas RA, Hansen DD, Cook N, Wessel D. Anatomic subtype and survival after reconstructive operation for hypoplastic left heart syndrome. J Thorac Cardiovasc Surg 1994;107:1121 8. [8] Forbess JM, Cook N, Roth SJ, Serraf A, Mayer JE, Jonas RA. Ten-year institutional experience with palliative surgery for hypoplastic left heart syndrome risk factors related to stage I mortality. Circulation 1995;92(Suppl II):II262 II266. [9] Lev M. Pathologic anatomy and interrelationship of the hypoplasia of the aortic tract complexes. Lab Invest 1952;1:61 70. [10] Noonan JA, Nadas AS. The hypoplastic left heart sydrome. An analysis of 101 cases. Pediatr Clin North Am 1958;5:1029 56. [11] Mahowald JM, Lucas RV, Edwards JE. Aortic valvular atresia associated cardiovascular anomalies. Ped Cardiol 1982;2:99 105.

592 C. Stamm et al. / European Journal of Cardio-thoracic Surgery 12 (1997) 587 592 [12] Hawkins JA, Doty DB. Aortic atresia: Morphologic characteristics affecting survival and operative palliation. J Thorac Cardiovasc Surg 1984;88:620 6. [13] Aiello VD, Ho SY, Anderson RH, Thiene G. Morphologic features of the hypoplastic left heart syndrome a reappraisal. Pediatr Pathol 1990;10:931 43. [14] Bharati S, Lev M. The surgical anatomy of hypoplasia of the aortic tract complex. J Thorac Cardiovasc Surg 1984;88:97 101. [15] Uemura H, Yagihara T, Kawashima Y, Yamamoto F, Nishigaki K, Matsuki O, Okada K, Kamiya T, Anderson RH. What factors affect ventricular performance after a Fontan-type operation?. J Thorac Cardiovasc Surg 1995;110:405 15. [16] Victor S, Nayak VM. The tricuspid valve is bicuspid. J Heart Valve Dis 1994;3:27 36. [17] Sutton JPIII, Ho SY, Vogel M, Anderson RH. Is the morphologically right atrioventricular valve tricuspid?. J Heart Valve Dis 1995;4:571 5. [18] Frater RW. The right-sided atrioventricular valve (Editorial). J Heart Valve Dis 1994;3:25 26.