Br Heart J 1984; 51: 492-7

Endocardial fibroelastosis and hypoplasia of the leftventricle in neonates without significant aortic stenosis

PHILIP C URSELL,* CATHERINE A NEILL, ROBERT H ANDERSON, SIEW Y HO,ANTON E BECKER, LEON M GERLIS

From the Department ofPaediatrics, Cardiothoracic Institute, Brompton Hospital, London; the Department ofPathology, Academisch Medisch Centnrm, University ofAmsterdam and Interuniversity Institute, the Netherlands;and the Cardiac JResearch Unit, Killingbeck Hospital, Leeds

suMMARY Endocardial fibroelastosis in neonates with hypoplasia of the left ventricle is usually

associated with severe aortic stenosis or atresia. In this study three hearts were examined, in whichsevere hypoplasia of the left ventricular cavity with myocardial hypertrophy and endocardialfibroelastosis were associated with small but non-stenotic subaortic outflow tracts and aortic valves.These features were contrasted with those of neonatal left heart hypoplasia in aortic stenosis andatresia. The index cases were examples of the very rare contracted form of endocardial fibroelastosis.

Endocardial fibroelastosis-thickening of theendocardial layer by abundant collagen and elastictissue-is uncommon and usually identified in associ-ation with malformations of the left ventricle. Whencardiac malformations are present the endocardialfibroelastosis is often considered to be secondary tothe malformation, although this is by no meansproved. Endocardial fibroelastosis lining a hypoplasticventricular cavity is, however, usually associated withaortic atresia or severe aortic stenosis. The primaryform of endocardial fibroelastosis is that which occursas a seemingly isolated phenomenon in anatomicallynormal hearts. Although its aetiology andpathogenesis are obscure, primary endocardialfibroelastosis has been related to various factors.1 2Infective3 and metabolic56 agents have been impli-cated as well as the effects of hypoxia7 or lymphaticobstruction.8 Other workers have focused on a non-specific response to raised intramyocardial tension.9Familial incidence is reported in humans and ani-mals,'01' but genetic mechanisms remain unclear.Irrespective of its cause this form of endocardialfibroelastosis, usually associated with a dilated leftventricle, can in most cases be classified as a conges-tive (dilated) cardiomyopathy of childhood.

Requests for reprints to Professor R H Anderson, Department ofPaediatrics, Cardiothoracic Institute, Brompton Hospital, FulhamRoad, London SW3 6HP.

*Present address: Columbia University, New York, USA.

Accepted for publication 1 December 1983

Nevertheless, there is another very rare form ofprimary endocardial fibroelastosis, the so calledrestrictive or contracted form.'2 In this type theendocardial fibroelastosis lines a small left ventricularcavity, but there is no associated mitral valve diseaseor significant outflow tract obstruction. Apart from itsinitial description,'2 we are unaware of any subse-quent detailed account of this entity, although Keithet al have reviewed it in general terms.'3 To date wehave seen three caseg of this rare contracted form ofprimary endocardial fibroelastosis. In this study, weanalysed the clinicopathological features with specialreference to left ventricular morphology and aorticroot size and compared them with those of cases ofhypoplastic left heart syndrome associated with aorticatresia or aortic stenosis.

Materials and methods

The first case (case 1) of neonatal fibroelastosis with-out significant left ventricular outflow tract obstruc-tion was seen recently at the Brompton Hospital,London. To ascertain if similar cases in infants lessthan 1 month old existed with this contracted form ofendocardial fibroelastosis we reviewed the cardiacpathology records at the Brompton Hospital, theHospital for Sick Children, London, the AcademischMedisch Centrum, Amsterdam, and the CardiacResearch Centre, Killingbeck Hospital, Leeds. Twosimilar cases (cases 2 and 3) were found in the Leedsrecords. We also discovered 46 cases of neonatal

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Endocardialfibroelastosis and left heart hypoplaTable Summa of cases

Cas No Age at Cladfixdig NecVfixding(das) MiWalvalve LVwall E ri Sie of Aoc valve

ahickun (i) am (mm)1 1 Pale and cynosed, Small, short Hyperiophied 3 35 il , non-stenotc

pr pses chordae (+++)2 2 PBaerand cyanosed, Small, short Hypertrophi d 1 6 Trikafiet, minimal stenosis

poor pul chordae +++3 3 PakPle d cyanosed, Almost normal Hypertrphied 1.5 6 Trileafiet, non-stenotic

poor puioes (++)

++, moderately; +++, severely; LV, left ventricular.

fibroelastosis in the presence of significant congenitalmalformations of the left side of the heart. From thesewe selected two cases for comparison with the indexcase. All the hearts had been fixed in 10% bufferedformaldehyde. After the heart in case 1 had beenphotographed and sectioned in four chamber longaxis planes (right angles to the inlet part of the ven-tricular septum) a block of tissue incorporating theleft atrium and left ventricle was removed and pre-pared for histological study using standard methods.In addition to haemotoxylin and eosin, sections werestained with Masson's trichrome and elastic vanGieson's stains.

Results

The clinical presentation, investigations, and nec-ropsy findings are shown in the Table.

ANATOMICAL FEATURESAll three hearts were normally structured and con-nected, and the salient features were in the left ventri-cle and its outflow tract. They were remarkably simi-lar in the three cases and can be illustrated by refer-ence to those in case 1. The mitral orifice was smallerthan normal, but the mitral valve leaflets were unre-markable. The tendinous chords of the mitral valve,however, were short and thick (Fig. la). The hyper-trophied slit-like left ventricle was completely linedby a dense white layer of fibrous tissue measuring upto 0.3 cm in thickness (Fig. lb). A thick white cord offibrous tissue traversed the ventricular cavity from theseptum to the anterolateral free wall. The aortic valvewas bicuspid but otherwise normal (Fig. lc), and theaortic annulus measured 0*5 cm in diameter. Thecalibre of the ascending aorta appeared small butmeasured at least 0*35 cm in diameter at all points(Fig. lb). Discrete coarctation of the aorta was notpresent. The duct was closed with a surgical clip.

HISTOLOGICAL FEATURESHistologically, the thickened endocardium was com-posed of numerous spindle shaped fibroblast-like cellsamidst abundant collagenous tissue and elastic fibres

lying parallel with the ventricular cavity (Fig. 2). Sev-eral slit-like crevices (sinusoids) lined by endocardialfibroelastosis extended from the left ventricular cavitythrough the inner one third of the myocardial wall. Inaddition, there was perivascular fibrosis of theintramyocardial vessels. Two small infarcts composedof calcified dense fibrous tissue were identified in themyocardium. The thick cord identified on grossexamination contained a central core of cardiac mus-cle cells around which there were concentric layers offibroelastotic tissue. Except for contraction bands insubendocardial muscle cells, the remainder of themyocardium was histologically normal.

Discussion

In 1960 Edwards classified endocardial fibroelastosisas occurring in a "dilated" and a "contracted" formbased upon the size of the left ventricle.12 Since thisclassification was introduced it has been used bypathologist and cardiologist alike.1415 Of the manycases of the contracted form of endocardial fibroelas-tosis, the overwhelming majority are associated withsignificant left ventricular outflow tract obstruction.They comprise the so called hypoplastic left heartsyndrome6 17 and some cases of critical neonatal aor-tic stenosis.'819 The contracted form of endocardialfibroelastosis without significant left ventricularoutflow tract obstruction or other major cardiac mal-formations is rarely reported.13 In neonates it is a veryrare condition.

Since the left ventricular outflow tract was not obs-tructed in any of our cases, they are examples of prim-ary endocardial fibroelastosis or at least primary car-diomyopathy with reactive endocardial fibroelastosis.The concept of endocardial fibroelastosis representingreactive tissue which increases in thickness with timehas been emphasised by others.41120 In our casesmuch of the thickness of the left ventricular wall wasfibroelastotic tissue. Even without the endocardialfibroelastosis, however, the myocardial hypertrophywas severe (Fig. lb). The relatively inelastic andpoorly compliant fibroelastotic tissue undoubtedlyfurther constrained the distensibility and compliance

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:411. ~~~~~~~~~~Leftventrifcle

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Endocardialfibroelastosis and left heart hypoplasia

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Fig. 2 Histological section ofthe left ventricle showing the abnormally thick endocardiwm (E) overlying myocardium (M). Slit-likecrevices (sinusoids (S)) are lined by thickened endocardiwn. A healed myocardial infarct (I) consisting ofcalcjfied densefibrous tissue ispresent within the subendocardial region. At higher magnjfication (inset) the endocardial tissue is seen to contain wavy dark stainingelasticfibres lying parallel.

of the left ventricle before and after birth.The small calibre of the ascending aorta was pre-

sumably a consequence of diminished blood flowthrough the ascending aorta secondary to left ven-tricular dysfunction in utero. Aortic size has been cor-related with left ventricular volume in animal fet-uses.21 In case 1 the diameter of the ascending aortacorresponded to that of a 26 week human fetus andin cases 2 and 3 to that of one of 28 weeks.22 Thisalmost certainly indicates that the left ventricular dis-ease antedated the twenty eighth week of gestation.We compared the cases of endocardial fibroelastosis

without significant outflow tract obstruction with acase of endocardial fibroelastosis associated with mod-erately severe aortic stenosis and a case of endocardialfibroelastosis associated with aortic atresia. The leftventricles of the two latter hearts were small teardropshaped cavities with appreciably hypertrophied ven-tricular walls (Fig. 3). There was a gradation in theamount of fibroelastotic tissue from less than 0*5 mmthickness in the case of aortic atresia to 3 mm in the

left ventricle of the Brompton case without significantoutflow tract obstruction. The mitral valves of all thehearts were somewhat hypoplastic but otherwisenormal. Patency of the mitral orifice appeared to be aprerequisite for the development of endocardialfibroelastosis in the left ventricle.'3 Clearly, the leftventricular cavity is grossly distorted when the "con-tracted" form of endocardial fibroelastosis is present.We believe that this is the major adverse factoraccounting for the usually poor outcome of thesepatients23: neonates with critical aortic stenosis, hypo-plasia of the ascending aorta, and endocardialfibroelastosis with sinusoids have a poor prognosiswith or without surgery.'8 19By limiting our study of endocardial fibroelastosis

to necropsy findings in neonates of less than 1 monthold we minimised complicating factors such as timeand treatment. Primary endocardial fibroelastosis inolder children may well be a process similar to thatoccurring in infants, but the onset of the disease is lesswell defined. In our cases the disorder was unequivoc-

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(c) (d)Fig. 3 Long aisfour chmber sewn though a heart with aoric stenouis ((a) and (b)) compared with a heart wih aoruc atrra ((c) and(d)). Note modem endocanfiiklfe t lnig of the kft vercl the heart wth a stenowc a c vale (AoV). RV, nght vencl;LV, kft vtricle; RA, rightam , LA, left atrium.

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ally of intrauterine onset. The course of the diseaseprocess was therefore less than 10 months and prob-ably less than four months since organogenesis wascomplete and the aortic root sizes were equal to or lessthan those of a 28 week fetus. By focusing on cases ofprimary endocardial fibroelastosis which haddeveloped over a relatively short and well definedperiod of time, the aetiology and pathogenesis of thisdisease process may be clarified. Certain other sci-entific tools, such as electron microscopy andimmunohistochemistry, may be of use in this regard.

At the time of the study CAN was a visiting professorfrom the Department of Paediatrics, Johns HopkinsUniversity, Maryland, USA. RHA and SYH are sup-ported by the Joseph Levy Foundation and the Brit-ish Heart Foundation. LMG is supported by theNational Heart Research Fund.

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3 Factor SM. Endocardial fibroelastosis: myocardial andvascular alterations associated with viral-like nuclear par-tides. Am HeartJ 1978; 96: 791-801.

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