Congenital atrioventricular block: histological aspects

M.D. Piercecchi-Martia,*, H. Mohamedb, C. Chauc, A. Liprandib, C. Fredouilleb

aService de Medecine Legale, CHU Timone 264 rue Saint-Pierre, 13005 Marseille, FrancebService d’Anatomie Pathologique et Neuropathologie, CHU Timone 264 rue Saint-Pierre,

13005 Marseille, FrancecPavillon Urgence Generale Mere Enfant, CHU Nord Chemin des Bourrely,

13015 Marseille, France

Received 17 January 2001; accepted 19 May 2003

Abstract

It is known that maternal immunological factors such as systemic disease are involved in the genesis of cardiac conduction

problems in the fetus but the histologic changes in the conduction system are less documented. We report the case of a 33-year-

old woman with no significant medical history. Her first pregnancy was induced by Clomifene. At 17 weeks of gestation, the

fetus presented sonographic abnormalities characteristic of a complete atrioventricular block. Biological investigations found

anti-SSA and -SSB antibodies. Clinical history search for systemic disease was positive for photosensitivity, lasting 10 years,

suggesting the diagnosis of systemic lupus erythematosus.

The patient was treated with prednisone 20 mg per day but fetal death occurred at 29 weeks of gestation. Histological

examination of the fetal heart showed an altered atrioventricular node and bundle of His with fibrosis, calcifications, endocardial

fibroelastosis and mononucleated inflammatory cells.

The search for these specific lesions can be determinant in establishing the disease pathogenesis; also, it is important to

eliminate this diagnosis in an unexplained fetal death.

# 2003 Elsevier Ireland Ltd. All rights reserved.

Keywords: Histopathology; Conduction system; Fetus; Forensic practice

1. Introduction

The maternal immunological factors responsible for

cardiac conduction abnormalities in the fetus are well

known. Systemic lupus erythematosus is the maternal

pathology incriminated in 80% of the cases. However,

only 25% of studies reported this diagnosis at the time

of the ultrasonographic detection of the fetal atrioventri-

cular block [1,2]. The cardiac damage is documented in 12

cases in the literature, only 3 cases of which are in the fetus

[3–10].

Further knowledge of these specific lesions may be a

determining element in the diagnosis of intrauterine fetal

death in the second trimester, because the heart block

cannot be recorded in the first sonographic examination.

We report an observation and detail the myocardial

damages.

2. Case report

2.1. Case history

A 33-year-old pregnant woman with no significant past

medical history presented ultrasonographic anomalies char-

acteristic of fetal complete atrioventricular block at 17

weeks of gestation. This was her first pregnancy, induced

by Clomifene. The heart was moderately dilated with ven-

tricular bradycardia at 60/min, in addition to atrioventricular

dissociation. There was no pericardial or pleural effusion.

No morphological anomalies could be detected.

Anti-SSA and anti-SSB antibodies were detected. Photo-

sensitivity for 10 years was reported in the clinical history.

Forensic Science International 136 (2003) 12–15

* Corresponding author. Tel.: þ33-491-38-63-85;

fax: þ33-491-38-79-77.

E-mail address: mpiercecchi@ap-hm.fr (M.D. Piercecchi-Marti).

0379-0738/$ – see front matter # 2003 Elsevier Ireland Ltd. All rights reserved.

doi:10.1016/S0379-0738(03)00224-X

This suggested the diagnosis of systemic lupus erythema-

tosus, and the patient was treated with prednisone 20 mg per

day. In spite of treatment, fetal death was observed at 29

weeks.

2.2. General autopsy findings

At autopsy, the male fetus presented normal anthropo-

metric parameters for gestational age. The weight was

1440 g, the crown-heel length was 43 cm, the crown-rump

length 28 cm, the head circumference 28 cm, and the foot-

length 6.5 cm.

Viscera were in place without anomaly in form or in

volume.

The heart weighed 12.5 g (normal weight) and presented

bilateral ventricular dilatation. Coronary distribution was

normal. The thickness of the right and left ventricles was

normal. There were no atrial or septal defects. Placenta was

normal.

2.3. Histological examination

Histological examination of the myocardium showed

moderate non-inflammatory fibrosis in the region of the

Fig. 1. Extensive intramural fibrosis and dystrophic calcifications in the right atrioventricular junction (original magnification: 100�). The

upper right inset is the magnification of the squared region in order to highlight the calcifications (original magnification: 400�).

Fig. 2. Longitudinal section of the atrioventricular junction with septal wall (gross photograph of the slide). The left upper inset is

the magnification of the white squared region and showed foci of lymphohistiocytic infiltrates in the atrioventricular. The right lower inset

is the magnification of the black squared region and showed segmental disappearance of the right bundle of His junction (original

magnification: 400�).

M.D. Piercecchi-Marti et al. / Forensic Science International 136 (2003) 12–15 13

atrioventricular node. The lesion involved mostly the atrio-

ventricular node and nervi nervorum with fibrosis of the

coronary adventitia.

Multiple calcifications were present in the atrioventricular

junction (Fig. 1), and in the interventricular septum, includ-

ing the first fourth of the bundle of His. Inflammatory foci

involving mononucleated cells, lymphocytes, and histio-

cytes (Fig. 2) were present all over the endocardium.

Orcein staining confirmed the presence of elastic fibers

associated with collagen fibers all over the septal endocar-

dium (Fig. 3), the right ventricle, and to a slight extent, the

left septal side. The fibroelastosis was responsible for lacera-

tion and segmental disappearance of the right bundle of His

(Fig. 2). The myocardium showed mild changes. There was

discrete interstitial edema without alteration of the myo-

cytes. Immunostaining by lymphocyte antibodies (Dako,

Trappes, France) detected sparsely disseminated lympho-

cytes in the myocardial interstitium.

Immunohistochemical study performed with anti-C9

antibody (a sensitive marker of early ischemic damages)

(The Binding-Side, Birmingham, UK) showed positive

expression in the cytoplasm of the myocytes surrounding

the fibrosis area.

Histological study of liver, skin, and placenta revealed no

specific changes.

3. Discussion

Congenital atrioventricular block is rare (1/20,000 preg-

nancies). It is usually complete (but first and second branch

block was also described) [11] and irreversible (but one

transitional case in neonatal period was reported) [12]. It can

be detected by ultrasonography from 16 weeks of gestation,

the time when the atrioventricular node-His connection

becomes functional, but the investigation is usually done

at 23 weeks.

Experimentally, it was found that the affection of the

conduction system is related to the passive transfer of

anti-SSA � anti-SSB antibodies of IgG type by endocytosis

at the level of trophoblastic cells. Antibodies fixed on the fetal

cardiac antigen induced direct cytotoxicity on the cells with

lymphocytic inflammatory reaction. On the other hand, they

interfered with calcium and potassium transport, resulting in

a ventricular repolarization problem [4]. It has been sug-

gested that the complement system may be involved in the

two mechanisms, yet our immunohistochemical study with

anti-C9 antibody (the binding side) failed to confirm that.

Anatomo-clinical correlation concerned 12 cases from 16

weeks gestation to 5.5 years and only 3 fetal cases [3–10].

Histological lesions are apparently specific and well defined

as regards their localization in the cardiac conduction sys-

tem. We can classify these lesions into early and late. In this

case, we observed the late one:

1. Early lesions (at 17–19 weeks of gestation): There is a

lymphohistocytic infiltration affecting the conduction

system and the myocardium starting with atrioventri-

cular node fibrosis [10,13].

2. Late lesions (beginning at 23 weeks of gestation):

Macroscopically, authors observe aneurysm of ventri-

cular septum [10], a unilateral or bilateral ventricular

dilation as in our report, a right ventricular hypertrophy,

and pericardial and pleural effusion. In the atrioven-

tricular node, the lesions are similar to ours and

correspond to collagenic fibrosis accompanied by

massive calcifications, and dissociation of the fibers of

the right bundle of His. Endocardial fibroelastosis is the

Fig. 3. Diffuse endocardial fibroelastosis (original magnification: 25�). In the left lower inset, fibroelastosis was observed with Orcein

staining (original magnification: 200�).

14 M.D. Piercecchi-Marti et al. / Forensic Science International 136 (2003) 12–15

consequence of the repair of the immunological

aggression.

Histochemical studies demonstrated the presence of IgG

anti-RO (SSA) antibody type in the myocardium of a still-

born who died at birth from a complete atrioventricular

block [9]. These depositions were not limited to the con-

duction tissue but diffused through all the myocardium in

spite of the absence of inflammatory infiltration [9,14].

Differential diagnosis must consider infectious myocar-

ditis of viral origin (coxsackies) [15]. One must search for

myocytic damage, microabscesses, and affection of other

organs; we did not observe this damage in our case. A

myocardial infarction may be also proposed but in our case

the lesions were not limited to the conduction system,

moreover the vascular walls and the lumina were free [16].

Calcification was described for trisomy 13 and 21 [17].

Apart from the dysmorphism and the characteristic malfor-

mations, inflammation affected the epicardium. There was

no fibrosis and the nodal tissue was not predominantly

involved. In our case, karyotype was normal.

For the fetus, it is generally admitted that if the ventricular

rate remains higher than 60/min, pregnancy can continue

until term but the fetus must be taken care of at birth [14].

Complications involve rapid cardiac failure, pericardial and

pleural effusions, tricuspid incompetence, and decreased

pressure in the aorta and pulmonary arteries; the mortality

reaches 31% by cardiac failure and syncopal attacks of

Adams–Stokes type [10].

Among patients, 10–20% will develop cutaneous lupus

and/or hepatic or hematologic alterations [18].

In conclusion, the search for these specific lesions in the

conduction system in an unexplained fetal death can be

determinant in forensic practice.

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