Severe Tricuspid Insufficiency as a Manifestation of Neonatal Lupus

Valve dysfunction is an infrequent condition in infants of anti-Ro/SSA-positive pregnancies, but a few cases have suggested an association between rupture of the atrioventricular (AV) valve tensor apparatus and maternal anti-Ro/SSA antibodies. In the present study, we describe a patient with severe tricuspid insufficiency due to a flail, whose mother has an asymptomatic rheumatological disorder, and the progression from fetal life to the moment surgery was performed.


Introduction
Neonatal lupus (NL) describes a clinical spectrum of cardiac and non-cardiac abnormalities observed in neonates and fetuses whose mothers have the auto-antibodies anti-SSA⁄ Ro (anti-Ro) and anti-SSB ⁄ La (anti-La). Congenital complete heart block is the most common and (recognized) wellknown cardiovascular manifestation of NL that can occur in utero or after birth. Nonetheless, manifestations such as endocardial fibroelastosis (EFE), pericarditis, myocarditis, cardiomyopathy or coronary artery disease may occur [1].
Valve dysfunction is an infrequent condition in infants of anti-Ro/SSA-positive pregnancies, but a few cases have suggested an association between rupture of the atrioventricular (AV) valve tensor apparatus and maternal anti-Ro/SSA antibodies. Different hypotheses for the mechanism by which these antibodies mediated the condition been suggested [1,2].
In the present study, we describe the case of a patient with valve dysfunction secondary to rupture of the papillary muscle of the tricuspid valve affected by maternal anti-Ro antibodies and we review the published data for infants of anti-Ro positive pregnancies with A-V valve insufficiency due to chordal rupture of the papillary muscles.

Case report
A 26-year-old first-gravida mother was checked routinely at 20 weeks of gestation. Fetal echocardiogram showed a structurally normal heart and focal areas of increased echogenicity at the level of the papillary muscles and chordae of both atrioventricular (AV) valves ( Figure 1). The heart rhythm was normal. Rheumatologic prenatal profile was positive for anti-Ro and anti-La antibodies and the mother was completely asymptomatic during pregnancy.
During the following weeks, those patchy echogenicity areas almost disappeared and only minimal residual patchy infiltrates limited to the tricuspid valve chordae were seen on an otherwise normal echocardiogram. Neither insufficiency nor stenosis was detected. Routine follow-up at 39 weeks of gestation showed pleural effusion that required ultrasound-guided drainage. Emergency cesarean section was performed due to fetal hydrops. A 2.2 kg female newborn was delivered and soon after birth required high-frequency ventilation and nitric oxide therapy in association with diuretic and inotropic support.   Tricuspid valve insufficiency worsened and transesophageal echocardiography revealed that the mechanism of the regurgitation was due to a flail of the anterior tricuspid valve leaflet.
The patient was operated thought a median sternotomy. Cardiopulmonary by-pass was achieved and after aortic cross-clamp, the heart was stopped with the infusion of anterograde hematic cold cardioplegia. A longitudinal auriculotomy showed a free prolapse of the anterior leaflet due to missing papillary muscle and respective cordae attachments. The free wall of the right ventricle was hypertrophic and a thick bundle muscle was partially detached from the free wall of the right ventricle to be used as a neo-papillary muscle. Then the anterior leaflet of the tricuspid valve was directly attached to the neo-papillary muscle The fetal injury occurs as a consequence of the transplacental passage of maternal autoantibodies against the intracellular ribonucleoproteins 48-kDa SSB/La, 52-kDa SSA/Ro, and 60-kDa SSA/Ro. SSA / Ro is a complex system that comprises at least two 52 and 60 kD molecular weight polypeptides, respectively. A small central portion of 52 kD Ro, from 200 to 239 amino acids, called p200 seems to have a major role since it could represent the specific region of the union of the anti-Ro associated with congenital heart block [1].
The cardiac manifestations associated with NL are the most serious. Although the most common disorder reported in the literature is complete heart block, which accounts for up to 60-90% of all congenital heart blocks [2], several manifestations have been reported, some of them not well known.
The clinical and serological features of NL syndrome have been extensively described; however, publications detailing the anatomical pathology findings in the heart are limited [3,4].
The majority of the initially reported cases have shown fibrosis and/or calcification of the atrioventricular (AV) node, but the disease can also extend to other areas of the conduction system, including the findings of progressive sinus node and infrahisian conduction system abnormalities, atrial flutter and, in several cases, sinoatrial (SA) nodal scarring has been described [5,6,7,8].
EFE has been previously demonstrated in pathology studies of anti-Ro/La-exposed fetuses with and without the presence of heart block, and it is currently acknowledged as part of the spectrum of cardiac NL [3,9,10,11].

Valvular abnormalities have been only rarely reported.
Nield et al [10]. described dystrophic and calcified mitral valve papillary muscles in the post-mortem study of an anti-La positive but anti-Ro negative female fetus with diffuse EFE, as well as calcification of the SA and AV nodes. Litsey et al [12] have previously reported one of the cases with tricuspid valve dysplasia.
Although the papillary muscles and chordae of the AV valves are common sites of patchy echogenicity, severe AV-valvular insufficiency due to dysfunction of the tensor apparatus has rarely been reported [1].
Cuneo et al. [4] has described several cases of fetal endocardial fibroelastosis with rupture of the valvular tensor apparatus. One of the afore-mentioned is an anti-Ro / SSA-positive case, in which the patient presented fetal endocardial fibroelastosis and postnatal echocardiogram with increased echogeninicity at the level of the tricuspid valvular apparatus. Spontaneous interruption of the tensioning device of the AV valve could also be seen, as well as severe tricuspid insufficiency. Consequently, the patient required surgery in which interruption of the anterior valvular junctions from the head of the papillary muscle was The last of the afore-mentioned cases related to tricuspid valve dysplasia has been reported by Fleming et al. [14] in which a mother presented prenatal diagnosis with anti-SSA / Ro positive. The fetus had complete AV block and fibroelastosis. The presence of an alteration in the papillary muscles and pulmonary stenosis was confirmed after birth, which required a pacemaker placement. 3 months afterward, there was an emergency in which the newborn presented a 50% saturation. The echocardiogram showed a bright echo in the distal papillary muscle with severe tricuspid regurgitation. The newborn was taken to surgery, where the rupture of the distal portion of the anterior papillary muscle was confirmed and repaired. The evolution is seen in the patient after surgery was favorable [14].
The pathogenesis of the papillary muscle chordal rupture may be similar to that proposed for the autoimmune AV block. Maternal anti Ro/La antibodies bind to fetal cardiocytes and inhibit the normal physiological removal of these apoptotic cells, resulting in inflammatory reaction and fibrosis of the cardiac conduction system. In the same way that autoantibodies bind to the specialized cells of the conduction system, they would also bind to the cardiac myocytes at the cords and/or the papillary muscles, evoking an inflammatory response with subsequent fibrosis and, ultimately, muscle chordal rupture [1].
Despite the scarcity of cases reported, there is some evidence that the most important histopathological findings have shown severe atrophy with the replacement of the myocytes by fibrosis and dystrophic calcifications of the papillary muscles. This contrasts with the finding of no histopathological lesions on the VA leaflets, as has been reported in patients with anti Ro-mediated AV block. The reason may lie in the different embryological origin of the valves and cords, which derive from the endocardium, in contrast with the papillary muscles, which derive from the myocardium. As other studies suggest, the immune-mediated injury is directed directly at the myocardial-derived cell lines [4].
Perhaps the initial inflammatory insult could be suppressed, although to date preventive treatments such as maternal steroids, intravenous immunoglobulin and plasmapheres is have not decreased the incidence, and their use in the prevention of heart block is currently very controversial. Maybe maternal exposure to hydroxychloroquine may decrease the risk of cardiac NL [15].
The spectrum of maternal anti-Ro/anti-La antibody-associated with fetal cardiac disease may have previously been underappreciated. Valvular abnormalities in the setting of anti-Ro-positive pregnancies have rarely been reported. We have described the rare clinical picture of a patient whose mother had anti-Ro-positive antibodies, resulting in AV valve insufficiency due to chordal rupture from the papillary muscles. These find-