Flail Tricuspid and Mitral Valve in Neonatal Lupus

Abstract

Background

Neonatal lupus erythematosus (NLE) typically presents as congenital heart block; flail atrioventricular valve leaflets is especially rare.

Case Summary

A neonate with flail tricuspid and mitral valve resulted in severe atrioventricular valve insufficiency. There were high anti-Ro60 antibody titers consistent with NLE. Steroids and immunoglobulins were administered. Mitral and tricuspid valve repairs were undertaken. An inability to wean from extracorporeal membrane oxygenation led to the mitral valve being replaced with a modified Melody valve and then mechanical mitral valve.

Discussion

This is the first reported case of NLE presenting with bilateral atrioventricular valve chordal rupture, necessitating early valve replacement. This highlights a severe manifestation of NLE and has implications for diagnosis, surveillance, and novel management strategies.

Take-Home Messages

NLE can present with atypical, life-threatening valvular pathology of both the tricuspid and mitral valve. The Melody valve offers a promising bridge to a definitive valve replacement in the mitral position.

Graphical Abstract

History of Presentation

A newborn boy was born at 41 + 2 weeks’ gestation by cesarean delivery, due to failure to progress, to a healthy 26-year-old primigravida woman. He was vigorous at birth with Apgar scores of 8 and 9 at 1 and 5 minutes, respectively, and he was admitted to the postpartum ward with his mother. At 24 hours of life, he became cyanotic. The preductal and postductal saturations were 62%. His heart rate and perfusion were adequate. A grade 3 pansystolic murmur was appreciated on examination. Low-flow oxygen did not improve his saturations. The neonate was started on a prostaglandin (PGE) infusion, empirical antibiotics, and transported emergently to the cardiac critical care unit.

Take-Home Messages

• •Neonatal lupus erythematosus can cause severe valvular dysfunction of both the tricuspid and mitral valve in the neonatal period, making early recognition and antibody testing essential.
• •In cases of severe valvular damage secondary to neonatal lupus erythematosus, a Melody valve may be a viable management option for neonatal mitral valve replacement.

Past Medical History

The pregnancy was uncomplicated with normal prenatal ultrasounds. The mother was healthy, aside from hypothyroidism, and had no known autoimmune disease.

Differential Diagnosis

The differential diagnosis considered for this cyanotic newborn included critical cyanotic heart disease, such as anatomic right ventricular outflow tract obstruction (ie, pulmonary atresia) with cyanosis due to decreased pulmonary blood flow in the setting of patent ductus arteriosus (PDA) closure, transposition of the great arteries with lack of adequate mixing at the atrial level, or total anomalous pulmonary venous return with obstruction. Other etiologies to consider included pulmonary or pulmonary vascular changes (ie, persistent pulmonary hypertension of the newborn), sepsis, central nervous system depression (ie, seizure activity, asphyxia), and metabolic diseases.

Investigations

In the cardiac critical care unit, the newborn was placed on noninvasive positive pressure ventilation for increased work of breathing. An echocardiogram revealed severe tricuspid regurgitation (TR) due to a flail anterior leaflet, with echo bright papillary muscles of both the tricuspid and mitral valves (MVs) (Figure 1). The right heart was dilated, suggesting an acute on chronic process. There was no significant antegrade pulmonary blood flow in the setting of the severe TR, consistent with functional pulmonary atresia. The PDA was small and restrictive. There was good biventricular systolic function. His electrocardiogram showed sinus rhythm with first-degree atrioventricular block (Figure 2).

Figure 1.

Echocardiogram on Day of Life 1 With the Flail Tricuspid Valve

Transthoracic apical 4-chamber images (2-dimensional and color Doppler) of severe tricuspid regurgitation due to flail anterior leaflet (arrow). The papillary muscles of both the tricuspid and mitral valve are shown. The right atrium and ventricle are dilated.

Figure 2.

Initial Electrocardiogram Showed Sinus Rhythm With First-Degree Atrioventricular Block

The flail tricuspid valve, echo bright papillary muscles, and first-degree block prompted a rheumatologic work-up. Anti-Ro60 antibody titers returned high (>1,374 CU), whereas the anti-Ro52 titers were modestly elevated (88 CU) and the anti-La titers were negative (7 CU). These findings confirmed the suspected diagnosis of neonatal lupus erythematosus (NLE).

Management and Outcome

Due to the potential for evolution of cardiac disease with high levels of circulating maternal antibodies, intravenous immunoglobulins (2 g/kg) and pulse steroids were promptly administered. For the functional nature of the pulmonary atresia in the setting of severe TR and high neonatal pulmonary vascular resistance, supportive measures were undertaken. PGE was trialed off unsuccessfully and restarted due to desaturations. On day of life (DOL) 10, the neonate suddenly became acutely cyanotic with decreased perfusion consistent with cardiogenic shock. He was intubated and started on inotropic support. Repeat echocardiogram showed a large PDA on PGE; however, a new flail anterior MV with severe mitral regurgitation (MR) was noted (Figure 3).

Figure 3.

Echocardiogram on Day of Life 10 When the Flail Mitral Valve Occurred

Transthoracic parasternal long-axis images (2-dimensional and color Doppler) of new flail anterior mitral valve (arrow) with severe mitral regurgitation.

The patient underwent emergent MV and tricuspid valve (TV) repairs, and PDA ligation. The MV repair consisted of artificial chords to A1 to A2 and P2 to P3, resection of secondary chords, and extension of the posterior leaflet with treated pericardium. The TV repair included artificial chords to the anterior leaflet, with partial annuloplasty and partial closure of the anteroseptal commissure. The postoperative transesophageal echocardiogram demonstrated mild to moderate MR, mild to moderate mitral stenosis, and mild to moderate TR with no significant inflow gradient, in the setting of severely reduced biventricular systolic function. He was transitioned from bypass to extracorporeal membrane oxygenation (ECMO) for myocardial recovery and transferred to the cardiac critical care unit with an open chest.

On DOL 16, the neonate underwent a successful clamp trial, with subsequent decannulation from ECMO. Unfortunately, post-decannulation, the patient decompensated requiring recannulation. Echocardiogram showed unchanged valvular findings of residual mild to moderate MR and mitral stenosis, and mild to moderate TR, with improved but persistently reduced biventricular dysfunction. Due to both systolic and diastolic dysfunction, it was difficult to ascertain the physiological impact of the MV disease and whether MV replacement would enable the patient to separate from mechanical support. There were extensive discussions within our heart center and with the family. On balance, it was recommended to proceed with MV replacement, albeit with uncertainty as to the impact. The parents preferred a high-risk opportunity to potentially prolong life and understood the likelihood of a prolonged intensive care unit stay even if MV replacement was successful in achieving separation from ECMO.

On DOL 21, the patient returned to the operating room for MV replacement with a modified Melody valve (Medtronic) (stented bovine venous valve). The valve was prepared with a 3.5-mm Goretax graft used as the sewing ring and a V cut into one of the sinuses oriented to the left ventricular outflow tract. The valve was dilated to 12 mm. Postoperative transesophageal echocardiogram showed the Melody valve in good position with mild MR and no stenosis, mild left ventricular outflow tract obstruction, moderate TR, and good function. Intraoperatively, he was placed back on central ECMO for biventricular dysfunction. After postoperative recovery of function, he was successfully decannulated from ECMO on DOL 27.

He was weaned from steroids over a period of 6 weeks, over which time the first-degree block on electrocardiogram resolved. As expected, he has had a prolonged recovery in the intensive care unit. At 4 months of age, there was progression of the left ventricular outflow tract obstruction and severe TR requiring a mitral mechanical valve replacement, left ventricular myectomy, subaortic ridge resection, and TV repair. The patient was discharged at 5 months of age.

Pathology

Pathology specimens of the right atrial endomyocardial tissue, obtained in the first surgery, showed mild and focal areas of fibroelastotic thickening, without evidence of inflammation. Pathology of myocardial and valvular tissue, obtained in the second surgery, showed myocardial necrosis, granulation tissue, chronic histiocytic inflammation, dystrophic calcification, and endocardial fibroelastosis (Figures 4 and 5).

Figure 4.

Gross Specimen

The pathology of myocardial and valvular tissue, obtained in the second surgery.

Figure 5.

Histology of the Mitral Valve Apparatus

The histology image excised mitral valve tissue which highlights the chordal fibrosis with calcification (A), and the papillary muscle tip with a CD68 stain which shows histocyte predominant inflammation (B).

Discussion

NLE is an acquired autoimmune disease occurring in fetuses and infants due to transplacental passage of anti-Ro (anti-Sjögren's syndrome-related antigen A) and, rarely, anti-La (Sjögren syndrome-related antigen B) antibodies.¹ Although the most common and well-known cardiac manifestation of NLE is complete heart block,¹ this case highlights the broad and potentially severe cardiac manifestations of NLE.

This is the first reported case, to our knowledge, of bilateral flail atrioventricular valves in the neonatal period without prenatal diagnosis or detection of maternal antibodies. It is important to recognize the echocardiographic and electrocardiographic features of NLE, to assess anti-Ro and anti-La antibody titers, and to institute anti-inflammatory therapy promptly to prevent further evolution of cardiac disease. Importantly, NLE may occur in the absence of maternal symptoms, known antibody status, or rheumatologic/autoimmune disease.² Prenatal detection likely did not occur in our case due a normal fetal heart rate and subtle, if any, findings present at the time of routine second trimester ultrasound screening.

The pathology suggests a chronic inflammatory process, which is in keeping with transplacental passage of maternal antibodies throughout gestation.³ Although anti-inflammatory therapy may not have mitigated the damage to the chordal architecture, it may have contributed to the restoration of normal conduction and myocardial function, thereby enabling our patient to survive.

The occurrence of both TV and MV flail leaflets in neonates with NLE is exceedingly rare, with only 4 cases in the literature.3, 4, 5, 6 Similar to the reported cases, the TV rupture occurred in the perinatal period. The presence of right heart dilation on neonatal echocardiogram suggests a rupture may have occurred in late gestation. Interestingly, our patient presented with cyanosis due to functional pulmonary atresia as the PDA was closing. The MV rupture occurred later but our patient had the earliest timing of rupture described in the literature, at DOL 10. This time course mirrors the transition from the right ventricle–dominant circulation in the fetus to the left ventricle–dominant circulation in postnatal life, suggesting that hemodynamic burden, in addition to chronic inflammation, plays an important role.

Surgical repair has been reported to be successful in cases of unilateral chordal rupture, but the mortality rate of bilateral chordal rupture is 50%.³ To our knowledge, our patient is the first reported case of neonatal MV replacement for this indication. Our institutional experience with using a modified Melody valve in the mitral position in children has been previously reported.⁷ Monitoring of left ventricular outflow obstruction is essential, particularly when the Melody valve is implanted in the neonatal period.

Conclusions

This case highlights a severe presentation of NLE with TV and MV flail leaflets, in the setting of unknown maternal antibody status. It is important to recognize the features of NLE beyond complete heart block, evaluate for the presence antibodies, and treat with anti-inflammatory therapy as adjunctive management to the critical heart disease. Despite bilateral valve repairs, our patient was unable to wean from ECMO and required replacement of the MV with a modified Melody valve and then mechanical MV. Although rare, a Melody valve may be an evolving option for neonates and infants with extensive and irreversible inflammatory-mediated damage to the chordal apparatus.

Funding Support and Author Disclosures

The authors have reported that they have no relationships relevant to the contents of this paper to disclose.