Endocardial Fibroelastosis as an Independent Predictor of Atrioventricular Valve Rupture in Maternal Autoimmune Antibody Exposed Fetus: A Systematic Review with Clinicopathologic Analysis

Abstract

Background: Neonatal lupus (NL) is a clinical syndrome that develops in the fetus as a result of maternal autoimmune antibodies. Congenital complete heart block (CHB) is the most common manifestation, while extranodal cardiac manifestations of NL, such as endocardial fibroelastosis (EFE) and myocarditis, are rare but more serious. Less is known about this atrioventricular valve rupture due to valvulitis as a consequence of maternal autoantibodies. We have described a case of cardiac neonatal lupus with an antenatally detected CHB patient who developed mitral and tricuspid valve chordal rupture at 45 days of age. We compared the cardiac histopathology and the fetal cardiac echocardiographic findings of this case with another fetus that was aborted after being antenatally diagnosed with CHB but without valvar rupture. A narrative analysis after a systematic review of the literature regarding atrioventricular valve apparatus rupture due to autoimmune etiology along with maternal characteristics, presentation, treatment, and outcome have been discussed in this article.

Objectives: To describe published data on atrioventricular valve rupture in neonatal lupus, including clinical presentation, diagnostic evaluation, management, and outcomes.

Methods: We conducted a PRISMA-compliant descriptive systematic examination of case reports that included accounts of lupus during pregnancy or in the newborn period that resulted in an atrioventricular valve rupture. We gathered information on the patient's demographics, the details of the valve rupture and other comorbidities, the maternal therapy, the clinical course, and the results. We also used a standardized method to evaluate the cases' quality. A total of 12 cases were investigated, with 11 cases drawn from 10 case reports or case series and 1 from our own experience.

Results: Tricuspid valve rupture (50%) is more common than mitral valve rupture (17%). Unlike mitral valve rupture, which occurs postnatally, the timing of tricuspid valve rupture is perinatal. A total of 33% of the patients had concomitant complete heart block, while 75% of the patients had endocardial fibroelastosis on an antenatal ultrasound. Antenatal changes pertaining to endocardial fibroelastosis can be seen as early as 19 weeks of gestation. Patients with both valve ruptures generally have a poor prognosis, especially if they occur at close intervals.

Conclusion: Atrioventricular valve rupture in neonatal lupus is rare. A majority of patients with valve rupture had antenatally detected endocardial fibroelastosis in the valvar apparatus. Appropriate and expedited surgical repair of ruptured atrioventricular valves is feasible and has a low mortality risk. Rupture of both atrioventricular valves occurring at close intervals carries a high mortality risk.

Keywords: anti La/SSB antibodies; anti-Ro/SSA antibodies; complete heart block; endocardial fibroelastosis; maternal autoantibodies; mitral valve rupture; neonatal lupus; tricuspid valve rupture.

Figure 1

Case A: (a) M-mode echocardiogram showing atrioventricular dissociation; ‘a’ shows atrial contractions and ‘V’ shows ventricular contractions. (b) Antenatal echocardiogram, four-chamber view, showing hyperechoic papillary muscles (white arrow) in the left ventricle (LV) and right ventricle (RV). RA—right atrium, LA—left atrium. (c) Antenatal echocardiogram, four-chamber view, showing mild tricuspid regurgitation (white arrow) and no mitral regurgitation with normal atrioventricular valves.

Figure 2

Case A—Postnatal electrocardiogram showing complete heart block. There is complete atrioventricular dissociation, an atrial rate of 125 bpm, and a ventricular rate of 52 bpm.

Figure 3

Case A: (a) Postnatal echocardiogram—four-chamber view showing normal mitral and tricuspid valves. Hyperechoic papillary muscles (yellow arrow) were noted. RA—right atrium, LA—left atrium, RV—right ventricle, LV—left ventricle. (b) Immediate postnatal echocardiogram, long axis view, showing no regurgitation of the mitral valve. Ao—Aorta. (c) Postnatal echocardiogram, short axis at the level just below the mitral valve, showing hyperechoic papillary muscles in the left (bottom) and right (top) ventricles (white arrow).

Figure 4

Case A: (a) Echocardiogram, four-chamber view with color doppler showing severe tricuspid regurgitation (pink arrow) and severe mitral regurgitation (green arrow) noted on day 45 of life. (b) Echocardiogram, four-chamber view, demonstrating ruptured chordae resulting in prolapse of tricuspid valve leaflets (white arrow) and mitral valve leaflets (pink arrow). *—Pericardial effusion. (c) 2D and color doppler long axis views of the mitral valve showing valve prolapse (pink arrow in 2D image) and severe mitral valve regurgitation (white arrow in color image) (d) Modified long axis view on a 2D echocardiogram, showing rupture of the tricuspid valve chordae (pink arrow) and severe tricuspid regurgitation (white arrow). (e) Echocardiogram, four-chamber view of ruptured mitral valve leaflet chordae causing mitral valve prolapse (white arrow). (f) X-plane color doppler image on a 2D echocardiogram showing severe mitral regurgitation (black arrow).

Figure 5

Case B: (a) M-mode echocardiogram showing atrioventricular dissociation in the fetus. A—atrial contractions; V—ventricular contractions. (b) Echocardiogram, four-chamber view—hyperechoic papillary muscle (white arrow in RV and LV).

Figure 6

(a) Case A—postmortem gross morphology: mitral valve with ruptured chordae of the anterior leaflet of the mitral valve resulting in shrunken leaflets (black arrow). Calcified chordae (blue arrow). (b) Case A—postmortem gross morphology: mitral valve with retraction and loss of leaflet tissue (black arrow). Calcified/fibrotic chordae (brown arrow). (c) Case B—postmortem gross morphology: left ventricle showing normal mitral valve leaflets (*). Fibrotic/calcified chordae and papillary muscle tips (black arrows).

Figure 7

Case A: (a) Hematoxylin and eosin-stained section (original magnification 4×) of the left ventricular papillary muscle with calcified tip (green arrow). *—ruptured chordae showing fibrosis. (b) Hematoxylin and eosin-stained section (original magnification 10×) of the atrioventricular node area with calcification (green arrow) and fibrosis (*). (c) Hematoxylin and eosin-stained section (original magnification 20×) of the myocardium (black arrow) and pericardium (light blue arrow) showing extensive subpericardial calcification (green arrow) extending to the myocardium. (d) Hematoxylin and eosin-stained section (original magnification 10×) of the coronary artery (black arrow), which showed no inflammation.

Figure 8

Case B: (a) Hematoxylin and eosin-stained section of the atrioventricular node (original magnification 10×)—calcification (black arrow), fibrosis (*), granulation tissue with neovascularization (red arrow). (b) Hematoxylin and eosin-stained section (original magnification 10×) of the atrioventricular node—acute inflammatory changes with granulation tissue (*), multinucleated giant cell (black arrow). (c) Hematoxylin and eosin-stained section (original magnification 4×) of the right ventricular papillary muscle with chordae. (d) Hematoxylin and eosin-stained section (original magnification 10×) of the right ventricular papillary muscle with chordae, fibrosis (green arrow), and calcification (black arrow).

Figure 9

PRISMA flow diagram for systemic review.

Figure 10

(a) Venn diagram showing tricuspid valve rupture (TV) in 50% (n = 6), mitral valve rupture (MV) in 17% (n = 2), and both mitral and tricuspid valve rupture (MV+TV) in 33% (n = 4). (b) Target chart showing patients with valve rupture (n = 12), of whom 75% (n = 9) had changes of endocardial fibroelastosis (EFE) reported and 33% (n= 4) had complete heart block (CHB).

Figure 11

Pie chart showing mothers who received no antenatal therapy (n = 5), steroids only (n = 4), and intravenous immunoglobulin (IVIG) and steroids (n = 3).

Figure 12

Bar chart showing the timing of rupture for the tricuspid valve (TV) and mitral valve (MV). X-axis: age of valve rupture from 34 to 40 weeks antenatal and subsequently postnatal. Y-axis: number of patients.

Figure 13

Bar chart showing valve involvement (blue) and mortality (orange). X-axis represents the valve involved. Y-axis shows the number of patients.