Myocarditis, flail tricuspid valve, and normal rhythm: an exceptional form of neonatal cardiac lupus.

Neonatal cardiac lupus is a rare, passively acquired autoimmune disease. We report a case of in utero myocarditis, confirmed postnatally, with papillary muscle rupture and severe tricuspid regurgitation after birth in the absence of conduction disturbances. Tricuspid repair was successfully performed with polytetrafluoroethylene neochordae. In this article, we discuss the pathophysiology, medical and surgical management, and implications at follow-up in this unique scenario.

[Familial predisposition and microbial etiology in dilated cardiomyopathy]. / Familiäre Prädisposition und mikrobielle Atiologie bei dilatativer Kardiomyopathie.

Cardiomyopathies are an important and diverse group of heart muscle diseases in which the heart muscle itself is structurally or functionally abnormal and in which coronary artery disease, hypertension, valvular and congenital heart disease are absent or do not sufficiently explain the observed myocardial abnormality. This often results in severe heart failure accompanied by arrhythmias and/or sudden death. Clinical and morphological diversity of cardiomyopathies can reflect the broad spectrum of distinct underlying molecular causes or genetic heterogeneity. In many cases the disease is inherited and is termed familial dilated cardiomyopathy (FDC), which may account for up to 30% of dilated cardiomyopathies (DCM). FDC is principally caused by genetic mutations in FDC genes that encode for cytoskeletal, nuclear and sarcomeric proteins in the cardiac myocyte. In addition, modifying genes, lifestyle and additional factors were reported to influence onset of disease, disease progression, and prognosis. The individual patient's phenotype may reflect a summation and/or interaction of the underlying mutation(s) with other genetic or environmental factors. During the last years major advances have been made in the understanding of the molecular and genetic basis of this type of disease. Nevertheless, much more progress in the identification of underlying mutations, susceptibility genes and modifier genes is important and indispensable for the development of new etiology-orientated forms of therapy. A pivotal role for autoimmunity in a substantial proportion of patients with DCM is supported by the presence of organ-specific autoantibodies, inflammatory infiltrates and pro-inflammatory cytotoxic cytokines. Furthermore, familial occurrence of DCM goes ahead with the presence of autoantibodies and abnormal cytokine profiles in first-degree relatives with asymptomatic left ventricular enlargement. These relatives suffer from a higher risk for the development of DCM after years. This suggests the involvement of a disrupted humoral and cellular immunity early in the development of the disease. There is reasonable clinical and experimental evidence, that DCM in addition may occur as late stage of cardiac infection and inflammation. The large spectrum of clinical forms depends on several factors such as genetic determinants of the infective agent, the genetics, age and gender of the host, and the host immunocompetence. In general, infectious agents, including viruses such as entero-, cytomegalo-, and adenoviruses, bacteria such as Borrelia burgdorferi or Chlamydia pneumoniae, protozoa and even fungi can cause inflammatory heart disease leading to DCM. The infectious agents most often identified in DCM nowadays are parvovirus B19, human herpesvirus 3, and Epstein-Barr virus. Persistence of these viruses within the myocardium is associated with reduction of ejection fraction after 6 months. For patients with suspected inflammatory heart disease the immunohistochemical detection of inflammatory infiltrates is related to poor outcome. Many faces of inflammatory heart disease coexist where different phases of the disease progress simultaneously: phase 1 is dominated by viral infection itself, phase 2 by the onset of (probably) multiple autoimmune reactions, and phase 3 by the progression to cardiac dilatation. Further investigations with regard to the etiology of structural heart diseases should include an intensive clinical investigation of the given patient. A possible family history including a pedigree should be ascertained and with regard to a possible inflammatory or viral heart disease, endomyocardial biopsies should be investigated by polymerase chain reaction and immunohistochemistry.

[Fetal ultrasonography and Doppler in isolated congenital heart block]. / Echographie et Doppler foetaux dans le bloc auriculoventriculaire congénital d'origine immunologique.

Isolated congenital heart block is linked to transplacental passage of maternal anti-SSA/Ro and/or anti-SSB/La antibodies that may be related to a connective tissue disease. Ultrasonography and Doppler are essential to screen fetus at risk. They allow the diagnosis of first- and second-degree blocks which are probably preliminary stages in conducting tissue's injury. In these situations, a maternal treatment by fluorinated steroids can be proposed because of its possible effect on partial blocks. However, these early signs of nodal injury can be lacking: some fetus present a complete heart block without previously detected less advanced block. Moreover, the significance of first-degree block is unclear since it could reverse spontaneously. Other markers of nodal injury would be valuable. In case of complete congenital heart block, ultrasonography is useful to detect congestive heart failure and help the obstetrical management when unfavorable prognostic signs occur.

Neonatal lupus erythematosus with congenital heart block and severe heart failure due to myocarditis and endocardititis of the mitral valve.

We report a case of neonatal lupus erythematosus (NLE) with congenital heart block and severe myocardial failure, which was followed from the 25th week of gestation because of fetal bradycardia. The child was delivered at the 37th week of gestation by elective cesarean section because of echocardiographically documented heart enlargement, pericardial effusion and moderate insufficiency of the mitral and tricuspid valves. In spite of immediate pacing, intubation and supportive treatment, the newborn developed progressive heart failure. Echocardiography showed endocarditis of the mitral valve and diffuse myocarditis. The heart failure resolved under steroid treatment. Our experience supports the early use of steroids in treating myocarditis due to NLE. Intrauterine steroid treatment in the presence of fetal hydrops and congenital heart block is discussed.

[Clinico-morphological changes in congenital carditis in children]. / Kliniko-morfologicheskie izmeneniia pri vrozhdennykh karditakh u detei.

The clinico-morphological alterations were analyzed in 6 deceased children with congenital carditis. Morbid anatomy examination demonstrated that all the patients had marked alterations on the part of the heart while 4 cases manifested associated injuries to the heart and to the brain. In half of the children, the disease had run its course in combination with immunodeficiency. In 2 cases, there was an etiological relationship between congenital carditis and intrauterine enterovirus Coxsackie infection which had been uneventful in pregnant mothers. In congenital carditis, the prognosis may be often unfavourable.

Congenital toxoplasmic myocarditis: case report of an unusual presentation.

Extensive calcification of the heart, involving predominantly the right ventricle and interventricular septum, was observed in a 3-h-old baby. The aetiology of the condition was attributed to infection by Toxoplasma gondii, based on the presence of several visceral lesions allied to the identification of the microorganism. The case is reported in view of the rarity of the type of the heart lesion. It is considered that calcification of the myocardium is secondary to vascular, inflammatory or toxic condition. The factors implicated in the pathogenesis of this unusual myocardial lesion are discussed.

[Clinical-instrumental diagnosis of myocardial diseases in the newborn infants and their treatment]. / Kliniko-instrumental'naia diagnostika zabolevanii miokarda u novorozhdennykh i ikh lechenie.

The authors provide the results of clinico-instrumental examinations of 120 neonates with myocardial pathology. Depending on the data obtained the clinical injuries to the myocardium were distributed into congenital myocarditis, hypertrophic cardiomyopathies and posthypoxic cardiopathies. Criteria for their diagnosis and treatment are described. The results of the follow-up studies of these children aged 6 months and 1 year are provided.

Systemic gas embolus: a discussion of its pathogenesis in the neonate, with a review of the literature.

We report, a term newborn infant with congenital vocal cord paralysis and congenital viral myocarditis. In her five days of life she developed a pneumomediastinum, pneumopericardium, subcutaneous emphysema, and terminally a pneumothorax and systemic air embolus. This unusual case is used to develop a concept of the pathogenesis of extraventilatory air, and is also represented in diagrammatic form.

Myocardial aneurysm in association with disseminated cytomegalovirus infection.

An infant with disseminated cytomegalovirus infection and apical aneurysm of the left ventricle died. At autopsy the coronary arteries were anatomically normal, but there was occlusion of the left anterior descending artery with an inflammatory lesion and corresponding organized thrombus. It seemed likely that cytomegalovirus infection acquired in utero may have induced an endothelial lesion, leading to thrombosis, occlusion, apical myocardial infarction, and eventual aneurysm formation.

[Fetal complete heart block with myocarditis and maternal SS-A-/AA-B/antibodies]. / Fetaler kompletter Herzblock und Myokarditis bei mütterlichen SS-A-/SS-B-Antikörpern.

We report on a newborn with fetal acquired heart block (CHB). CHB is a rare, irreversible defect, commonly occurring in conjunction with myocarditis in the neonatal lupus syndrome. Development of CHB is strongly associated with maternal anti-SS-A(Ro)/SS-B(La) antibodies. Intrauterine therapy of CHB is not possible. Concomitant myocarditis, however, can be treated effectively with dexamethasone. Mothers with an elevated risk of fetal CHB can be identified by their history (underlying systemic connective tissue disease, previous pregnancies with CHB), an immunogenetic predisposition (HLA-DR3) and analysis of the SS-A/SS-B antibody pattern. In these pregnancies prevention of CHB with plasmapheresis plus dexamethasone during pregnancy may be possible.

[The role of congenital Enterovirus infection in the pathogenesis of suppurative and inflammatory diseases in newborn infants]. / Uchastie vrozhdennoi énterovirusnoi infektsii v patogeneze gnoino-vospalitel'nykh zabolevanii u novorozhdennykh.

Newborns with suppurative-inflammatory disease were found to be at high risk of intrauterine infection with Coxsackie enteroviruses from mothers with persistent enterovirus infection; in 54.9%, congenital Coxsackie virus infection was confirmed by virus antigen identification in the urine sediment cells and autopsy material. Coxsackie A viruses were identified in 68.7% of sepsis cases, 42.6% with local purulent infection foci, and in only 6.7% of practically healthy neonates. Specific features of the clinical course are analysed together with the pathohistological picture of congenital enterovirus infection associated with the vertical virus transmission from the mother having a persistent form of this infection. A suggestion is proposed that the severe course of suppurative-inflammatory conditions and the general character of neonatal bacterial infection are largely determined by the immunodeficient states which are etiologically related to congenital enterovirus infections.

Immunohistologic evidence supports apoptosis, IgG deposition, and novel macrophage/fibroblast crosstalk in the pathologic cascade leading to congenital heart block.

OBJECTIVE: To assess in vivo the pathologic cascade leading to fibrosis in congenital heart block (CHB). In vitro studies suggest that CHB is initiated via apoptosis, resulting in translocation of SSA/Ro and SSB/La antigens and surface binding by maternal autoantibodies. These opsonized cardiocytes are phagocytosed by macrophages, which secrete factors inducing fibrosis. METHODS: Immunohistochemistry analysis was performed on formalin-fixed sections of 4 fetal hearts identified in utero as having CHB or isolated myocarditis; mothers had anti-SSA/Ro and anti-SSB/La antibodies. RESULTS: Apoptosis was most extensive in fetuses dying early and most pronounced in regions containing conduction tissue. Deposition of IgG was observed in hearts from fetuses with CHB/myocarditis, but not in 3 control hearts, and was colocalized with apoptotic cells. Giant cells and macrophages (frequently seen proximal to IgG and apoptotic cells) were present in septal and thickened fibrous subendocardial regions, most apparent in the youngest fetuses. Septal tissue also revealed extensive areas of fibrosis and microcalcification in which a predominant smooth muscle actin (SMA)-positive infiltrate (myofibroblast scarring phenotype) was observed. In contrast, there were no macrophages or SMA-positive cells (other than those lining blood vessels) in septal tissue from control hearts, although rare macrophages were seen in the working myocardium. CONCLUSION: In summary, findings in this unique autopsy material paralleled those in in vitro studies. These data support the notion of exaggerated apoptosis, probably due to ongoing inflammation caused by IgG binding and ingestion by macrophages. Transdifferentiation of cardiac fibroblasts to a scarring phenotype may be a pathologic process initiated by maternal antibodies, and persistence of this phenotype even after birth may relate to the progression of block seen in some infants postpartum.

Diagnostic and perinatal management of fetal extrasystole.

Fifty fetuses referred to the Polish Mother's Memorial Hospital for fetal echocardiography between January 1, 1991 and June 1, 1995 were evaluated. The mean fetal gestational age at the time of diagnosis of arrhythmia was 34.1 weeks, and the mean gestational age at the time of delivery was 38.7 weeks. Checkup echocardiographic examinations were performed every 10-14 days, for a mean 2.4 studies per fetus. In most cases (48/50, 96%), premature atrial contractions were present during the first echocardiography examination. The fetal heart study was normal in 30 cases; in 7 (14%) there was tricuspid valve regurgitation, in 7 (14%) an atrial septal aneurysm, in 4 congenital heart defects, in 1 myocardial hypertrophy, and in 1 disproportion in the four-chamber view. Of the 50 fetuses, 43 underwent regular echocardiographic monitoring alone; in 7 cases, based on the presence of additional echocardiographic findings, pharmacotherapy was applied (digoxin, verapamil, or both). Three neonates died after delivery owing to malformations in two cases (one critical aortic stenosis, one spina bifida plus hygroma colli) and due to myocarditis in one case. In six of seven newborns treated in utero, myocarditis was diagnosed after birth (including the one with neonatal demise). Most of the newborns were in good condition after birth, their mean Apgar score being 8.6 and the mean birth weight 3259 g. We concluded that most extrasystoles represent an isolated anomaly, not affecting the fetal condition. Their presence should not influence the obstetric care and may require only echocardiographic monitoring. In most of our cases the premature contractions subsided after birth, although sometimes they preceded fetal supraventricular tachycardia or appeared after congenital myocarditis.