Congenital heart block : a study of diagnostics, pathogenesis, prognosis and treatment

Abstract: Congenital heart block (CHB) is a rare condition with considerable mortality. In most patients the disease is associated with fetal exposure to maternal SSA-Ro and/or SSB-La autoantibodies (AB) and develops in fetal life. Accuracy in fetal diagnostics is important to distinguish benign from life threatening conditions. Transplacental steroid treatment to improve survival has been tried but the effect is unclear. The majority of exposed children do not develop CHB, but sometimes transitory conduction abnormalities, normalizing at birth, with unknown outcome in childhood. Pacemaker (PM) therapy to CHB patients is lifesaving, but does not always prevent development of heart failure. The aims of this thesis were to study: The differential diagnostics in fetal bradycardia (paper I), the effect of transplacental steroid treatment and risk factors associated with a poor outcome (paper II), the clinical pathogenesis of antibody exposure (paper III) and PM treatment in young patients with complete atrioventricular block (CAVB) (paper IV). In paper I, the diagnostic accuracy with Echo Doppler techniques was studied retrospectively in a regional cohort of 65 patients with fetal bradycardia. We found that the bradyarrhythmic mechanism was identified correctly in all but one patient. Benign blocked atrial bigeminies showed close resemblance to second-degree AVB in a few cases, but could be differentiated with meticulous measurements. In paper II, the effects of exposure to transplacental treatment with fluorinated steroids in fetal second- and third degree AVB were studied retrospectively in a multicenter, multinational setting of 175 patients. Ninety-one percent were alive at birth and survival rate in the neonatal period was 93%, similar in treated and untreated fetuses. Risk factors (RF) associated with a poor outcome were gestational age < 20 weeks, ventricular rate =50, hydrops and impaired left ventricular function (LVF) at diagnosis. The presence of =1 RF was associated with a 10-fold increase in mortality before birth and a 6-fold increase in the neonatal period, independent of treatment. In paper III, the effects of prenatal exposure to maternal autoantibodies on heart function and conduction properties were investigated in a cross-sectional follow-up of pre-school children who did not develop fetal complete heart block. Sixteen patients who developed AV time interval prolongation in utero (group A) were compared with 41 who did not (group B). Ten percent (6/57) exposed to maternal autoantibodies in fetal life had developed first- degree AVB at follow-up, in spite of a normal ECG at birth or at 1 month of age. All 6 had prolonged AV-time intervals in utero. LVF in terms of M-mode, was normal in all patients, but myocardial performance index was slightly higher in group A. In paper IV, the outcome of young patients with CAVB and PM was studied retrospectively in a national cohort of 127 patients. Survival rate after 9 years of PM treatment was 96% and 8% developed LV dysfunction. There was a gender difference in cardiac status prior to PM but not at FU. Exposure to antibodies did not change the outcome significantly, but diagnosis <1 month of age and LV dysfunction before PM were associated with a poor outcome.