B ergm an FETAL ECHO DOPPLER FOR EARLY DETECTION OF CONGENITAL HEART BLOCK

Background: Fetal echo Doppler methods, detecting prolonged atrioventricular (AV) time intervals a mechanical PR interval corresponding to the electrical PR interval in ECG, have been proposed for surveillance of pregnancies at risk of complete congenital heart block (CCHB). The aim of this thesis was; to validate these Doppler methods by comparing AV time intervals from left ventricular inflow (MV), inflow and aortic outflow (MV-Ao) and superior vena cava and aortic flow (SVC-Ao) with ECG in newborns (Paper I); to investigate the significance of mechanical components in AV time prolongation (Paper II); to evaluate the diagnostic precision in a target population (Paper III) and to verify childhood outcome of fetuses, exposed to maternal anti-SSA/Ro antibodies (SSA),(Paper IV). Results: Paper I In 22 healthy newborns, close positive linear relationships to the PR interval were demonstrated for all approaches. Doppler techniques using the aortic flow to indicate ventricular activation overestimated the PR interval; limits of agreement (mean difference±2SD) were +32±15.4 ms (MV-Ao) and +22±14.0 ms (SVC-Ao). The MV approach, excluding the isovolumetric contraction time (ICT) by using mitral closure to indicate ventricular activation, did not overestimate the PR interval but were found to underestimate the PR intervals as time intervals increased. Paper II In 78 fetuses exposed to SSA, followed weekly during 18 to 24 gestational weeks (g.w.), strong positive relationships were found between ICT and MV-Ao time intervals (r = 0.91, p < 0.001), as well as between ICT and time intervals obtained from the SVC and aorta (r = 0.85, p < 0.001). ICT was estimated to contribute more than 50% of the total AV time prolongation. Paper III The prevalence of first-degree AV block at birth was 13.8% in our cohort of 95 fetuses exposed to SSA. MV-Ao and SVC-Ao time intervals with a 95% reference range had a sensitivity of 91.7% and NPV of 98.4%. Corresponding PPV/LR+ for MV-Ao and SVCAo were 42.3%/4.5 and 47.8%/ 5.7 respectively. ROC curves generated optimal cut offs at 134-138 ms (MV-Ao) and 132-138 ms (SVC-Ao). MV demonstrated a sensitivity of just 50%. Paper IV Pre school outcome of 57 children, fetally exposed to SSA, demonstrated longer PR interval in individuals with fetally prolonged Doppler AV time intervals (group A) compared to individuals with normal fetal Doppler (group B), 140±24 ms vs. 121 ± 13 ms (p<0.01). First degree AV block (1°AVB) developed in 6 cases in group A, despite normal ECG at 1 month of age. Prenatal Doppler predicted 1°AVB with a sensitivity of 100 %, PPV 37.5%, LR+ 5.1 and NPV 100%. Signs of mild myocardial impairment were seen in one case. Conclusion: Fetal echo Doppler is suitable for early detection of fetuses with prolonged AV time intervals, indicating first degree AV block and/or mildly impaired cardiac performance. However, an isolated prolonged AV time interval is rarely a predicting sign of developing CCHB. These observations suggest that a prolonged AV time interval is an indication for closer surveillance, withholding treatment with fluorinated steroids until detection of signs of second-degree AV block or endomyocardial disease. LIST OF PUBLICATIONS I. G Bergman, L-A Jacobsson, M Wahren-Herlenius, S-E Sonesson. Doppler Echocardiographic and Electrocardiographic Atrioventricular Time Intervals in Newborn Infants: Evaluation of Techniques for Surveillance of Fetuses at Risk for Congenital Heart Block Ultrasound Obstet Gynecol. 2006 Jul;28(1):57-62 II. G Bergman, H Eliasson, K Bremme, M Wahren-Herlenius, S-E Sonesson. Anti-Ro52/SSA antibody exposed fetuses with prolonged atrioventricular time intervals show signs of decreased cardiac performance Ultrasound Obstet Gynecol. 2009 Nov;34(5):543-9 III. G Bergman, M Wahren-Herlenius, S-E Sonesson. Diagnostic precision of Doppler flow echocardiography in fetuses at risk for atrioventricular block Ultrasound Obstet Gynecol. 2009. DOI 10.1002/uog.7532 IV. G Bergman*, H Eliasson*, L-A Mohlkert, M Wahren-Herlenius, S-E Sonesson. Children exposed to anti-SSA/Ro52 antibodies. A mid term follow up study of conduction and myocardial function *Equal contribution (Manuscript in process) The papers are referred to by their Roman numerals in the thesis.